FitSugar

Stressed Out? Jaw massage

FitSugar — Wed, 29 Nov 2006 14:45:00 -0800

When you're stressed out do you clench your jaw? If you answered yes you are not alone, because at least there are two of us. It's an unconscious habit and when I am stressed it can get bad. Even a little painful. Here's what I do in those moments and you should try it too.

Make fists with both of your hands and put your knuckles just under your cheek bones. Move your knuckles up and down, then side to side. Try different places between your cheek bone and your jaw bone. Chances are, you will find little pockets of tightness just waiting to be massaged.

Then allow your jaw to drop and take a nice BIG yawn - this gives the area a bit of a stretch and will get some much needed oxygen to your brain.

Fit's Tip: The jaw joint was made to move up and down, not side to side. So it isn't a great idea to move your chin from side to side.

Periodontal disease

FitSugar — Wed, 08 Oct 2008 17:35:31 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Symptoms of Periodontal Disease

Symptoms of periodontal disease include red and swollen gums, persistent bad breath, and gum recession and loose teeth. Smoking, certain types of illnesses (diabetes), older age, and other factors increase the risk for periodontal disease. If you have periodontal disease, your dentist may refer you to a periodontist, a dentist who specializes in treating this condition.

Practice Good Dental Hygiene

Consistent good dental hygiene can help prevent gingivitis and periodontitis. The American Dental Association recommends that everyone:

Brush twice daily with a fluoride toothpaste (be sure to replace toothbrushes every 3 - 4 months).
Clean between the teeth with floss or an interdental cleaner.
Eat a well-balanced diet and limit between meal snacks.
Have regular visits with a dentist for teeth cleaning and oral examinations.

Mouthwashes

In 2007, the American Dental Association stated that antimicrobial mouthwashes may provide additional oral health benefits for preventing and reducing gingivitis and plaque. However, they are not a substitute for daily brushing and flossing.

Research

Intensive treatment of periodontal disease may help reduce inflammation and improve blood flow throughout the body, according to a small study published in 2007 in the New England Journal of Medicine. In the study of patients with severe periodontitis, intensive treatment ultimately resulted in improved endothelial function. Poor endothelial function is associated with increased risk for atherosclerosis and heart disease. Researchers are investigating the connection between periodontal disease and heart disease, and whether treatment of periodontal disease can reduce heart disease risk.

Introduction

Periodontal disease refers to a group of problems that arise in the sulcus, the gap between the gum and the tooth.

The part of the mouth that consists of the gum and supporting structures is called the periodontium. It is made up of the following parts:

Gum (gingiva). When healthy, the gingiva is pale pink, firm, and does not move. It has a smooth or speckled texture. The gingival tissue between teeth is shaped like a wedge.
The space between the gum and tooth, called the sulcus
Root surface (the cementum)
Connective tissue
Bone. The crest of the supporting bone, which can be viewed on x-rays, is normally 2 mm below the point where the crown of the tooth meets the root (the cementoenamel junction).

The structure of the tooth includes dentin, pulp and other tissues, blood vessels, and nerves imbedded in the bony jaw. Above the gum line, the tooth is protected by the hard enamel covering.

Periodontal diseases are generally divided into two groups:

Gingivitis, which causes lesions (wounds) that affect the gums
Periodontitis, which damages the bone and connective tissue that supports the teeth

The process starts with bacteria. Even in healthy mouths, the sulcus is teeming with bacteria, but they tend to be harmless varieties. Periodontal disease develops usually because of two events in the oral cavity: an increase in bacteria quantity and a change in balance of bacterial types from harmless to disease-causing bacteria. These harmful bacteria increase in mass and thickness until they form a film called plaque.

Click the icon to see an image of plaque and damaged gum tissue.

In healthy mouths, plaque itself actually provides some barrier against outside bacterial invasion. When it accumulates to excessive levels, however, plaque sticks to the surfaces of the teeth and adjacent gums and causes cellular injury, with subsequent swelling, redness, and heat.

When plaque is allowed to remain in the periodontal area, it transforms into calculus (commonly known as tartar ). This material has a rock-like consistency and grabs onto the tooth surface. It is much more difficult to remove than plaque, which is a soft mass.

The most important component leading to the disease process, however, is the body's persistent immune response to the bacterial plaque. Specific immune factors are released that cause inflammation and damage that eventually destroys the support structures and bone and can lead to tooth loss.

Gingivitis is an inflammation of the gingiva, or gums. Is nearly always chronic, but an acute form infrequently occurs.

Chronic Gingivitis. Ordinary chronic gingivitis affects over 90% of the population. It is characterized by tender, red, swollen gums that bleed easily and may be responsible for bad breath (halitosis) in some cases. Treatment is very effective if initiated early in the course of gingivitis. Without good management, however, the problem can progress.

Periodontitis is characterized by the following:

Gum inflammation, with redness and bleeding.
Deep pockets (greater than 3 mm in depth) form between the gum and the tooth.
Loose teeth, caused by loss of connective tissue structures and bone.

Gingivitis precedes periodontitis, although it doesn't always lead to this more severe condition. In fact, some experts believe it is an entirely different disease. There are different categories of periodontal disease, including:

Chronic Periodontitis. Chronic periodontitis (also referred to as adult periodontitis) may begin in adolescence as a slowly progressing disease that becomes clinically significant in the mid-30s and continues throughout life. Some experts question whether it is a chronic, unrelenting condition and instead suggest that it waxes and wanes depending on the response of the immune system.

Aggressive Periodontitis. Aggressive periodontitis (also referred to as early onset periodontitis) often occurs in young people. It is subdivided according to whether it begins before or after puberty. Immune deficiencies and a genetic link have been shown to be possible factors for all types of aggressive periodontitis. If the condition is localized and treated, the outlook is positive. People with severe and widespread aggressive periodontitis are at high risk for tooth loss.

Periodontitis that occurs before puberty is very rare. It begins with the eruption of primary teeth in the first year and causes severe inflammation and bone and tooth loss.
Juvenile periodontitis begins at puberty and is defined by severe bone loss around the first molars and incisors. It is more common in girls than in boys. The clinical signs -- such as inflammation, bleeding, and heavy plaque accumulation -- are not present in this relatively rare disease. The treatment is the same as in chronic periodontitis.
Rapidly progressive periodontitis occurs in the early 20s to mid-30s. Severe inflammation and rapid bone and connective tissue loss occur, and tooth loss is possible within a year of onset.

Disease-Related Periodontitis. Periodontitis can also be associated with a number of systemic diseases, including type 1 diabetes, Down syndrome, AIDS, and several rare disorders of white blood cells.

Acute Necrotizing Periodontal Disease. Acute necrotizing periodontal disease is an acute infection in the gums. It is characterized by:

Black, dead tissue (necrosis)
Spontaneous bleeding
Rapid onset of pain
Bad odor
Blunted gum tissue (tissue is normally cone-shaped)

Stress, poor diet, smoking, and viral infections are predisposing factors for this acute necrotizing periodontal disease.

Symptoms

In general, symptoms progress over time and include:

Red and Swollen Gums
Gum Bleeding. Bleeding of the gums, even during brushing, is a sign of inflammation and the major marker of periodontal disease. One exception is juvenile periodontitis, in which symptoms are mild or even absent. It should be noted that the gums of smokers with periodontal disease tend to bleed less than nonsmokers.
Bad Breath. Debris and bacteria can cause a bad taste in the mouth and persistent bad breath.
Gum Recession and Loose Teeth. As the disease advances the gums recede, and supporting structure of bone is lost. Teeth loosen, sometimes causing a change in the way the upper and lower teeth fit together when biting down or a change in the fit of partial dentures.

Abnormally bulging, protruding, or swollen gums are a possible sign of disease.

Click the icon to see an image of recessed gums.

Abscesses. Deepening periodontal pockets between the gums and bone can become blocked by tartar or food particles. Infection-fighting white blood cells become trapped and die. Pus forms, and an abscess develops. Abscesses can destroy both gum and tooth tissue, cause nearby teeth to become loose and painful, and may cause fever and swollen lymph nodes.

Click the icon to see an image of a tooth abscess.

Pain is usually not a symptom, which partly explains why the disease may become advanced before treatment is sought and why some patients avoid treatment even after periodontitis is diagnosed.

Causes

Periodontal disease is marked by bacterial overgrowth. However, a persistent immune response to chronic infections in the mouth is believed to play a major role in gum destruction.

In the healthy mouth, more than 350 species of microorganisms have been found. Periodontal infections are linked to fewer than 5% of these species. Healthy and disease-causing bacteria can generally be grouped into two categories:

The harmless or helpful bacteria are usually known as gram positive aerobic bacteria.
In periodontal disease, the bacterial balance shifts over to gram negative anaerobic bacteria. Inflammatory disease and injury cannot develop without these bacteria.

Following are some of the bacteria most implicated in periodontal disease and bone loss:

Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. These two bacteria appear to be particularly likely to cause aggressive periodontal disease. Both P. gingivalis and A. actinomycetemcomitans, along with multiple deep pockets in the gum, are associated with resistance to standard treatments for gum disease. P. gingivalis may double the risk for serious gum disease. P. gingivalis produces enzymes, such as one called arginine-specific cysteine proteinase, which may be the specific destructive factors that disrupt the immune system and lead to subsequent periodontal connective tissue destruction.
Bacteroides forsythus is also strongly linked to periodontal disease.
Other bacteria associated with periodontal disease are Treponema denticola, T. socranskii, and P. intermedia. These bacteria, together with P. gingivalis, are frequently present at the same sites, and are associated with deep periodontal pockets.

Some bacteria are related to gingivitis, but not plaque development. They include various streptococcal species.

Evidence now suggests that periodontal disease is an autoimmune disorder, in which immune factors in the body attack the person's own cells and tissue -- in this case, those in the gum. It appears to work as follows:

The bacteria that form plaque and tartar release toxins that stimulate the immune system to overproduce powerful infection-fighting factors called cytokines.
Ordinarily, cytokines are important for healing. In excess, however, they can cause inflammation and severe damage. Cytokines of particular importance in periodontal disease are known as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta, which are very active in the mouth, and are important in causing destructive inflammation.
In addition, white blood cells produced by the immune response to bacteria also release a family of enzymes called matrix metalloproteinases (MMPs), which break down connective tissue.

Studies suggest that this inflammatory response may have damaging effects not only in the gums but also in organs throughout the body, including the heart.

Certain herpes viruses (herpes simplex and varicella-zoster virus, the cause of chickenpox and shingles) are known causes of gingivitis. Other herpes viruses (cytomegalovirus and Epstein-Barr) may also play a role in the onset or progression of some types of periodontal disease, including aggressive and severe chronic periodontal disease. All herpes viruses go through an active phase followed by a latent phase and possibly reactivation.

Some experts theorize that these viruses may cause periodontal disease in different ways, including release of tissue-destructive cytokines, overgrowth of periodontal bacteria, suppressing immune factors, and initiation of other disease processes that lead to cell death.

Risk Factors

More than 75% of American adults have some form of gum disease, but according to a major survey, only 60% have any significant knowledge about the problem. Gum inflammation and ulcers are common, and not all people with these problems develop periodontal disease. Still, about 30% of people are genetically susceptible to periodontal disease. Other factors also put individuals at higher risk.

Lack of Oral Hygiene. Lack of oral hygiene encourages bacterial buildup and plaque formation.

Sugar and Acid. The bacteria that cause periodontal disease thrive in acidic environments. Therefore, eating sugars and other foods that increase the acidity in the mouth increase bacterial counts.

Poorly Contoured Restorations. Poorly contoured restorations (fillings or crowns) that provide traps for debris and plaque can also contribute to its formation.

Anatomical Tooth Abnormalities. Abnormal tooth structure can increase the risk.

Wisdom Teeth. Wisdom teeth, also called third molars, can be a major breeding ground for the bacteria that cause periodontal disease. In fact, for patients in their 20s, periodontal disease is most likely to occur around the wisdom teeth. Research suggests that periodontitis can occur in wisdom teeth that have broken through the gum as well as teeth that are impacted (buried). Periodontal disease can also be present even in patients with wisdom teeth who do not have any symptoms. Experts recommend that adolescents and young adults with wisdom teeth should have a dentist check for signs of periodontal disease

Children and Adolescents. Gingivitis, in varying degrees, is nearly a universal finding in children and adolescents. In rare genetic cases, children and adolescents are subject to destructive forms of the disease. Researchers have also observed some of the organisms seen in periodontal disease in young children without signs of gum problems. Healthy children, however, do not generally harbor two primary periodontal bacteria, P. gingivalis and T. denticola. The disease is also uncommon in teenagers.

Adults. One survey reported that 3.6% of adults between the ages of 18 - 34 had periodontal disease. As people age, the risk for periodontal disease increases. Over half of American adults have gingivitis surrounding 3 - 4 teeth, and 30% have significant periodontal disease surrounding 3 - 4 teeth. In a study of people over 70 years old, 86% had at least moderate periodontitis and over a quarter of them had lost their teeth.

About three-quarters of periodontal office visits are made by women, even though women tend to take better care of their teeth than men. Female hormones affect the gums, and women are particularly susceptible to periodontal problems. Hormone-influenced gingivitis appears in some adolescents, in some pregnant women, and is occasionally a side effect of birth control medication.

Before Menstruation. Gingivitis may flare up in some women a few days before they menstruate, when progesterone levels are high. Gum inflammation may also occur during ovulation. Progesterone dilates blood vessels causing inflammation, and blocks the repair of collagen, the structural protein that supports the gums.

Pregnancy. Hormonal changes during pregnancy can aggravate existing gingivitis, which typically worsens around the second month and reaches a peak in the eighth month. Pregnancy does not cause gum disease, and simple preventive oral hygiene can help maintain healthy gums. Any pregnancy-related gingivitis usually resolves within a few months of delivery. Because periodontal disease can increase the risk for low-weight infants and cause other complications, it is important for pregnant women to see a dentist.

Oral Contraceptives. Some studies report that oral contraceptives containing the synthetic progesterone desogestrel (but not dienogest, another common progesterone) increase the risk for periodontal disease.

Menopause. Estrogen deficiency after menopause reduces bone mineral density, which can lead to bone loss. Bone loss is associated with both periodontal disease and osteoporosis. Bone loss in the alveolar bone (which holds the tooth in place) may be a major predictor of tooth loss in postmenopausal women. Periodontal disease is the main cause of alveolar bone loss. During menopause, some women may also develop a rare condition called menopausal gingivostomatitis, in which the gums are dry, shiny, and bleed easily. Women may also experience abnormal tastes and sensations (such as salty, spicy, acidic, burning) in the mouth.

Periodontal disease often occurs in members of the same family. Genetics, intimacy, hygiene, or a mixture of factors may be responsible. Studies have found that children of parents with periodontitis are 12 times more likely to have the bacteria thought to be responsible for causing plaque and, eventually, periodontal disease.

Genetic Factors. Genetic factors may play the critical role in half the cases of periodontal disease. Up to 30% of the population may have some genetic susceptibility to periodontal disease. For example, some people with severe periodontal disease have genetic factors that affect the immune factor interleukin-1 (IL-1), a cytokine involved in the inflammatory response. Such individuals are up to 20 times more likely to develop advanced periodontitis than those without these genetic factors. Early onset and rapidly progressive periodontal disease also have strong genetic components.

Intimacy. Intimate partners and spouses of people with periodontal disease may also be at risk. Researchers have found that the bacteria P. gingivalis may be contagious after exposure to an infected person over a long period of time. There is no risk from short exposure such as after a fast kiss or when sharing an eating utensil.

Smoking is the single major preventable risk factor for periodontal disease. The habit can cause bone loss and gum recession even in the absence of periodontal disease. A number of studies indicate that smoking and nicotine increase inflammation by reducing oxygen in gum tissue and triggering an over-production of immune factors called cytokines (specifically ones called interleukins). In excess, cytokines are harmful to cells and tissue.

Furthermore, when nicotine combines with oral bacteria, such as P. gingivalis, the effect produces even greater levels of cytokines and eventually leads to periodontal connective tissue breakdown. Studies suggest that smokers are 11 times more likely than nonsmokers to harbor the bacteria that cause periodontal disease and four times more likely to have advanced periodontal disease. In one study more than 40% of smokers lost their teeth by the end of their lives.

The risk of periodontal disease increases with the number of cigarettes smoked per day. Smoking cigars and pipes carries the same risks as smoking cigarettes. Exposure to secondhand smoke is also associated with a 50 - 60% increased risk for developing periodontal disease, according to one study. Fortunately, when smokers quit, their periodontal health gradually recovers to a state comparable to that of nonsmokers.

Diabetes. Much evidence exists on the link between type 1 and 2 diabetes and periodontal disease. Diabetes causes changes in blood vessels, and high levels of specific inflammatory chemicals such as interleukins, that significantly increase the chances of periodontal disease. High levels of triglycerides (which are common in type 2 diabetes) also appear to impair periodontal health. Obesity, common in people with type 2 diabetes, may also predispose a person to gum disease. Controlling both type 1 and 2 diabetes may help reduce periodontal problems. For children with diabetes, good oral hygiene should begin at a young age. A 2006 study suggested that gum problems can start as early as 6 years of age in children with diabetes.

Osteoporosis and Osteonecrosis. Osteoporosis (loss of bone density) has been associated with periodontal disease in postmenopausal women. There have also been a few reports of osteonecrosis (bone decay) of the jaw in patients who take oral bisphosphonate drugs such as alendronate (Fosamax). Symptoms of osteonecrosis of the jaw include loose teeth, exposed jawbone, pain or swelling in the jaw, gum infections, and poor healing of the gums. As a precaution, the American Dental Association (ADA) recommends that patients who are prescribed bisphosphonate drugs get a thorough dental exam before beginning drug therapy, or as soon as possible after beginning therapy. The ADA also recommends that patients who take oral bisphosphonate drugs should discuss with their dentists any potential risks from dental procedures (such as extractions and implants) that involve the jawbone. In any case, be sure to inform your dentist if you are taking a bisphosphonate drug.

Osteoporosis is a condition marked by progressive loss of bone density, thinning of bone tissue, and increased risk of fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements can reduce and may even reverse loss of bone density.

Giving intravenous bisphosphonates to patients being treated for bone cancer, or other cancers that have spread to the bone, increases their risk for developing osteonecrosis by 1 - 10%. Patients who take oral bisphosphonate drugs also have a slight risk, but 94% of osteonecrosis of the jaw cases involve patients who received bisphosphonates intravenously. If possible, see a dentist for a complete oral exam before beginning bisphosphonate therapy. In any case, be sure to inform your dentist if you are receiving intravenous bisphosphonates. Your dentist or oral surgeon may need to take special precautions when performing dental surgery

Herpes-Related Gingivitis. Herpes virus is a common cause of gingivitis in children and has become increasingly common in adults. It typically starts out with a purplish color and "boggy" sensation in the gums. Multiple blisters may form across the mucus membranes in the mouth and gums, followed by ulcers. They usually resolve in 7 - 14 days.

HIV-Associated Gingivitis. HIV-associated gingivitis has been reported in 15 - 50% of patients with HIV or AIDS. HIV-positive individuals harbor larger numbers of periodontal bacteria (candida albicans, P. gingivalis, black-pigmented anaerobic rods, and A. actinomycetemcomitans) than people without HIV. Severe pain is characteristic, along with odor, spontaneous bleeding, ulcers, and swollen, bright red gums. The inflammation never recedes, but halitosis and acute episodes can be managed by conventional cleaning treatments. Its severest form, known as necrotizing stomatitis, can be diagnostic for AIDS. In addition to bleeding, the gums in the front of the mouth are a yellowish-gray color, and bone thrusts out.

Autoimmune Diseases. Autoimmune conditions (Crohn's disease, multiple sclerosis, rheumatoid arthritis, lupus erythematosus, CREST syndrome) have been associated with a higher incidence of periodontal disease. Some research suggests that periodontal disease may even play some causal role. For example, one study suggested that P. gingivalis, one of the major bacteria in periodontal disease, was associated with destructive processes in the brain leading to multiple sclerosis. Still, more research is needed to determine a definitive association between these diseases.

Other Diseases. People with tuberculosis, syphilis, Wegener's granulomatosis, amyloidosis, and many genetic disorders are also at higher risk for periodontitis.

Vitamin C helps the body repair and maintain connective tissue, and its antioxidant effects are important in the presence of tissue-destroying oxidants in periodontal disease. Research indicates that vitamin C deficiency contributes to periodontal disease. A study of more than 12,000 adults found that people who consumed less than the recommended daily allowance of vitamin C, 60 mg (about one orange) were 1.5 times more likely to develop severe gingivitis than those who consumed more than 180 mg each day. Vitamin C levels are especially depleted in smokers. Eating citrus fruits high in vitamin C (such as grapefruit) may be helpful for patients with periodontitis.

Click the icon to see an image of the benefits of vitamin C.

Click the icon to see an image of the sources of vitamin C.

Dental disease is most likely to affect the poor. Children and the elderly suffer the worst oral care, and ethnic minorities follow. In the United States, the lack of access to dental insurance is a contributing factor. In a survey of residents of five states (Arizona, California, Hawaii, Oregon, and Wisconsin), the rate of total tooth loss was less than 20%. In three states (Kentucky, Louisiana, and West Virginia) it was greater than 40%.

Gingival overgrowth can be a side effect of nearly 20 different drugs, most commonly phenytoin (Dilantin), cyclosporine (Sandimmune), and a short-acting form of the calcium channel blocker nifedipine (Procardia).

Several other conditions can also cause gum inflammation, and some have been associated with periodontal disease. They include:

Mouth breathing
Psychologic stress. Stress can affect the immune system. Some studies suggest that stress can influence the development of chronic inflammatory diseases, like periodontitis.
Alcohol abuse. One study reported a higher incidence of periodontal disease, tooth decay, and possibly precancerous areas in patients who abuse alcohol.
Canker sores (aphthous ulcers)

Click the icon to see an image of a canker sore.

Self-injury in psychologically disturbed patients
Hereditary gingival fibromatosis. A rare genetic disease associated with both gum overgrowth and hairiness. It is often associated with gingivitis and periodontal disease.
Desquamative gingivitis. With this condition the outer layer of the gum tissue desquamates (peels away), exposing an acutely red surface. It usually occurs as a result of an allergic reaction or of skin diseases such as lichen planus, benign mucous membrane pemphigoid, bullous pemphigoid, and pemphigus vulgaris. (Bacteria may also play a role in this gum disease.) This condition generally resolves when the underlying problem is treated. It is fairly common in middle-aged women.

Complications

The ultimate outcome of uncontrolled periodontal disease is tooth loss. As the destructive factors cause the breakdown of bone and connective tissue, teeth lose their anchor.

A much less severe but nevertheless distressing problem caused by periodontal disease is bad breath, although coatings on the tongue may contribute more to bad breath than periodontal disease.

Studies have reported that people who have heart disease have a 1.5 - 4 times increased risk for periodontal disease. (The risk is highest for patients with extensive gum disease, bleeding from every tooth.) Acute coronary syndrome, high blood pressure (hypertension), and high cholesterol have also been associated with periodontal disease.

Periodontal disease has also been linked to stroke and coronary artery disease (CAD). The more severe the periodontitis, the greater the risk for heart problems. Many experts, however, are still not sure whether periodontal disease is a risk factor for stroke or a marker that reflects various risk factors common to both conditions.

A stroke is caused by a loss of blood circulation to areas of the brain. The blockage usually occurs when a clot or piece of atherosclerotic plaque breaks away from another area of the body and lodges within the blood vessels of the brain.

Recent evidence suggests that the inflammatory response may be the common element. This is an over-reaction of the immune system that causes injury to tissues in the body. A common link between patients with heart conditions and periodontal disease may be elevated levels of C-reactive protein (CRP), a marker for the inflammatory response. Some experts believe that immune factors causing this response are released into the bloodstream during periodontal disease and cause injury in the arteries supplying blood to the heart.

Other evidence suggests that the periodontal disease bacteria themselves -- particularly P. gingivalis, T. denticola, T. forsythia, and streptococci species -- may be the main culprit. In 2005, results from the NIH-sponsored Oral Infections and Vascular Disease Epidemiology Study (INVEST) determined an association between cardiovascular disease and the bacteria that cause periodontal disease. In this study, higher levels of periodontal bacteria were associated with thicker carotid arteries (a predictor of heart attack and stroke), regardless of C-reactive protein levels. While this study's findings are an important advance in understanding the relationship between periodontal and heart disease, it is still not clear if periodontal disease actually causes heart disease. Researchers hope that future results from INVEST will clarify this issue.

Experts are still not sure if treating gum disease can reduce the risks of heart disease and improve health outcomes for patients with periodontal disease and vascular heart problems. Studies have been mixed, but research is ongoing.

Diabetes is not only a risk factor for periodontal disease -- periodontal disease itself can worsen diabetes. Some evidence suggests that the bacteria that causes periodontal disease may enter the bloodstream and activate cytokines (damaging immune system factors), which then destroy cells in the pancreas where insulin is produced. Some studies indicate that treating periodontal disease can reduce the need for insulin and improve blood sugar control in some people with diabetes.

Bacteria that reproduce in the mouth can also be carried into the airways in the throat and lungs, increasing the risks for respiratory diseases and worsening chronic lung conditions, such as emphysema.

Click the icon to see an image of emphysema.

Many studies strongly indicate that bacterial infections that cause moderate-to-severe periodontal disease in pregnant women can increase the risk for premature delivery and low birth weight infants. The more severe the infection, the greater the risk to the baby. Research indicates that bacteria from gum disease and tooth decay may trigger the same factors in the immune system as genital and urinary tract infections. These biologic substances, called prostaglandins and tumor necrosis factor, produce inflammation in the cervix and uterus that can cause premature dilation and contractions. Research also suggests that periodontal disease increases the risk for preeclampsia, a life-threatening disorder that occurs in mid- to late pregnancy and is characterized by high blood pressure.

Experts recommend that women have a periodontal examination before becoming pregnant or as soon as possible thereafter. Because women with diabetes are at higher risk for periodontal disease, it is especially important that they see a dentist early in pregnancy. Experts are still not sure if treating periodontal disease can improve birth outcomes. A 2006 study in the New England Journal of Medicine indicated that the treatment does not affect pre-term birth or birth weight. However, the researchers reported that periodontal treatment is definitely safe for pregnant women.

Prevention

Healthy habits and good oral hygiene are critical in preventing gum disease. Regular and effective tooth brushing and mouth washing, however, are effective only above and slightly below the gum line. Once periodontal disease develops, more intensive treatments are needed.

It is important to reduce both the quantity and, in particular, the frequency of sugar intake. Avoid snacks and drinks with sugar (other than natural sugars found in fruits and vegetables). Eat sugar-containing foods with meals, ideally followed by brushing. Since fruit juices can also cause tooth erosion in children, parents should emphasize milk and water.

Smoking may play a significant role in over half the cases of chronic periodontal disease, according to research published in 2000. For smokers, quitting is one of the most important steps toward regaining periodontal health.

Fluoride treatment in children has helped to account for the decline in periodontal disease in adults. Because fluoride prevents decay, back molars, which keep the teeth in place, are spared, and are thus less vulnerable to bacteria. Even before teeth first erupt, babies' gums should be wiped clean with a bit of gauze bearing a dab of fluoride toothpaste. Supplementation with fluoride tablets or drops may be recommended for children 6 months or older who drink unfluoridated water or who are at risk for dental problems. A prescription from the child's pediatrician or dentist is required.

Some dentists recommend a fluoride gel for adult patients who are still at risk for tooth decay or sensitivity, but extra fluoride is generally not necessary for adults who use fluoride toothpaste.

Periodontitis is a silent disease. People with the disease rarely experience pain and may not be aware of the problem. A periodontal examination by a general dentist once or twice a year should reveal any incipient or progressive problems. A full mouth series of x-rays is advised every 2 - 3 years. This will alert the dentist to early bone loss and other disorders of the oral cavity.

Dentists now often perform Periodontal Screening and Recording (PSR) using a probe to measure gum pockets. Previously performed only by periodontists, this procedure is now encouraged as part of a regular dental examination. The dentist will identify any areas where deep pocketing has occurred, where the health of the gingiva appears compromised, and where there is undue mobility of teeth. It is the general dentist's responsibility to identify periodontal disease and inform the patient. If the condition is severe, the dentist may want to refer the patient to a periodontist.

Correct tooth brushing, mouth cleansing, and flossing should be everyone's defense against periodontal disease. (However, good hygiene is probably not sufficient to prevent periodontal disease in many people. Regular visits to a dentist are extremely important, especially for high-risk individuals.)

Brushing Guidelines. The following are some recommendations for brushing:

Use a dry brush. One study reported that when people brushed their teeth without toothpaste first, using a soft dry brush, their plaque deposits were reduced by 67%, and gum bleeding dropped by 50%.
No brush of any size, shape, or gimmick is effective if it is incorrectly positioned in the mouth. Place the brush where the gum meets the tooth, with bristles resting along each tooth at a 45-degree angle.
Begin by dry brushing the inside the bottom row of teeth, then the inner top teeth, and last the outer surfaces.
Wiggle the brush back and forth so the bristles extend under the gum line.
Scrub the broad, biting surfaces of the back teeth.
Dry brushing should take about a minute and a half.
A paste is then applied, and the teeth should again be brushed in the same way.
The tongue should be scrubbed for a total of about 30 seconds. A tongue scraper used with an anti-bacterial mouthwash (such as Listerine) is more effective than a toothbrush in removing bacteria.
Rinse the toothbrush thoroughly and then tap it on the edge of the sink at least five times to get rid of debris.
Flossing should finish the process. A mouthwash may also be used.

If brushing after each meal is not possible, rinsing the mouth with water after eating can reduce bacteria by 30%.

Toothbrushes. A vast assortment of brushes of varying sizes and shapes are available, and each manufacturer makes its claim for the benefits of a particular brush. Look for the American Dental Association (ADA) seal on both electric and regular brushes.

In spite of the wide variety of nonelectric toothbrushes, both in shape and bristle design, a study of eight brands found no significant differences in effectiveness among them.

Electric toothbrushes, particularly those with a stationary grip and revolving tufts of bristles, can be advantageous for some people with physical disabilities. Electric toothbrushes with heads that move back and forth up to 4,200 times a minute remove significantly more plaque than ordinary brushes. Even more high-tech brushes are now available that use sound waves to remove plaque.

In general, studies have reported no differences between electric and manual toothbrushes in their ability to remove plaque. (One study showed considerable improvement in groups using sonic toothbrushes, particularly in those with moderate periodontal disease.) Experts recommend, however, that if a regular toothbrush works, it isn't necessary to buy an expensive electric one.

For individuals with average dexterity, a four- or five-rowed, soft, nylon-bristled toothbrush is sufficient. The most important factor in buying any toothbrush, electric or manual, is to choose one with a soft head. Soft bristles get into crevices easier and do not irritate the gums, thereby reducing the risk of exposing teeth below the gum line compared to hard brushes.

Experts generally recommend replacing toothbrushes every 1 - 3 months. Not only do they become breeding grounds for bacteria, but the worn bristles are less effective at removing plaque.

Toothpaste. The object of a good toothpaste is to reduce the development of plaque and eliminate periodontal-causing microorganisms without destroying the organisms that are important for a healthy mouth. All brands should show ADA approval. Even a good toothpaste, however, cannot be delivered past 3 mm below the gum line, where periodontitis develops.

Toothpastes are a combination of abrasives, binders, colors, detergents, flavors, fluoride, humectants, preservatives, and artificial sweeteners. Avoid highly abrasive toothpastes, especially for individuals whose gums have receded.

Ingredients contained in toothpastes may include:

Fluoride. Most commercial toothpastes contain fluoride, which both strengthens tooth enamel against decay and enhances remineralization of the enamel. Fluoride also inhibits acid-loving bacteria, especially after eating, when the mouth is more acidic. This antibacterial activity may help control plaque.
Triclosan. Triclosan is an anti-bacterial substance that may help reduce mild gingivitis.
Metal salts. Metal salts, such as stannous and zinc, serve mostly as anti-bacterial substances in toothpastes. Stannous fluoride gel toothpastes do not reduce plaque, however, even though they have some effect against the bacteria that cause it, but slightly reduce gingivitis.
Peroxide and baking soda. Toothpastes with these ingredients claim to have a whitening action, but while they may help remove stains there is little evidence they whiten the actual color of the teeth. In addition, these substances appear to offer no benefits against gum disease.
Antibacterial sugar substitutes (xylitol), and detergents (delmopinol)

Mouthwashes. The American Dental Association recommends (in addition to daily brushing and flossing) antimicrobial mouthwash to help prevent and reduce plaque and gingivitis, and fluoride mouthwashes to help provide additional protection against tooth decay.

Chlorhexidine (Peridex or PerioGard) is an antimicrobial mouthwash available by prescription only. It reduces plaque by 55% and gingivitis by 30 - 45%. Patients should rinse for 1 minute twice daily. They should wait at least 30 minutes (and preferably 2 hours) between brushing and rinsing since chlorhexidine can be inactivated by certain compounds in toothpastes. It has a bitter taste. It also binds to tannins, which are in tea, coffee, and red wine, so it has tendency to stain teeth in people who drink these beverages. Studies are mixed as to its effectiveness for preventing or reducing periodontal disease.
Listerine is another antimicrobial mouthwash. It is composed of essential oils and is available over the counter. It reduces plaque and gingivitis, when used for 30 seconds twice a day. It leaves a burning sensation in the mouth that most people better tolerate after a few days of use. The usual regimen is to rinse twice a day. (Listerine PocketPaks, which are strips that dissolve on the tongue, have no proven effects on plague and gingivitis.)
Mouthwashes containing cetylpyridinium (Scope, Cepacol) have moderate antimicrobial effect on plaque, but only if they are used an hour after brushing. None are as effective as Listerine or chlorhexidine, but they may still have some value for people who cannot tolerate the other mouthwashes.
Mouthwashes containing stannous fluoride and amine fluoride (Meridol) are moderately effective, but are also not as effective as effective as Listerine or chlorhexidine.
Fluoride mouthwashes (Act) are helpful in preventing cavities.
Mouthwashes that contain alcohol are dangerous for children and should be kept away from them.

Flossing. The use of dental floss, either waxed or unwaxed, is critical in cleaning between the teeth where the toothbrush bristles cannot reach. In spite of this, nearly two-thirds of people do not floss.

To floss correctly, the following steps may be helpful:

Break off about 18 inches of floss and wind most of it around the middle finger of one hand and the rest around the other middle finger.
Hold the floss between the thumbs and forefingers and gently guide and rub it back and forth between the teeth.
When it reaches the gum line, the floss should be curved around each tooth and slid gently back and forth against the gum.
Finally, rub gently up and down against the tooth. Repeat with each tooth, including the outside of the back teeth.
If, on repeated flossing attempts, the floss becomes shredded or cannot be removed easily from between the teeth, a rough crown or overhanging filling may be the cause. In such cases, the restoration should be redone. Such areas create spaces for the collection of food debris, plaque, and calculus.

Here are some tips in choosing the right floss or flossing device:

Use a floss that does not shred or break.
Avoid a very thin floss, which can cut the gum if brought down with too much force or not guided along the side of the tooth.
A floss threader is an invaluable aid for the person who has bridgework. Made of plastic, it looks like a needle with a huge eye, or loop. A piece of floss is threaded into the loop, which can then be inserted between the bridge and the gum. The floss that is carried through with it can then be used to clean underneath the false tooth or teeth and along the sides of the abutting teeth.
Another handy device for cleaning under bridges is a Proxabrush, which is an interdental cleaner. This is a tiny narrow brush that can be worked in between the natural teeth and around the attached false tooth or teeth.
Special toothpicks such as Stim-U-Dent may be effective for wide spaces between teeth but should never replace flossing. Standard toothpicks should never be used for regular hygiene.
Electronic products, such as water piks, are also helpful. These devices are expensive but may improve flossing compliance.

Producing Saliva and Drinking Water. Saliva is important for diluting the toxins created by plaque. Drinking at least 7 glasses of water a day helps reduce inflammation in the mouth by producing more saliva. Increasing water intake is particularly important as one ages, when less saliva is produced.

Diagnosis

The dental practitioner typically performs a number of procedures to determine a diagnosis of periodontal disease.

The dentist will first take a medical history to reveal any past or present periodontal problems, any underlying diseases that might be contributing to the problem, and any medications the patient is taking. After noting the general state of oral hygiene, the dentist may ask about the quality of home dental care.

Inspection of the Gum Area. The dentist inspects the color and shape of gingival tissue on the cheek (buccal) side and the tongue (lingual) side of every tooth and compares these qualities to the healthy ideal. Redness, puffiness, and bleeding upon probing indicate inflammation. If the gum formation between teeth is blunt and not pointed, acute necrotizing periodontal disease may be indicated.

Periodontal Screening and Recording (PSR). PSR is a painless procedure used to measure and determine the severity of periodontal disease:

The dentist uses a mirror and a periodontal probe, a fine instrument calibrated in millimeters (mm), which is used to measure pocket depth. (A new automatic probing device may prove to be even more sensitive and accurate than the standard manual probe that most dentists use.)
The probe is held along the length of the tooth with the tip placed in the pocket. The tip of the probe will then touch the point where the connective tissue attaches to the tooth.
The dentist will "walk" the probe to six specified points on each tooth, three on the buccal (cheek) and three on the lingual (tongue) sides. The dentist measures the depth of the probe at each point.
Pocket depths greater than 3 mm indicate disease.

These measurements help determine the condition of the connective tissue and amount of gingival overgrowth or recession. PSR appears to be even more reliable than x-rays in diagnosing gum disease.

Testing Tooth Movement. Tooth mobility is determined by pushing each tooth between two instrument handles and observing any movement. Mobility is a strong indicator of bone support loss.

X-rays. X-rays are taken to show any loss of bone structure supporting the teeth. Eighteen x-rays make up the full mouth series necessary for diagnosis.

Treatment

Studies support the effectiveness of active treatment combined with a strict maintenance program for patients with periodontal disease. In one study, for example, people with periodontal disease who were inconsistent in caring for their gums after treatment had 5.6 times the risk for tooth loss as those who were very vigilant.

Some dentists have reported a success rate of 85% when professional treatment and good home maintenance are combined. Treatment helps nonsmokers more than smokers, particularly when pockets are deep and persistent. Some studies suggest that periodontal treatment in people with type 2 diabetes helps improve blood sugar levels. Whether treatment will help reduce other health risks, including heart attack and stroke, is unknown.

Treatment Goals. Once periodontal disease has been identified, the goals of treatment are:

To arrest and control the progress of the disease
To leave the periodontal tissues in an easily maintainable state
If possible, to restore the supporting structures, which include bone, gum tissue, and ligaments

Treatment Phases. To achieve these goals, there are various approaches:

Initial cleaning, scaling, and curettage
Surgery -- if needed for reducing deep pockets that remain underneath the gum after extensive cleaning sessions
Low-dose oral or topical antibiotics
Maintenance

After the active treatment is completed and the mouth is in a relative state of health, the patient should have regular cleanings lasting 45 minutes to 1 hour, approximately every 3 months. These may be done by the dental hygienist, the periodontist, or the general dentist. The patient may alternate between them. Home care, of course, must be continued.

Antibiotics Before Treatment. In cases where the individual has a mitral valve prolapse or history of rheumatic heart disease, pretreatment with an appropriate antibiotic is required before any dental work, including cleaning. This is necessary to prevent the possibility of bacterial endocarditis, which can be life threatening.

Scaling, polishing, and sometimes curettage are used to manage periodontal disease. They are usually accomplished in a series of three to four visits spaced about a week apart. (Patients might ask their dentist about the gas nitrous oxide, which is helpful for many patients and may reduce the visits to a single one.) The dental hygienist or practitioner generally uses both ultrasonic and manual instruments to remove calculus.

Calculus above the gum is easily seen. The dental professional usually detects calculus below the gum by careful probing with an instrument.
The hygienist or dentist may use an ultrasonic instrument for removal of the more accessible calculus. This probe-like device vibrates at a frequency range higher than is audible to the human ear. Some people with low tolerance for the ultrasonic probe may wish to request nitrous oxide.
A spray of water is used with ultrasound to prevent overheating and to flush out the debris that is dislodged.
The dental professional will scrape the plaque from above and below the gum line (called scaling). When the probe contacts the rock-like calculus, deposits fracture off the tooth fairly efficiently.
The hygienist or dentist will then smooth the rough spots on the tooth. Smoothing the surface helps remove bacteria that collect there (root planing) and also helps the gums reattach.
Polishing is the finishing procedure. It uses a rubber cup with an abrasive paste to remove plaque and stains on the crown portion of the tooth. It produces a smooth surface, making it temporarily harder for plaque to adhere.

After the cleaning procedure, the dentist will check the pocket depths around the teeth after the cleaning process has been completed. Further treatment needs are determined by the results of these initial sessions:

If the cleaning processes have reduced inflammation, observation only is needed.
If an abscess is present, surgery may be required.

Finally, the dental hygienist or practitioner should offer thorough instructions on home care to insure the removal of bacteria on a daily basis. This includes proper use of the toothbrush, paste, mouth rinses, floss, floss threaders, and proxabrushes. Home care can effectively eliminate the plaque above the gums and down to 2 mm below the gums.

Gingival curettage removes the soft tissue lining of the periodontal pockets in order to completely eliminate bacteria and diseased tissue. It may be used along with scaling and root planing, but achieves a deeper and more complete cleaning. Evidence indicates, however, that it does not contribute any additional benefits beyond simple scaling and planing.

Surgery allows access for deep cleaning of the root surface, removal of diseased tissue, and repositioning and shaping of the bones, gum, and tissues supporting the teeth. Surgical procedures vary depending on the individual diagnosis and needs of the patient. The basic procedure is known as open flap curettage. It involves:

The periodontal surgeon lifts, or flaps, the gums away from the tooth and surrounding bone.
The diseased root surfaces are cleaned and curetted (scraped) to remove deposits.
Gum tissue is replaced into positions to minimize pocket depth.
The periodontist may also contour the remaining bone and attempt to regenerate lost bone and gingival attachment through bone grafts and guided tissue regeneration or the use of enamel matrix protein derivatives.

There is some debate about whether this procedure is any more effective in preventing disease progression than non-surgical therapies, such as low-dose doxycycline, short-term antibiotics, or antibiotic gels. Some studies have reported that although surgical treatment reduced pocket depth more than non-surgical therapies for at least a year after the procedure, benefits from surgery do not persist beyond 5 years, except in very deep pockets.

Postsurgery Pain and Discomfort. Post-surgery discomfort is usually managed easily with over-the-counter medications such as ibuprofen. If discomfort is severe, stronger analgesics may be prescribed. Some patients experience sensitivity to hot or cold temperatures from exposed roots. These problems can be managed with topical fluoride treatments or, in severe cases, with dental restoration.

Guided Tissue Regeneration. A more advanced technique, called guided tissue regeneration, is used to stimulate bone and gum tissue growth:

First, the root surfaces and diseased bone are meticulously cleaned out. Preventing bacterial contamination is very important. The more residual bacteria, the greater the chance that the treatment will fail.
A specialized piece of fabric is sewn around the tooth to cover the crater in the bone left after the cleaning. It is either absorbable or nonabsorbable. (Some studies report highly beneficial results with new absorbable materials, including those coated with the antibiotic doxycycline.)
The gum is then sewn over the fabric. The fabric prevents the gum tissue from growing down into the bone defect and allows the bone and the attachment to the root to regenerate.
After 4 - 6 weeks, the nonabsorbable fabric must be removed using a minor surgical procedure. The absorbable membrane may be left in. In general, there is little difference in outcome between absorbable and nonabsorbable procedures. The absorbable fabric may not be as effective as standard grafts if gum tissue is thin, although newer materials may prove to produce better results.

Bone Grafting. In some cases of severe bone loss, the surgeon may attempt to encourage regrowth and restoration of bone tissue that has been lost through the disease process. This involves bone grafting:

The surgeon places bone graft material into the defect.
The material may be either bone from the same patient or a substance called decalcified freeze-dried bone allografts (DFDBA) which is obtained from a donor.
This material then stimulates new bone growth in the area.

Enamel Matrix Protein Derivative. Amelogenin is a derivative of a major protein in the structure (the matrix) of enamel that helps stimulate gum tissue growth. A gel containing amelogenin (Emdogain) is applied during surgery and forms a coat over the roots of the teeth. The gel itself dissolves after 2 days, leaving the active substance behind. Studies report that it is safe and may significantly reduce the effects of periodontal disease. One study suggested that the benefits, as indicated by bone attachment, can persist for at least 4 years. (Results were similar to guided tissue regeneration.)

Gum grafting techniques can also be very useful for improving the looks of the gum as well as adding support to the teeth. During this procedure, the periodontist takes gum tissue from the palate or another donor source to cover the exposed root in order to even the gum line and reduce sensitivity. Other procedures are available to improve the look of the gums and teeth. The gum line can be sculpted to improve uneven or excess gums and to cover exposed roots as gums recede.

Periodontists report that they are achieving great success with tooth implants in patients who have lost teeth due to periodontal disease. The average cost for a single implant is high, however, and one implant requires 5 - 7 months for completion.

Medications

Antibiotics are often used in combination with surgery, curettage, or alone to eliminate or prevent disease-causing bacteria after periodontal procedures. They are being investigated in oral forms as well as in topical forms that are applied directly to the gum. Increasingly, dental professionals are finding that local application of antibiotics is more effective than periodontal surgery alone. They may even prove to be an alternative to surgery.

Some experts are concerned, however, that long-term use of antibiotics increases the risk of bacterial resistance to these drugs, which is a growing health problem in general. Of some encouragement was a 2000 review, which indicated that low-dose antibiotics do not increase the risk of bacterial resistance. However, long-term studies are still needed

Antibiotics given orally and at standard doses have some limited applications for periodontal disease. They are typically given for an acute infection. Long-term use of antibiotics is advised for the control of juvenile periodontitis, refractory periodontitis, rapidly progressing periodontitis, and prepubertal periodontitis. Specific antibiotics used in periodontal disease include:

Tetracycline antibiotics -- which include tetracycline hydrochloride, doxycycline, and minocycline -- are the primary drugs used. They not only have anti-bacterial actions but also reduce inflammation and help block collagenase, the protein that destroys connective tissue and bone, even in low doses. In fact, these two actions seem to contribute most to periodontal protection, rather than their antibacterial properties. Short-term use of standard-dose doxycycline (a 10-day treatment) is used for treating acute periodontal infections and for eliminating inflammation. Topical application and long-term use of these antibiotics are showing particular promise.
Some macrolide antibiotics (roxithromycin) may have actions against inflammation and growth involved in periodontal disease.
Some quinolone antibiotics (moxifloxacin, ciprofloxacin) may specifically target A. actinomycetemcomitans, an important bacteria in periodontal disease.
Metronidazole (Flagyl) in combination with tetracycline or amoxicillin (a penicillin) may be used for severe and chronic periodontal disease.

There is growing bacterial resistance to many of these antibiotics, such as roxithromycin and metronidazole, therefore limiting their use in periodontal disease. One study indicated, however, that 3 months after antibiotic administration, the percentage of bacteria that could be eliminated with standard antibiotics returned to normal.

Topical application of antibiotics to the gum surface does not affect the entire body like oral antibiotics do, and they are preferred whenever possible. Studies suggest that, in combination with scaling and planing, any of these approaches are very effective for periodontal health.

Several different topical applications are showing promise, including:

Atridox is a doxycycline gel that conforms to the gum surface and then solidifies. Over the next few days, it releases the antibiotics.
Elyzol is a gel or strip applied to the gum that is composed of metronidazole. It has unique actions that are effective against parasites as well as bacteria. Studies suggest that Atridox, which contains doxycycline, may be more effective than Elyzol. (In one study, however, the doxycycline gel worked faster, but metronidazole achieved a greater bacterial reduction.)
PerioChip is a chip that is placed into the gum pocket after scaling. Over time, it slowly releases chlorhexidine, a powerful bacteria-killing antiseptic. Early studies report benefits in reducing pocket depths, but it is still not known whether these improvements are sustained.
Minocycline microspheres (Arestin) contain antibiotics in tiny capsules, which are applied to the gums after scaling and planing. Studies report that they are more effective in reducing pocket depth and bone loss than standard periodontal maintenance. Patients obtain these benefits regardless of their smoking status, age gender, or extent of the periodontal disease.
Actisite is a thin strip similar to dental floss, which is treated with tetracycline hydrochloride. The treated thread is temporarily inserted between the tooth and gum. (Using multiple strips may be more beneficial than using a single strip.) This was one of the first topical applications of antibiotics. Other topical approaches are being increasingly used.

Subantimicrobial Dose Doxycycline (Periostat). Subantimicrobial dose doxycycline (SDD) is a term used for a treatment that uses very low doses (20 mg) of doxycycline (Periostat). Although doxycycline is a tetracycline antibiotic, the doses used are too low to affect bacteria. However, at these dose levels, the drug blocks matrix metalloproteinases (MMPs) -- enzymes that destroy the connective tissues holding the teeth. Periostat is taken twice a day for months. There is some concern that such long-term use may pose a risk for the development of antibiotic-resistant bacteria or other, still unknown, adverse effects. The doses used in this treatment, however, are too low to have any effect on bacteria, so some experts believe this risk is very low. In fact, several 12-month studies report significant improvements in tooth attachment and pocket depth with no increased incidence of side effects. [Taking a common nonsteroidal anti-inflammatory drug, such as aspirin or ibuprofen (Advil) along with doxycycline, may enhance the effectiveness of this treatment.]

Chemically Modified Tetracyclines. Other tetracyclines are being developed that inhibit MMPs but have no antibiotic properties, which would, theoretically, avoid possible long-term problems with antibiotic resistance.

Other Treatments

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). NSAIDs are drugs that block factors that cause inflammation and pain.

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), indomethacin (Indocin).

These drugs are used not only for relieving pain in periodontal disease but also for slowing the disease process. NSAIDs block inflammatory enzymes triggered by cytokines, which are important immune factors in periodontal disease. A number of NSAIDs have been investigated and have been shown to reduce gingivitis and slow progression of periodontal disease.

In one study, long-term use of oral flurbiprofen (Ansaid) resulted in significantly lower bone loss, although disease progression returned when the drug was stopped.

Investigators are also studying rinses, creams, and other topical forms of NSAIDs. For example, a cream containing ketoprofen appears to reduce bone loss. (Ketoprofen is of particular interest because it blocks not only COX-2 but also another pathway involved in the disease process.)

Warning about NSAIDs: Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding.

Gels containing growth factors -- including substances called recombinant human (rh), platelet-derived growth factor-BB (PDGF-BB), and (rh) insulin-like growth factor-I (IGF-I) -- are showing promise for restoring bone.

Research is underway to find a vaccine against periodontal disease. To date, animal studies show promise, but an effective vaccine for people is years away.

Researchers are investigating the use of photodynamic therapy (PDT) as an alternative to antibiotic drugs. PDT destroys periodontal bacteria by applying photosensitive drugs to oral regions and exposing the drug-treated area to a light or laser. Research appears promising but is still in its preliminary stages.

Resources

www.nidcr.nih.gov -- National Institute of Dental and Craniofacial Research
www.perio.org -- American Academy of Periodontology
www.ada.org -- American Dental Association
www.aaoms.org -- American Association of Oral and Maxillofacial Surgeons

References

Amaliya , Timmerman MF, Abbas F, Loos BG, Van der Weijden GA, Van Winkelhoff AJ, et al. Java project on periodontal diseases: the relationship between vitamin C and the severity of periodontitis. J Clin Periodontol. 2007 Apr;34(4):299-304.

de Oliveira RR, Schwartz-Filho HO, Novaes AB Jr, Taba M Jr. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: a preliminary randomized controlled clinical study. J Periodontol. 2007 Jun;78(6):965-73.

Kolahi J, Soolari A. Rinsing with chlorhexidine gluconate solution after brushing and flossing teeth: a systematic review of effectiveness. Quintessence Int. 2006 Sep;37(:605-12.

Persson GR, Yeates J, Persson RE, Hirschi-Imfeld R, Weibel M, Kiyak HA. The impact of a low-frequency chlorhexidine rinsing schedule on the subgingival microbiota (the TEETH clinical trial). J Periodontol. 2007 Sep;78(9):1751-8.

Staudte H, Sigusch BW, Glockmann E. Grapefruit consumption improves vitamin C status in periodontitis patients. Br Dent J. 2005 Aug 27;199(4):213-7, discussion 210.

Review Date:
1/26/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Headaches - tension

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Managing Tension-Type Heada...
Medications
Treatment
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Global Prevalence of Tension-Type Headache

Tension-type headaches account for nearly half of all headaches, according to a 2007 study in Cephalagia. The researchers estimated that more people are disabled by tension-type headache than by migraine.

Causes of Tension-Type Headaches

Doctors are not really sure why tension-type headaches occur. Possible causes include muscle contractions or changes in brain chemicals. Several studies in 2006 and 2007 presented the theory that tension-type headaches may be due to myofascial trigger points in the shoulders and neck, as well as poor head posture. Some researchers suggest that tension-type headaches may be related to fibromyalgia, a condition that is also characterized by myofascial pain.

Tension-type headaches may be triggered by:

Chronic poor posture
Overwork and stress
Lack of sleep
Dental problems, including temporomandibular joint disorder (TMJ)
Certain types of foods
Skipping meals
Medication overuse
Hormonal changes related to menstruation

Managing Tension-Type Headaches

Acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), or ketoprofen (Actron, Orudis KT) can usually provide pain relief for tension-type headache attacks. Patients who have chronic headaches sometimes take amitriptyline (Elavil), a prescription tricyclic antidepressant, to help prevent attacks. Exercise, stress reduction, and relaxation techniques are very important lifestyle approaches for controlling tension-type headaches.

Introduction

Most people are familiar with headaches, the all too common affliction marked by throbbing, piercing, or vise-like pain around much or a part of the head. There are many different kinds of headaches, and they range from being an infrequent annoyance to a persistent, severe, and disabling medical condition.

The brain itself is insensitive to pain, so that is not what hurts when a headache arises. The pain, instead, occurs in the following locations:

The tissues covering the brain
The attaching structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Doctors categorize headaches as either primary or secondary, which helps to distinguish the many different kinds of headaches and to determine appropriate treatments for each.

Primary Headaches. A headache is considered primary when a disease or other medical condition does not cause it. Most primary headaches fall into three main types: Tension-type, migraine, and cluster headaches.

Tension headache is the most common primary headache and accounts for 90% of all headaches.
Neurovascular headaches are the second most frequently occurring primary headaches and include migraines (the more common) and cluster headaches. Such headaches are caused by an interaction between blood vessel and nerve abnormalities. [See In-Depth Report #97: Migraine headaches and In-DepthReport #99: Cluster headaches.]

Headaches are usually caused by muscle tension, vascular problems, or both. Migraines are vascular in origin, and may be preceded by visual disturbances, loss of peripheral vision, and fatigue. Over-the-counter pain medications can relieve most headaches.

Symptoms of migraine and tension-type headaches often overlap, and a diagnosis is sometimes difficult.

Secondary Headaches. Secondary headaches are caused by other medical conditions, such as sinus infections, neck injuries, and strokes. About 2% of headaches are secondary to abnormalities or infections in the nasal or sinus passages, and they are commonly referred to as sinus headaches.

Chronic Daily Headaches. The International Headache Society's classification system includes a category called chronic daily headaches. They may originate as tension headaches, migraines, or a combination of these or other headache types. Chronic daily headaches affect 4 - 5% of the population.

Click the icon to see an image of the different types of headache.

Chronic daily headaches are defined as any benign headache that occurs at least 15 days a month and is not associated with a serious neurologic abnormality. Most people with these headaches have them daily, or almost daily, and they can be quite debilitating.

Chronic daily headaches are, in turn, subdivided into two categories:

Short-duration headaches last fewer than 4 hours. The most common short-acting chronic headaches are cluster headaches.
Long-duration headaches last more than 4 hours. Tension-type headaches are the most common type of long-duration chronic (recurring) headaches and, in fact, the most common type of chronic headaches in general.

General Description. Tension-type headaches, also called muscle contraction headaches or simply tension headaches, are the most common of all headaches. Tension-type headaches can last minutes to days and have the following characteristics:

The pain is commonly described as a tight feeling, as if the head were in a vise. It usually occurs on both sides of the head and is often experienced in the forehead, in the back of the head and neck, or in both regions. Soreness in the shoulders or neck is common.
Depression, anxiety, and sleeping problems may accompany persistent headaches.
Sufferers of tension-type headaches may also have migraine-like symptoms, including being sensitive to light or noise (but not both). Some patients also may suffer from visual disturbances. (Such symptoms in tension headaches, however, tend to be less severe than in migraine. Tension headaches also do not cause nausea or limit activities to the degree that migraines do.)

Types of Tension Headache. In 2004, the International Headache Society updated its original 1988 classification criteria. Tension-type headaches are now divided into the following four classifications:

Frequent episodic tension-type headache. Headaches occur at least once but not more than 15 days per month for at least 3 months (a minimum of 12 days but not more than 180 days per year). Headaches last from at least 30 minutes to 7 days.
Infrequent episodic tension-type headache. At least 10 episodes of headache that occur less than 1 day per month (12 days per year). Because these headaches occur infrequently, they do not impact a patient's quality of life as severely as frequent episodic headaches and may not require attention from a medical professional.
Chronic tension-type headache. Headaches occur at least 15 days per month for at least 3 months (180 days per year). The headache persists for hours at a time and may be continuous.
Probable tension-type headache. Probable tension headaches may be classified as probable frequent episodic, probable infrequent episodic, or probable chronic. They have most, but not all, of the symptoms of tension-type headaches and are not attributed to migraine without aura or other neurological disorders. Probable chronic tension-type headache may be related to medication overuse.

Migraine Headache: General Description of Its Course. Migraine is now recognized as a chronic illness, not simply as a headache. These headaches are often classified by whether or not auras accompany them:

Common migraines are without auras. About 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times.

In general, there are four symptom phases to a migraine (although they may not all occur in every patient): the prodrome phase, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Prodrome symptoms include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in between 20 - 25% of patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from four to 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity.
Nausea, sometimes with vomiting.
Visual symptoms.
Facial tingling or numbness.
Extreme sensitivity to light and noise.
Looking pale and feeling cold.
Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

Cluster Headache. Cluster headaches are very painful events. Patients typically awaken a few hours after they go to sleep with the following symptoms:

Very severe, stabbing pain centered in one eye.
Excessive tearing, a drooping eyelid, and one stuffy or runny nostril, all on the same side as the pain.
Feelings of intense restlessness are common. People in the throes of a cluster headache may pace the floor or may even bang their heads against the wall in an attempt to cope with the pain.
Cluster headaches often have a cycle with the following pattern:
Attacks themselves are usually brief, lasting 30 - 90 minutes, although they can persist for up to 3 hours.
During an active period, sufferers can experience as few as one attack every other day to one or more daily. In a rare form of cluster headache, known as chronic paroxysmal hemicrania, as many as six attacks per day can occur.
An active period of recurrent cluster attacks typically extends over 4 - 12 weeks.
Headache-free periods last several months to even years.

Hemicrania Continua. Hemicrania continua is a rare form of chronic headache. Such headaches occur on one side of the face, mostly in women. The patient generally experiences continuous low-level headache with periodic attacks that can last days to weeks. (About 10% of patients experience remissions.) The actual attacks can be mild to severe, and may resemble migraines. The headaches can usually be treated successfully with NSAIDs such as indomethacin (Indocin). Migraine medications are typically not as helpful.

Prognosis

Both episodic tension-type headache and chronic daily headache affect quality of life. Tension-type headache episodes are rarely disabling, however, and rarely require emergency treatment. If they do, usually there is a migraine component occurring with the tension-type headache.

Nevertheless, although they are not medically dangerous, chronic tension headaches have a negative impact on quality of life, families, and work productivity. Several studies have reported lower quality of life with any chronic daily headache compared to those with no headaches or who have only episodic ones. In one study, people with tension-type headaches tended to have higher anxiety and lower quality of life during a headache attack than people with migraines (who, however, were less able to cope during a migraine attack).

In one study, two-thirds of patients with chronic tension-type headaches reported daily or near daily headaches for an average of 7 years. Only 12% reported headaches occurring less than 20 days a month. In the study, 74% of the patients had to take some time off from work because of the headaches, and about a third reported impaired sleep, less energy, and reduced emotional well-being on 10 or more days a month. Most were able to carry out their daily responsibilities even when in pain, although at lower than normal capacity. This and other studies report a strong association between anxiety and depression and chronic tension-type headaches.

Causes

There does not appear to be a single cause of chronic tension-type headache. Many factors are likely involved.

One of the most popular theories on the cause of tension-type headaches involves muscle contraction in the head, neck, and shoulders. There are several ideas about how muscle tension may produce these headaches.

The most common cause of tension-type headaches is muscle contraction in the head, neck or shoulders.

Studies have suggested that tension-type headache sufferers may have higher-than-average muscle tenderness in the face and head that make them more susceptible to headache after muscle contractions. A few studies suggest that some patients with chronic headaches may be overly sensitive to pain in general or may overestimate muscle contraction pain.

One theory suggests that sustained tension or stress that produces muscle contractions in the tender areas around the skull constrict blood vessels. Blood flow is reduced so oxygen is blocked and waste matter builds up, resulting in pain.

Still, pain can last long after the muscles have relaxed, and clear evidence is lacking on how or even if muscle contractions are a major cause of tension headache.

Researchers are increasingly finding evidence to support factors that are common to both migraine and tension-type headache. Some research suggests that both problems may result from a continuum of abnormalities in the central nervous system (the nerves in the brain and spine). Such changes trigger a progression of symptoms starting with mild sensations, developing into tension headache, and finally, progressing in some people to a migraine.

Serotonin and Other Neurotransmitter Levels. Neurotransmitters are chemical messengers in the brain. Serotonin is a neurotransmitter (chemical messenger in the brain) that is important for sleep, well-being, and other factors that affect quality of life. Abnormalities in serotonin levels have been observed in both tension-type and migraine headache sufferers. Altered levels of other neurotransmitters, importantly dopamine and stress hormones, also occur with migraine and tension-type headaches.

Dopamine, for example, may act as a stimulant of the migraine process. Some evidence suggests that certain genetic factors make people oversensitive to the effects of dopamine, which include nerve cell excitation. Such nerve-cell over-activity could trigger the events in the brain leading to migraine. The prodromal symptoms (mood changes, yawning, drowsiness), for example, have been associated with increased dopamine activity. Dopamine receptors are also involved in regulation of blood flow in the brain.

Reduced Magnesium Levels. Magnesium deficiencies have been observed in people with both tension-type and migraine headaches. Researchers have noted a drop in magnesium levels before or during a migraine attack. Magnesium plays a role in nerve cell function. Reduced levels could be a destabilizing factor, causing the nerves in the brain to misfire, possibly even accounting for the auras that many sufferers experience.

Nitric Oxide. Other research suggests that over-excitable neurons release nitric oxide, a small molecular messenger, which may be important in triggering in most primary headaches (tension-type, cluster, and migraines). Elevated levels have been observed in blood cells of patients with tension-type headache. Some evidence suggests that the release of this molecule in blood vessels may activate nerve pathways in the brain, muscles, or elsewhere and increase pain.

Estrogen Fluctuations in Women. Tension-type headaches and migraine headaches are more common in females during adolescence and adulthood. Most likely hormone fluctuations, rather than whether levels are elevated or low, trigger headaches. Some research suggests that fluctuations in estrogen levels may impact levels of serotonin and other pain-modulating substances that affect these headaches.

Inflammation in the Maxillary Nerve. Early studies suggest that some chronic tension-type and migraine headaches may be caused by inflammation in the nerve that runs behind the cheekbone (the maxillary nerve) -- not around the covering of the brain. In fact, some work using ice water for reducing swelling in areas of the gums above the last upper molars has relieved some severe migraine and tension-type headaches.

Genetic factors appear to play a role in predisposing people to recurrent tension headaches. One study of twins suggested that the chances of inheriting the susceptibility to recurring headaches (both migraine and tension) were about 70% in close relatives. The trait is equal in both boys and girls. Because such headaches tend to occur more in females, however, hormonal, social, psychological, or other factors must play a role in their development.

Tension-type headache has been highly associated with an intense response to stress. Some studies suggest that patients with chronic tension-type headaches have more general feelings of anxiety or depression and are less able to express their emotions. One study indicated that patients with tension headaches tend to perceive everyday events as more stressful than those without headaches. Some research even suggests that tension-type headache victims may have some biological predisposition for translating stress into muscle contraction. Still, the link between stress and tension-type headaches is not fully understood, and some evidence challenges any causal association.

Whiplash, concussions, and other head and neck injuries, even mild ones, may result in persistent tension-type or migraine headaches in both adults and children. Such headaches should be treated as if they were the primary types. The risk for tension headaches may persist for years after the injury.

Myofascial pain involves the fascia (connective tissue) and muscles. Some researchers think that tension-type headaches may be linked to myofascial trigger points in the neck and shoulder muscles. Trigger points are knots in the muscle tissue that can cause tightness, weakness, and intense pain in various areas of the body. (For example, a trigger point in the shoulder may result in headache.) Because fibromyalgia is also characterized by myofascial pain, researchers are exploring whether there may be an association between this condition and tension-type headache. [See In-Depth Report #76: Fibromyalgia.]

Medication Overuse (Rebound) Headache. About a third of persistent headaches -- whether chronic migraine or tension-type -- are medication-overuse headaches. These are the result of a rebound effect caused by the regular overuse of headache medications. Nearly any headache medication can produce this effect. In one study of headache sufferers, medication-overuse headaches developed after an average of 1.7 years of regular use of triptans (18 doses a month), after 2.7 years of ergot use (37 doses as month), and after 4.8 years using painkillers (114 doses a month). Regular use of painkillers for any chronic problem (such as arthritis) poses a 2% risk for medication-overuse headache, with risk being highest in people who already have primary headaches, especially migraines.

Chronic Migraines. In some cases, migraines naturally evolve into chronic, daily headaches referred to as transformed migraines.

About 90% of people seeking help for headaches have a primary headache. The rest are secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.

Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. Sinus headaches can occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. They even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve, which is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area that the brain may interpret as headache. Pain is usually on one side. Even if it affects both sides of the head it is usually more severe on one side. The quality of the headache may be difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck).

Temporomandibular Joint Disorder. Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction (TMJ, also known as TMD), which is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders. This condition often coexists with chronic tension headache.

Click the icon to see an image of temporomandibular joint dysfunction.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Brain Tumor. Fear of brain tumor is common among people with headaches, but headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraines or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, evidence suggests that hypertension does not cause headaches. An exception is malignant hypertension, an uncommon medical emergency in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention.

Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.

Head Injuries. It is obvious that a significant blow to the head will cause pain. In most cases, the pain is similar to tension-type headache and is treated in the same way as the primary headache. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding, and monitoring is important.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain, which may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Risk Factors

Tension-type headaches are the most common headaches, accounting for nearly half of all headaches. According to one study, nearly 40% of Americans have at least one episode of tension headache during the course of a year. Some reports estimate that over 85% of women and about 63% of men will have a tension-type headache at some point during a year. Nearly everyone has at least one tension-type headache during their lifetime.

Surveys indicate that about 3 - 5% of the general population has chronic tension-type headache, with the prevalence being higher in women.

About 40% of people with tension-type headaches first have them before they are age 20, and another 40% first experience them between ages 20 - 40. Most of the remaining headache sufferers first have tension-type headaches in the decade between ages 40 - 50. Chronic tension-type headache tends to occur in older adults.

Headaches in Children. Headaches are rare before age 4 but increase in prevalence throughout childhood, reaching a peak around age 13. In one large study, about 7% of seven year olds and 15% of 11 year olds had headaches. Ten percent of these childhood headaches were recurrent. In many of these patients, chronic headaches persist into adulthood. In addition, as adults these patients have a tendency to develop multiple physical or psychiatric complaints, such as back pain, muscle aches, digestive complaints, and depression.

Studies have found that only a minority of chronic childhood headaches are due to physical conditions, such as head injuries or medical problems. In one study, over 62% of children with tension-type headache episodes suffered some form of emotional disorder. In the study, every child reported the presence of a stress factor.

Psychological factors associated with childhood tension-type headaches include:

Sleep problems. According to one study, more than two-thirds of children who experience chronic daily headaches suffer from sleep disturbances, especially difficulty falling asleep.
Moderate or severe depression.
Emotional rigidity in a child and more repressed anger than their peers.
Family stress. This includes maternal illness or separation, family bereavement, relationship problems, mental illness in a family member, and other stressful family events.
Problems at school. According to a National Headache Foundation survey, nearly 30% of children miss school because of headaches. For many children, the start of the school season can be a particularly stressful time.

The National Headache Foundation recommends these tips for parents:

Keep a diary of child’s headaches noting time of onset, length and intensity of attack, location of pain, and food triggers.
Make sure child gets plenty of sleep at regular times.
Avoid changes in child’s eating routing (hunger and eating at irregular times can trigger headaches).
Discuss any headache concerns with child’s doctor.

The following conditions can make people susceptible to tension-type headaches.

Chronic poor posture
Chronic overwork
Upper respiratory tract infections, such as colds and flu
Sleep disorders. Sleep problems, such as insomnia, sleep apnea, or habitual snoring, are common in all primary headaches. Headache can disturb sleep, but sleep disorders may also contribute directly to tension headache, particularly those that occur at night or early morning. (In one study, treating people who had chronic headaches for sleep apnea cured the headaches in many cases.)
Obesity
Hypothyroidism (decreased thyroid function)
Dental problems
Allergies
Substance or alcohol abuse
Temporomandibular joint dysfunction (TMJ, also called TMD). This is a condition in which there are abnormalities in the jaw joints. TMJ itself can cause headache, and it also often coexists with chronic tension headache.

Certain triggers, including the following, may cause headache episodes in people with chronic tension-type headaches:

Specific stressful events
Not eating on time
Fatigue or lack of sleep
Crying. In one study, only stress, anxiety, and menstruation were more important headache triggers in women.
Withdrawal from over-used substances (caffeine, nicotine, alcohol, pain relievers)
Eyestrain
Intense physical exertion, including sexual activity. Athletes are at higher risk for headaches. Patients with tension-type headaches should not avoid exercise, however. Ordinary levels of physical activity do not usually precipitate these headaches. Furthermore, a sedentary lifestyle may increase the risks for stress and obesity and thereby for tension headaches in susceptible people.
Certain foods, such as chocolate, cheese, and the flavor enhancer monosodium glutamate (MSG), are commonly cited as triggers for tension headaches as they are for migraines.
Medications (overuse of headache medications, nitrates, certain anti-depressants, some drugs used to treat high blood pressure, and many others.)
Hormonal changes, such as specific menstrual phases, in women.

Weather conditions, certain smells, smoke, and light, which can set off migraines, are not common triggers for tension-type headaches.

The rapid consumption of ice cream or other very cold foods or beverages is a well-known trigger of sudden headache pain -- the so-called "ice cream" headache. It can be easily prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Drinking a glass of room-temperature water quickly relieves the pain.

Diagnosis

Diagnosing the cause of persistent daily headache is difficult, even for expert doctors. Studies report that people who visit the emergency room with disabling headache are often misdiagnosed as tension-type headaches instead of migraines. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

Extensive testing may be advised for anyone with a chronic, daily headache. Tracking times of medications, withdrawal, and headache, using the headache diary, is usually very helpful in diagnosis.

According to the International Headache Society, a diagnosis of tension-type headache is suggested by the following symptoms:

Pressing or tightening (but non-pulsating) feeling
Mild-to-moderate pain on both sides of the head
Not aggravated by routine physical activity (walking, etc.)

In episodic tension-type headaches:

No nausea or vomiting
Photophobia (intolerance of light) or phonophobia (intolerance of sound) may be absent or one of these symptoms (but not both) may be present

In chronic tension-type headaches:

No vomiting
No moderate or severe nausea
No more than one of the following symptoms: Mild nausea, photophobia, or phonophobia
Some types of chronic tension headache may include tenderness upon manual palpitation of the head (pericranial tenderness).

Differentiating Medication-Overuse (Rebound) Headache from Tension-Type Headache. About a third of persistent headaches are the result of the rebound effect caused by the overuse of headache medications (formerly called rebound headaches).

Usually in such cases, medications have been taken on an ongoing basis for more than 3 days each week. If patients stop taking these drugs, the headaches come back. The patient then starts taking the drugs again. Eventually the headache simply persists and medications are no longer effective. Even after successful medication withdrawal, relapse is common, particularly with drugs that contain caffeine, so doctors should check for this type of headache even in patients who have previously been treated.

Medications implicated in medication-overuse headache include barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.) Simple painkillers, such as aspirin or ibuprofen, are less likely causes of medication-overuse headaches.

Differentiating Tension Headaches from Chronic Migraines. It is often difficult to differentiate between chronic migraine and chronic tension-type headaches. The McGill Pain Questionnaire may be useful for ruling out migraine. According to a 2003 study, patients with migraine who answer the questionnaire report significantly more severe specific symptoms (throbbing, stabbing, gnawing, hot, sickening, exhausting) than those with tension-type headaches. There is very little difference between these headaches, however, in scores of overall severity of the pain.

For an accurate diagnosis, the patient should describe the following:

Duration and frequency of headaches
Recent changes in their character
Location of the pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting. (These are seen most often with migraines.)
Behaviors during a headache. Different behaviors may help distinguish between migraine and tension headaches. People with tension headaches tend to relieve pain by massaging the scalp, temples, or the nape of the neck. People with migraines are more likely to compress the forehead and temples (tying a scarf around the head) or to apply cold to the area. They also tend to isolate themselves, lie down, induce vomiting, and use more pillows than usual. (None of these maneuvers do much good in relieving either headache, unfortunately.)

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches. Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache.

Researchers are investigating triggers of headaches to determine if certain ones are more likely to set off different primary headaches. In general, however, the same stimuli seem to trigger any of the primary headaches, although people with migraines may be more sensitive to some of them (weather, certain smells, light, and smoke) than people with tension headaches.

Tracking medications is an important way of identifying medication-overuse headache or transformed migraine.

Be sure to attempt to define the intensity of the headache. There are different scoring symptoms available that help communicate the severity of the pain to the doctor. For instance, the following is a number system that can be helpful:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work/activities

3 = Distracts from work/activities

4 = Makes work/activities very difficult

5 = Incapacitating

The patient should report any other conditions that might be associated with headache, including but not limited to the following:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
An uncharacteristic dietary changes
Any current medications or recent withdrawal from any drugs, including over-the-counter or natural remedies
Any history of caffeine, alcohol, or drug abuse
Any serious stress, depression, and anxiety
The doctor will also need the patient's general medical and family history, particularly concerning headaches or other diseases such as epilepsy. Migraine, in particular, tends to run in families.

In order to diagnose a chronic headache, the doctor will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor will also examine the eyes to rule out pressure build-up in the eye as a cause of headache. The doctor may ask questions to test short-term memory and related aspects of mental function.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headache that wakes them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headache.

They are not recommended for patients with migraine and with no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out other conditions, particularly chronic sinusitis, which, in one study, occurred in 20% of patients with chronic headache. Other findings include aneurysms, benign or cancerous growths, and other abnormalities in the brain.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, which are only performed if there is reason to suspect an underlying disease.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition believing it to be one of their usual headaches. Such patients should immediately call a doctor if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea, and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Managing Tension-Type Headaches

Given the very high prevalence of tension-type headaches, some experts express frustration over the lack of serious scientific attention given to this problem. Unfortunately, few tension headache sufferers seek medical help for their problem, and 60% of those with severe headaches use only over-the-counter medications. Many patients fear that they will not be taken seriously by their doctor or believe the widespread misperceptions that their problem is due solely to stress. With medications, relaxation training, lifestyle changes, and other therapies, over 90% of patients can be helped.

Fortunately, most acute tension-type headaches get better without any treatment, and simple over-the-counter pain relievers such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) can treat mild symptoms.

The most common pain relievers are:

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol)
Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail)

Acetaminophen may be effective for moderate-to-severe headaches only at high doses (1,000 mg), while NSAIDs can be effective at lower doses. One study indicated that ibuprofen and naproxen were more effective than aspirin or acetaminophen.

There are few proven therapies for treating or preventing chronic tension-type headaches, and studies are weak. To date, the major treatments used for chronic tension-type headache are a group of antidepressants called tricyclics, and cognitive-behavior therapy. Used alone either of these approaches achieves modest benefits, at best. A combination, however, may be very helpful in some cases.

Some research suggests the following steps in treating this condition:

Because many chronic daily headaches are due to over-use of headache medications, withdrawal from such drugs is the first action. (NSAIDs or other painkillers should not be used to prevent chronic tension-type headaches.)
Cognitive behavioral therapies, including relaxation and stress-reduction techniques, should be used next for managing headaches. They should be the first option for children and adolescents with chronic headaches.
If medication withdrawal and psychological methods fail to bring improvement, tricyclic antidepressants are tried next in combination with cognitive therapy.
Physical therapy, massage therapy, or acupuncture may help some people.

If headaches develop because of medication overuse, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may only need to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient usually has the option of stopping abruptly or gradually and should expect the following course:

Most headache drugs can be stopped abruptly, but the patient should be sure to check with the doctor before withdrawal. Certain non-headache medications, such as anti-anxiety drugs or beta-blockers, require gradual withdrawal.
If the patient chooses to taper off standard headache medications, withdrawal should be completed within three days or shorter. Otherwise the patient may become discouraged.
No matter which approach is used for stopping medication, the patient must expect a period of worsening headache for a few days afterward. Alternative pain relievers may be administered during the first days to help withdrawal.
Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).

Studies suggest that nearly half of patients with medication-overuse headaches relapse. According to one study, the relapse rate may be much higher for tension headaches (73%) than for migraine headaches (22%). More research is needed to determine the optimal methods for drug withdrawal. On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward.

Medications

The standard treatments for tension-type headaches are non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, and tricyclic antidepressants, usually amitriptyline (Elavil, Endep).

Several pain relievers are helpful for mild-to-moderate headaches. They should not be used to prevent headaches, however.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). NSAIDs are common pain relievers that block prostaglandins, substances that dilate blood vessels and cause inflammation and pain. NSAIDs are usually the first drugs tried for almost any kind of headache. There are dozens of NSAIDs. Aspirin is the most common, but it is not as effective for acute tension-type headache as other NSAIDs. Common NSAIDs include:

Over-the-counter NSAIDs. Aspirin, ibuprofen (Motrin), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs. Diclofenac (Voltaren, Cataflam, Solaraze), tolmetin (Tolectin), indomethacin (Indocin)

Patients should be aware that long-term use of high-dose NSAIDs may increase the risk for stomach bleeding and heart problems, including heart attack and stroke.

Acetaminophen. Acetaminophen (Tylenol) is a good alternative to NSAIDs when stomach distress, ulcers, or allergic reactions prohibit their use. A high dose (1,000 mg), however, is needed for this drug to be effective for headaches. Midrin (a combination of a drug that narrows blood vessels, a mild sedative, and acetaminophen) may be very helpful for tension-type headaches.

Acetaminophen does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly. Acetaminophen may cause serious kidney problems in people who already have kidney disease. It also may interact with certain medications, including the blood thinner warfarin.

Antidepressants known as tricyclics are most often used for prevention of severe chronic tension-type headaches. Newer selective serotonin-reuptake inhibitors (SSRIs) antidepressants are also sometimes used in milder cases.

Tricyclic Antidepressants. Tricyclics are not only useful for depression but also appear to help relieve muscle pain and improve sleep. They are sometimes classified in one of two categories: tertiary or secondary amines:

Tertiary amines include amitriptyline (Elavil) and imipramine (Tofranil). Amitriptyline is the tricyclic most commonly used for tension-type headache. These drugs tend to cause more drowsiness than secondary amines, which may be helpful for patients with sleep problems.)
Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects than tertiary amines, but they are just as toxic in high amounts.

Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), trimipramine (Surmontil), mianserin (Bolvidon), and dothiepin (Prothiaden).

Unfortunately, these drugs can lose effectiveness over time. Side effects are also fairly common with these medications. Drowsiness is the most common, but may vary by specific drug. In addition, side effects most often reported include dry mouth, constipation, blurred vision, sexual dysfunction, weight gain, trouble urinating, heart rhythm problems, and dizziness. Blood pressure may also drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects, including heart rhythm problems, which can be dangerous for some patients with certain heart diseases. These drugs can be fatal with overdose.

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa). Because they act on serotonin specifically, they have fewer side effects than the older antidepressants, such as monoamine oxidase inhibitors (MAOIs), which affect a number of chemicals in the body. SSRIs take 2 - 4 weeks to be effective in most adults and sometimes longer, up to 12 weeks, so their value for treating headaches is limited.

Side effects may include nausea, stomach problems, agitation, insomnia, mild tremor, impulsivity, temporary weight gain or loss, and sexual dysfunction. Death from overdose is extremely rare. Serious interactions can occur with other antidepressants, such as tricyclics and MAOIs.

Designer Antidepressants. Several drugs target other neurotransmitters, such as norepinephrine, alone or in addition to serotonin, and are showing promise for prevention of tension-type headache. The following are some examples:

In one study, bupropion (Wellbutrin) was as effective as a tricyclic in preventing tension-type headaches.
Nefazodone (Serzone), a fast-acting designer antidepressant, was particularly beneficial in a study of patients with chronic daily headaches. After 3 months of treatment, symptoms were reduced by half in over 70% of patients. Nearly 60% of them said their symptoms improved over 75%.
Venlafaxine (Effexor), a designer antidepressant that targets both serotonin and the brain chemical norepinephrine, is showing promise for preventing chronic tension-type headaches (as well as migraines). In one study, patients who took the extended-release form of the drug for 6 months went from an average of 24 tension headaches a month to 15.
Mirtazapine (Remeron) is a unique antidepressant known as a 5-HT2 blocker. It may indirectly enhance the affects of both serotonin and norepinephrine. In one study, it was as effective in treating chronic tension-type headache as the tricyclic Elavil. Mirtazapine has significantly fewer side effects than tricyclics, although it may slightly raise cholesterol and triglyceride levels. It may also cause blurred vision and slight weight gain.

Mild anti-anxiety drugs are occasionally used as an adjunct in treating chronic headaches to decrease muscle contraction or to calm anxiety symptoms during periods of extreme stress. They include alprazolam (Xanax) and clonazepam (Klonopin). They tend to be highly addictive, however, and patients should therefore use them only on a short-term basis.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea, but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these drugs.

Opioids. Opioids, such as codeine or hydrocodone, are sometimes prescribed for severe headaches, although their use is controversial because of the risk for addiction. Methadone is showing promise for patients who do not respond to standard treatments. These drugs are narcotics, however, and may be subject to abuse. Patients must be monitored and reevaluated regularly. Overuse of these drugs can reduce their effectiveness and lead to medication-overuse headaches, so it is important for a doctor to supervise this type of medication. Long-term, high-dosage use of some of these drugs can also lead to kidney disease and ulcers. Other, less serious side effects include gastrointestinal upset, dizziness, and ringing in the ears (tinnitus).

Sedatives. Barbiturates, particularly butalbital (Butalan) and its combinations (Fioricet, Axocet), are occasionally prescribed if other medications fail to provide relief. These drugs are sedatives that also contain pain relievers. Because they pose a very high risk for alcohol-like intoxication, dependence and drug-induced headaches during withdrawal, they should be used very sparingly. Some experts believe they should not be used at all for headaches.

Valproate. In some studies, the anticonvulsant medication valproate has been effective for stopping headaches in some patients with persistent migraines and tension-type chronic daily headaches. In one study, 75% of patients with either type of headache experienced at least a 50% reduction in headache frequency and severity. Minor side effects occurred in a third of the patients. Other anti-seizure medications are under investigation.

Botulinum Toxin. Botulinum toxin A (Botox) injections are now widely used to relax muscles and reduce skin wrinkles. They are also being investigated for chronic daily headaches, which include tension-type headache. This potentially deadly toxin is very safe when tiny amounts are injected into small muscles. In a 2003 study of various headache types (including tension-type headache), over 85% of all the patients had fewer headaches per month and the intensity of the pain. Several 2005 studies reported that Botox injections every 3 months might help patients with chronic daily headaches have fewer headaches. However, other studies have reported no benefit. Botox is not approved for headache treatment.

It should be noted that Botox also causes headaches in about 1% of cases. In some cases, the headaches can be very severe and long lasting (from 8 days to a month). Some researchers suggest that either a contaminated batch of Botox or a specific injection technique may be the cause, but additional investigation is needed.

Tizanidine. Tizanidine (Zanaflex) is a muscle relaxant that is emerging as a possible effective preventive drug in chronic tension-type headaches. Called an alpha2-adrenergic agonist, it blocks the release and effectiveness of a stress chemical in the body called norepinephrine and may also help prevent muscle spasms. Studies have reported that nearly 70% of patients with chronic tension-type headaches experienced a reduction in headache symptoms of 50% or more. It also appears to help patients experiencing medication-overuse headache to withdraw from medications. Side effects are usually minor and include fatigue and dry mouth, although patients taking the drug need to be monitored periodically for potential liver damage.

Nitric Oxide Synthase Inhibitors. Nitric oxide synthase inhibitors block nitric oxide, which may play a role in increasing nerve activity that leads to headache. Drugs being investigated include L-NG methyl arginine hydrochloride (L-NMMA) and L-NG-nitro-arginine. Studies suggest they may be very helpful in reducing chronic tension-type pain.

Treatment

In cases where abnormalities or injuries in the cervical spine (the spinal bones in the neck) cause headaches, a cervical epidural nerve block may be beneficial in treating and preventing further pain. This procedure involves injecting small amounts of a corticosteroid and anesthetic into spaces between the vertebrae in the neck to block the nerves. Some patients have reported significant pain relief from this procedure.

Dental Adjustment. Some reports suggest that dental adjustment to help teeth bite down evenly might help some people with temporomandibular joint disorder and chronic headaches. The results indicated that dental adjustments may be helpful. A systematic review in 2003, however, reported no headache relief from this approach.

Nociceptive Trigeminal Inhibition. A dental device called the NTI (nociceptive trigeminal inhibition) tension suppression system has been approved for relief of headaches due to jaw clenching during the night. The small plastic mouthpiece is fitted by a dentist and slips over the two front teeth, preventing teeth clenching at night. Preliminary studies report some benefits for relief of migraines and associated tension-type headaches.

Techniques using acupuncture points on the body have become popular for managing pain. Studies do show some benefits.

Standard Acupuncture. A major 2001 analysis of 26 trials of acupuncture suggested that it may have some benefit for tension headache, but the evidence to date is not completely convincing. Some studies comparing short-term acupuncture to sham (dummy) procedures report no benefits. A 2005 study suggested that acupuncture may help tension-type headache, but needling at non-acupuncture points worked just as well. This suggests a placebo effect may account for the headache relief experienced by acupuncture patients.

Acupuncture, hypnosis and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Percutaneous Electrical Nerve Stimulation. A technique called percutaneous electrical nerve stimulation (PENS) uses low-level electrical pulses delivered through acupuncture needles into soft tissue. Patients are barely aware of the sensation. Some studies are showing some benefits, but strong evidence is still lacking to confirm or refute its benefits.

Acupressure. One acupressure practitioner reports that pressing for 60 seconds on the web space between the forefinger and thumb of the dominant hand erases headache in patients with migraine and tension-type headaches. The specific spot pressed should be the most tender point in the web area. The patient should then lie down for about 15 minutes.

Two investigational procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and relax, and then the process is stopped. Discomfort is minimal. Small studies are reporting some help in relieving a number of conditions that cause chronic pain, including tension headache.

Spinal manipulation by chiropractors or osteopaths may have some benefits for preventing tension-type headaches. Evidence is stronger on benefits of spinal manipulation for patients with headaches originating from nerve or muscular problems in the neck. Some researchers believe that tension-type headaches relieved by spinal manipulation are probably really caused by neck problems.

In a small 2006 study, daily relaxation exercises combined with three sessions of osteopathic treatment helped reduce the frequency -- but not the intensity -- of tension-type headaches. Another 2006 study suggested that physical therapy that incorporates a craniocervical (head and neck) training program may help reduce tension-type headache frequency, intensity, and duration as well as reduce the need for pain medication. In the 6-week program, patients performed 10-minute exercises twice a day. The exercises were designed to retrain muscles in the head, neck, and shoulders. The benefits of these exercises lasted up to 6 months after the program had ended.

Lifestyle Changes

Good health habits -- including adequate sleep, healthy diet, regular exercise, and good stress management -- are important, along with the following specific measures for headache management. Quitting smoking is essential in reducing the risks for all headaches.

An ancient and potentially effective remedy for tension headaches uses pressure applied to the head (such as a headband or a towel wrapped around the head) plus either heat or cold. In one study, 87% of headache sufferers experienced significant relief, and the rest reported moderate relief while they were wearing special headbands that could be tightened. They applied packs that were frozen or heated in a microwave. (Either heat or cold packs were useful, although people with tension headaches generally preferred cold packs.)

A healthy diet rich in fresh fruits and vegetables and whole grains and low in saturated fats (animal fats) is important to everyone. Fish (particularly oily fish, such as salmon and tuna) and soy are protein sources that may be a good alternative to red meats.

Caffeine. In some people with headaches, caffeine appears to be an excellent companion to medications. One study found that the caffeine equivalent of two and a half of cups of coffee can help treat a tension-type headache by itself. Many medications contain combinations of pain or anxiety relievers and caffeine, which boosts pain-relieving potency and counters drowsiness. Taking ibuprofen along with caffeine is even more effective than either substance alone. (It should be noted that in some people with migraines, the tannin found in coffee or tea may be a trigger for the headache. In addition, withdrawal from caffeine is a major cause of headache.)

Headaches that occur during the night and early morning may be related to sleep disorders. One study reported that treating an underlying sleep disorder, such as sleep apnea or insomnia, in patients who also had headaches resulted in headache cure or improvement in all patients except those who suffered from restless legs syndrome.

Several stress-reduction methods are available that may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. Such approaches may be especially helpful for children and pregnant women with chronic headaches. (For information on acupuncture and spinal manipulation, see the Treatment section of this report.)

Among the stress reduction techniques that may be helpful are:

Guided imagery. (This uses body awareness and visualization of pleasant or positive images.)
Biofeedback. This technique works when patients develop awareness of their physical responses and learn to feed this information back to the brain for the purpose of replicating that response. It is often used to reduce muscle tension. One interesting and sometimes effective technique for headaches is called thermal biofeedback. It is based on the concept that hand-warming reduces blood flow to the brain and so relieves headache. The patient learns techniques (such as using specific images) that can raise the temperatures of the hand during a headache. Studies suggest the approach has been helpful in children with tension and migraine headaches.
Autogenic training. This approach combines elements of meditation, relaxation, and self-hypnosis. In one study, it reduced headache frequency and use of medications in patients with tension-type and migraine headaches. It was more successful for tension-type headache.
Massage therapy. In one study, massage therapy of the neck and shoulder muscles reduced the frequency of chronic daily tension-type headaches within the first week of treatment. (It did not have any effect on the intensity of headaches, however.)
Reflexology, an alternative massage method that manipulates the feet, was associated with improvement in 81% of patients with tension or migraine headaches. Patients reported an improvement in energy, well-being, and increased ability to understand the cause of the headaches. In the study, 19% went off medication.
Muscle relaxation exercises.
Self-hypnosis.
Breathing exercises. Studies have reported that correct and rhythmic breathing from the diaphragm can sometimes relieve tension-type headaches. Such breathing exercises may be particularly beneficial when performed with physical movements. (Yoga, in fact, is a practice that combines both and has been helpful in people with headaches.)

Any of these therapies may be used in conjunction with drug therapy.

Numerous herbal remedies are promoted for tension-type headache. It is important that anyone taking herbal or so-called natural remedies be aware of the lack of regulations governing their quality and effectiveness.

Essential Oils. Some patients find relief using two drops of peppermint, eucalyptus, or lavender oil added to one cup of water. The patient soaks a cloth in the solution and applies it as a compress to the head.

Herbs. Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the Food and Drug Administration (FDA) to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for headache:

Feverfew is the most studied herbal remedy for headaches. It does appear to help some people. However, like all effective headache remedies, long-term use can cause a rebound effect. Some experts recommend purchasing feverfew in dried leaf form. Feverfew is generally safe, but side effects can be distressing, particularly canker sores in the mouth (5 - 15% of cases) and stomach distress. Pregnant women or women hoping to become pregnant should not take this herb. People with any blood-clotting disorders should not take it.
Valerian has sedative qualities and is listed on the FDA's list of generally safe products. However, its effects can be dangerously increased if it is used with pharmaceutical sedatives. High doses of valerian can cause blurred vision, excitability, vivid dreams, and changes in heart rhythm.
Comfrey is an herbal remedy used to treat several inflammatory problems. Evidence suggests that comfrey is toxic to the liver. Animal studies have reported a possible cancer risk. It is banned in several countries.

Resources

www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.i-h-s.org -- International Headache Society

References

Anderson RE, Seniscal C. A comparison of selected osteopathic treatment and relaxation for tension-type headaches. Headache. 2006 Sep;46(:1273-80.

Fernandez-de-Las-Penas C, Alonso-Blanco C, Cuadrado ML, Gerwin RD, Pareja JA. Myofascial trigger points and their relationship to headache clinical parameters in chronic tension-type headache. Headache. 2006 Sep;46(:1264-72.

Fernandez-de-Las-Penas C, Cuadrado ML, Pareja JA. Myofascial trigger points, neck mobility, and forward head posture in episodic tension-type headache. Headache. 2007 May;47(5):662-72.

Lenaerts ME, Gill PS. At the crossroads between tension-type headache and fibromyalgia. Curr Pain Headache Rep. 2006 Dec;10(6):463-6.

Stovner Lj, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007 Mar;27(3):193-210.

van Ettekoven H, Lucas C. Efficacy of physiotherapy including a craniocervical training programme for tension-type headache; a randomized clinical trial. Cephalalgia. 2006 Aug;26(:983-91.

Zissis NP, Harmoussi S, Vlaikidis N, Mitsikostas D, Thomaidis T, Georgiadis G, et al. A randomized, double-blind, placebo-controlled study of venlafaxine XR in out-patients with tension-type headache. Cephalalgia. 2007 Apr;27(4):315-24. Epub 2007 Mar 7.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Osteoporosis

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Fractures
Risk Factors
Diagnosis
Lifestyle Changes
Medications
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the Food and Drug Administration (FDA) approved zoledronic acid (Reclast) for postmenopausal osteoporosis treatment. Zoledronic acid is given as an injection once a year. A 2007 study in the New England Journal of Medicine indicated that zoledronic acid can significantly reduce the risk of spine, hip, and other fractures.
In 2007, the FDA approved raloxifene (Evista) for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis.

Calcium and Vitamin D for Osteoporosis Prevention

In 2007, the Food and Drug Administration proposed allowing manufacturers of food and supplements to put a health claim on their products stating that the combination of calcium and vitamin D can reduce the risk of osteoporosis.
In 2007, the National Osteoporosis Foundation updated its daily intake guidelines to recommend 1,200 mg of calcium, and 800 - 1,000 IU of vitamin D3, for adults age 50 and older.
Calcium plus vitamin D is effective in preventing osteoporosis in people age 50 years and older, according to a 2007 review in the Lancet. The researchers found that a minimum of 1,200 mg of calcium and at least 800 IU of vitamin D per day gave the most protection.

Fosamax: Taking a Break (Without Breaking a Bone)

Women at low risk for fracture may be able to temporarily stop taking alendronate (Fosamax) after 5 years, suggests a 2006 study in the Journal of the American Medical Association.

Antidepressants and Osteoporosis Risk

Selective serotonin reuptake inhibitors (SSRIs), the most commonly used class of antidepressants, may increase the risk for bone loss in both older men and women, according to several studies published in 2007 in the Archives of Internal Medicine. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). The researchers did not find that other types of antidepressants are associated with reduced bone mineral density.

Introduction

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. Osteoporosis is diagnosed when bone density has decreased to the point where fractures occur with mild stress.

The skeleton consists of groups of bones which protect and move the body.

Until a healthy person is around age 40, the process of breaking down and building up bone by cells called osteoclasts and osteoblasts is a nearly perfectly coupled system, with one phase stimulating the other. As a person ages, or in the presence of certain conditions, this system breaks down and the two processes become out of sync. The reasons why this occurs during aging are not clear. Some individuals have a very high turnover rate of bone, some have a very gradual turnover, but the breakdown of bone eventually overtakes the build-up.

The Function of Bones. The skeleton has a dual function:

It provides structural support for muscles and organs.
It also serves as a depot for the body’s calcium and other essential minerals, such as phosphorus and magnesium.

The skeleton holds 99% of the body’s calcium. The remaining 1% circulates in the blood and is essential for crucial bodily functions, ranging from muscle contraction to nerve function to blood clotting.

Bone Turnover: the Breakdown and Growth of Bones. Like other organs in the body, bone tissue is constantly being broken down and reformed again. This turnover is necessary for growth, for repair of minor damage that occurs from everyday stress, and for the maintenance of a properly functioning body. Two essential cells are involved in this process:

Osteoblast cells are produced by bone cells and are the bone builders. They rebuild the skeleton, first by filling in the holes with collagen, and then by laying down crystals of calcium and phosphorus.
Osteoclast cells are formed from certain blood cells and are responsible for the breakdown, or resorption, of the skeleton. These cells dig holes into the bone and release the small amounts of calcium into the bloodstream that are necessary for other vital functions.

Each year, about 10 - 30% of the adult skeleton is remodeled in this way. The bone build up (formation)-break down (resorption) balance is controlled by a complex mix of hormones and chemical factors. If bone resorption occurs at a greater rate than bone build up, your bone loses density and puts you at risk for osteoporosis.

In women, estrogen loss after menopause is associated with rapid resorption and loss of bone density. This group, then, is at highest risk for osteoporosis and therefore for fracture.

There are two primary kinds of osteoporosis: type I and type II:

Type I. Type I, or high turnover, osteoporosis occurs in 5 - 20% of women, most often between the ages of 50 and 75. This is because of the sudden postmenopausal decrease in estrogen levels, which results in a rapid depletion of calcium from the skeleton. This is associated with fractures that occur when the vertebrae compress together, causing a collapse of the spine. It is also associated with fractures of the hip, wrist, or forearm caused by falls or minor accidents. Women have a higher risk for type 1 osteoporosis than men.
Type II. Type II, or low turnover, osteoporosis (also known as age-related or senile osteoporosis) results when the process of resorption and formation of bone are no longer coordinated, and bone breakdown overcomes bone building. (This occurs with age in everyone to some degree.) Type II osteoporosis affects both men and women and is primarily associated with leg and spinal fractures. Older women can have both type I and type II osteoporosis.

Click the icon to see an image of a compression fracture.

What determines the existence of osteoporosis, whether type I or type II, is the amount of calcium left in the skeleton and whether it places a person at risk for fracture. Someone who has exceptionally dense bones to begin with will probably never lose enough calcium to reach the point where osteoporosis occurs, whereas a person who has low bone density could easily develop osteoporosis despite losing only a relatively small amount of calcium.

Secondary osteoporosis is caused by other conditions, such as hormonal imbalances, diseases, or medications (such as corticosteroids or anti-seizure drugs).

Click the icon to see an image of osteoporosis.

Causes

Because the patterns of reforming and resorbing bone often vary from patient to patient, experts believe several different factors account for this problem. Important chemicals (such as estrogen, parathyroid hormone, and vitamin D) and blood factors that affect cell growth are involved with this process. Changes in levels of any of these factors could play a role in the development of osteoporosis.

Although ordinarily associated with women, sex hormones play a role in osteoporosis in both genders, most likely by controlling the birth and duration of life of both osteoclasts (bone breakers) and osteoblasts (bone builders).

Women and Estrogen. Experts are still puzzled by the rapid decline in bone density after menopause, when a woman’s ovaries stop producing estrogen. Estrogen comes in several forms:

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

The most potent form of estrogen is estradiol. Estradiol deficiency appears to be a very strong factor in the development of osteoporosis.
The other important but less powerful estrogens are estrone and estriol.

The ovaries produce most of the estrogen in the body, but it can also be formed in other tissues, such as body fat, skin, and muscle. After menopause, some amounts of estrogen continue to be manufactured in the peripheral body fat. Even though the ovaries have stopped producing estrogens directly, they continue to be a source of the male hormone testosterone, which converts into estradiol.

Estrogen may have an impact on bone density in various ways:

Estrogen’s most important effect on osteoporosis appears to be prevention of bone breakdown (resorption). Some research suggests that estrogen may control the life span of osteoclasts, the cells responsible for bone breakdown.
One study reported that part of estrogen’s beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Men and Androgens and Estrogen. In men, the most important androgen (male hormone) is testosterone, which is produced in the testes. Other androgens are produced in the adrenal glands. Androgens are converted to estrogen in various parts of a man’s body, including bone.

Click the icon to see an image of the adrenal glands.

Studies have suggested that the loss of estrogen as well as testosterone may contribute to bone loss in elderly men. In one study, elderly men were first given a drug that blocked their normal hormones and then were given estrogen and testosterone patches. When the estrogen patch was removed, the bone breakdown process accelerated. When both patches were removed, the number of the bone-building cells (the osteoblasts) decreased. In other words, both hormones appeared to be integral to bone function in men.

Low levels of vitamin D and high levels of parathyroid hormone (PTH) are associated with hip fracture in women after menopause:

Vitamin D is a vitamin with hormone-like properties. It is essential for the absorption of calcium into the bone and for normal bone growth. Lower levels result in impaired calcium absorption, which in turn causes an increase in PTH.
Parathyroid hormone (PTH) is produced by the parathyroid glands. These are four small glands located on the surface of the thyroid gland. They are the most important regulators of calcium levels in the blood. When calcium levels are low, the glands secrete more PTH, which then increases blood calcium levels. High persistent levels of PTH stimulate bone resorption (bone loss).

Click the icon to see an image of the benefits of vitamin D.

Click the icon to see an image of the sources of vitamin D.

Click the icon to see an image of the parathyroid glands.

Several studies on family members, including twins, have strongly suggested that genetic factors help determine bone density. Some examples include the following:

Of particular interest are genetic factors that affect vitamin D, a critical nutrient for calcium absorption in the body.
Many studies are looking at abnormalities in genes that may cause deficiencies in estrogen receptors, molecules that help estrogen work on cells. Estrogen is important in maintaining bone density in both men and women.

Corticosteroids. More than 30 million Americans have disorders that are commonly treated using corticosteroid drugs (also called glucocorticoids or steroids). Oral corticosteroids can reduce bone mass in both men and women. It is not clear whether inhaled steroids carry the same risks, but some studies indicate that they may cause bone loss when taken at higher doses for long periods of time. (Children on inhaled steroids may have temporary impaired growth, but they do not appear to be at risk for bone loss.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs) -- a class of antidepressants that includes fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- may be associated with bone loss in both older men and women, according to two 2007 studies in the Archives of Internal Medicine. The researchers did not find an increased risk for bone loss with other types of antidepressants.

Diuretics. Diuretics, which are used to treat high blood pressure, have different effects on osteoporosis, depending on the type. Loop diuretics, such as furosemide (Lasix), increase the kidneys’ excretion of calcium, which can lead to thinning bones. Thiazide diuretics, on the other hand, protect against bone loss, but this protective effect ends after use is discontinued.

Contraceptives. Hormonal contraceptives that use progestin without estrogen (such as Depo-Provera injection or other progestin-based contraceptives), can cause loss of bone density. For this reason, the Food and Drug Administration (FDA) recommends that Depo-Provera injections should not be used for longer than 2 years. Some, but not all, studies suggest that combination estrogen-progestin oral contraceptives increase the risk for osteoporosis later in life. Women who take birth control pills should be sure to get adequate calcium and vitamin D from diet or supplements.

Other Medications. Anti-epileptic (anti-seizure) drugs increase the risk for bone loss (as does epilepsy itself). Other drugs that increase the risk for bone loss include the blood-thinning drug heparin, and hormonal drugs that suppress estrogen (such as gonadotropin-releasing hormone agonists). A 2006 study in the Journal of the American Medical Association suggested that long-term (greater than 1 year) use of proton-pump inhibitors (PPIs) may increase the risk for hip fractures. PPIs are used to treat gastroesophageal reflux disease (heartburn) and include omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium).

Predisposing Medical Conditions. Osteoporosis can be secondary to several other conditions, including alcoholism, diabetes, hyperthyroidism, epilepsy, chronic liver or kidney disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, hypogonadism (impaired development of reproductive organs), lymphoma, hyperparathyroidism, and rare genetic disorders such as Marfan and Ehlers-Danlos syndrome.

Symptoms

Many people confuse osteoporosis with arthritis and believe they can wait for symptoms such as swelling and joint pain to occur before seeing a doctor. However, the mechanisms that cause arthritis are entirely different from those in osteoporosis. Osteoporosis usually becomes quite advanced before symptoms appear.

All too often, osteoporosis becomes apparent in dramatic fashion: a fracture of a vertebra (backbone), hip, forearm, or any bony site if sufficient bone mass is lost. These fractures frequently occur after apparently minor trauma, such as bending over, lifting, jumping, or falling from the standing position.

Pain, disfigurement, and debilitation are common in the latter stages of the disease. Early spinal compression fractures may go undetected for a long time, but after a large percentage of calcium has been lost, the vertebrae in the spine start to collapse, gradually causing a stooped posture called kyphosis, or a "dowager’s hump." Although this is usually painless, patients may lose as much as 6 inches in height.

Click the icon to see an image of osteoporosis.

Fractures

Bone density loss from osteoporosis is a major cause of disability and death in the elderly, mostly due to subsequent fractures. The lifetime risk of spinal fracture in women is about one in three, and that for hip fracture is one in six. Women at highest risk for fractures are those with low bone density plus a history of fractures, particularly nonviolent fractures.

Click the icon to see an animation about osteoporosis.

Each year, there are an estimated 500,000 spinal fractures, 300,000 hip fractures, 200,000 broken wrists and 300,000 fractures of other bones. About 80% of these fractures occur after relatively minor falls or accidents.

Between 25 - 60% of women older than age 60 develop spinal compression fractures. Studies on men with osteoporosis report that they have a 6% risk for hip fracture and between 16 - 25% risk for any fractures related to osteoporosis.

Click the icon to see an image of a compression fracture.

Click the icon to see an image of a hip fracture.

Unfortunately, studies continue to report inadequate treatment after a fracture. In a major 2003 study, for example, only 8.4% of women who had sustained fractures were tested for osteoporosis. Worse, less than half of these women received any treatment for osteoporosis. Overall, in the study fewer than 4% of men and half of women who had sustained fractures were evaluated and treated according to recommended guidelines. The older a woman was, the less likely she was to have adequate treatment.

Risk Factors for Fracture and Falling. The risk for fracture itself in people with low bone density is compounded by certain features. Having multiple risk factors for osteoporosis itself poses a higher risk for fractures. However, not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture.

Falling, of course, is the primary risk factor for fracture. So, additional risk factors for fracture are those that increase the risk for falling. They include:

Having chronic medical problems (emphysema, heart disease, stroke, arthritis, and depression), with the risk increasing with multiple health problems. Such problems may account for 30% of falls in older women.
Taking multiple medications (especially tranquilizers and antidepressants).
Poor physical function, importantly slow gait and reduced muscle strength. Inactivity that results in weak thigh muscles and poor balance particularly puts any older person at risk for fracture and particularly those with low bone density.
Poor concentration or mental impairment.
Impaired vision.
Hazardous environment (such as the presence of throw rugs in the house).

Between 25 - 36% of women who experience a hip fracture die within a year afterward, and about a quarter of the patients require nursing home treatment. The mortality rates after major fractures may be even higher in older men than in older women. Mortality rates after hip fractures declined from the 1960s through the early 1980s, but they have since leveled off. Whether or not medical advances can improve mortality rates in the future, prevention of osteoporosis is extremely important.

Risk Factors

Gender. An estimated 10 million adults in the United States have osteoporosis and another 34 million have low bone mass that places them at risk for developing osteoporosis. A 2004 report from the Surgeon General's office estimates that by 2020, half of all Americans over age 50 could be at risk for this condition. Eighty percent of people with osteoporosis are women. Men start with higher bone density and lose calcium at a slower rate than women, which is why their risk is far lower. Nevertheless, after age 50, bone loss increases and, according to recent studies, more rapidly than previously thought.

Ethnicity. Although adults from all ethnic groups are susceptible to developing osteoporosis, Caucasian and Asian women and men face a comparatively greater risk. About 20% of non-Hispanic white and Asian women older than age 50 have osteoporosis, and over 50% are at risk due to low bone mass. Osteoporosis affects 10% of Hispanic women (49% at risk) and 5% of non-Hispanic black women (35% at risk). Body type can also be a factor. Osteoporosis is more common in women who have a small, thin body frame and bone structure.

Events associated with estrogen deficiencies are the primary risk factors for osteoporosis in women.

Natural and Surgical Causes of Estrogen Deficiency.

Menopause. Within 5 years after menopause, the risk for fracture increases dramatically. Fractures occurring during this period are more likely to occur in the wrist or spine than the hip, but their occurrence is a strong predictor of later severe osteoporosis and hip fracture.
Surgical removal of ovaries.
Missing periods for 3 months or longer.
Never giving birth.
Pregnancy and nursing do not increase the risk for osteoporosis even though during those times calcium is diverted from the mother to the baby. A factor believed to be associated with reduced bone density is elevated at a constant level during nursing, but as the baby is weaned, levels of the factor decline and bone formation is restored.

Female Athlete Triad. In athletes, excessive exercise plays a major role in many cases of anorexia (and, to a lesser degree, bulimia), which in turn increases the risk for low estrogen levels and bone loss. The term "female athlete triad" in fact, is now a common and serious disorder facing young female athletes and dancers and describes the combined presence of the following problems:

Osteoporosis
Amenorrhea (absence or irregular menstruation)
Eating disorders

Some specific risk factors in men include:

Hormonal deficiencies, including both testosterone and estrogen, which occur in older men (although much more slowly than in women). Estrogen deficiencies may also play a major role in osteoporosis in older men. It is unknown yet what normal estrogen levels are in men.
Medical conditions that can reduce testosterone levels, such as prostate cancer treatments, testicular surgery, and mumps.
Hypogonadism, which is a severe deficiency in the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones.

Of concern, are studies suggesting that men who have osteoporosis and suffer hip fractures are far less likely to be tested and treated for low bone density than are women. In one study, only 27% of men were treated for osteoporosis compared to 71% of women.

Dietary Factors. Diet plays an important role in preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies, of course, are important factors in the risk for osteoporosis. Other dietary factors may also be harmful or protective for certain people.

Calcium requires adequate vitamin D in order to be absorbed by the body. In the United States, many food sources of calcium such as milk are fortified with vitamin D.

Click the icon to see an image of the sources of calcium.

Lack of Exercise. Lack of exercise can put thinner people at risk for osteoporosis.

Being Underweight. Being underweight is a risk factor for osteoporosis in men as well as women. (Shortness, thinness, and narrow hips all increase the risk for fracture in people with low bone density.)

Lack of Sunlight. The photochemical effect of sunlight on the skin is a primary source for vitamin D. Bone formation peaks in the summer and bone breakdown increases in the winter. People who avoid sun exposure to prevent skin cancer may be at risk for vitamin D deficiency, particularly it they are elderly.

Click the icon to see an image of the sources of vitamin D.

Smoking. Women who smoke, particularly after menopause, have a significantly greater chance of spine and hip fractures than those who don’t smoke. Men who smoke also have lower bone density.

Diabetes. Diabetes changes bone quality and density and increases the risk for osteoporosis, but the effects differ depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fracture.
Type 2 diabetes, on the other hand, is associated with an increased bone density. In such cases, the bone quality itself may be impaired, since people with type 2 diabetes are still at higher risk for fractures.

Older patients with any diabetes type are at high risk for falling, which compounds the risk for fracture.

The maximum density that bones achieved during the growing years is a major factor in whether a person goes on to develop osteoporosis. Persons, usually women, who never develop peak bone mass in early life are at high risk for osteoporosis later on. Children at risk for low peak bone mass include children who are:

Born prematurely
Have anorexia nervosa (more common in girls)
Young, highly competitive athletes
Take oral corticosteroid drugs (inhaled steroids, which are common in asthma treatments, appear to pose a very low risk or none at all)
Have certain medical conditions (cystic fibrosis, epilepsy, inflammatory bowel disease, and celiac disease)
Have delayed puberty

Although to a large extent genetics predict bone health, exercise and good nutrition during the first three decades of life (when peak bone mass is reached) are still excellent safeguards against osteoporosis (and countless other health problems).

Diagnosis

About 20 - 30% of Caucasian women in the U.S. can expect to be affected by osteoporosis, including having a spinal fracture, after age 60. Hispanic, Asian, and Native American women have an even higher risk. Nearly all of them are unaware of the condition and so fail to seek a diagnosis. Even worse, studies continue to report inadequate evaluation for osteoporosis even after a fracture.

Evidence suggests that screening for osteoporosis can help prevent fractures. Expert groups now recommend bone density screening for the following people:

All women over age 65.
Any postmenopausal women under 65 years with risk factors for osteoporosis (being thin, being a smoker, having a family history of osteoporosis, corticosteroids use, or any serious high-risk condition, such as hyperthyroidism or early menopause).
Any older men or women who suffer a fracture. (Unfortunately, studies suggest that only a minority of these patients are evaluated and treated for osteoporosis. Men are especially less likely to be tested.)

Whether perimenopausal women should be screened is unclear. (Perimenopause is the period that extends a few years before and after menopause, usually ages 50 - 59.) Some experts believe that women as young as 21 who have strong risk factors for osteoporosis (such as anorexia or absence of menstruation due to over-exercising) should consider being tested. It is also important that older women continue to get bone density tests. A 2006 study found that only 10% of women over age 75 receive bone density screenings, even though they are the age group most likely to have hip fractures.

Bone Densitometry. The standard technique for determining bone density is a form of bone densitometry called dual-energy x-ray absorptiometry (DEXA). DEXA is simple and painless and takes 2 - 4 minutes. The machine measures bone density by detecting the extent to which bones absorb photons that are generated by very low-level x-rays. (Photons are atomic particles with no charge.) Measurements of bone mineral density are generally given as the average concentrations of calcium in areas that are scanned.

A bone density scan measures the density of bone in a person. The lower the density of a bone the higher the risk of fractures. A bone scan, along with a patient's medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing the patient to only a small amount of radiation.

Bone mineral density is usually measured at the hip rather than the spine or wrist, which appears to be the most predictive of hip fracture. (Hip fractures are the most dangerous fractures, particularly in women older than sixty.) The bone density in the spine may also be measured. (Spinal bone density in older people however may be misleading. Bone density in this group may increase because of compression on the spinal bones from arthritic changes in the spine. Therefore, bone density measurements may be normal or even high, but the patient may actually be at risk for fracture.)

Click the icon to see an image of a hip fracture.

Ultrasound. Ultrasound techniques measure bone density in the heels, fingers, and leg bones. In early studies, advanced ultrasound techniques, such as quantitative ultrasound (QUS), are promising for improving accuracy in predicting fractures when used with DEXA. Ultrasound itself is less expensive than DEXA and uses no radiation. Ultrasound bone tests are sometimes given at health fairs or other non-medical settings. It should be noted that these results typically vary widely from measurements of the hipbone and are not reliable when used alone.

Quantitative Computed Tomography. Quantitative computed tomography (QCT) scans, a form of CT scans, can provide highly detailed information about spinal density. Radiation doses from this technique are higher than the others. Whether QCT predicts fracture risk accurately is, however, unknown.

Osteoporosis is diagnosed when bone density has decreased to the point where fractures will happen with mild stress, the so-called fracture threshold. This is determined by measuring bone density and comparing the results with the norm. However, low scores on bone density are not very accurate in determining fracture risk without consideration of other risk factors for fracture.

In general, doctors take the following steps to determine osteoporosis:

Bone mineral density ) is measured, typically in the hipbone, using bone densitometry.
Measurements of bone mineral density are given as mg/cm.² This is the average concentration of bone mineral in the areas that are being scanned. In general, bone is normal if results are greater than 833 mg/cm.² Low bone density (osteopenia) is between 833 and 648 mg/cm.² Osteoporosis is diagnosed with results below 648 mg/cm.²

These measurements still do not always indicate the true risk for fracture. The doctor also assesses risk factors and other considerations. The next step is to compare the patient's bone mineral density to normal bone density, which is defined as the average bone mineral density in the hipbones of premenopausal Caucasian women. (This group is used as the basis for the norm because of their high risk and greater proportion in the American population.)

The health professional then uses this comparison to determine her standard deviation (SD) from this norm. Standard deviation results are given as Z and T scores:

A T score gives the standard deviation of the patient in relationship to the norm in young adults. Doctors often use the T-score and other risk factors to determine the risk for fracture.
A Z score gives the standard deviation of the patient in relationship to the norm in her own age group. Z scores may be used to monitor the effects of treatments in women who have been diagnosed with osteoporosis.

For example, the lifetime risks for a younger woman with a specific T-score would be higher than the same scores in an older woman because the younger woman would have a longer time to lose bone density. In general, the T scores in a 55-year-old woman suggest the following degrees of risk for hip fracture.

One standard deviation or less below the norm indicates normal bone mineral density. (This carries a lifetime chance for a hip fracture of up to about 20%, depending on age and other risk factors.)
Between 1 and 2.5 standard deviation s below normal defines osteopenia, which is low bone density. This carries between a 20 - 50% lifetime risk for fracture.
More than 2.5 standard deviation s predicts osteoporosis and over a 60% chance for hip fracture. Additional risk factors increase the risk. They include low weight, smoking, risks for falling, and especially a history of previous fractures. For example, in women 65 years old with low bone density but no adverse factors, the risk for fracture is 4.3% in 1 year and 28.6% over 5 years. In similar women with a previous fracture, the probability of fracture at 1 year is 11% and at 5 years is 71.8%.

Not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture. Techniques to measure bone strength may better identify women at higher or lower risk.

Note: Because the standards are based on Caucasian women, they do not necessarily apply to men, children, or to non-Caucasian women. For example, men have a lower risk for fracture at the same standard deviations as women. Researchers are attempting to establish risk guidelines for these groups as well.

Laboratory blood or urine tests for identifying certain markers of bone loss may prove to be useful in certain cases:

High levels of the chemicals deoxypyridinoline and C-telopeptide in the blood may indicate increased risk for hip fracture. These substances are produced when bone is broken down.
A urine test detecting a substance called N-telopeptide may indicate bone loss (although it is not associated with any risk for fracture).

Lifestyle Changes

Because osteoporosis affects such a considerable portion of the female population, total prevention may not be possible, particularly for high-risk groups. Once a woman goes through menopause and more rapid bone depletion occurs, the line between prevention and treatment blurs. Despite their lower risk for osteoporosis, men should also protect their bones with the same healthy lifestyle habits.

Exercise is very important for slowing the progression of osteoporosis. Although mild exercise does not protect bones, moderate exercise (more than 3 days a week for more than a total of 90 minutes a week) reduces the risk for osteoporosis and fracture in both older men and women. Everyone who is in good health should aim for more. Exercise should be regular and life-long. Before beginning any strenuous exercise program, older patients, those at risk or those who have serious medical conditions, should talk to their doctors.

Specific exercises may be better than others, depending on the age group:

Children should begin exercising before adolescence, since bone mass increases during puberty and reaches its peak between ages 20 and 30. Some evidence suggests that exercise may help develop bone mass in teenagers more effectively than high calcium intake. High-intensity exercises may be particularly bone-strengthening in young people. (Such regimes should not be confused with the athlete-triad -- intense competitive exercise, eating disorders, and menstrual irregularities -- that causes osteoporosis in young athletes.)
Weight-bearing exercise applies tension to muscle and bone and, in young people, encourages the body to compensate for the added stress, increasing bone density by as much as 2 - 8% a year. In premenopausal women these exercises are very protective. (Young men need high-intensity exercises to increase bone mass.) Careful weight training is also very beneficial for elderly people, especially women.
Regular brisk long walks improve bone density and mobility and may relieve osteoarthritic pain. High-impact exercises can be very bone-protective in young and middle-aged adults who have no precluding medical or physical conditions. Most older individuals should avoid high-impact aerobic exercises (step aerobics), which increase the risk for osteoporotic fractures. (Older people, particularly women who engage in jumping exercises should do so under supervision.) Although low-impact aerobic exercises such as swimming and bicycling do not increase bone density, they are excellent for cardiovascular fitness and should be part of a regular regimen.
Exercises specifically targeted to strengthen the back help prevent fractures later on in life and can be beneficial in improving posture and reducing kyphosis (hunchback), even in people with existing severe conditions.
Low-impact exercises that improve concentration, balance, and strength, particularly yoga and tai chi, have been found to decrease the risk of falling. In one study, tai chi reduced the risk of falling by almost half.

Exercise plays an important role in the retention of bone density in the aging person. Studies show that exercises requiring muscles to pull on bones cause the bones to retain and possibly gain density.

Click the icon to see an image of osteoporosis.

In 2007, the Food and Drug Administration (FDA) proposed a new health claim for foods and dietary supplements that contain calcium and vitamin D. The FDA’s recommendation will allow manufacturers of these products to state that the combination of calcium and vitamin D can reduce the risk of osteoporosis. Also in 2007, the National Osteoporosis Foundation (NOF) updated its recommendations for getting enough calcium and vitamin D3. The NOF now recommends 1,200 mg of calcium/day and 800 - 1,200 I.U. of vitamin D3/day for adults age 50 and older. (For strong bones, people need enough of both calcium and vitamin D.)

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. Many studies, including a 2007 review in the Lancet, show that a combination of calcium and vitamin D can help prevent osteoporosis. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve slightly (by 1%) hip bone density
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

The medical community has differing views on how to interpret these findings. Some doctors recommend that women over age 60 should still consider taking calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether or not you should take calcium supplements.

Appropriate Daily Doses. Recommended daily amounts of calcium depend on age and risk factors:

In young people, children ages 3 - 8 should take 800 mg of calcium per day, while children and adolescents ages 9 - 17 need 1,300 mg per day. Teenage girls who do not have enough calcium in their diets should consider taking supplements, which can help build bone density during these critical years.
The standard recommended dose for people over age 50 is about 1,200 mg per day, but actual dosage may be higher or lower depending on risk factors. Even doses of 1,000 mg may help preserve bone in many postmenopausal women without osteoporosis, including during winter months (when bone loss is greatest). In women who have already experienced osteoporosis-related fractures, however, 1,000 mg daily may not add any protective benefits without bone-building medication.
Some experts suggest that all pregnant women, adolescents, and those on corticosteroids take 1,000 - 1,300 mg of calcium every day.
Breast-feeding women should have 2,000 mg per day.

Forms of Calcium Supplements. There are several different kinds of calcium supplements, such as calcium carbonate (Caltrate, Os-Cal, Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions. Their value in preserving bones depends on many different factors:

Calcium Concentrations. Forty percent of calcium carbonate is actually calcium, whereas calcium citrate is 24% calcium, and calcium gluconate is only 9% calcium.
Calcium Absorption Capabilities. The calcium must also be absorbed from the stomach into the bloodstream. Calcium citrate is better absorbed than many other calcium compounds. It was reported to be the first calcium supplement to preserve bone density after menopause. (Calcium citrate also increases iron absorption. Milk and other calcium compounds tend to reduce iron absorption.) One simple method for testing the absorbency of a particular brand of calcium tablet is to place it in a glass of white vinegar at full strength and check to be sure that it breaks up within 30 minutes. Taking large amounts of antacids can impair calcium absorption. People should take calcium supplements after meals.

Side Effects. Calcium supplements, even at normal doses of about 1,000 mg a day, can increase the risk for kidney stones. People should be careful not to exceed the upper limit of 2,500 mg per day. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.) Calcium may boost the effects of drugs used to treat osteoporosis.

Click the icon to see an image of kidney stones.

Although not a specific side effect of calcium, there has been much public concern about reports of a small amount of lead in calcium supplements. Although exposure to high levels of lead can cause health problems, the amount in such supplements is very small and may pose little or no hazard.

Vitamin D. Vitamin D helps the stomach and the gastrointestinal tract absorb calcium. It also is the essential companion to calcium in maintaining strong bones. Moreover, vitamin D protects against osteoporosis only in combination with calcium.

Click the icon to see an image of the benefits of vitamin D.

Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. People also can get it from dietary supplements.

As a person ages, vitamin D levels decline. They also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of the sources of vitamin D.

Most current adult guidelines recommend:

400 IU (10 mcg) for people aged 50 - 60.
600 IU (15 mcg) for those over age 70 who do not have sufficient exposure to sunlight. (Evidence suggests that higher doses of vitamin D -- up to 1,000 IU per day -- may help prevent fractures in people with osteoporosis.)

There are various recommendations for daily vitamin D intake. In 2007, the National Osteoporosis Foundation updated its guidelines to recommend 400 - 800 IU of vitamin D3 for adults younger than age 50, and 800 - 1,000 IU of vitamin D3 for adults age 50 and older. Vitamin D3, also called cholecalciferol, is the form of vitamin D that is best for bone health. In addition to supplements, food sources for vitamin D3 include fortified milk, egg yolks, saltwater fish, and liver.

In 2007, the U.S. National Institute of Health’s Office of Dietary Supplements released a report regarding vitamin D and bone health. Researchers were not able to definitely separate the effect of vitamin D from that of calcium, as most clinical trials evaluate the combination of these supplements. The report did indicate that a combination of daily vitamin D3 (700 - 800 IU) and calcium (500 - 1,200 mg) decreases the risks of falls, fractures, and bone loss in elderly people (ages 62 - 85 years).

Sufficient sunlight exposure and drinking milk fortified with vitamin D supply most people’s normal needs for vitamin D. One cup of whole milk provides about 100 IU of vitamin D.

Vitamin D is toxic in doses above 2,000 IU a day. No one should exceed the recommended daily intake of vitamin D except under the direction of a doctor.

Many people could become deficient in vitamin D as they avoid sunlight to prevent skin cancers and instead increase their intake of milk products, such as yogurt and skim milk, which may have little vitamin D. Such individuals may need to take supplements. People with darker skin have a higher risk for vitamin D deficiency than those with lighter skin.

Vitamin D derivatives are being investigated for treating osteoporosis. Calcitriol (Calcijex, Rocaltrol), for example, is a prescription-form of vitamin D that can increase bone mass and decrease the rate of spinal fractures. However, calcitriol increases the risk for high blood calcium levels (hypercalcemia) and requires frequent monitoring.

Vitamin K. Vitamin K has properties that protect bone and prevent fracture. Because intestinal bacteria produce vitamin K, and the vitamin is found in leafy vegetables, deficiencies are rare. Some evidence suggests, however, that people may not be consuming enough of this nutrient. Vitamin K affects blood clotting, and taking supplements is not recommended without first talking to a doctor. Vitamin K2 (menatetrenone), a form of vitamin K, may help prevent fractures in people with osteoporosis.

Click the icon to see an image of the benefits of vitamin K.

Click the icon to see an image of the sources of vitamin K.

Vitamin B12. Studies suggest that people need the right amounts of vitamin B12 and folic acid to maintain their bone mineral density.

Vitamin A. High amounts of dietary vitamin A reduce bone density and may even increase the risk for fracture in postmenopausal women. (A form of vitamin A, retinoic acid, has been found to stimulate bone breakdown.)

The DASH Diet and Low Sodium. Perhaps a good general approach for people at risk for osteoporosis (or almost any adult) is the DASH diet plus sodium (salt) restriction. The DASH (Dietary Approaches to Stop Hypertension) diet is used to help people with hypertension maintain healthy blood pressures. A 2003 study also reported that it might help protect bones and improve cholesterol levels. This diet not only is rich in important nutrients and fiber but also includes foods that contain far more potassium, calcium, and magnesium, than are found in the average American diet. All of these minerals are important for bone protection. The dietary recommendations are as follows:

Avoid saturated fat (although include calcium-rich dairy products that are no- or low-fat). When choosing fats, select monounsaturated oils, such as olive or canola oils. These fats are also found in some fish. Although no one wants to be overweight, even a slight excess of fat helps protect bones. In one study, women who ate more fat in their diet were, on average, better able to absorb calcium than were women who had been put on a low-fat, high-fiber diet.
Choose whole grains over white flour or pasta products. Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, magnesium, and other minerals that are important for bone (as well as heart) protection.
Choose protein preferably from fish, poultry, or soy products. Soy in combination with fiber-rich foods or supplements may have specific benefits. Oily fish may also be particularly beneficial. They contain omega-3 fatty acids, which have been associated with heart and nerve protection.

Salt Restriction. Reducing salt may protect both the heart and the bones. High sodium intake interferes with calcium retention. Note: Fast foods and commercial snacks are usually high in sodium and have been linked with weak bones.

Dairy Products and Calcium-Rich Foods. Although some studies have reported that dairy products benefit the bones, it is not entirely clear if high-calcium diets reduce the risk for fractures compared to adequate intake of vitamin D. Until more is known, people should be sure their diets have sufficient calcium. Dietary calcium is available from many good sources.

Milk and Dairy Products. The best source of calcium in the diet is from milk fortified with vitamin D. Four glasses of milk provide about 1,200 mg of calcium. (Skim milk and yogurt products, unfortunately, are often low in vitamin D, which is important for calcium absorption.) According to a 2003 study, girls who have low milk intake increase their risk for fracture in adulthood. One report even suggests that milk proteins actually slow bone break down. It is not clear, however, if drinking milk after menopause offers any significant bone protection.
Other Calcium-Rich Foods. Other calcium-rich foods include shrimp, canned salmon or sardines, black strap molasses, calcium-fortified tofu, and almonds. A number of commercial foods, including orange juice and some cereals, are now calcium fortified. Dark green vegetables (broccoli, kale, turnip greens) are rich in calcium but little of it is absorbed (kale is best).

Click the icon to see an image of milk and the facial bones.

Mineral-Rich Fruits and Vegetables.

Potassium. Potassium may be very important for strong bones and may help counteract negative effects of high-protein diets. Potassium-rich fruits include bananas, oranges, prunes, and cantaloupes, and vegetables that contain potassium include carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli.
Magnesium. Some studies have observed that low levels of magnesium may contribute to thinning bones. Some studies suggest that magnesium supplements help suppress the cycle that leads to bone loss. Experts recommend 350 mg a day for supplements. However, excessive magnesium may be harmful in people with diabetes or kidney disease. Foods rich in magnesium include dairy products, spinach, potatoes, beets, nuts, sole, and halibut.
Other Minerals. Phosphorous, boron, and zinc have also been associated with bone protection.

Protein. Protein may be important for frail older people for improving muscle strength. Researchers, meanwhile, have associated both low and high protein intake with bone loss. Protein deficiencies appear to trigger hormonal changes that increase bone breakdown. On the other hand, high protein intake increases urinary calcium loss, which can impair bone density in people with low-calcium diets. High-protein diets, however, do not appear to cause bone loss if calcium intake is also high. The bottom line is to eat enough protein but to balance it with plenty of calcium-rich, and other mineral-rich, foods.

The protein source (meat, soy, or fish) may have some effect on bone density, although the effects are not clear. Studies are mixed on whether protein from meat has a positive or negative effect on bone loss. In any case, the best sources of protein for bone protection may be from oily fish or soy.

Choosing protein from fish (especially oily fish such as sardines, salmon, mackerel, fresh tuna, and herring) is a good option. Oily fish are high in vitamin D, which is bone protective. Such fish are also heart protective. Wild salmon has a much higher vitamin D content than farmed salmon. American brands of canned tuna, meanwhile, generally do not contain significant amounts of vitamin D.
Soy may have some modest protection against bone loss. Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. In particular, the isoflavone genistein is being studied for its effects on bone health. A small 2007 study indicated that genistein supplements, when taken with vitamin D and calcium, may help improve bone density in postmenopausal women with thinning bones. (However, other studies indicate that soy has no effect on bone density in healthy premenopausal women.) Soy food products that also contain calcium, such as tofu, may be particularly beneficial. In such cases, 3 ounces of tofu supply 60% of daily calcium requirements.

Alcohol. Alcohol has different effects on bones depending on how much is consumed. One study found that women older than age 65 who drank one to two drinks (1 - 2 oz) of alcohol weekly had higher bone density than non-drinkers. Alcohol in moderate amounts may reduce parathyroid hormone and increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Cola, Coffee, Tea and Caffeine. One study suggested that drinking tea regularly may help protect bones. Nevertheless, there has been some concern that caffeine consumption, particularly from coffee, may increase calcium levels in urine and reduce levels in the body. In one trial, consumption of lots of coffee (9 or more cups per day) was associated with an increased risk of hip fractures in women, but not in men. However, not all studies support a risk. Some evidence suggests that caffeine may pose a danger for bone loss only in elderly thin women -- but not in those who have normal or high weight. Drinking carbonated beverages, particularly cola, may increase the risk for bone fractures in people with low bone density.

Everyone who smokes should quit. The risk for osteoporosis from smoking appears to diminish after quitting.

An important component in reducing the risk for fractures is preventing falls. Risk factors for falling include:

Slow walking
Inability to walk in a straight line
Certain medications (such as tranquilizers and sleeping pills)
Low blood pressure when rising in the morning
Poor vision

Recommendations for preventing falls or fractures from falls in elderly people include:

Exercise to maintain strength and balance if there are no conflicting medical conditions. In one study of older people, this was the single best intervention for preventing falls.
Do not use loose rugs on the floors.
Move any obstructions to walking, such as loose cords or very low pieces of furniture, away from traveled areas.
Rooms should be well lit.
Have regular eye checkups.
Try wearing hip pads. Hip pads are specially designed to protect hipbones against falls and are worn under clothing. Evidence on their protection against fractures is weak, however, particularly since compliance is poor. Nevertheless, newer hip pads that are thinner and made with newer materials may be helpful and more appealing.
Wear thinner, hard-soled shoes. Studies indicate these shoes are just as comfortable as the popular resilient-soled footwear, but they may be difficult to find. Soft-soled high-resilient so-called athletic footwear may contribute to impaired balance and dangerous falls, in part, because these cushioned shoes offer less stability.

Medications

Many drugs are available to treat osteoporosis. Unfortunately, studies continue to report that doctors fail to evaluate and adequately treat both men and women for this condition, even after a fracture. According to one study of women over age 60, fewer than 2% were evaluated for osteoporosis or spinal fracture by their doctors. Among those who were diagnosed, only 36% received appropriate medication. Among adults who had sustained fractures, less than 5% of men and fewer than half of women were evaluated and treated according to recommended guidelines, indicated two other studies. In one of the studies, only 24% of women received treatment for osteoporosis after a fracture. In both studies, the older a woman was, the less likely she was to have adequate evaluation or treatment.

Drugs Used to Treat Osteoporosis. Two types of drugs are used to treat osteoporosis:

Antiresorptive Drugs. Antiresorptives include bisphosphonates, hormone replacement therapy, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. These drugs block resorption (preventing bone break down), which slows the rate of bone remodeling, but they cannot rebuild bone. Because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
Anabolic, or Bone-Forming, Drugs. Drugs that rebuild bone are known as anabolics. The primary anabolic drug is low-dose parathyroid hormone (PTH), which is administered through injections. This medicine is proving to be very effective in restoring bone and preventing fractions. PTH is still relatively new, and long-term effects are still unknown. Fluoride is another bone-building drug, but it has limitations and is not commonly used.

Both types of drugs are effective in preventing bone loss and fractures, although they vary in their effectiveness and safety.

Bisphosphonates are antiresorptive drugs. They are the primary drugs for preventing and treating osteoporosis. They can help reduce the risk of both spinal and hip fractures, including among patients with prior bone breaks.

Studies indicate that these drugs are effective and safe for at least 10 years. Eventually, however, bone loss continues with bisphosphonates. This may be due to the fact that bone breakdown is one of two phases in a continuous process of rebuilding bone. Over time, just blocking resorption will interrupt this process and impair the second half of the process -- bone formation. Some researchers think that this problem may be overcome by building bone for a couple of years with parathyroid hormone (PTH), then following this treatment with bisphosphonates to prevent the breakdown of bone. (Administering the two drugs simultaneously is not effective because bisphosphonates interfere with the way PTH works.)

A 2006 study of the bisphosphonate alendronate (Fosamax), the most widely used osteoporosis drug, indicated that women at low risk for fracture may be able to stop using the drug after 5 years without increasing their fracture risk for another 5 years. However, the Journal of the American Medical Association study also suggested that it is safer for women at high risk for spine fractures to keep taking alendronate on a continuous basis.

Candidates. National Osteoporosis Foundation guidelines recommend that the following people should take or consider bisphosphonates:

Women with a below-normal bone density of 2.5 standard deviation or greater and no history of fractures
Women with below-normal bone density 1 standard deviation or more and a history of fractures

Brands. Bisphosphonates are available in different forms:

Oral bisphosphonates. These pills include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva). Alendronate and risedronate are taken once a week. In 2005, ibandronate was approved as the first once-monthly pill. Risedronate is also available in a pill that contains calcium. Risedronate and alendronate are approved for both men and women.
Injectable bisphosphonates. In 2007, zoledronic acid (Reclast) was approved as the first once-yearly injection treatment for osteoporosis. The injectable form of ibandronate (Boniva), approved in 2006, requires injections 4 times a year. Injectable bisphosphonates are an alternative for patients who may have difficulty swallowing pills or sitting upright after oral bisphosphonate treatment.

Side Effects. The most distressing side effects of bisphosphonates are gastrointestinal problems, particularly stomach cramps and heartburn. These symptoms are very common and occur in nearly half of all patients. Other side effects may include irritation of the esophagus (the tube that connects the mouth to the stomach) and ulcers in the esophagus or stomach. Some patients may experience muscle and joint pain. To avoid stomach problems, doctors recommend:

Take the pill on an empty stomach in the morning with 6 - 8 ounces of water (not juice or carbonated or mineral water).
After taking the pill, remain in an upright position. Do not eat or drink for at least 30 - 60 minutes. (Check your drug’s dosing instructions for exact time.)
If you develop chest pain, heartburn, or difficulty swallowing, stop taking the drug and see your doctor.

Osteonecrosis (bone death) of the jaw is a rare side effect that has occurred mainly in patients who received intravenous bisphosphonates for cancer treatment (not osteoporosis). Many of these patients had major dental procedures before developing osteonecrosis. However, this bone decay condition has also been reported in some patients who have taken bisphosphonates by mouth (mainly alendronate). Symptoms may include jaw pain or swelling, gum infections, and poor healing of the gums. Talk to your doctor or dentist if you experience any jaw or gum discomfort while taking a bisphosphonate drug.

Raloxifene (Evista) belongs to a class of drugs called selective estrogen-receptor modulators (SERMs). These drugs are similar, but not identical, to estrogen. Raloxifene provides the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers. Raloxifene was approved in 1997 to prevent osteoporosis in postmenopausal women, and in 1999 for the treatment of osteoporosis in postmenopausal women. In 2007, the Food and Drug Administration approved raloxifene for prevention of breast cancer in postmenopausal women with osteoporosis, as well as postmenopausal women at high risk for invasive breast cancer.

While there are many SERM drugs, raloxifene is the only one approved for both treatment and prevention of osteoporosis. Only postmenopausal women who have or are at risk for osteoporosis should take this drug. Studies indicate that raloxifene can stop the thinning of bone and help build better quality and stronger bone.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location, depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Side Effects. Raloxifene increases the risk for blood clots in the veins. Because of this side effect, raloxifene also increases the risk for stroke (but not other types of heart disease). These side effects, though rare, are very serious. Women should not take this drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease. More common mild side effects include hot flashes and leg cramps.

Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and an injected form (Calcimar). Calcitonin is not used to prevent osteoporosis. It treats osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture.

Side Effects. Side effects include headache, dizziness, anorexia, diarrhea, skin rashes, and edema (swelling). The most common adverse effect experienced with the injection is nausea, with or without vomiting. This occurs less often with the nasal spray. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Also, many people who take calcitonin develop resistance or allergic reactions after long-term use.

Although high persistent levels of parathyroid hormone (PTH) can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulate bone production and increase bone mineral density. In clinical studies, teriparatide (Forteo), a drug made from selected amino acids found in parathyroid hormone, reduced the risk for spinal and non-spinal fractures by 50 - 65%. It may prove to be a very useful drug for men with osteoporosis. Unlike most treatments for osteoporosis, including bisphosphonates, the benefits may persist even after the injections have been stopped.

Although the treatment requires injections, researchers are investigating a nasal spray version of PTH. In addition to easing patient discomfort, there is some preliminary evidence that nasal-administered PTH may be better absorbed than injections. Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.

Early animal studies did report bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. However, people with Paget disease, (a disorder in which bone thickens but also, oddly, weakens), should not take parathyroid hormone, since they are at higher than normal risk for bone tumors.

Hormone replacement therapy (HRT) is sometimes used to prevent osteoporosis. A Women’s Health Initiative (WHI) study found that women who received estrogen, or estrogen plus progestin, therapy had fewer fractures than women who received placebo.

However, WHI studies have also shown that estrogen increases the risk for breast cancer, blood clots, strokes, and heart attacks. For this reason, women need to balance the benefits that HRT has on bone-loss protection, with the risks it carries for other serious health conditions. The Food and Drug Administration recommends that women first try other medications for prevention of osteoporosis.

HRT is available in many different forms, including pills and skin patches. [See In-Depth Report #40: Menopause.]

New SERMs. Bazedoxifene (Viviant) is a new selective estrogen receptor modulator (SERM) that is in phase III clinical trials. In research presented at the 2007 annual meeting of the American Society for Bone and Mineral Research (ASBMR), bazedoxifene reduced new cases of non-spine fracture by 52% compared to placebo.
Biologic Drugs. Denosumab is a humanized monoclonal antibody injectable drug currently in phase III studies. It targets the RANK ligand, a protein involved with cells that break down bone (osteoclasts). Results presented at the 2007 ASBMR meeting indicated that denosumab may help increase bone mineral density by as much as 10.6%. Odanacatib is another biologic drug showing promise in phase IIB trials. Odanacatib inhibits cathepsin K, a protein that also plays a role in osteoclast activity.
Strontium. Strontium, a chemical element found in bone, may help increase bone formation and decrease bone resorption. NB S101 is a strontium drug currently in phase II trials.

Treatment

Nonsurgical treatments for fractures include braces, plaster cases, and manipulation of the fracture. Such approaches have not been well studied to determine an optimal method, and patients should discuss all options with their doctors.

Reconstructive surgery is usually used for hip fractures and should be performed within 48 hours, assuming the patient has no other complicating medical conditions. After surgery, the patient should be mobilized within the first day. In one study, protein supplements helped people with hip fractures recover more quickly and reduced bone loss.

Percutaneous vertebroplasty and kyphoplasty are surgical procedures used to lessen pain. Research to date suggests that they are safe and provide pain relief for many patients. In some cases they may increase height. There have been few controlled trials, however, and more research is needed to determine long-term effects.

Percutaneous Vertebroplasty. Percutaneous vertebroplasty involves the injection of a cement-like bone substitute into damaged vertebrae. It is proving useful for stabilizing the spine and relieving pain in patients with spinal compression fractures due to osteoporosis or cancer. Success rates of over 90% have been reported. Serious complications occur in fewer than 1% of cases.

Kyphoplasty. Kyphoplasty is a variant of percutaneous vertebroplasty that may help prevent kyphosis (hunchback) in patients whose spines have collapsed. The procedure inserts a balloon into the fractured vertebrae. As the balloon inflates, the spine is moved upward, to its original location. The balloon is then removed, and the bone and the core of the newly-erect vertebrae are filled with cement. In one 2003 study, short-term symptom relief improved by 70% and was immediate. Long-term effectiveness is not yet known.

Resources

www.nof.org -- National Osteoporosis Foundation
www.niams.nih.gov/Health_Info/Bone -- National Institutes of Health, Osteoporosis and Related Bone Diseases
www.menopause.org -- North American Menopause Society
www.asbmr.org -- American Society for Bone and Mineral Research
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases

References

Agency for Healthcare Research and Quality. Effectiveness and Safety of Vitamin D in Relation to Bone Health, Structured Abstract. August 2007. Rockville, MD.

Bilezikian JP. Osteonecrosis of the jaw -- do bisphosphonates pose a risk? N Engl J Med. 2006 Nov 30;355(22):2278-81.

Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22.

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38.

Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun 25;167(12):1240-5.

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007 Jun 25;167(12):1246-51.

Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47.

Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25;370(9588):657-66.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Coronary artery disease

FitSugar — Wed, 08 Oct 2008 17:35:07 -0700

In This Report

Highlights
Introduction
Prognosis
Risk Factors
Diagnosis
Managing Heart Disease
Anti-Clotting Medications...
Other Medications
Surgery
Coronary Artery Bypass Graf...
Angioplasty and Stents
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Angioplasty Versus Drugs

Angioplasty works no better than drug therapy (high blood pressure, cholesterol, anti-platelet, and other medication) in preventing heart attack and stroke in patients with stable coronary artery disease (CAD), according to an important New England Journal of Medicine study. Experts still recommend angioplasty for patients with unstable or severe CAD.

Stents

Stents coated with drugs may have a slightly higher risk of causing blood clots than bare metal stents, according to FDA meetings held in late 2006. Researchers still need to conduct more research before reaching final conclusions.
Drug-coated stents work well when they are used for patients with specific types of heart conditions, indicate several studies published in the New England Journal of Medicine. However, problems may develop when these stents are used for “off-label” purposes. Experts are also concerned that both bare metal and drug-coated stents may be used too frequently.
Patients who receive a drug-coated stent must take both aspirin and an anti-platelet thienopyridine drug (usually clopidogrel) for at least 1 year after the stent is inserted, advises an important statement from the American Heart Association. Patients who cannot take a thienopyridine drug should receive a bare metal stent instead of a drug-coated stent.

Anti-Bleeding Drugs for Coronary Artery Bypass Graft (CAGB)

Aprotinin (Trasylol), a drug used to control bleeding during CABG, is more dangerous than other types of anti-bleeding drugs, according to a 2007 study in the Journal of the American Medical Association. Many experts now recommend against its use.

Diagnosis

Blood tests for biomarkers do not provide much more predictive information than standard disease risk factors, suggest several recent studies. In a 2006 study published in the New England Journal of Medicine, researchers found that risk factors such as high blood pressure, high cholesterol, and diabetes are still the best methods for predicting the likelihood of heart disease and heart-related death.

Introduction

The heart is the human body's hardest working organ. Throughout life it continuously pumps blood enriched with oxygen and vital nutrients through a network of arteries to all parts of the body's tissues.

The external structures of the heart include the ventricles, atria, arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The vessels colored blue indicate the transport of blood with relatively low content of oxygen and high content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high content of oxygen and low content of carbon dioxide.

In order to perform the difficult task of pumping blood to the rest of the body, the heart muscle itself needs a plentiful supply of oxygen-rich blood, which is provided through a network of coronary arteries. These arteries carry oxygen-rich blood to the heart's muscular walls (the myocardium).

Click the icon to see an image of the anterior heart arteries.

If blood flow to the myocardium is interrupted, an injury known as an infarct occurs. This is also known as myocardial infarction or, more commonly, a heart attack.

Click the icon to see an animation about coronary artery disease.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). This causes blockage of arteries (ischemia ) and prevents oxygen-rich blood from reaching the heart. There are many steps in the process leading to atherosclerosis, some not fully understood.

Click the icon to see an image of atherosclerosis.

Increasingly, however, researchers are studying the interactions between cholesterol and processes known as oxidation and the inflammatory response.

Cholesterol and Lipoproteins. The story begins with cholesterol and sphere-shaped bodies called lipoproteins that transport cholesterol.

Cholesterol is a white, crystalline substance that is found in all animal cells and in animal-based foods. It is critical for many functions, but under certain conditions cholesterol can have harmful effects.
The lipoproteins that transport cholesterol are referred to by their size. The most commonly known are low-density lipoproteins (LDL) and high density lipoproteins (HDL). LDL is often referred to as the "bad" cholesterol and HDL as the "good" cholesterol.

Click the icon to see an image of cholesterol inside an artery.

Oxidation. The damaging process called oxidation is an important trigger in the atherosclerosis story.

Oxidation is a chemical process in the body caused by the release of unstable particles known as oxygen-free radicals. It is one of the normal processes in the body, but under certain conditions (such as exposure to cigarette smoke or other environment stresses) these free radicals are overproduced.
In excess amounts, they can be very dangerous, causing damaging inflammation and even affecting genetic material in cells.
In heart disease, free radicals are released in artery linings and oxidize low-density lipoproteins (LDL). The oxidized LDL is the basis for cholesterol build-up on the artery walls and damage leading to heart disease.

Inflammatory Response. For the arteries to harden there must be a persistent reaction in the body that causes ongoing harm. Researchers now believe that this reaction is an immune process known as the inflammatory response. The following is one theory about how the inflammatory response contributes to heart disease:

The injuries to the arteries during oxidation signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. These factors initiate the inflammatory response.
Macrophages literally "eat" foreign debris, in this case oxidized LDL cholesterol.
The process converts LDL cholesterol into foamy material that attaches to the smooth muscle cells of the arteries. The cholesterol becomes mushy and accumulates on artery walls.
Over time the cholesterol dries and forms a hard plaque, which causes further injury to the walls of the arteries.
In response to this additional harm, the immune system releases other factors called cytokines. These are powerful inflammatory molecules that attract more white blood cells and perpetuate the whole cycle, causing persistent injury to the arteries.

Click the icon to see an image of atherosclerosis.

Evidence is growing that the inflammatory response may be present not only in local plaques in single arteries but also throughout the arteries leading to the heart.

Blockage in the Arteries. Eventually these calcified (hardened) arteries become narrower (a condition known as stenosis).

As this narrowing and hardening process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart.
Such oxygen deprivation in vital cells is called ischemia. When it affects the coronary arteries, it causes injury to the tissues of the heart.
Injured inner vessel walls also fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity. (Nitric oxide has complex effects and may increase inflammation in the arteries.)
These narrow and inelastic arteries not only slow down blood flow but also become vulnerable to injury and tears.

Click the icon to see an image of coronary artery blockage

The End Result: Heart Attack. Heart attack can occur as a result of one or two effects of atherosclerosis.

(1) If the artery becomes completely blocked and ischemia becomes so extensive that oxygen-bearing tissues around the heart die.

(2) If the plaque itself develops fissures or tears. Blood platelets adhere to the site to seal off the plaque, and a blood clot (thrombus) forms. A heart attack can then occur if the formed blood clot completely blocks the passage of oxygen-rich blood to the heart.

Click the icon to see an image of the developmental process of atherosclerosis.

Angina is the primary symptom of coronary artery disease and, in severe cases, of a heart attack. It is typically experienced as chest pain and occurs when the heart muscle does not get as much blood (hence as much oxygen) as it needs for a given level of work (ischemia). Angina is usually referred to as one of two states:

Click the icon to see an image about angina.

Stable Angina (which is predictable)
Unstable Angina (which is less predictable and a sign of a more serious situation)

Angina itself is not a disease. Much evidence indicates that onset of angina less than 48 hours before a heart attack may be protective, possibly by conditioning the heart to resist the damage resulting from the attack. Angina may be experienced in different ways and can be mild, moderate, or severe.

Click the icon to see an image of angina.

Specific factors are typically considered in determining whether symptoms indicate angina:

Quality of the pain. Angina pain is typically described by patients as squeezing, heavy, suffocating, or griplike. It is rarely described as stabbing or burning. Changing one's position or breathing in and out does not affect the pain. The intensity of the pain does not always relate to the severity of the medical problem. Some people may feel a crushing pain from mild ischemia, while others might experience only mild discomfort from severe ischemia. In some cases, the patient experiences shortness of breath, fatigue, or palpitations instead of pain. In others, the ischemia is entirely asymptomatic ("silent ischemia").
Duration. A typical angina attack lasts minutes. If it is more fleeting or lasts for hours, it is probably not angina.
Location. Pain is usually in the chest under the breast bone. It often radiates to the neck, jaw, or left shoulder and arm. Less commonly, patients report symptoms that radiate to the right arm or back.
Triggers of Angina. Angina is usually triggered by physical exertion, emotional stress, or exposure to cold.
Factors that Relieve Angina. Angina is usually relieved by rest or by taking nitroglycerine under the tongue.

Stable Angina. Stable angina is predictable chest pain. Although less serious than unstable angina, it can be extremely painful. It is usually relieved by rest and responds well to medical treatment (typically nitroglycerin). Any event that increases oxygen demand can cause an angina attack. Some typical triggers include:

Exercise
Cold weather
Emotional tension
Large meals

Angina attacks can occur at any time during the day, but most occur between 6 a.m. and noon.

Unstable Angina and Acute Coronary Syndrome. Unstable angina is a much more serious situation and is often an intermediate stage between stable angina and a heart attack, in which an artery leading to the heart (a coronary artery) becomes completely blocked. A patient is usually diagnosed with unstable angina under one or more of the following conditions:

Pain awakens a patient or occurs during rest.
A patient who has never experienced angina has severe or moderate pain during mild exertion (walking two level blocks or climbing one flight of stairs).
Stable angina has progressed in severity and frequency within a 2-month period, and medications are less effective in relieving its pain.

Unstable angina is now usually discussed as part of a condition called acute coronary syndrome (ACS). ACS also includes people with a condition called NSTEMI (non ST-segment elevation myocardial infarction) -- also referred to as non-Q wave heart attack. With NSTEMI, the blood tests suggest a developing heart attack. These conditions are less severe than heart attacks but may develop into full-blown attacks without aggressive treatment. [See In-Depth Report #12: Heart attack and acute coronary syndrome.]

Prinzmetal's Angina. A third type of angina, called variant or Prinzmetal's angina, is caused by a spasm of a coronary artery. It almost always occurs when the patient is at rest. About two-thirds of people with it have severe atherosclerosis in at least one major blood vessel. Irregular heartbeats are common, but the pain is generally relieved immediately with standard treatment.

Click the icon to see an image of a coronary artery spasm.

Silent Ischemia. Some people with severe coronary artery disease do not experience angina pain. This condition is known as silent ischemia, which some experts attribute to abnormal processing of heart pain by the brain. This is a dangerous condition because patients have no warning signs of heart disease. Some studies suggest that people with silent ischemia experience higher complication and mortality rates than those with angina pain. (Angina pain may actually protect the heart by conditioning it before a heart attack.)

Syndrome X. Syndrome X is a condition that occurs when patients have atypical angina chest pain. Their electrocardiograms are abnormal during a stress test, but they have no signs of blocked arteries. It is more likely to occur in women. Although it unclear what causes this condition, imaging tests suggest that Syndrome X may also be caused by ischemia, as is angina.

Prognosis

According to a 2007 report, nearly 16 million Americans have coronary artery disease. In the U.S., coronary artery disease is the leading killer of both men and women. In 2004, nearly 500,000 people died because of CAD. On the positive side, heart attack mortality rates have been declining. Half of men and 63% of women who die of heart disease do not have angina or other warning symptoms prior to their fatal attacks. Although at this time no tests can reliably predict whether a heart attack will occur, experts estimate that up to 30% of fatal attacks and many follow-up surgeries could be avoided with healthy lifestyle changes and by sticking to medical treatments. Two-thirds of patients who have suffered a first heart attack, however, do not take the necessary steps to prevent another.

The following syndromes suggest different degrees of severity among patients with heart disease.

Stable Angina. This condition can usually be managed with lifestyle measures and medications, such as low-dose aspirin. The more severe the angina, however, the greater the chance for progressing to a more serious condition.

Acute Coronary Syndromes (ACS). ACS includes severe and sudden heart conditions that require aggressive treatment but have not developed into a full-blown heart attack. ACS refers to either unstable angina or NSTEMI (non ST-segment elevation myocardial infarction). NSTEMI is also known as non Q-wave myocardial infarction.

Angina is a specific type of pain in the chest caused by inadequate blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).

Unstable angina is potentially serious and chest pain is persistent, but blood tests do not show markers for heart attack.
With NSTEMI, the blood tests suggest a developing heart attack, but, most likely, injury in the arteries is less serious than with a full-blown heart attack.

Most discussions of the treatment of unstable angina now refer to acute coronary syndrome. Doctors use the presence of a number of factors to help predict which ACS patients are most at risk for developing a heart attack.

First, patients are categorized by whether they have a history of heart disease or risk factors for heart disease (such as diabetes, high blood pressure, peripheral artery disease) or other complicating conditions (such as lung disease, heart failure). The doctor also evaluates the severity of the angina. Other factors that pose a high risk for ACS include:

Age 65 years or older
Evidence of severe heart tissue injury
Having a lighter weight
Having a history of severe chronic angina
Having abnormal lung sounds called rales (a bubbling or crackling sound) on examination
ST-segment deviation
Having either very slow or very fast heat beats
Having very low blood pressure

Heart Attack. A full-blown heart attack occurs with severe damage to the heart, which blocks oxygen.

ANYONE WHO BELIEVES THEY ARE HAVING A HEART ATTACK SHOULD IMMEDIATELY CALL THE EMERGENCY MEDICAL SYSTEM (911 IN THE UNITED STATES).

People with known heart disease and any unusual chest pain or other symptoms of heart attack that do not clear up with medications should go to the hospital. The degree of pain and the specific symptoms before a heart attack vary greatly among individuals. Symptoms can be abrupt, gradual, or intermittent.

Chest Pain. People with heart disease or risk factors should be concerned about any chest pain, usually precipitated by exercise or stress, that interrupts normal activities and does not clear up after resting or taking angina medications. Chest symptoms might be experienced as follows:

Pain is typically felt as a crushing weight against the chest, accompanied by profuse sweating. The pain may radiate to the left shoulder and arm, the neck or jaw, and even infrequently to the right arm. The arm may be tingling or numb.
Some people may have only a tingling sensation or a sense of fullness, squeezing, or pressure in the chest.
In some patients with a history of heart disease, chest pain is mild. Such patients may have experienced unexplained fatigue, depression, and ill health within a month of a heart attack. Although chest pain is the classic symptom, it occurs in only about half of patients with a heart attack.

Other Common Symptoms.

Nausea, vomiting, and cold sweats
A feeling of indigestion or heartburn
Fainting
A great fear of impending death, a phenomena known as angor animi

Atypical Symptoms. Some studies suggest that nearly half of patients with heart attack do not have chest pain as the primary symptom. Common atypical symptoms of a heart attack include:

Shortness of breath
Cardiac arrest
Dizziness, weakness, and fainting
Abdominal pain

Patients most likely to have atypical symptoms are women and the very elderly (although they can certainly have classic heart attack symptoms as well).

In one study, 52% of elderly people with acute coronary syndrome had atypical symptoms that included shortness of breath, nausea, profuse sweating, pain in the arms, and fainting. Such symptoms were more likely to occur in people with personal or family history of heart disease.
Before a heart attack, women are more likely than men to be nauseous and experience pain high in the abdomen or chest. Their first symptom may be extreme fatigue after physical activity rather than chest pain. Chest pain in women is also more likely to be caused by non-heart problems than in men.

Symptoms That Are Less Likely to Indicate a Heart Attack. The following symptoms are less likely to be due to a heart attack:

Sharp pain brought on by lung movements or coughing
Pain that is mainly or only in the middle or lower abdomen
Pain that can be pinpointed with the top of one finger
Pain that can be reproduced by moving or pressing on the chest wall or arms
Pain that is constant and lasts for hours (although no one should wait hours if they suspect they are having a heart attack)
Pain that is very brief and lasts for a few seconds
Pain that spreads to the legs

However, the presence of these symptoms does not always rule out a serious heart event.

Chest pain is a very common symptom in the emergency room, but heart problems account for only 10 - 33% of all episodes.

The most common causes of chest pain are muscular and bone problems. Problems affecting the ribs and chest muscles include injured muscles, fractures, arthritis, spasms, and infections.

Other causes of chest pain include:

Anxiety attacks
Gastrointestinal disorders (gallstone attacks, peptic ulcer disease, hiatal hernia, heartburn)
Asthma
Spasm in the coronary artery
Abnormalities of the heart muscle
Rupture of the aorta
Collapsed lung
Acute inflammation of the heart
Blood clot in the lung
High thyroid levels (hyperthyroidism)
Anemia
Vasculitis (a group of disorders that cause inflammation of the blood vessels)
Exposure to high altitudes (rare)

Individuals who experience symptoms of a heart attack should take the following actions:

For angina patients, take one nitroglycerin dose either as an under-the-tongue tablet or in spray form at the onset of symptoms. Take another dose every 5 minutes up to three doses or when the pain is relieved, whichever comes first.
Call 911 or the local emergency number. This should be the first action taken if angina patients continue to experience chest pain after taking the full three doses of nitroglycerin. However, only 20% of heart attacks occur in patients with long-standing angina. Therefore, anyone who has heart disease or risk factors for it and experiences heart attack symptoms should contact emergency services.
The patient should chew an aspirin (250 - 500 mg) and be sure that emergency health providers are informed of this so an additional dose is not given.
Patients with chest pain should go immediately to the nearest emergency room, preferably traveling by ambulance. They should not drive themselves.

Click the icon to see an image about heart attack symptoms.

Click the icon to see another image about heart attack symptoms.

Risk Factors

Over 13 million Americans have had angina, a heart attack, or both. Each year, about 1.2 million people will experience a serious heart event. About 25% of all Americans have one or more risk factors for heart disease. Most risk factors for heart disease are related to lifestyle and environmental factors.

Over the past decades, heart disease rates declined in both men and women as they quit smoking and improved dietary habits. This rate, however, has stabilized in recent years, most likely because of the dramatic increase in obesity in the U.S. and other industrialized nations. There have also been minimal changes in other risk factors, including smoking, sedentary behavior, and blood pressure control. Some risk factors cannot be changed, including age, gender, and genetics. Nevertheless, their effects can still be modified with healthy lifestyle changes.

Heart disease may be prevented with a healthy diet and regular exercise, and by quitting smoking if you smoke. Follow your health care provider's recommendations for the treatment and prevention of heart disease.

The American Heart Association guidelines for preventing heart disease recommend:

Improve Cholesterol. People with at least two risk factors and a 10-year risk for heart disease or stroke of more than 20% should aim for LDL levels of less than 100 mg/dl. Statins are now used in more cases.

Keep Blood Pressure Low. People in normal health should have a blood pressure reading of 120/80 mm Hg or less. According to the latest guidelines, blood pressure readings of 120/80 are considered normal, readings of 140/90 or higher indicate hypertension, and readings in between the two are called pre-hypertension. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 mm Hg or less, while others should be no higher than 140/90 mm Hg.

Exercise. Everyone in normal health should engage in at least moderate physical activity for a minimum of 30 minutes on most, if not all, days of the week.

Healthy Diet. Everyone should aim for a diet that contains a healthy balance of fruits, vegetables, grains, fish, nuts, legumes, poultry, lean meat, and low-fat dairy items. Avoid saturated fats and trans-fatty acids.

Quit Smoking. Also avoid exposure to secondhand smoke.

Maintain Weight. People should aim for a BMI index of 18.5 - 24.9.

Taking Aspirin. People whose risk for heart disease within 10 years is 10% or more should take a low-dose aspirin every day, unless they have medical reasons to avoid aspirin.

Control Diabetes. People with diabetes should aim for fast blood glucose levels of less than 110 mg/dl and hemoglobin A1C or less than 7%.

Control Atrial Fibrillation. People with atrial fibrillation should use anticoagulants to reduce the risk for blood clots.

Age. About 85% of people who die from heart disease are over the age of 65.

Gender. Coronary artery disease and heart attacks are much more common in middle-aged men. Women have, on average, 10 - 15 more years of heart disease-free life than do men, but as women age, they catch up to men. Women, in fact, are more likely to have angina than men. Younger women with heart disease often do not have the same symptoms as their male counterparts and may be less likely to be diagnosed correctly. They are also more likely than men to die after a heart attack.

In 2007, the American Heart Association issued updated guidelines focusing on prevention of heart disease in women. The new guidelines recommend:

Healthy diet (fresh fruits and vegetables, low-fat dairy products, salt and saturated fat restrictions, alcohol moderation)
Eating oily fish (such as salmon) at least twice a week. Women with existing heart disease should consider taking fish oil supplements of 850 – 1,000 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DPA).
Increased physical activity (60 – 90 minutes, preferably 7 days a week)
Quitting smoking
Low-dose aspirin therapy for all women age 65 years and older who can safely take aspirin. High-risk women may require 75 – 325 mg / day; lower-risk women may benefit from 81 mg a day or 100 mg every other day.

Genetic Factors. Genetics are involved in increasing the likelihood of developing important risk factors such as diabetes and high blood pressure. For example, one genetic variant called apolipoprotein E4 (ApoE4) affects cholesterol levels, particularly those associated with heart disease.

Ethnicity. African-American women face the highest risk for death from heart disease, and their rate of heart attacks is increasing. (Mortality rates in men do not differ much by race.) Native American men have a lower risk for heart disease than Caucasian men, and Hispanics have the lowest risk for heart disease of all major American population groups.

African-Americans face a number of biologic and social dangers to their hearts.

They have a higher prevalence of diabetes and hypertension than do Caucasians.
They tend to have poorer diets, higher stress levels, and less access to health care.
All African-Americans risk discrimination in obtaining optimal treatments, but women may be at particular risk for unequal treatment. In one study in which female actors portrayed heart patients, African-American women were 60% less likely to receive aggressive (and expensive) diagnostic tests than African-American men or any Caucasians, even though they presented with similar symptoms.
While African-Americans comprise 13% of the U.S. population, African-Americans have comprised only 2 - 9% of subjects in most major research trials, so knowledge about their specific risks is limited.
Some African-Americans with coronary artery disease appear to have a genetic trait that increases the danger of triglycerides, which may be particularly hazardous for women.

Click the icon to see an image about ethnicity and heart disease risks.

Cholesterol. In spite of its bad press, cholesterol is an essential nutrient necessary for many cellular functions. However, when certain cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol responsible for many heart problems. Triglycerides are another type of lipid (fat molecule) that can be bad for the heart. High-density lipoprotein (HDL) cholesterol is the "good" cholesterol that helps protect against heart disease. Doctors test for a "total cholesterol" profile that includes measurements for LDL, HDL, and triglycerides. The ratio of these lipids can affect heart disease risk.

For example, according to one study, men with total cholesterol levels over 240 mg/dl have a risk that is two to four times higher than men whose cholesterol is below 200. A number of studies have demonstrated that reducing LDL and total cholesterol levels and boosting high-density lipoprotein (HDL) levels can improve survival and prevent heart attacks in people with and without heart disease.

It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by the Friedewald formula: LDL=TC-HDL-TG/5. (LDL=low-density lipoprotein; TC= total cholesterol; HDL=high-density lipoprotein; TG=triglycerides.)

Click the icon to see an image about serum cholesterol.

Cholesterol Goals. In 2004, the National Cholesterol Education Program updated its clinical practice guidelines. The new recommendations set lower treatment goals for LDL levels based on a patient's risk factors for heart disease.

These risk factors include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides

Having two or more of these risk factors indicates a greater than 20% chance of having a heart attack within 10 years.


Risk Level	Goal (d/L)	Optimal Goal(d/L)
Very High Risk	70	70
High Risk	100	70
Moderate Risk	130	100
Low Risk	160	130

LDL cholesterol, together with other risk factors for heart disease, is the best determinant for whether cholesterol therapy is needed and whether it is working properly. In particular, the new guidelines emphasize lower LDL levels and earlier treatment for people with coronary artery disease, or other forms of atherosclerosis, and diabetes.


Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
Less than 200 mg/dL is desirable. Between 200 and 239 is borderline. Over 240 is high.	70 mg/dL or less is the new goal for very high-risk patients (recent heart attack; current active or unstable cardiovascular or cerebrovascular disease; or two multiple risk factors as defined above.) Below 100 mg/dl is optimal for everyone. It should be the goal for high-risk people including those with existing heart disease, diabetes, or two or more risk factors for heart disease; 70 mg/dL is an optimal goal for these individuals. 130 mg/dl or below for people with two or more risk factors; 100 mg/dL is the optimal goal. 160 mg/dl or less for people at less risk (one or zero risk factors); 130 mg/dL is the optimal goal. Anything over 160 is high with levels over 190 being very high. LDL levels over 190 require medication even with no other cardiac risk factors present.	Levels above 40 mg/dL are desirable; levels above 60 mg/DL are optimal.	Below 150 mg/dL is normal. 150-199 is borderline high. 200-499 is high. Over 500 is very high.
*Risk factors for heart disease include a family history of early heart problems before age 55 for men, before age 65 for women, smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dl. People with two or more of these risk factors may have a 10-year risk of heart attack that exceeds 20%, and may therefore need to aim for LDL levels of 100 mg/dL or below.

Other Lipids. Elevated levels of other fatty molecules (lipids) are also now thought to be important indicators of heart disease risk. Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), or lp(a). This lipoprotein falls somewhere in density between HDL and LDL and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause.

[See In-Depth Report #23: Cholesterol; and In-Depth Report #43: Heart-healthy diet.]

High blood pressure, or hypertension, has long been a proven cause of coronary artery disease. Blood pressure is categorized as normal, prehypertensive, and hypertensive (which is further divided as Stage 1 or 2 according to severity). High blood pressure is generally considered to be a blood pressure reading greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic). Blood pressure readings in the prehypertension category (120 - 139 systolic or 80 - 89 diastolic) indicate an increased risk for developing hypertension. [See Table Blood Pressure Ranges.]

A normal blood pressure reading is 120/80 mm Hg or lower. Most people with high blood pressure should aim for a goal of below 140/90 mm Hg. Patients with certain health problems should aim lower (blood pressure in patients with kidney disease, heart failure, or diabetes should be equal to or lower than 130/80 mm Hg.)

Click the icon to see an image about hypertension.


Blood Pressure Category	Ranges for Most Adults (systolic/diastolic)
Normal Blood Pressure (systolic/diastolic)	Systolic below 120 mm Hg Diastolic below 80 mm Hg
Prehypertension (Formerly Classified as Normal to High-Normal Blood Pressure)	Systolic 120 to 139 mm Hg Diastolic 80 to 89 mm Hg (NOTE: 139/89 or below should be the minimum goal for everyone. People with diabetes or chronic kidney disease should strive for 130/80 or less.)
Mild Hypertension (Stage 1)	Systolic 140 to 159 mm Hg Diastolic 90 to 99 mm Hg
Moderate-to-Severe Hypertension (Stage 2)	Systolic over 160 mm Hg and/or Diastolic over 100 mm Hg
Note: If one of the measurements is in a higher category than the other, the higher measurement is usually used to determine the stage. For example, if systolic pressure is 165 (Stage 2) and diastolic is 92 (Stage 1), the patient would still be diagnosed with Stage 2 hypertension. A high systolic pressure should be a major focus of concern in most adults.

American obesity is at epidemic levels in all age groups. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels are usually high while HDL (beneficial cholesterol) levels tend to be low, both risk factors for heart disease. Obesity has other effects (hypertension, increase in inflammation) that pose major risks to the heart.

Click the icon to see an image of childhood obesity.

Obesity is particularly hazardous when it is one of the components of the metabolic syndrome. This syndrome is diagnosed when three of the following are present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. A 2002 study estimated that 24% of the population now has this condition. Obesity is highly linked with type 2 diabetes, and diabetes itself poses a significant risk for high cholesterol levels and heart disease.

Some obese patients with coronary artery disease may consider having bariatric surgery (stomach bypass) to lose excess weight. The weight lost after surgery can help improve blood pressure, cholesterol, blood sugar and other factors associated with CAD. A 2005 study reported that bariatric surgery is safe for patients with CAD who cannot lose weight with diet and exercise, which should always be tried first.

[See In-Depth Report #53: Weight control and diet.]

People who are sedentary are almost twice as likely to suffer heart attacks as are people who exercise regularly. Exercise has a number of effects that benefit the heart and circulation, including:

Improving cholesterol and lipid levels
Reducing inflammation in the arteries
Assisting weight loss programs
Helping to keep blood vessels flexible and open

Studies continue to show that physical activity and avoiding high-fat foods are the two most successful means of reaching and maintaining heart healthy levels of fitness and weight.

Experts have been attempting to define how much exercise is needed to produce heart benefits. In 2002, a well-conducted study on overweight adults confirmed previous research that reported beneficial changes in cholesterol and lipid levels even when people performed low amounts of moderate or high intensity exercise (walking or jogging 12 miles a week). However, more intense exercise is required to significantly change cholesterol levels, notably by increasing HDL (the so-called good cholesterol). Overweight people who have trouble losing pounds can still achieve considerable heart benefits by exercising. Resistance (weight) training has also been associated with heart protection. Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Click the icon to see an image about exercise.

Click the icon to see an image about hypertension and lifestyle changes.

Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise, which can be particularly helpful for older people.

Sudden strenuous exercise (such as snow shoveling and mowing lawns) puts many people at risk for angina and heart attack. Activities that involve raising the arms above the head may also be risky. Patients with angina should never exercise shortly after eating. People with risk factors for heart disease should seek medical clearance and a detailed exercise prescription. And all people, including healthy individuals, should listen carefully to their bodies for signs of distress as they exercise. [See In-Depth Report #29: Exercise.]

Heart disease and stroke are the leading causes of death in people with diabetes. People with diabetes are at risk for the following heart-risk conditions, and the more of these conditions they have, the worse the outlook.

High blood pressure (hypertension). Up to 75% of cardiovascular problems in people with diabetes may be due to hypertension.
Very unhealthy cholesterol and lipid balances (high triglyceride levels and lower HDL).
Blood clotting problems.
Impaired nerve function (neuropathy), which can also damage the heart. Some experts estimate that the mortality rates from neuropathy-related heart conditions range from 15 - 53%.

People with both diabetes and heart disease may have a higher risk for silent ischemia, a condition in which people have blocked arteries but do not experience the angina, the chest pain that signals heart disease. [See In-Depth Report #9: Diabetes - type 1; or In-Depth Report #60: Diabetes - type 2.]

Peripheral artery disease (PAD) occurs when atherosclerosis affects the extremities, particularly the feet and legs. The major risk factors for heart disease and stroke are also the most important risk factors for PAD. (The combination of such conditions with PAD also produces more severe forms of heart or circulatory disease.) Although signs of heart disease are detected in only 20 - 40% of patients with PAD after an initial diagnosis, studies suggest that when intense heart-diagnostics tests are performed, such as angiography or thallium stress tests, co-existing heart disease is detected in up to 90% of all PAD patients. [See In-Depth Report #102: Peripheral artery disease.]

Smokers in their 30s and 40s have a heart-attack rate that is five times higher than their nonsmoking peers. Cigarette smoking may be directly responsible for at least 20% of all deaths from heart disease, or about 120,000 deaths annually. Smoking cigars may increase the risk of early death from heart disease, although evidence is much stronger for cigarette smoking. Although heavy cigarette smokers are at greatest risk, a 2002 study suggested that people who smoke as few as three cigarettes a day are at higher risk for blood vessel abnormalities that endanger the heart. Regular exposure to passive smoke also increases the risk of heart disease in nonsmokers. [See In-Depth Report #41: Smoking.]

Eating habits can be protective or dangerous to the heart. Avoiding saturated fats and trans-fatty acids is particularly important for controlling cholesterol.

Diet plays an important role in the health of the heart. In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cut down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey.)
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Stress. The effects of mental stress on heart disease are controversial. Stress can affect the heart when it activates the sympathetic nervous system (the automatic part of the nervous system that affects many organs, including the heart). Some studies suggest an association between acute stress and a higher risk for serious cardiac events, such as heart rhythm abnormalities and heart attacks, in people with heart disease. However, not all studies report strong evidence that stress has any effect on the heart, particularly in people without any history of heart disease. [See In-Depth Report #31: Stress.]

Depression. Depression increases the severity of heart attack and may even worsen a patient's response to medication for heart disease. Although people with heart disease may become depressed, this does not explain entirely the link between the two problems. Data suggest that depression itself may be a risk factor for heart disease as well as its increased severity.

A number of studies indicate that depression has biologic effects on the heart, including blood clotting and heart rate. One study, for example, reported an association between depression and a greater risk for death from heart problems even in people without a history of heart disease. Even mild depression, which includes feelings of hopelessness experienced over many years, may harm the heart. A 2007 study suggested that depressive symptoms (fatigue, loss of appetite) may be a sign of thickening arteries, the early stage of coronary artery disease. [See In-Depth Report #8: Depression.]

Benefits of Moderate Drinking. Several studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate alcohol consumption can help boost HDL levels. Alcohol may also prevent blood clots and inflammation. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit.

Adverse Effects of Heavy Drinking. By contrast, heavy drinking harms the heart. In fact, heart disease is the leading cause of death in alcoholics. Evidence suggests that people who consume more than three drinks a day have abnormal blood clotting factors. Heavy alcohol consumption can raise blood pressure, and binge drinking may increase the risk for hemorrhagic stroke (caused by bleeding in the brain). Large doses of alcohol can trigger irregular heartbeats, which can be dangerous in people with existing heart disease.

Pregnant women and people who can't drink moderately should not drink at all.

Homocysteine and Vitamin B Deficiencies. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements do help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took B vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Click the icon to see the benefits of vitamin B.

Click the icon to see the food sources of vitamin B.

C-Reactive Protein. C-reactive protein is a product of the inflammatory process. Evidence increasingly suggests that high levels may predict future heart disease. It is not known if the protein plays any causal role or whether it is simply a marker for other factors in the disease process.

C. pneumoniae and Other Infectious Organisms. Some microorganisms and viruses have been under suspicion for triggering the inflammation and damage in the arteries that contribute to heart disease. The strongest evidence to date supports a possible role from Chlamydia (C.) pneumoniae (a non-bacterial organism that causes mild pneumonia in young adults). C. pneumoniae has been detected in plaques in the arteries of patients with heart disease. In some studies, evidence of previous infection has been associated with a higher risk for heart events.

Other studies also suggest that cytomegalovirus (CMV), a common virus, may have similar effects. Many people, however, have been infected with these organisms, and no clear association has been found with any of these infections.(H. pylori, the bacteria that causes peptic ulcers, has also been studied for heart effects, but evidence is very weak on any link.)

Erectile Dysfunction. Recent research suggests that erectile dysfunction may be a warning sign of coronary artery disease, even in men who are not considered at risk for the condition. Some studies indicate that men with erectile dysfunction have higher levels of C-reactive protein and more symptoms of atherosclerosis than men without erectile problems.

Periodontal Disease. A number of studies support an association between periodontal disease and cardiovascular disorders. According to a 2003 major analysis, periodontal (gum) disease is associated with a 20% higher risk for ischemic stroke and heart disease. (The added risk may be even higher in adults under 65.) Recent evidence is pointing to the inflammatory response as the common element.

Click the icon to see an image of gum disease.

Anemia. Anemia has adverse effects on the heart and increases the severity of cardiac conditions, including heart failure and heart attacks. A 2002 study suggested that anemia may even be a risk factor for heart disease itself. Blood transfusions after a heart attack improve survival rates in elderly patients who are anemic.

Iron Overload. An inherited disease called hemochromatosis, in which the intestinal tract absorbs too much iron from food, has been associated with atherosclerosis and heart attack. About 10% of Caucasians carry the gene for this condition. There is no strong evidence that excess iron levels in people without hemochromatosis can contribute to heart disease.

Sleep Apnea. Obstructive sleep apnea is a condition in which tissues in the upper throat collapse at intervals during sleep, thereby blocking the passage of air. It has been strongly associated with high blood pressure and obesity, but is also associated with heart disease and heart attacks, regardless of these risk factors. Some evidence suggests that obstructive apneas cause an increase in stiffness and inflammation in the arteries.

Some inborn or natural conditions are not risk factors themselves but have been associated with a higher incidence of heart disease or its consequences:

Factors Before Birth and In Infancy. Low weight at birth and in the womb has been associated with later heart disease in a few studies. Some suggest, however, that this may just reflect poor nutrition in the mother, which appears to affect life-long risk.

Seasonal Differences. More deaths from heart disease occur in December and January, and the fewest in the summertime. Although lower temperatures and snow shoveling may play a role in some cases, more winter deaths have been reported even in warm regions. Holiday stress or fewer daylight hours have been suggested as other reasons for these higher winter rates.

Physical Characteristics. Male pattern baldness, hair in the ear canals, and creased earlobes are associated with a higher risk for heart disease in Caucasian males.

Click the icon to see an image of an ear lobe crease.

Diagnosis

Many tests can diagnose possible heart disease. The choice of which (and how many) tests to perform depends on the patient's risk factors, history of heart problems, and current symptoms. Usually the tests begin with the simplest and may progress to more complicated ones.

Doctors routinely check for high blood pressure and unhealthy cholesterol levels in all older adults. Specific tests are also important in people who may have risk factors or symptoms of diabetes. Doctors may also test for homocysteine, the protein albumin, and blood clotting factors, especially fibrinogen.

An electrocardiogram (ECG) measures and records the electrical activity of the heart. Between 25 - 50% of people who suffer from angina or have silent ischemia, however, have normal ECG readings. The waves measured by the ECG correspond to the contraction and relaxation pattern of the different parts of the heart. Specific waves seen on an ECG are named with letters:

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

P. The P wave is associated with the contractions of the atria (the two chambers in the heart that receive blood from outside).
QRS. The QRS is a series of waves associated with ventricular contractions. (The ventricles are the two major pumping chambers in the heart.)
T and U. These waves follow the ventricular contractions.

The most important wave patterns in diagnosing and determining treatment for heart disease and heart attack are called ST elevations and Q waves.

A depressed or horizontal ST wave suggests some blockage and the presence of a heart disease, even if there is no angina present. (This finding, however, is not very accurate, particularly in women, and can occur without heart problems).
ST elevations and Q waves are the most important wave patterns in diagnosing and determining treatment for a heart attack. They suggest that an artery to the heart is blocked, and that the full thickness of the heart muscle is damaged. ST segment elevations do not always mean the patient has a heart attack. And, some heart attack patients do not have elevated ST segments. Other factors are important in making a diagnosis.

The primary value of exercise stress tests is not to detect coronary artery disease but to help determine the severity and predict the outcome of an existing heart condition. It is considered for the following people:

Patients with possible or probable angina and low or intermediate risk for adverse heart events.
Selected adults who do not have symptoms of heart disease but are at moderate risk to high risk for developing heart disease (a 10 - 20% chance within 10 years). Moreover, heart blockage without angina (silent ischemia) may suggest a more severe condition, at least in men.

Basic Procedure. A stress test (exercise tolerance test) monitors the patient's heart rhythms, blood pressure, and clinical status. It can tell how well the heart handles work and if parts of the heart have decreased blood supply. A typical stress test involves:

The patient walks on a treadmill or rides a stationary bicycle. Exercise continues until the heart is beating at least 85% of its maximum rate, until symptoms of heart trouble occur (changes in blood pressure, heart rhythm abnormalities, angina, fatigue), or the patient simply wants to stop.
For patients who cannot exercise, the doctor may administer dobutamine or arbutamine, which are drugs that simulate the stress of exercise.
An ECG is used to monitor heart rhythms during a stress test. (An echocardiogram or more advanced imaging technique may also be used to visualize the actions of the heart and blood flow.)

More than 25% of patients stop exercising before they reach their own maximum limits because of fear of a heart event. Patients should be reassured that the activities performed in the test under the guidance of a professional are safe.

Interpreting Results. To accurately assess heart problems, experts look at a number of findings derived from the ECG and other tools during exercise. They include:

Exercise capacity. This is a measure of a person's capacity to reach certain metabolic rates.
Heart rate and ST waves. On ECGs, doctors specifically look for abnormalities in part of the wave tracing called an ST segment. A certain type of ST segment depression may suggest the presence of heart disease. However, gender, drugs and other medical conditions can affect the ST segment. Using a measurement that adjusts the ST segment to heart rate improves accuracy.
Dukes Treadmill Score. This important score uses the number of minutes a patient can exercise and other factors that are present in patients with exercise-limiting angina.
Heart rate recovery.
Chronotropic index. This is the percentage of the heart-rate reserve that is used during the exercise. A result of 80% or less suggests a significant risk for serious heart problems in most patients.
Changes in systolic blood pressure.

Using these and other measures, doctors can determine risk fairly accurately, particularly for men of any age with chronic stable angina. The test has limitations, however, and some are significant. For example, a 2002 study indicated that in patients with suspected unstable angina the chances for a future adverse heart event remain high even if the exercise test shows low risk. In addition, for many reasons, the test is less accurate in women, and an echocardiogram may be a more accurate procedure for them. About 10% of patients, particularly younger people, will have false positive test results. In such cases, test results indicate abnormalities when there are no heart problems.

An echocardiogram is a noninvasive test that uses ultrasound images of the heart. This test is more expensive than an ECG, but it can be very valuable, particularly when used with a stress test, to detect the location and extent of heart muscle damage. It appears to be more accurate for women than ECG stress tests, but at this time it is not routinely recommended as a replacement for most women.

Computed tomography (CT) scans used alone or with ECG may be used to detect calcium deposits on the arterial walls, which are strong indicators of current and future coronary artery disease. The presence of calcium does not always signify narrowing of the arteries. But, the absence of calcification in the arteries indicates the patient has no risk for heart disease.

Advanced CT techniques are improving accuracy:

Click the icon to see an image of a CT scan.

Electron Beam Computed Tomography. Electron beam computed tomography (EBCT) is a CT technique that scans the heart so quickly that the motion of the heart appears frozen. This procedure identifies calcification and stratifies cardiac risk accurately.
Multidetector Computed Tomography. Another CT technique called multidetector computed tomography (MDCT) is able to take pictures of the entire heart in 1 millimeter slices in the time it takes for a patient to hold one breath. A 2006 study indicated that MDCT tends to have a high “false-positive” rate (indicating disease when it is not actually there), but for some patients the test may be helpful in ruling out coronary artery disease.

Some expert groups recommend CT scans in selected patients who have an intermediate risk (10 - 20% chance of heart disease within 10 years). For some of these patients, EBCT may be preferred over exercise stress testing, but most experts recommend a stress test as the main diagnostic tool. In general, the use of these expensive imaging tests is probably not very helpful for people at low or high risk. (For people with high risk, the additional information from these tests would not add much value.) More research is needed to determine the benefits of CT scanning in specific individuals.

Radionuclide procedures use imaging techniques and computer analyses to plot and detect the passage of radioactive tracers through the region of the heart. Such tracing elements are typically given intravenously. Radionuclide imaging is useful for diagnosing and determining:

Severity of unstable angina when less expensive diagnostic approaches are unavailable or unreliable
Severity of chronic coronary artery disease
Success of surgeries for coronary artery disease.
Whether a heart attack has occurred

Various imaging techniques may be used with radionuclide procedures, including:

Planar scintigraphy uses a special overhead camera and is the oldest scanning technique.
Single-photon emission computed tomography (SPECT) uses a camera that rotates around the patient and takes pictures of "slices" of the heart. It is more accurate than planar imaging in precisely locating problems in the arteries.
Positron-emission tomographic (PET) scanners employ multiple rings that surround the patients, which detect and record atomic particles (photons) that are emitted by the tracer elements (such as radioactive oxygen, nitrogen, or carbon). It is more expensive and less widely available than SPECT.

Myocardial Perfusion (Blood Flow) Imaging Test (also called the Thallium Stress Test). This radionuclide test is typically used with an exercise stress test to determine blood flow to the heart muscles. It is a reliable measure of severe heart events. It may be useful in determining the need for angiography if CT scans have detected calcification in the arteries. About a minute before the patient is ready to stop exercising, the doctor administers a radioactive tracer into the intravenous line. (Tracers include thallium, technetium, or sestamibi.) Immediately afterwards, the patient lies down for a heart scan, usually with a planar scintigraphy or with SPECT. If the scan detects damage, more images are taken 3 or 4 hours later. Damage due to a prior heart attack will persist when the heart scan is repeated. Injury caused by angina, however, will have resolved by that time.

Radionuclide Angiography. This is a technique for visualizing the chambers and major blood vessels of the heart. It uses an injected radioactive tracer and can be performed during exercise, at rest, or with use of stress-inducing drugs. It is an excellent test for assessing the heart's pumping action and for determining the severity of coronary artery disease. It is an alternative to echocardiograms in certain situations.

Click the icon to see an internal view of the heart.

Magnetic Resonance Angiography (MRA). MRA is a very promising noninvasive imaging technique that can provide three-dimensional images of the major arteries to the heart and identify disease with high accuracy. Experts believe this approach will eventually be a good alternative to angiography.

Click the icon to see an image of a MRI.

Angiography is an invasive test. It is used for patients who show strong evidence for severe obstruction on stress and other tests, and for patients with acute coronary syndrome.

A narrow tube is inserted into an artery, usually in the leg or arm, and then threaded up through the body to the coronary arteries.
A dye is injected into the tube, and an x-ray records the flow of dye through the arteries.
This process provides a map of the coronary circulation, revealing any blocked areas.

Click the icon to see an image of dye in the coronary artery.

Major complications include stroke, heart attacks, and kidney damage. These risks are very low (about 0.1%), however, if the procedure is done in an experienced medical center (one that performs at least 300 of these operations every year). Allergic reactions can also occur. The procedure is expensive, and between 10 - 30% of patients who have this procedure have normal results.

When heart cells become damaged, they release different enzymes and other molecules into the bloodstream. Elevated levels of such markers of heart damage in the blood or urine may help predict a heart attack in patients with severe chest pain and help determine treatment. Some of these factors include:

Troponins. The proteins cardiac troponin T and I are released when the heart muscle is damaged. Both are proving to be among the best diagnostic indications of heart attacks. They help to identify many individuals with ACS who might otherwise be misdiagnosed.
Creatine kinase myocardial band (CK-MB). CK-MB has been a standard marker, but the MB fraction is not as accurate as troponin levels, since elevated levels can appear in people without heart injury.
Myoglobin. Myoglobin is a protein found in heart muscles. It is released early in the injured heart, and it may be useful in combination with CK-MB and the troponins.
Newer biomarkers, including C-reactive protein (CRP), homocysteine, B-type natriuretic peptide (BNP), urinary albumin, and fibrinogen.

Several 2006 studies that evaluated how well biomarkers predict risk of heart events concluded that they do not provide much more useful information than standard risk factors (high blood pressure, unhealthy cholesterol levels, diabetes). At this time, most experts feel that these standard disease risk factors provide the best predictors of the likelihood of developing coronary artery disease, heart attack, or stroke.

Managing Heart Disease

The approach for managing any degree of coronary artery disease involves lifestyle changes. Depending on severity and individual conditions, patients may need one or more medications, surgery, or both.

Healthy diet, regular exercise and quitting smoking if you are a smoker may prevent heart disease. Follow your health care provider's recommendations for treatment and prevention of heart disease.

Experts have come up with a mnemonic device (ABCDE) for remembering 10 factors that are fundamental for management of stable angina and coronary artery disease:

A. Aspirin and anti-angina drugs

B. Blood pressure and beta-blockers

C. Cholesterol-lowering drugs (typically statins) and cigarettes (stopping)

D. Diet and diabetes control

E. Exercise and education

Unstable angina is now usually classified with non-Q myocardial infarction as acute coronary syndrome (ACS) in professional discussions of treatments. ACS usually requires more aggressive treatments, including surgery. [ACS is more fully discussed in In-Depth Report #12: Heart attack and acute coronary syndrome.]

Click the icon to see an image about angina.

Anti-Clotting Medications

Anti-clotting drugs that inhibit or break up blood clots are used at every stage of heart disease. They are generally classified as either antiplatelets or anticoagulants. All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Antiplatelet Drugs. These drugs prevent formation of blood platelets. Platelets are very small disc-shaped blood cells that are important for blood clotting.

Aspirin. Aspirin is an antiplatelet. It is the most common anti-clotting drug. Nearly anyone with existing heart disease or at risk for it is advised to take a low-dose aspirin every day.
Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are thienopyridines, another type of anti-platelet drug.
Glycoprotein IIb/IIIa Inhibitors. These powerful blood-thinning drugs include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are used after angioplasty surgery and stent placement.

Click the icon to see an image about blood.

Anticoagulants. Anticoagulants help thin blood and include:

Heparin
Warfarin (Coumadin)
Direct thrombin inhibitors

Aspirin. Aspirin is known as a nonsteroidal anti-inflammatory drug (NSAID). It stops blood platelets, which are major clotting factors, from sticking together to form a blood clot. A daily low-dose aspirin (75 - 325 mg) is usually the first choice for preventing heart disease in high-risk individuals. Aspirin can prevent by 25 – 50% the risk of heart attacks and death in people with existing heart disease and a history of heart attack. It also reduces the risk for stroke. According to a 2006 review, aspirin works equally well for both men and women.

Click the icon to see an image about stomach ulcers.

Side effects from prolonged use of aspirin may include stomach ulcers and bleeding. (There may be a slight increased risk for bleeding-related strokes, which are very uncommon, however. Furthermore, this risk may be outweighed by protection against the more common type of stroke, which is caused by artery blockage.)

Clopidogreland Ticlopidine. Clopidogrel (Plavix) and ticlopidine (Ticlide) are anti-platelet drugs known as thienopyridines. When taken with aspirin, these drugs can significantly reduce the risk for heart attack and stroke in patients with acute coronary syndrome (unstable angina or early signs of heart attack). The combination of aspirin and a thienopyridine is essential for patients who have a drug-eluting stent. According to a 2007 American Heart Association advisory, patients who have a drug-eluting stent must take both aspirin and a thienopyridine for at least 1 year after the stent is inserted. Many experts recommend clopidogrel instead of ticlopidine because ticlopidine has been associated with dangerous blood disorders, particularly thrombocytopenia.

Clopidogrel is also recommended for patients who are undergoing angioplasty. For patients having coronary bypass surgery, it should be withheld for at least 5 -7 days prior to surgery because of a significant bleeding risk. Researchers are investigating whether clopidogrel and aspirin together are better than aspirin alone in reducing the risks following coronary bypass surgery. A 2006 study suggested that for some patients with heart disease, clopidogrel plus aspirin does not work better than aspirin alone for preventing a first heart attack or stroke.

Click the icon to see an image of the developmental process of atherosclerosis.

Click the icon to see an image about atherosclerosis.

Anticoagulants are drugs that prevent or delay blood coagulation and the formation of blood clots. Heparin has been the standard anticoagulant, but a number of drugs are now available that are proving to be better choices in many cases.

Standard (Unfractionated) Heparin. The heparin referred to as unfractionated heparin has been the standard for years and is used alone or in combination with aspirin for managing unstable angina. It is no longer the recommended first choice, however, for this patient group. It must be intravenously administered and monitored with frequent blood tests. The major complication is thrombocytopenia (a severe drop in platelets). This condition is extremely serious and can become life-threatening, particularly with bleeding in various body tissues. Alternatives include low-molecular weight heparin and direct thrombin inhibitors.

Low-Molecular Weight Heparin. Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep) are drugs known as low-molecular weight heparins (LMWHs). Many doctors now recommend these drugs over standard heparin for patients with unstable angina (unless bypass surgery is being planned). They have similar rates of survival, recurring angina, and bleeding as standard heparin. However, they pose lower risks for heart attack, repeat angioplasties, and thrombocytopenia. They require injections but do not require the ongoing monitoring that standard heparin does. Patients may even be able to self-administer LMWHs as people with diabetes do insulin.

Warfarin. Warfarin (Coumadin) is an oral anticoagulant. It prevents clots by inhibiting vitamin K. Warfarin is used with aspirin after a heart attack to prevent another one and to prevent blood clots in patients with atrial fibrillation. Warfarin is also proving to be more effective than aspirin for preventing heart attacks in patients with acute coronary syndromes. Warfarin therapy poses a dangerous risk for bleeding and blood coagulation must be monitored with frequent blood tests.

Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI was hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaparoid (Orgaran), lepirudin (Refludan), desirudin (Revasc), and ximelagatran (Exanta). Many of these drugs are used along with warfarin and may be good options for patients who develop thrombocytopenia with heparin use. DTIs may prove to be superior to standard heparin for patients with acute coronary syndrome.

Other Medications

Nitrates have been used in the treatment of angina for over 100 years. These drugs release nitric oxide, thereby relaxing the smooth muscles in blood vessels. Many nitrate preparations are available. The most commonly used are nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates can be absorbed from the gastrointestinal tract (oral tablet), skin (ointment or patch), or from under the tongue (sublingual tablet or spray).

Rapid Acting Nitrates. Rapid-acting nitrates are used to treat acute attacks. Nitroglycerin is the most widely used drug for this purpose. It can be administered under the tongue (sublingually or as a spray) or pocketed between the upper lip and gum (buccally) and can relieve angina within minutes. The procedure for taking nitroglycerin during an attack is as follows:

At the onset of an angina attack, the patient administers one sublingual or buccal tablet or one metered dose of the spray.
If the pain is not relieved within 5 minutes the patient takes a second dose; a third can be taken after another 5 minutes if symptoms persist.
If pain continues after a total of three doses in 15 minutes, the patient should go immediately to the nearest emergency room.

Nitroglycerin is very volatile so its potency can be easily lost. Patients should take the following precautions:

Keep no more than 100 tablets on hand, stored in their original container.
When first opened, the cotton filler should be discarded, and the cap screwed on tightly immediately after each use.
A supply should always be kept close at hand in case of an attack, with the rest kept in a cool dry place.

Intermediate to Long-Term Nitrates. Sublingual tablets of isosorbide dinitrate have a somewhat slower onset of action than nitroglycerin and are useful for preventing exercise angina. Ointments, patches, and oral tablets are used for longer-term prevention of angina attacks:

Transdermal patches are applied in the morning to any hair- or injury-free area on the chest, back, stomach, thigh, or upper arm. Hands should be washed after each patch or ointment application, and sites of application should be rotated to avoid skin irritation.
Nitroglycerin ointment is applied by measuring out an even amount on an applicator paper and then placing, not rubbing or massaging, it on the chest, stomach, or thigh. Any ointment that remains from the previous application should be removed.

Long-acting forms may lose their effectiveness over time, so doctors generally schedule nitrate-free breaks to prevent tolerance. Some concern exists that nitrate-free periods might increase the risk for angina and adverse heart events. One large study, however, found no increased danger when patients used a nitroglycerine patch with scheduled breaks. The use of high blood pressure drugs known as ACE inhibitors may help prevent tolerance to nitrates.

Side Effects. Nitrates have many side effects, some of which can be serious.

Common side effects of nitrates include headaches, dizziness, nausea and vomiting, blurred vision, fast heartbeat, sweating, and flushing on the face and neck. Low blood pressure and dizziness can be relieved by lying down with the legs elevated. These effects are significantly worsened by alcohol, beta-blockers, calcium channel blockers, sildenafil (Viagra), and certain antidepressants. The doctor may prescribe medicines to lessen these side effects. Patients should contact their doctor if these side effects are persistent or severe.

Serious side effects requiring immediate medical help include fever, joint or chest pain, sore throat, skin rash (especially on the face), unusual bleeding or bruising, weight gain, and swelling of the ankles.

Withdrawal. Withdrawal from nitrates should be gradual. Abrupt termination may cause angina attacks.

Beta-blockers are useful for preventing angina attacks and reducing high blood pressure. They reduce the heart's oxygen demand by slowing the heart rate and lowering blood pressure. They are recognized for reducing deaths from heart disease and from heart surgeries, including angiography and coronary bypass. Beta-blockers are the drugs of choice for older patients with stable angina and may also be beneficial for people with silent ischemia. They are, however, less useful for the treatment of Prinzmetal’s angina. Beta-blockers are often prescribed along with other drugs such as nitrates, calcium channel blockers, or statins. A 2006 study suggested that beta-blockers and statins may help stabilize coronary artery disease and prevent the development of heart attacks.

Specific Beta-blockers. Beta-blockers include propranolol (Inderal), carvedilol (Coreg), bisoprolol (Zebeta), acebutolol (Sectral), atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol-XL), and esmolol (Brevibloc). A nasal spray form of propranolol appears to be very helpful in reducing exercise-induced angina attacks.

Side Effects. Beta-blocker side effects include fatigue, lethargy, vivid dreams and nightmares, depression, memory loss, and dizziness. They can lower HDL (“good”) cholesterol. Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. These beta-blockers should not be used by patients with asthma, emphysema, or chronic bronchitis.

Patients should never abruptly stop taking these drugs. The sudden withdrawal of beta-blockers can rapidly increase heart rate and blood pressure. The doctor may advise a patient to slowly decrease the dose before stopping completely.

Calcium channel blockers reduce heart rate and slightly dilate the blood vessels of the heart, thereby decreasing oxygen demand and increasing oxygen supply. They also reduce blood pressure. CCBs vary chemically, however, and although some are helpful, others may even be dangerous for certain patients with angina.

Click the icon to see an image of the anterior heart arteries.

Long-acting nifedipine (Adalat, Procardia) and nisoldipine (Sular) and newer CCBs, such as amlodipine (Norvasc) and nicardipine (Cardene), may be beneficial for some patients with angina. They can be considered alone for patients who cannot tolerate beta-blockers, but may provide the best results when used in combination with a beta-blocker. Studies suggest that they reduce the need for repeat angioplasties. Their effects on other outcomes, including mortality rates and heart attack, are less clear.
Short-acting CCBs, including short-acting forms of verapamil, diltiazem, nifedipine, and nicardipine, are helpful for many patients with Prinzmetal's angina. However, short-acting forms of certain CCBs, such as nifedipine and nisoldipine, have been associated with severe and even dangerous side effects, including an increase in heart attacks and sudden death in some patients with unstable angina. They also increase the risk for adverse effects in patients with stable angina. Short-acting CCBs are, therefore, not used for stable or unstable angina.

There is no strong evidence that any calcium channel blockers improve survival rates. Overdose can cause dangerously low blood pressure and slow heart beats. Patients with heart failure have a higher risk for death with these drugs and should not take them. No one taking any calcium channel blocker should withdraw abruptly because such action could dangerously increase the risk of high blood pressure. Note: Grapefruit and Seville oranges boost the effects of CCBs, sometimes to toxic levels. (Regular oranges do not appear to pose any hazard.)

Angiotensin converting enzyme (ACE) inhibitors are important heart-protective drugs, particularly for people with diabetes and high blood pressure. They reduce the production of angiotensin, a chemical that causes arteries to narrow, and so are commonly used to lower blood pressure. They may also reduce risk for heart attack, stroke, complications of diabetes, and death in patients at high risk for heart disease.

ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril).

Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. In the past, doctors sometimes avoided giving aspirin to patients who were taking ACE inhibitors because the combination was believed to cause kidney problems. But, a 2005 study of patients with both coronary artery disease and heart failure found that taking aspirin and ACE inhibitord together is safe. The researchers also noted that taking aspirin with an ACE inhibitor can significantly reduce the risk of death for older patients with CAD and heart failure. [See In-Depth Report #14: High blood pressure.]

In 2004, the National Cholesterol Education Program issued updated recommendations on how to control cholesterol levels. These guidelines emphasize that patients should lower their LDL (“bad”) cholesterol and recommend that more people take LDL-lowering medication. Lowering LDL cholesterol and raising HDL (“good”) cholesterol can significantly reduce the risks of heart disease. Several different types of drugs (statins, bile-acid binding resins, niacin, and fibrates) are used to treat cholesterol. [See In-Depth Report #23: Cholesterol.]

Statins are the most important of these drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. A 2005 review found that the more that statins lower LDL, the more they reduce CAD and other heart disease risks.

An important 2006 study found that aggressive treatment with statins may have the potential to reverse coronary artery disease. In the study, rosuvastatin reduced fatty plaque in the arteries in addition to improving LDL and HDL cholesterol levels. However, a follow-up 2007 study of rosuvastatin indicated that while the drug slowed the rate of atherosclerotic progression, it did not reverse heart disease. Future studies will continue to investigate this issue.

Side effects of statins may include stomach upset, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The main safety concern with statins is an uncommon condition called myopathy, which can cause muscle and joint pain and possible muscle damage. Doctors will immediately stop statin therapy if myopathy occurs. Patients should talk to their doctor about any unusual muscle discomfort or weakness, or if their urine becomes brown-colored. Statins can also affect the liver, particularly at higher doses, so patients taking these drugs should receive regular liver function tests.

Click the icon to see an image of cholesterol.

Influenza Vaccinations (Flu Shots). Evidence suggests influenza vaccinations help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of at risk people are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.

Antibiotics. Researchers have investigated antibiotics for treating patients with heart disease and past infection of the bacteria Chlamydia pneumoniae. Results from several recent large-scale clinical trials suggest that antibiotic treatment provides no benefit in preventing heart attack or other cardiac events in patients with coronary artery disease. In addition, a 2006 study indicated that short-term treatment with the antibiotic clarithromycin may increase the risk for death in patients with coronary artery disease. While it is still possible that C. pneumoniae may play a role in triggering inflammatory responses associated with ACS, antibiotic therapy is no longer considered appropriate for treatment or prevention of heart disease.

Ranolazine (Ranexa) was approved in 2006 for treatment of chronic angina. It is recommended for patients who have not responded to other angina drugs. Ranolazine is taken in combination with amlodipine, beta blockers, or nitrates. The drug appears to work better in men than in women

Gene Therapy and Angiogenesis. Proteins known as growth factors are being investigated for their ability to grow new blood vessels for supplying oxygen to the heart. After promising small trials, two large studies of genetically engineered forms of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF [GenerX]) failed to detect any benefits. Studies on therapies that actually genetically encode these proteins are underway.

Testosterone Supplements. Some trials using testosterone supplements or patches have reported improved exercise-induced blood flow in the coronary arteries and improvement in angina in some cases. Supplements of this male hormone, however, may increase the risk for prostate cancer. Experts suggest that testosterone be used only in older men with significant deficiencies in testosterone.

Selective Estrogen-Receptor Modulators (SERMs). Selective estrogen-receptor modulators (SERMs), including raloxifene (Evista), have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. Raloxifene may have some heart benefits, although it poses a risk for deep vein blood clots, which may have long-term implications for patients with heart problems. A major study is underway to determine its effects on the heart.

Surgery

Surgery is usually recommended for patients who have:

Unstable angina that does not respond promptly to medical treatment
Severe recurrent episodes of angina that last more than 20 minutes
Acute coronary syndrome
Severe coronary artery disease (severe angina, multi-artery involvement, evidence of ischemia), particularly if abnormalities are evident in the left ventricle of the heart, the main pumping chamber

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Researchers have been investigating whether surgery offers any advantages if used as an early treatment for mild angina. A major analysis in 2003 reported that the use of angioplasty in patients with mild heart blockage did not reduce the risk for heart attack or death over the long term. A landmark 2007 study found that angioplasty was no better than drug therapy for preventing heart attack and stroke in patients with stable coronary artery disease. (For more information, see Angioplasty and Stents.)

Two effective surgical procedures for heart patients are:

Coronary artery bypass grafting (commonly called bypass or CABG)
Percutaneous coronary intervention (commonly called angioplasty or PCI), usually with coronary artery stent placement

Click the icon to see an image about bypass grafting.

Each of these procedures is described below.

Studies have generally reported similar survival rates with either procedure. There are some differences, however, and decision often depends on individual conditions. Patients considering surgery should discuss all options and risks with their doctor. No surgical procedure cures coronary artery disease, and patients must continue to rigorously maintain a healthy lifestyle and any necessary medications. For some patients, lifestyle changes and medications may be able to control the disease without surgery or angioplasty.

Considerations for Choosing Angioplasty with Stent Placement. Angioplasty has the following advantages for most patients. It is:

Less invasive than bypass. (Although a minimally invasive variation of bypass surgery may reduce this distinction.)
Less expensive than bypass. (Although the postoperative need for more medications and the high risk for repeat procedures to reopen the artery may reduce the long-term difference in cost between the two procedures.)
Life-saving emergency procedure for many patients with heart attacks. (The use of bypass after a heart attack has much higher mortality rates than when it is used electively and its use is controversial in heart attack patients.)

It has the following disadvantages:

The blood vessels can close up again (restenosis) so that patients require additional procedures. (New blood thinning drugs, coronary stent coatings, and radiation treatments may help to significantly reduce restenosis rates. However, there is also some indication that stents, especially drug-eluting stents, may increase the risk for blood clots.)
It is not as appropriate as bypass for many patients with angina (people with diabetes, elderly patients, or those with multi-vessel blockage). Increasingly, however, angioplasty is proving to be as safe and as effective as bypass in many high-risk patients. Patients should be sure to discuss with their doctors the relevant risks and benefits of angioplasty and bypass.

Considerations for Choosing Bypass. Bypass is usually the appropriate procedure in patients with high-risk conditions, such as:

Multi-vessel blockage. (In one report comparing surgery to angioplasty in patients with two or three blocked vessels, the mortality rate 1 year after bypass was 0.8% and after angioplasty was 2.5%. About 80% of patients in the study were men.)
Diabetes. (Bypass produces significantly higher survival rates in these patients. Some experts believe angioplasty should rarely, if ever, be used in this population.)
Being elderly.
Certain structural features, such as a left main artery narrowed by 50% or more or a very long diseased portion of the artery.

Considerations for Women. Studies have reported higher mortality rates in women than in men after any heart surgery. Some experts theorize that on average women may be older and sicker when they have a heart operation. A 2002 study, however, suggested that when women with acute coronary syndromes are given the same aggressive and early treatment as men are, their survival rates are equal or even better.

In addition to angioplasty and bypass procedures, a number of other procedures are available or under investigation for coronary artery disease. They include:

Atherectomy
Myocardial Laser Revascularization
Enhanced External Counterpulsation (EECP)

Coronary Artery Bypass Graft Surgery

Coronary artery bypass graft surgery (CABG) is a good alternative to angioplasty for many patients, but it is very invasive. The surgery involves the following processes:

Click the icon to see an animation about CABG.

The chest is opened, and the blood is rerouted through a lung-heart machine.
The heart is stopped during the procedure.
Large blood vessels supply the grafts, which are used to reroute the blood. The blood vessel grafts are transplanted in front of and beyond the blocked arteries, so the blood flows through the new vessels around the blockage.
The standard grafts now use arteries taken from the chest wall. Studies are reporting that with such grafts arteries remain open in 90% of cases after 15 years.
In general, patients with triple bypass procedures stay in the hospital for 5 days. Those with one-vessel bypass may be able to go home in 3 days.

Click the icon to see an illustrated series detailing a heart bypass surgery.

In spite of the invasive nature of this procedure, elective bypass procedures produce better long-term survival rates than angioplasty, particularly in patients with diabetes and multi-vessel blockage. Overall mortality rates after this procedure range from 1% to slightly over 2%. The risk for stroke or heart attack after a bypass operation ranges from 1.3 - 5%. Finding a surgeon who performs at least 100 of the procedures a year helps reduce the risk for complications.

Blood clots may form in the new graft, closing it up or narrowing the treated vessel over time. Therapy with aspirin and other anti-clotting drugs help keep the graft open and working properly. For long-term prevention of closure, as well as for slowing progression of atherosclerosis, aggressive treatment with cholesterol-lowering drugs may be more beneficial than standard anti-clotting drugs.

Bleeding is also a potential complication of CABG. Anti-bleeding (also called hemorrhage-sparing) drugs are sometimes used to limit blood loss in patients who undergo this surgery. In 2006, concerns were raised about one of these drugs, aprotinin (Trasylol). Data suggested that aprotinin seriously increased the risks for kidney failure, heart failure, and stroke.

An important study, published in 2007 in the Journal of the American Medical Association, compared aprotinin with two anti-fibrinolytic drugs, aminocaproic acid (Amicar) and tranexamic acid (Cyklokapron), which are also used to control blood loss. The study of nearly 4,000 patients who had CABG found that over a 5-year period, the death rate for patients who took aprotinin was 21%, and patients had a 48% increased risk of dying. By comparison, the death rate was 16% for aminocaproic acid, 15% for tranexamic acid, and 13% for no anti-bleeding drug. Because aprotinin is more expensive as well as potentially more dangerous than other anti-bleeding drugs, experts are now recommending against its use in CABG.

Minimally invasive bypass (also called buttonhole or keyhole bypass) surgeries are exciting advances in basic bypass surgery. Studies indicate good success of these procedures for patients with disease in single vessels. They are also being investigated for multiple vessels.

One variation of minimally invasive bypass uses a four-inch incision. The surgeon works on the front of the heart while it is beating slowly. To date, there have been no differences in cardiac events or later mental complications between this so-called off-pump procedure and the standard bypass procedure.
In another variation, the heart is stopped, and the patient is put on a machine that reroutes the blood through a device that keeps it oxygenated. Fiberoptic scopes and instruments are passed through a number of finger-sized incisions. The surgeon works on all sides of the heart, guided by a video image from a tiny camera inserted through a 4-inch incision.
Some advanced heart centers now use robotic systems, which allow the surgeon to perform extremely delicate maneuvers on tiny vessels through pencil-size incisions. They are not yet used for the whole bypass process.

Eventually, minimally invasive bypass procedures may prove to be less expensive, require a shorter hospital stay, and have fewer complications than conventional coronary artery bypass surgery -- or even angioplasty. At this time, however, they are experimental procedures, performed in only a few medical centers for select candidates. Long term-success rates are unknown.

Angioplasty and Stents

Percutaneous coronary intervention (PCI), also called angioplasty, involves procedures such as percutaneous transluminal coronary angioplasty (PTCA) that help open the blocked artery.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

A typical angioplasty procedure follows these steps:

The cardiologist threads a narrow catheter (a tube) containing a catheter into the blocked vessel.
The doctor opens the blocked vessel using balloon angioplasty, in which the surgeon passes a tiny deflated balloon through the catheter to the vessel.
The balloon is inflated to compress the plaque against the walls of the artery, flattening it out so that blood can once again flow through the blood vessel freely.
In order to keep the artery open afterwards, surgeons use a device called a coronary stent, an expandable metal mesh tube that is implanted during angioplasty at the site of the blockage. (In some cases, a stent may be used as the initial opening device instead of balloon angioplasty.)
Once in place, the stent pushes against the wall of the artery to keep it open.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

Complications occur in about 10% of patients (about 80% within the first day). Outcomes are better in hospital settings with experienced teams and backup.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty surgery.

The most important long-term complication is reclosure (restenosis), which can lead to heart attack if not treated with a repeat procedure. Stenting and other advances have helped significantly in preventing reclosure and reducing heart attack rates. Nevertheless, a repeat procedure is still needed to restore the opening in 10 - 15% of procedures that use stents.

PCI (angioplasty) has been proven to help reduce the frequency of angina attacks. It is commonly recommended for patients who have critically blocked arteries or have already had a recent, acute heart attack. PCI can also help improve survival and prevent heart attacks in patients with acute coronary syndrome (ACS). However, doctors have been uncertain about angioplasty’s benefits for survival and heart attack prevention in lower-risk patients with stable coronary artery disease.

In 2007, a landmark study was published in the New England Journal of Medicine and presented at the 2007 meeting of the American College of Cardiology. The COURAGE study found that PCI works no better than standard heart medication (drugs to control blood pressure, lower cholesterol, and prevent blood clots) in preventing heart attack, stroke, and hospitalization in patients with stable coronary artery disease. Based on this study’s findings, experts are now recommending angioplasty only for patients who have severe heart disease. For patients with stable heart disease, drug therapy may be sufficient enough treatment and allow them to safely defer having surgery.

Angioplasty is less invasive than bypass surgery, requiring only one night in the hospital. Recuperation takes about a week. Chest pain after the procedure is very common and usually due to problems other than ischemia. Mild chest pain is even more common when a stent is used, possibly because the artery is stretched.

Reclosure of the artery during or shortly after angioplasty often occurs. A number of anti-clotting drugs are used to help prevent this.

Aspirin and the anti-platelet drug clopidogrel (Plavix) are often used to prevent reclosure during the procedure.
A high dose of the anticoagulant heparin is typically given before the operation.
Intravenous glycoprotein IIb/IIIa inhibitors, powerful drugs that block platelets, also prevent reclosure after stenting in many high-risk patients, and evidence now strongly suggests that they reduce rates of heart attack and death. Eptifibatide (Integrilin) and tirofiban (Aggrastat) are the standard drugs used during angioplasty. They may be most effective if administered during angioplasty, rather than beforehand.

All of these drugs pose a risk for bleeding complications.

Narrowing or reclosing of the artery (restenosis) can occur within a year of angioplasty or even longer in 15 - 60% of angioplasty patients. Coronary stents, anti-clotting drugs, and other advances have reduced these events significantly, but have not eliminated the problem. Theories for the cause of restenosis include:

The release of oxidants (damaging unstable particles) at the surgical site may cause injury and activate immune factors that produce cellular overgrowth in smooth muscles of the blood vessels.
Other activities, including scarring, may remodel and narrow the blood vessels. (This is most likely the reason for restenosis in patients with stents.)

Symptoms of restenosis include chest pain on exertion. (Heart attacks, however, do not usually occur with such events.) The narrowing of the artery in this case is not due to blood clots, so anti-clotting drugs are not useful. Restenosis usually requires a repeat operation. A number of approaches, mostly investigative, have been developed to prevent restenosis after angioplasty.

Drug-Coated Stents. Stents coated with the drugs sirolimus (Rapamune) or paclitaxel (Taxol) have been increasingly used in the last several years. Drug-eluting stents (as they are also called) can help prevent restenosis. However, because drug-eluting stents reduce arterial tissue growth, they can increase the risks of blood clots. In late 2006, the FDA held several meetings to discuss the increased risks of blood clots associated with drug-eluting stents. The committees found that drug-eluting stents do appear to have a small increased risk of blood clots compared to bare metal stents, but not enough research has been conducted to fully determine their risks for heart attack and death.

Five studies published in the New England Journal of Medicine in March 2007 indicated that drug-eluting stents are safe and effective for patients with coronary artery disease when they are used for FDA-approved indications. Problems have arisen when these stents are used for “off-label” purposes in patients with more complicated health problems. There is still some concern as to whether all stents (both bare metal and drug eluting) are used too frequently for patients who may be better served by drugs or bypass surgery.

In February 2007, the American Heart Association and other professional organization issued an extremely important joint advisory statement. The statement advises that all patients who have drug-eluting stents must continue to take aspirin and clopidogrel (or, rarely, ticlopidine) for at least 1 year after the stent is inserted to reduce the risk of blood clots. Clopidogrel and ticlopidine are thienopyridine drugs that, like aspirin, help prevent blood platelets from clumping together. It is very important that patients who have drug-eluting stents take both aspirin and a thienopyridine drug. If for some reason patients cannot take a thienopyridine drug, they should receive a bare metal stent instead of a drug-eluting stent.

Coronary Artery Brachytherapy. Radiation treatment called coronary artery brachytherapy (Gamma One, Beta-Cath) can slow the cell growth in the arteries that causes restenosis. With this approach, any blockage in the stent is first removed, and a tube with an inflatable balloon is inserted. The surgeon then implants a temporary device that delivers radiation. Brachytherapy has shown excellent results in preventing restenosis and significantly reducing heart events and improving survival. Brachytherapy is also showing promise in preventing restenosis in stented artery grafts that were put in place after bypass surgery and later failed. However, several 2006 studies in the Journal of the American Medical Association indicated that drug-coated stents may work better than brachytherapy in preventing restenosis in failed stents. In these studies, the drug-coated stents were inserted inside the original bare metal stents.

Medications. A number of medications are being studied for prevention of restenosis, although benefits to date have been modest. Other drugs under investigation include statins, various anti-clotting drugs, and B vitamins.

Other Procedures. Other procedures under investigation to keep the arteries open use ultrasound, "soft" x-rays, and cryotherapy (very low temperatures).

Other Treatments

Transmyocardial laser revascularization (TMLR) applies laser energy directly to areas in the heart where blockage has occurred, creating 10 - 50 tiny channels. TMLR is recommended for patients with severe angina who have not responded to surgical bypass or angioplasty procedures. TMLR is not suitable for patients who have severely damaged heart muscles. A variant called percutaneous transmyocardial laser revascularization uses a small laser (a holmium YAG laser), which is smaller than the device used in TMLR and does not require open chest surgery and a general anesthetic.

Patients report improved symptoms and exercise tolerance. Both procedures carry risks for serious complications, however, including some that can be life-threatening. It is not clear if either TMLR procedure improves survival, and, in one study, the quality of life afterwards was less than with standard heart surgeries.

A noninvasive technique called enhanced external counterpulsation (EECP) has been used successfully by over a million people in China. The technique uses an air pump that inflates and deflates pressurized cuffs around the legs, causing blood to be pushed into the heart.

EECP may help patients with angina who have not had pain relief from nitrate drugs and who do not qualify as candidates for bypass or angioplasty. In different studies, it has relieved angina in over 75% of patients who used it and reduced the need for medication. The benefits persist, and there is some evidence that it produces actual cellular changes that benefit the heart. In 2002, the FDA approved EECP for the treatment of heart failure but some insurance companies still consider its use “experimental” and will not pay for it. EECP is not recommended for patients with arrhythmia, serious heart valve problems, or peripheral artery disease.

Atherectomy procedures clear the narrowed arteries by using an approach called debulking. All of these procedures use a catheter (a thin tube) that is inserted into an artery (usually in the groin) and threaded up to the blockage. Devices are inserted through the tube to remove the plaque. They include:

Rotational atherectomy, which uses a tiny cutter spinning at 2,500 rpm
Extractional atherectomy, which "shaves" the plaque
Directional atherectomy, which slices the plaques

Although they are successful in opening arteries, they offer no advantages over standard angioplasty and are used only for special cases.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology

References

Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimalmedical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007 Mar 28;297(12):1344-53. Epub 2007 Mar 25.

Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007 Jan 10;297(2):159-68. Epub 2006 Dec 5.

Folsom AR, Chambless LE, Ballantyne CM, Coresh J, Heiss G, Wu KK, et al. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study. Arch Intern Med. 2006 Jul 10;166(13):1368-73.

Garcia MJ, Lessick J, Hoffmann MH; CATSCAN Study Investigators. Accuracy of 16-row multidetector computed tomography for the assessment of coronary artery stenosis. JAMA. 2006 Jul 26;296(4):403-11.

Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007 Feb 13;115(6):813-8. Epub 2007 Jan 15.

Kastrati A, Mehilli J, Pache J, Kaiser C, Valgimigli M, Kelbaek H, et al. Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):1030-9. Epub 2007 Feb 12.

Lagerqvist B, James SK, Stenestrand U, Lindback J, Nilsson T, Wallentin L; SCAAR Study Group. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med. 2007 Mar 8;356(10):1009-19. Epub 2007 Feb 12.

Lloyd-Jones DM, Liu K, Tian L, Greenland P. Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease. Ann Intern Med. 2006 Jul 4;145(1):35-42.

Maisel WH. Unanswered questions--drug-eluting stents and the risk of late thrombosis. N Engl J Med. 2007 Mar 8;356(10):981-4. Epub 2007 Feb 12.

Mangano DT, Miao Y, Vuylsteke A, Tudor IC, Juneja R, Filipescu D, et al. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA. 2007 Feb 7;297(5):471-9.

Mangano DT, Tudor IC, Dietzel C; Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006 Jan 26;354(4):353-65.

Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 2007 Mar 8;356(10):1020-9. Epub 2007 Feb 12.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007 Feb 7;297(5):499-508.

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. Epub 2006 Dec 28.

Spaulding C, Daemen J, Boersma E, Cutlip DE, Serruys PW. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):989-97. Epub 2007 Feb 12.

Stewart JC, Janicki DL, Muldoon MF, Sutton-Tyrrell K, Kamarck TW. Negative emotions and 3-year progression of subclinical atherosclerosis. Arch Gen Psychiatry. 2007 Feb;64(2):225-33.

Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007 Mar 8;356(10):998-1008. Epub 2007 Feb 12.

Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006 Dec 21;355(25):2631-9.

Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Migraine headaches

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Treatment Approaches
Medications Used for Treatm...
Prevention
Medications Used for Preven...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Migraine Surveys

About 17.1% of women and 5.6% of men suffer migraines, according to the 2007 American Migraine Prevalence and Prevention survey. Nearly a third of respondents reported 3 or more migraine attacks per month. Over half were severely impaired or needed bed rest during attacks. Although many patients met the criteria for preventive medication, only a small percentage actually received it.
About 20% of patients with migraine take potentially addictive opioid and barbiturate drugs, even though these drugs have not been approved by the Food and Drug Administration (FDA) for migraine treatment, according to a 2007 survey commissioned by the U.S. National Headache Foundation.

FDA Actions

The opioid drug fentanyl (Fentora) should not be prescribed "off-label" to patients with migraine or other severe headaches, warns the FDA, following several reports of drug-related deaths. Fentanyl is approved only for treating cancer pain.
In 2007, the FDA pulled 15 unapproved ergotamine preparations off the market because they lacked a warning label describing the risks for serious drug interactions.

Migraines in Adolescents

Many adolescents may stop having migraines, or transition to less severe types of headaches, when they reach adulthood, suggests a small 2006 study in Neurology.
Zolmitriptan (Zomig) nasal spray appears to be safe and effective for adolescent migraine, indicates a 2007 study in Pediatrics. Zolmitriptan, like all migraine drugs, is currently approved only for adults.

Sumatriptan-Naproxen Combination

A combination of the triptan drug sumatriptan (Imitrex) and the nonsteroidal anti-inflammatory drug naproxen (Aleve) works better for migraine pain relief than either drug alone, according to a 2007 study in the Journal of the American Medical Association.

Introduction

The pain from a headache does not start from inside the brain. (The brain itself can not feel pain.) Instead, headache pain begins in one or more of the following locations:

The tissues covering the brain
The structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Headache is generally categorized as primary or secondary.

Primary Headache. A headache is considered primary when a disease or other medical condition does not cause it.

Tension headache is the most common primary headache and accounts for 90% of all headaches. [See In-Depth Report # 11: Tension headaches.]
Neurovascular headaches are the second most common primary headaches. This type includes migraines and cluster headaches. [See In-Depth Report # 99: Cluster headaches.] Such headaches are caused by an interaction between blood vessel and nerve abnormalities.

Click the icon to see a depiction of migraine cause.

Secondary Headache. Secondary headaches are caused by other medical conditions, such as sinusitis, neck injuries or abnormalities, and stroke. About 2% of headaches are secondary headaches caused by abnormalities or infections in the nasal or sinus passages. [See "Causes of Secondary Headaches," in this report.]

It is not uncommon for someone to experience a combination of headache types.

Click the icon to see a comparison of headache symptoms.

Migraine is now recognized as a chronic illness, not simply as a headache. About 28 million people suffer from migraines annually. They are often classified by whether or not auras (seeing bright "spots" or "stars") accompany them:

Common migraines are without auras. About 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times.

In general, there are four phases to a migraine (although they may not all occur in every patient): The prodrome phase, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Prodrome symptoms include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in 1 in 5 patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from 4 - 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity
Nausea, sometimes with vomiting
Visual symptoms
Facial tingling or numbness
Extreme sensitivity to light and noise
Looking pale and feeling cold

Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

In some cases, patients eventually experience on-going and chronic headaches. In fact, in an analysis using two different diagnostic methods, between 87 - 90% of daily chronic headaches were actually migraines. Some doctors believe that, unless otherwise demonstrated, any chronic headache consisting of episodes of disabling pain that recur regularly over years should be considered as a migraine.

Chronic migraines may occur from overuse of migraine medications (called a rebound headache) or may develop over time (called transformed migraine).

Rebound Headache. The most common cause of chronic migraine is the rebound effect, which is a cycle caused by overuse of migraine medications. The process involves the following:

Patients typically have taken pain medication for more than 3 days a week on an ongoing basis.
When the patients stop taking medication, they experience a rebound headache.
They start taking the drugs again.
Eventually the headache simply persists, and medications are no longer effective.

Medications implicated in rebound migraines include nonprescription painkillers (acetaminophen, aspirin, ibuprofen), barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.)

Transformed Migraines. In some cases, migraines themselves evolve into chronic, daily headaches called transformed migraines. Such headaches resemble tension headaches but are more likely to be accompanied by gastrointestinal distress and mental or visual disturbances and, in women, to be affected by menstrual cycles. In one study, the risk for transformed migraines were associated with other factors, including allergies, asthma, hypothyroidism, hypertension, and a daily intake of caffeine.

Migraines are defined by the number and length of attacks and whether an aura is present.

Definition of Migraines without Auras (Common Migraine). To be defined as a migraine without aura, a patient should have at least five attacks that have the following characteristics:

A. Each untreated, or unsuccessfully treated, attack must last 4 - 72 hours.

B. It must have at least two of the following four characteristics:

Pain on one side of the head
Pulsing or throbbing pain
Pain severe enough to impair or prevent daily activities
Pain must be intensified by exertion, such as walking up stairs

C. During a headache at least one of the following symptoms must also be present:

Nausea, vomiting or both
Sensitivity to light and noise

In addition, other neurologic or medical conditions that might be causing this pain must be ruled out, or, if they do occur, they are not related in time to the suspected migraine.

Definition of Migraines with Auras (Classic Migraine). To be defined as a migraine with aura, the patients must have at least two attacks that have three out of four of the following events.

At least one fully reversible aura symptom suggesting the headache starts in the cerebral cortex or brain stem.
At least one aura symptom that develops gradually over more than 4 minutes ,or two or more aura symptoms that occur in succession.
No single aura symptom that lasts more than 1 hour. (There may be successive aura symptoms that extend that time, but each one should not last more than 60 minutes.)
The headache itself may begin before, at the same time, or at an interval of no more than an hour after the aura.

As with common migraines, other neurologic or medical conditions that might be causing this pain must be ruled out or if they occur, they are not related in time to the suspected migraine.

Click the icon to see a definition of a migraine.

Although migraine is considered to be a specific chronic illness, it has various presentations that occur in different individuals.

Menstrual Migraines. Migraines are often tied to a woman’s menstrual cycle. Researchers think that estrogen plays a role. About half of women with migraines report an association with menstruation. Compared to migraines that occur at other times of the month, menstrual migraines tend to be more severe, last longer, and not have auras. Triptan drugs can provide relief and may also help prevent these types of migraines.

The highest incidence of migraines typically occurs during the early follicular phase, (beginning of menstruation). A 2005 study found that women are 1.7 times more likely to have a migraine during the 2 days before menstruation begins. But, women are 2.5 times more likely to have a migraine during the first 3 days of menstruation. During this time, migraines are more likely to be severe, with symptoms that include vomiting.

Ophthalmoplegic Migraine. This very rare headache tends to occur in younger adults. The pain centers around one eye and is usually less intense than in a standard migraine. It may be accompanied by vomiting, double vision, a droopy eyelid, and paralysis of eye muscles. Attacks can last from hours to months. A computed tomography (CT) or magnetic resonance imaging (MRI) scan may be needed to rule out an aneurysm (a rupture blood vessel) in the brain.

Retinal Migraine. Symptoms of retinal migraine are short-term blind spots or total blindness in one eye that lasts less than an hour. A headache may precede or occur with the eye symptoms. Sometimes retinal migraines develop without headache. Other eye and neurologic disorders must be ruled out.

Basilar Migraine. Considered a subtype of migraine with aura, this migraine starts in the basilar artery, which forms at the base of the skull. It occurs mainly in young people. Symptoms may include vertigo (the room spins), ringing in the ears, slurred speech, unsteadiness, possibly loss of consciousness, and severe headaches.

Familial Hemiplegic Migraine. This is a very rare inherited genetic migraine disease. It can cause temporary paralysis on one side of the body, vision problems, and vertigo. These symptoms occur about 10 - 90 minutes before the headache.

Status Migrainosus. This is a serious and rare migraine. It is so severe and lasts so long that it requires hospitalization.

About 90% of people seeking help for headaches have a primary headache disorder. The balance of secondary headaches is caused by an underlying disorder that produces the headache as a symptom. Many conditions cause headaches as a symptom. Some of the most common are listed below.

Sinus Headache. Many primary headaches, including migraine, are misdiagnosed as sinus headaches. Nearly 9 in 10 patients who think they have sinus headaches actually have or probably have had a migraine. Sinus headaches occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but telling the difference between these two kinds of headache is difficult, particularly if a headache is the only symptom of sinusitis. The two may even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (Rarely, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headache Due to Neck Problems. Some headaches may be caused by abnormalities of the neck muscles resulting from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck). Nerves in the neck converge in the trigeminal nerve in the face and can generate pain signals that the brain may interpret as headache. Pain is usually on one side. Even if it affects both sides of the head, it is usually more severe on one side. The quality of the headache may be similar to an aching tension headache or a mild migraine without aura.

Temporomandibular Joint Dysfunction. Temporomandibular joint dysfunction (TMJ) is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders.

Brain Tumor. Fear of having a brain tumor is common among people with headaches, but a headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraine or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the two are rarely associated. An exception is malignant hypertension, an uncommon medical emergency, in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Head Injuries. It is obvious that a significant blow to the head will cause pain. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. In very rare instances, ordinary physical strain may injure or weaken the meninges, causing a leakage of cerebrovascular fluid (the fluid that bathes the brain). This can cause severe headache and nausea, which are relieved by lying flat. The condition is very treatable. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain. (It may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing.) Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Click the icon to see an image of the sinuses.

Prognosis

For many people, migraines eventually go into remission and sometimes disappear completely, particularly as they age. Estrogen decline after menopause may be responsible for remission in some older women. One study reported that the following people with migraines (called migraineurs) have a better chance of remission if they have:

A family history of migraine with aura
Migraines that are not triggered by light
No other primary headaches

According to another study, a history of head trauma or oral contraceptive use predicted a poorer long-term outlook.

Migraine or severe headache is a risk factor for stroke in both men and women, especially before age 50. About 19% of all strokes occur in people with a history of migraine. Research indicates that migraine also increases the risk for other types of heart problems.

Migraine with aura carries a higher risk for stroke than without auras. A 2005 analysis of over 12,000 participants from an atherosclerosis risk study found that migraine with aura was significantly associated with higher risk for stroke and transient ischemic attacks. Another 2005 study suggested that people who experience migraine with aura tend to have more cardiovascular risk factors than people without migraine. These risk factors included worse cholesterol profile, higher blood pressure, early history of heart disease and stroke, and greater likelihood of using oral contraceptives.

Results from a 2005 study showed that women who have migraine with aura are at increased risk of ischemic stroke compared with those who do not have auras and those who have non-migraine headaches. Women under age 55 had the highest risk, with more than double the risk. A 2006 Women’s Health Study of women ages 45 and older found that migraine with aura also increases women’s risk for heart attack, angina, and death due to ischemic heart disease (in which blood flow is decreased due to narrowing of coronary arteries). Migraine without aura did not increase heart disease and stroke risks.

Studies suggest specific stroke risk factors for younger women with migraines, particularly those with auras. Smoking, high blood pressure, and birth control pills considerably raise one's risk 10 - 20 times.

Researchers are also studying the relationship between patent foramen ovale (PFO) and migraine. A PFO is a hole in the wall dividing the upper left and right heart chambers. About half of patients with PFO have severe migraines with aura. Researchers are investigating whether surgical repair of the PFO may help control migraines in patients with this heart condition.

Migraine and other headaches associated with aura may increase the risk for retina damage (retinopathy) among middle-aged people, suggests a 2007 study.

The negative impact of migraines on quality of life, families, and even work productivity is significant and often underrated as a serious complication. Studies indicate that people with migraines have poorer social interactions and emotional health than patients with chronic medical illnesses, including asthma, diabetes, and arthritis. Anxiety (particularly panic disorders) and major depression are also strongly associated with migraines.

A 2005 National Headache Foundation-sponsored survey of migraine sufferers reported that:

90% of people with migraines could not function normally on the day of a migraine attack
80% experienced abnormal sensitivity to light and noise
75% experienced nausea and vomiting
30% required bed rest
25% missed at least 1 day of work due to migraine in past 3 months

Effect of Pregnancy on Migraines. In one study, pregnant women with tension or migraine headaches experienced 80% fewer headaches, usually after the end of the first trimester.

Effect of Migraine on the Pregnant Woman or Fetus. Migraine headaches do not pose any added risks during pregnancy to the mother or the fetus, although women with migraines may be at higher risk for having smaller (but not premature) babies.

Causes

Until recently, the general theory on the migraine process rested solely on the idea that abnormalities of blood vessel (vascular) systems in the head were responsible for migraines. Now, however, doctors tend to believe that migraine starts with an underlying central nervous system disorder. When triggered by various stimuli, this disorder sets off a chain of neurologic and biochemical events, some of which subsequently affect the brain's vascular system. No experimental model fully explains the migraine process.

There is certainly a strong genetic component in migraine with or without auras. Researchers have located a single genetic mutation responsible for the very rare familial hemiplegic migraine, but several genes are likely to be involved in the great majority of migraine cases. Numerous chemicals, structures, nerve pathways, and other players involved in the process are under investigation.

Central Nervous Disorder. One theory that attempts to integrate many of the known events in the migraine process is as follows:

Stress or some unknown factor triggers the release of certain protein fragments called peptides (Substance P, calcitonin gene-related peptide, and others).
These peptides dilate blood vessels and produce an inflammatory response that triggers over-excitation of the nerve cells in the trigeminal pathway. [This nerve pathway runs from the brain stem to the head and face. These nerves spread to the meninges (the membrane covering of the brain).]
While the brain itself is insensitive to pain, the meninges and blood vessels around the brain are sensitive to pain. Some doctors suggest that pain occurs when blood drains from the center of the head to the blood vessels around the brain.
Auras are believed to be a response to blood flow changes that cause a rapid reduction in brain activity that reaches the cerebral cortex (the outer layer of the brain), referred to as spreading depression. This effect may be visualized as an electrical wave spreading through the brain just as a wave of water is caused by the dropping of a pebble. Some research suggests that in people with auras, the cortical spreading depression itself activates the inflammation in the trigeminal nerves that triggers pain in the meninges.

One theory of the cause of migraine is a central nervous system (CNS) disorder. The CNS consists of the brain and spinal cord. In migraine, various stimuli may cause a series of neurologic and biochemical events that affect the brain's vascular system.

Abnormal Calcium Channels. Some migraines may be due to abnormalities in the channels within cells that transport the electrical ions calcium, magnesium, sodium, and potassium. Calcium channels appear to play a particularly critical role in migraine:

Calcium channels regulate the release of serotonin, an important neurotransmitter in the migraine process. (A neurotransmitter is a chemical messenger that allows communication between nerves in the brain.)
Magnesium interacts with calcium channels, and magnesium deficiencies have been detected in the brains of patients with migraine.
Calcium channels also play a major role in cortical spreading depression, the brain event that appears to be important in migraine symptoms.

Some patients with migraines may inherit one or more factors that impair calcium channels, making them susceptible to headaches. For example, mutations in a gene that encodes calcium channels appears to be responsible for familial hemiplegic migraine.

Researchers are also investigating factors that are common to both migraines and tension-type headaches. Some research suggests that both problems may result from a continuum of abnormalities in the central nervous system (the nerves in the brain and spine). Such changes trigger a progression of symptoms starting with mild sensations, developing into tension headache, and finally, progressing in some people to a migraine.

Dopamine, for example, may act as a stimulant of the migraine process. Some evidence suggests that certain genetic factors make people over-sensitive to the effects of dopamine, which include nerve cell excitation. Such nerve-cell over-activity could trigger the events in the brain leading to migraine. The prodromal symptoms (mood changes, yawning, drowsiness), for example, have been associated with increased dopamine activity. Dopamine receptors are also involved in regulation of blood flow in the brain.

Nitric Oxide. Other research suggests that over-excitable neurons release nitric oxide, a small molecular messenger that may be important in triggering in most primary headaches (tension-type, cluster, and migraines). Elevated levels have been observed in blood cells of patients with tension-type headache. Some evidence suggests that the release of this molecule in blood vessels may activate nerve pathways in the brain, muscles, or elsewhere and increase pain.

Estrogen Fluctuations in Women. Tension-type headaches and migraine headaches are slightly more common in females during adolescence and adulthood. Most likely hormone fluctuations, rather than whether levels are elevated or low, trigger headaches. Some research suggests that fluctuations in estrogen levels may impact levels of serotonin and other pain-modulating substances that affect these headaches.

A wide range of events and conditions can alter conditions in the brain that bring on nerve excitation and trigger migraines. They include, but are not limited to:

Emotional stress
Intense physical exertion (exercise, lifting, and even bowel movements or sexual activity)
Abrupt weather changes
Bright or flickering lights
High altitude
Travel motion
Lack of sleep
Low blood sugar and fasting
Chemicals found in certain foods. More than 100 foods may potentially trigger migraine headache. Caffeine is one such trigger. Caffeine withdrawal can also trigger migraines in people who are accustomed to caffeine. Experts recommend that patients keep a headache diary to track which foods trigger migraine.

Risk Factors

About 30 million Americans suffer from migraine headaches. They affect about 17% of all women and 6% of men. In fact, 70% of all migraine sufferers are women. Migraine is more prevalent among women throughout the world and in every culture. Although the incidence of migraine is similar for boys and girls during childhood, it increases in girls after puberty. Most people with migraine have 1 - 4 attacks per month.

Hormone Fluctuations in Women. Most migraines in women develop during the hormonally active years between adolescence and menopause. Fluctuations of estrogen and progesterone, rather than their presence, appear to increase the risk for migraines and their severity in some women.

About half of women with migraines report headaches associated with their menstrual cycle, although true menstrual migraines may actually be less common. True menstrual migraines tend not to have auras and to increase in prevalence between 2 days before and 5 days after the onset of period.
The first 3 months of pregnancy can worsen migraines in some women, although one study reported that pregnancy had little effect one way or the other on severity in most women with chronic headaches.
Women whose migraines are affected by pregnancy or menstruation are also likely to have worse migraines if they take oral contraceptives or hormone replacement therapies.

General Age of Onset. More than 20% of adults with migraines report that their headaches started before age 10, and over 45% say they started before age 20. The incidence of migraine declines in both men and women after age 40.

Migraine in Children. Migraine headaches occur in all ages and can appear in children as young as 4 years of age. Migraines in children are equally prevalent in boys and girls. Studies estimate that about 4 – 10% of all children suffer from migraine. Research indicates that overweight children may be especially susceptible to headaches, although this association is most likely due to poor nutrition and lack of exercise rather than excess weight. Children who have sleep problems, especially difficulty falling asleep, may also be more prone to migraines.

A small 2006 study indicated that some adolescents with migraine may eventually grow out of their condition. By the end of the 10-year study, 38% of patients had stopped having migraines, and 20% had transitioned into less severe tension-type headache. Children with a family history of migraine were more likely to continue having migraines.

Migraine Onset in Older Adults. Although uncommon, late-life migraine occurs in about 1% of the population, usually in men. In such cases, it often occurs as migraine with visual disturbances but without headache.

Migraine headaches can be inherited. If both parents suffer from migraines, their children have a 75% chance of getting them. When only one parent gets migraines, there is a 50% chance that children will be afflicted.

Caucasians have a higher risk than either African-Americans or Asians. Worldwide, one study reported that migraines are most common in North America. They are slightly less prevalent in South America and Europe and far less common in Asia and Africa. Investigators believe that the differences are due to genetic variations, not lifestyle factors.

People with migraine have a higher incidence of other medical conditions, including:

Asthma and allergies. These conditions have also been associated with a higher risk for conversion from having periodic migraines attacks to a chronic form (transformed migraines).
H. pylori infection. People who are infected with the bacteria H. pylori, the major cause of peptic ulcers, are at higher risk for migraines.
Epilepsy. Patients with epilepsy are twice as likely to have migraines as the general population.
Fibromyalgia
Systemic lupus erythematosus
Raynaud syndrome
Mitral valve prolapse
Narcolepsy

One study suggested that women with migraines tend to over-respond to stressful situations. In the study, they were more likely than other women to be diligent, conscientious, and overly sensitive to pressure from others. More likely, however, a person's family history of migraine, rather than any personality trait, is the important risk factor.

Diagnosis

Anyone, including children, who has recurring or persistent headaches should consult a doctor. There are no blood tests or imaging techniques that can be used to diagnose migraine headaches. A diagnosis will be made on the basis of history and physical exam, and, if necessary, tests may be necessary to rule out other diseases or conditions that may be causing the headaches. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

For an accurate diagnosis, the patient should describe:

Duration and frequency of headaches
Recent changes in their character
Location of pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting
Behaviors during a headache. This may help distinguish between migraine and tension headaches. The predominant behavior with tension headaches is massaging the scalp, temples, or the nape of the neck. A person with migraines is more apt to use compression (such as tying a scarf around the forehead and temples) or to apply cold. They also tend to isolate themselves, lie down, induce vomiting, and use more pillows than usual. (None of these maneuvers do much good in relieving either headache, unfortunately.)

The presence of auras or other visual disturbances do not always identify migraine:

Patients with severe sinus infections may experience double vision or visual loss. (This is an emergency condition, since it indicates the infection has spread to areas around the eyes.)
Many migraine sufferers have no auras.
Many elderly people with late-onset migraine have auras but no pain.

Note all conditions, including any foods eaten, preceding an attack. Often two or more triggers interact to produce a headache. For example, a combination of weather changes and fatigue can make headaches more likely than the presence of just one of these events.
Keep a migraine record for at least three menstrual cycles. For women, this can help to confirm or refute a diagnosis of menstrual migraine.
Track medications. This is important for identifying possible rebound headache or transformed migraine.
Attempt to define the intensity of the headache using a number system, such as:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work/activities

3 = Distracts from work/activities

4 = Makes work/activities very difficult

5 = Incapacitating

The patient should report any other conditions that might be associated with headache, including but not limited to:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
Any uncharacteristic dietary changes
Any current medications or recent withdrawals from any drugs, including over-the-counter or natural remedies.
Any history of caffeine, alcohol, or drug abuse.
Any serious stress, depression, and anxiety.

The doctor will also need a general medical and family history of headaches or diseases, such as epilepsy, that may increase their risk. Migraine tends to run in families.

In order to diagnose a chronic headache, the doctor will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor may ask questions to test short-term memory and related aspects of mental function.

Extensive testing may be advised for anyone with a chronic, daily headache. Tracking times of medications, withdrawal, and headache, using the headache diary, is usually very helpful in diagnosis.

Differentiating Rebound Headaches from Transformed Migraines. Migraines that evolve to chronic headaches must be first differentiated between natural transformed migraines and rebound headaches (the most common cause of persistent migraines):

A transformed migraine is usually more consistent in its severity and its location than a rebound headache.
Transformed migraines are less sensitive to triggers than rebound headaches.

Differentiating Transformed from Tension Headaches. Once rebound headache is ruled out, the doctor must then differentiate natural transformed migraines from tension headaches:

In most cases of transformed migraine (but not tension headache), gastrointestinal or neurologic symptoms are present.
Transformed migraine is also frequently associated with menstrual fluctuations in women.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headaches that wake them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headaches.

They are not recommended for patients with migraine and with no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out brain disorders or headaches caused by chronic sinusitis.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other imaging tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT). These tests are only performed if there is reason to suspect an underlying disease or as part of clinical studies.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of not only the bony structures but also the soft tissues. Clear images of organs and structures, such as the brain, muscles, joints, veins and arteries, as well as of tumors and hemorrhages, may be obtained with or without the injection of contrasting dye.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition by believing it to be one of their usual headaches. Such patients should call a doctor promptly if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Treatment Approaches

Many effective headache remedies are available for treating a migraine attack. Still, a study that analyzed over 800,000 cases of migraine reported that most migraines are not treated according to any recommended guidelines. In the study, 30% of patients were treated with potentially addictive opioids -- most often merepidine (Demerol). Furthermore, 70% of these patients were not offered effective and available anti-migraine drugs. Anti-nausea drugs that have no effect on headaches were used six times more often than drugs that reduce headaches.

A 2007 survey of migraine sufferers, commissioned by the U.S. National Headache Foundation, reported that 20% of patients are prescribed non-approved medications containing opioids or barbiturates. The survey also indicated that patients who take non-approved drugs are more likely to experience drug-related side effects. For mild migraines, non-prescription treatments (Excedrin Migraine, Advil Migraine, Motrin Migraine Pain) are the best first choice. For severe migraines, doctors recommend starting with a triptan drug.

Preventive treatment, used to stop migraine attacks before they happen, may help many patients. According to another 2007 survey, more than 1 in 4 patients with migraine are candidates for preventive therapy but most do not receive it.

As many as 30% of patients with migraine also have accompanying headaches resulting from tension, drugs, infections, or other causes. It is important to distinguish between headache types in order to determine appropriate treatment.

General Guidelines. The general goals of treatment are:

Choose drugs with as few side effects as possible. Patients should talk to their doctors about various methods for administering the medication (pills, injections, nasal spray, or rectal suppositories) and begin with the one they believe will be the least distressing.
Treat the attack rapidly, within an hour of symptom onset if possible. Start with low doses, and build up dosage slowly.
Try to minimize the use of back-up or "rescue medications." (A rescue medication is typically a narcotic opiate drug, which is used for pain relief when other medications fail.)
Try to guard against rebound effect. Nearly all drugs used for migraine can cause rebound headache, and patients should not take any the drugs for longer than 2 days per week.
It may take 2 - 4 months for any drug to be effective.

Stepped-Up Treatment Approach. Some doctors recommend a stepped-up treatment course for an acute migraine attack. This involves starting with the least potent treatments and taking increasingly more powerful drugs until the pain stops. In this approach, patients may need up to five different medications to achieve pain relief. A typical stepped-up approach is the following:

The patient should first use nonprescription pain relievers (NSAIDs, Excedrin Migraine) and stress-reduction techniques.
If these are not effective within 2 hours, the patient should take migraine-specific drugs. Triptans are the first choice, then ergot derivatives.
Patients with migraines associated with severe nausea or vomiting may use injected or rectally administered drugs. Nausea itself should be treated with specific anti-nausea drugs, such as metoclopramide (Reglan).
If migraine medications fail to relieve symptoms within 4 hours, rescue drugs (opioids, corticosteroids) may be used.

Stratified Approach. Many doctors and patients now prefer the stratified approach. The doctor first estimates the severity of the patient's condition based on his or her history. Then, depending on the severity of a typical attack, the doctor decides whether the patient should start with more or less powerful drugs at the first signs of the migraine:

Patients with less disabling migraines start with general pain relievers.
Patients with a history of moderate-to-severe migraines start with migraine-specific prescription medicine, such as a triptan, at the onset of mild pain.

Some studies report dramatic relief with the stratified approach. In one study, zolmitriptan, a newer triptan, reduced the intensity of headaches within 2 hours in 70% of patients with moderate pain but only in 44% of those with severe headaches.

Side effects can be severe with many migraine drugs, although newer drugs, such as the recent generation triptans, may provide effective early relief without significant side effects.

Studies estimate that between 5 - 10% of children have migraines but that the disorder is underdiagnosed in children. An interesting study reported that when children drew pictures in response to their doctors' questions about their migraines, the doctors were able to tell the difference between migraine and non-migraine headaches in the majority of cases.

Symptoms in Children. The standard diagnostic criteria for migraine in adults may apply to only about two-thirds of migraines in children and adolescents. For example, doctors have seen the following differences:

Headaches tend to last for a shorter time (as little as an hour) in children.
Migraine pain tends to occur in the face and on both sides of the head in two-thirds of child patients.
Children often have a form of migraine known as a migraine equivalent or abdominal migraine, which does not cause a headache at all. Instead, children experience periodic bouts of nausea and vomiting (called cyclic vomiting syndrome) or other secondary symptoms found in adult migraine, such as a reaction against light or sound. Cyclic vomiting may occur in nearly 2% of school-aged children with or without a migraine association.
Migraine triggers in children are similar to those in adults, but common ones in children are anxiety and fear, and eating ice cream.

Outlook in Children. Migraine in children is disabling, as it is in adults, and they tend to lose more school days than other children. Children with frequent headaches may also be at higher risk for headaches in adulthood and also for other physical and psychiatric problems. However, some children who have migraine eventually stop having attacks when they reach adulthood, or have less severe types of headaches.

Treatments in Children. Most children with migraines may need only mild pain relievers and home remedies (such as ginger tea) to treat their headaches. The American Academy of Neurology’s 2004 practice guidelines for children and adolescents recommend the following drug treatments:

For children age 6 years and older, ibuprofen (Advil) is recommended. Acetaminophen (Tylenol) may also be effective. Acetaminophen works faster than ibuprofen, but the effects of ibuprofen last longer.
For adolescents age 12 years and older, sumaptriptan (Imitrex) nasal spray is recommended.

Preventive Measures in Children. Non-medication methods, including biofeedback and muscle relaxation techniques may be helpful. In one study of children with migraines and poor sleep habits, who were taught how to sleep better instructions without using medications had significantly fewer migraine attacks.

If these methods fail, then preventive drugs may be used, although evidence is weak on the effectiveness of standard migraine preventive drugs in children.

If medication overuse causes rebound migraines develop, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may need only to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient can usually stop abruptly or gradually. The patient should expect the following:

Most headache drugs can be stopped abruptly, but the patient should talk to their doctor first. Certain non-headache medications, such as anti-anxiety drugs or beta-blockers, require gradual withdrawal.
If the patient chooses to taper off standard headache medications, withdrawal should be completed within three days.
The patient may take other pain medicines during the first days. Examples of drugs that may be used include dihydroergotamine (with or without metoclopramide), NSAIDs (in mild cases), corticosteroids, or valproate.
The patient must expect their headache to get worse after they stop taking their medications, no matter which method they use. Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).
If the symptoms do not respond to treatment and cause severe nausea and vomiting, the patient may need to be hospitalized.

On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward, and one study reported that 82% of patients significantly improved 4 months after medication withdrawal.

Medications Used for Treatment

Many different medications are used to treat migraines. However, the Food and Drug Administration (FDA) has specifically approved only the following types of drugs for migraine treatment:

Non-prescription drugs: Excedrin Migraine, Advil Migraine, Motrin Migraine Pain
Prescription drugs: Triptans and ergotamine

Other types of drugs, including opioids and barbiturates, are sometimes prescribed off-label for migraine treatment. Opioids and barbiturates have not been approved by the FDA for migraine relief, and they can be addictive.

All FDA-approved migraine treatments are approved only for adults. No migraine products have officially been approved for use in children.

Some patients with mild migraines respond well to over-the-counter (OTC) painkillers, particularly if they take the medicine at the very first sign of an attack.

The Food and Drug Administration has approved three OTC (nonprescription) products to treat migraine. Excedrin Migraine (a combination of aspirin, acetaminophen, and caffeine) was the first such medication approved for the temporary relieve of migraine and its symptoms. Studies have reported significant relief in nearly 70% of patients. It may also help menstrual migraines. Advil Migraine and Motrin Migraine Pain, both containing ibuprofen, are also approved to treat migraine headache.

Cooling Pads. Cooling pads may help during an attack. Some products (Migraine Ice, TheraPatch Headache Cool Gel) use a pad containing a gel that cools the skin for up to 4 hours and can be placed on the forehead, temple, or back of the neck.

Non-steroidal anti-inflammatory drugs (NSAIDs) include aspirin, ibuprofen, and naproxen. They were among the first types of drugs tried to treat mild-to-moderate migraines. Aspirin, ibuprofen (Advil, Motrin), and naproxen (Anaprox, Aleve) are all available without prescription. Naproxen may have specific benefits for migraine. A 2007 study indicated that a combination of naproxen and sumatriptan provides better migraine pain relief than either drug alone.

Other types of NSAIDs are available only by prescription. Some studies indicate that the NSAID combination diclofenac-potassium (Cataflam) may work faster than the migraine drug sumatriptan (Imitrex) and help reduce nausea. The combination is not appropriate for people allergic to aspirin or at risk for bleeding.

Injectable NSAIDs, particularly ketorolac (Toradol), may be very effective for severe and persistent migraines. A 2003 study found that intravenous ketorolac provided greater pain relief than nasal sumatriptan (Imitrex). A 2005 study presented at the annual meeting of the American Headache Society reported that intravenous ketorolac was more effective than opioid drugs for late-stage treatment of severe migraine attacks.

COX-2s are a class of prescription drugs that have the anti-inflammatory effects of NSAIDs, but do not upset most people's stomachs. However, most of these drugs have been withdrawn from the U.S. market due to increased risk for heart attack and stroke. Celecoxib (Celebrex) is the only available COX-2, and it has a strong warning label alerting users of the potential for heart attack, stroke, and serious gastrointestinal problems. (The warning is the same one the Food and Drug Administration recommended for the labels of prescription NSAIDs in 2005.)

NSAID Side Effects. High dosages and long-term use of NSAIDs can increase the risk for heart problems, kidney problems, and stomach bleeding. In April 2005, the FDA asked drug manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in people taking these drugs. The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Triptans (also referred to as serotonin agonists) were the first drugs specifically developed for use against migraine. They are the most important migraine drugs currently available. They help maintain serotonin levels in the brain, and so specifically target one of the major components in the migraine process.

Triptans are recommended as first-line drugs for adult patients with moderate-to-severe migraines when NSAIDs are not effective. Triptans have the following benefits:

They are effective for most patients with migraine, as well as patients with combination tension and migraine headaches.
They do not have the sedative effect of other migraine drugs.
Withdrawal after overuse appears to be shorter and less severe than with other migraine medications

Sumatriptan. Sumatriptan (Imitrex) has the longest track record and is the most studied of all triptans. It is available as a fast-dissolving pill, nasal spray, or injection. Injected sumatriptan works the fastest of all the triptans and is the most effective, but it can cause pain at the injection site. The nasal spray form bypasses the stomach and is absorbed more quickly than the oral form. Some patients report relief as soon as 15 minutes after administration. The spray tends to work less well when a person has nasal congestion from cold or allergy. It may also leave a bad taste. Sumatriptan is effective for many patients, but headache recurs in 20 - 40% of people within 24 hours after taking the drug.

A 2007 study in the Journal of the American Medical Association suggested that a combination of sumatriptan and naproxen works better than either drug alone.

Other Triptans. Newer triptans include almotriptan (Axert), zolmitriptan (Zomig), naratriptan (Amerge), rizatriptan (Maxalt), frovatriptan (Frova), and eletriptan (Relpax). Comparison studies with sumatriptan suggest that some of the newer drugs have fewer side effects and are superior to sumatriptan for providing immediate, sustained, and consistent pain relief. Recurrence rates are also lower. They are also being investigated for prevention under certain circumstances, such as menstrual migraines, but benefits appear limited.

Studies on newer triptans indicate:

Almotriptan is as effective as oral sumatriptan and may have fewer side effects, particularly chest pain, than most other triptans.
Rizatriptan may have the most rapid effects of all oral triptans. Zolmitriptan also has a more rapid effect than sumatriptan (although there appears to be no significant difference in adverse effects). Both rizatriptan and zolmitriptan are also available as rapidly dissolving wafers.
Eleptriptan is also very rapidly effective at high doses, but at those levels may have significant adverse effects. (To date, it does not seem to have any advantages over other triptans in head-to-head comparisons.)
Naratriptan and frovatriptan have a delayed response but long duration, few side effects, and lower risk for recurrence than with sumatriptan. Some evidence suggests that they may have specific benefits for stopping prolonged migraines and may even play a role in prevention.
Frovatriptan: A large study of more than 500 women with an average 12-year history of menstrual migraines examined the use of frovatriptan for the short-term prevention of such headaches. Researchers found that the migraines disappeared in over half of the women on the higher dose (5 mg) of frovatriptan.
Zolmitriptan (Zomig): Several studies indicate that zomitriptan nasal spray may be safe and effective for adolescents. In one study, zolmitriptan relieved pain within 2 hours for nearly half of the children (aged 12 - 17 years) enrolled in the trial. Zolmitriptan nasal spray is approved only for adults.

Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, can include:

Tingling and numbness in the toes
Sensations of warmth
Discomfort in the ear, nose, and throat
Nausea
Drowsiness
Dizziness
Muscle weakness
Heaviness, pain, or both in the chest. (About 40% of patients taking sumatriptan experience these symptoms, and they are major factors in discontinuing the drug. Newer drugs, such as almotriptan, produce fewer chest symptoms.)
Rapid heart rate

Complications of Triptans. The following are potentially serious problems.

Complications of heart and circulation. Triptans narrow (constrict) blood vessels. Because of this effect, spasms in the blood vessels may occur and cause serious side effects, including stroke and heart attack. Such events are rare, but patients with an existing history or risk factors for these conditions should generally avoid triptans.
Serotonin syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptan drugs used to treat migraine, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) -- such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- and selective serotonin/norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with a SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.

The following people should avoid triptans or take them with caution and only with the advisement of a doctor:

Anyone with a history or any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
People taking antidepressants that increase serotonin levels.
Children and adolescents. They may be safe, but controlled studies are needed to confirm this. (Triptans should not, in any case, be the first-line treatment for children.)
People with basilar or hemiplegic migraines. (Triptans are not indicated for these migraineurs.)
There is no evidence to date of any higher risk for birth defects in pregnant women who take triptans. Still, women should be cautious about taking any medications during pregnancy and discuss any possible adverse effects with their doctors.

Drugs containing ergotamine (commonly called ergots) constrict smooth muscles, including those in blood vessels, and are useful for migraine. They were the first anti-migraine drugs available. Ergotamine is available by prescription in the following preparations:

Dihydroergotamine (DHE) is an ergot derivative. It is administered as a nasal spray form (Migranal) or by injection, which can be performed at home.
Ergotamine is available tablets taken by mouth, tablets taken under the tongue (sublingual), and rectal suppositories. Some of the tablet forms of ergotamine contain caffeine.

Ergotamine’s role since the introduction of triptans is now less certain. Only the rectal forms of ergotamine are superior to rectal triptans. Injected, oral, and nasal-spray forms are all inferior to the triptans. Ergotamine may still be helpful for patients with status migrainous or those with frequent recurring headaches.

Side Effects. Side effects of ergotamine include:

Nausea
Dizziness
Tingling sensations
Muscle cramps
Chest or abdominal pain

The following are potentially serious problems:

Toxicity. Ergotamine is toxic at high levels.
Adverse effects on blood vessels. Ergot can cause persistent blood vessel contractions, which may pose a danger for people with heart disease or risk factors for heart attack or stroke.

Internal scarring (fibrosis). Scarring can occur in the areas around the lungs, heart, or kidneys. It is often reversible if the drug is stopped.

The following patients should avoid ergots:

Pregnant women. Ergots can cause miscarriage.
People over age 60.
Patients with serious, chronic health problems, particularly those of the heart and circulation.

Ergotamine can interact with other medications, such as antifungal drugs and some antibiotics. All ergotamine products approved by the Food and Drug Administration (FDA) contain a "black box" warning in the prescription label explaining these drug interactions. In 2007, the FDA pulled 15 unapproved older ergotamine products off the market, in part because they lacked this warning label. The five FDA-approved ergotamine products that remain on the market are:

Migergot suppository (marketed by G and W Labs)
Ergotamine Tartrate and Caffeine tablets (marketed by Mikart and West Ward)
Cafergot tablets (marketed by Sandoz)
Ergomar sublingual tablets (marketed by Rosedale Therapeutics)

Nasal drops containing lidocaine, a local anesthetic, can provide effective and quick pain relief within 15 minutes for many migraine sufferers. However, lidocaine has certain downsides:

It is rather difficult to administer. Patients must be lying down with their head dangling.
The headache often relapses in an hour, and other drugs must then be used.
Side effects include unpleasant taste, burning sensation, and facial numbness.

However, the drug does not cause drowsiness or heart rhythm disturbances as some other migraine treatments do. It should not be used for any other form of headache.

If the pain is very severe and does respond to other drugs, doctors may try painkillers containing opioids. Opioid drugs include morphine, codeine, meperidine (Demerol), and oxycodone (Oxycontin)]. Butorphanol is an opioid in nasal spray form that may be useful as a rescue treatment when others fail.

Opioids are not approved for migraine treatment and should not be used as first-line therapy. Nevertheless, many opioid products are prescribed to patients with migraine, sometimes with dangerous results. In 2007, following reports of several drug-related deaths, the Food and Drug Administration warned that the cancer pain pill fentanyl (Fentora) should not be used to treat patients with migraine or others conditions for which the drug is not specifically approved.

Side Effects. Side effects for all opioids include drowsiness, impaired judgment, nausea, and constipation. There is a risk for addiction, and these drugs can become ineffective with long-term use for chronic migraines. Doctors should not prescribe opioids to patients at risk for drug abuse, including those with personality or psychiatric disorders.

Metoclopramide (Reglan) is used in combinations with other drugs to treat the nausea and vomiting that occurs with other drugs and with migraine itself. Metoclopramide and other anti-nausea drugs, such as domperidone (Motilium), may help the intestine better absorb migraine medications.

New drugs in clinical trials include tonabersat (a gap junction blocker), trexima (a combination triptan and non-steroidal anti-inflammatory drug), GW274150 (a nitric oxide synthase inhibitor), and MK-0974 (a calcitonin gene-related peptide antagonist). Researchers are also investigating a nasal spray containing capsaicin, the chemical found in cayenne peppers.

Prevention

There are several ways to prevent migraine attacks. You should try a healthy diet, the right amount of sleep, and non-drug approaches, such as biofeedback, first for prevention.

Behavioral techniques that reduce stress and empower the patient may help some people with migraines. Studies report between 35 - 50% reduction in migraine and tension-type headaches with these approaches. They generally include:

Biofeedback therapy
Cognitive-behavioral therapy
Relaxation techniques

Behavioral methods may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. They may be particularly beneficial for children, adolescents, and pregnant and nursing women, and anyone who cannot take most migraine medications.

Biofeedback. Studies have demonstrated some effectiveness from biofeedback for migraine headaches. Biofeedback training teaches the patient to monitor and modify physical responses, such as muscle tension, using special instruments for feedback.

Cognitive Behavioral Therapy. Behavioral therapy may be useful alone but is particularly beneficial for patients who are on preventive drug treatments. It typically uses the headache diary to track activities and headaches. The patient then works with the therapist to change or add behaviors or medications that will reduce the frequency and severity of attacks.

Alternative non-drug therapies used for headache management and prevention include hypnosis, meditation, visualization and guided imagery, acupuncture, acupressure, yoga, and other relaxation exercises. There is no clear evidence that any of these techniques have specific value for migraines.

Some studies report the following:

Acupuncture. Acupuncture is a Chinese medicine technique that uses thin needles to stimulate specific points aligned with energy pathways in the body. Studies have showed mixed results on the benefits of acupuncture for migraine. A 2005 study published in the Journal of the American Medical Association reported that acupuncture was no more effective than sham acupuncture (needles placed at non-acupuncture points) in preventing migraines. More than 300 people were enrolled in this randomized trial. A 2006 study of 960 people, published in Lancet Neurology, found that real acupuncture, sham acupuncture, and standard drug treatment were all equally effective in preventing migraine attacks.
Relaxation Techniques. Muscle relaxation techniques may be helpful. One study reported that relaxation treatments appeared to help adolescents with migraine but not tension headaches.

Hormonal drugs, such as oral contraceptives or hormone replacement therapy, have a mixed effect on women with migraines. Oral contraceptives have been associated with worse headaches in 18 - 50% of women and have also been linked to a higher risk for stroke in women with classic migraines (with auras). Young women should avoid or stop oral contraception if they have classic migraines, migraines that worsen or change character after oral contraceptives , if they have close relatives with stroke or heart disease, or if they smoke.

Some evidence suggests, however, that oral contraceptives may help prevent true menstrual migraines (which do not have auras). In such cases, their benefits may outweigh the low risk of a serious adverse event. Keeping a migraine record for at least three menstrual cycles can help confirm whether a woman actually has a true menstrual migraine.

Making a few minor changes in your lifestyle can make your migraines more bearable. Improving sleep habits is important for everyone, and especially those with headaches. What you eat also has a huge impact on migraines, so dietary changes can be extremely beneficial, too.

Avoiding Food Triggers. Avoiding foods that trigger migraine is an important preventive measure. Common food triggers include monosodium glutamate (MSG), processed lunch meats that contain nitrates, dried fruits that contain sulfites, aged cheese, alcohol and red wine, chocolate, and caffeine. However, people’s responses to triggers differ. Keeping a headache diary that tracks diet and headache onset can help identify individual food triggers.

Healthy Diet. One study indicated that a diet low in fat and high in complex carbohydrates may significantly reduce the frequency, severity, and duration of migraine headaches. Such a diet is healthy in general, in any case.

Eating Regularly. Eating regularly is important to prevent low blood sugar. People with migraines who fast periodically for religious reasons might consider taking preventive medications.

Fish Oil. Some studies suggest that omega-3 fatty acids, which are found in fish oil, have anti-inflammatory and nerve protecting actions. These fatty acids can be found in oily fish, such as salmon, mackerel, or sardines. They can also be obtained in supplements of specific omega-3 compounds (DHA-EPA).

Exercise is certainly helpful for relieving stress. An analysis of several studies reported that aerobic exercise in particular might help prevent migraines. It is important, however, to warm up gradually before beginning a session, since sudden, vigorous exercise might actually precipitate or aggravate a migraine attack.

Manufacturers of herbal remedies and dietary supplements do not need Food and Drug Administration approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Riboflavin (Vitamin B2). There is reasonable evidence on the benefits of vitamin B2 for migraine sufferers. In one study, patients who took 400 mg of vitamin B2 (riboflavin) reduced their migraine attacks by half, although the vitamin had no effect on the severity or duration of migraines that did occur. In another study, it helped increase the effectiveness of beta-blockers, drugs used to prevent migraines in some people. Vitamin B2 is generally safe, although some people taking high doses develop diarrhea.

Magnesium Supplements. Studies have reported a higher rate of magnesium deficiencies in some patients with migraine, such as those with menstrual migraines. Magnesium helps relax blood vessels. Some patients report relief from supplements.

Feverfew. Feverfew is the most studied herbal remedy for headaches and is effective in some cases. However, like all effective headache remedies, overuse can cause a rebound effect.

Ginger. In general, herbal medicines should never be used by children or pregnant or nursing women without medical counsel. One exception may be ginger, which has no side effects and can be eaten in powder or fresh form, as long as quantities are not excessive. Some people have reported less pain and frequency of migraines while taking ginger, and children can take it without danger.

Medications Used for Prevention

The Food and Drug Administration has approved four drugs for prevention of migraine:

Propanolol (Inderal)
Timolol (Blacadrene)
Divalproex sodium (Depakote)
Topiramate (Topamax)

Propanolol and timolol are beta-blocker drugs. Divalproex and topiramate are anti-seizure drugs. Many other drugs are also being used or investigated for preventing migraines.

Beta-blockers are usually prescribed to reduce high blood pressure. Some beta-blockers, however, are also useful in reducing the frequency of migraine attacks and their severity when they occur. Propranolol (Inderal) and timolol (Blocadren) have been approved specifically for prevention of migraine. Metoprolol (Toprol), atenolol (Tenormin), and nadolol (Corgard) are also being studied for migraine prevention.

Side Effects. Side effects may include:

Fatigue and lethargy are common.
Some people experience vivid dreams and nightmares, depression, and memory loss.
Dizziness and lightheadedness may occur upon standing.
Exercise capacity may be reduced.
Other side effects may include cold extremities, asthma, decreased heart function, gastrointestinal problems, and sexual dysfunction.

If side effects occur, the patient should call a doctor, but it is extremely important not to stop the drug abruptly. Some evidence suggests that people with migraines who have had a stroke should avoid beta-blockers.

Anti-seizure drugs, also called anti-epileptic drugs or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. GABA may also have a role in migraines. These drugs are commonly used for epilepsy and bipolar disease. Anti-seizure drugs are more expensive than other drugs. They also have significant side effects. Divalproex sodium (Depakote) and topiramate (Topamax) are the only anti-seizure drugs that are approved for migraine prevention. However, if patients do not respond to either of these drugs, doctors may try other types of anti-seizure medications.

Divalproex Sodium (Depakote). Divalproex sodium (Depakote) was first approved in 1996 for migraine prevention. A once-a-day formulation of divalproex (Depakote ER) was approved in 2000. Doctors sometimes prescribe a similar drug, valproate (Depakene). Pregnant patients should not use these drugs, as they may cause birth defects.

Topiramate (Topamax). In 2004, the Food and Drug Administration approved topiramate for prevention of migraines in adults. Studies from 2006 indicated that the drug works well when used on a long-term basis. Patients in these studies experienced significantly fewer migraines for up to 14 months. Topiramate’s most common side effect is a tingling sensation in the arms and legs. Weight loss is also a side effect. In clinical trials, patients lost an average of 3.8% of their body weight.

Other Anti-Seizure Drugs Under Investigation. Researchers are studying other types of anti-seizure drugs for migraine prevention. These include levetiracetam (Keppra), gabapentin (Neurontin), pregabalin (Lyrica), zonisamide (Zonegran), tiagabine (Gabitril), and the investigational drug lacosamide (LCM).

Side Effects. Anti-seizure medication's side effects vary by drug but may include:

Nausea and vomiting
Diarrhea
Cramps
Hair loss
Dizziness
Sleepiness
Blurred vision
Weight gain
Valproate and divalproex can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver

Amitriptyline (Elavil, Endep), a tricyclic antidepressant drug, has been used for many years as a first-line treatment for migraine prevention. It may work best for patients who also have depression or insomnia. Tricyclics can have significant side effects, including disturbances in heart rhythms, and can be fatal in overdose. Although other tricyclic antidepressants may have fewer side effects than amitritpyline, they do not appear to be particularly effective for migraine prevention.

Researchers have investigated newer types of antidepressants, including serotonin-reuptake inhibitors(SSRIs), such as fluoxetine (Prozac). However, studies to date do not indicate that SSRIs are helpful for migraine prevention.

Muscle Relaxants. Botulinum toxin A (Botox) injection, a common wrinkle treatment, causes small muscles to relax. This approach is now being used with some success for treating disorders that involve over-excited muscle activity, including myofascial pain syndrome and migraine. One study reported complete migraine relief in more than half of patients being tested and improvement of more than 50% in another 35% of patients. Relief lasted 3 - 4 months with no adverse effects. A study presented at the 2005 meeting of the American Headache Society reported that patients who regularly received Botox injections every 3 months reduced both the frequency of migraine attacks and their reliance on pain medications

Angiotensin Converting Enzyme Inhibitors. Commonly used for treating high blood pressure, angiotensin converting enzyme (ACE) inhibitors block the production of the protein angiotensin, which constricts blood vessels and may be involved in migraine. Studies using the ACE inhibitor lisinopril (Prinivil, Zestril) are reporting significant reduction in migraine attacks.

Angiotensin-Receptor Blockers. Angiotensin-receptor blockers (ARBs) have actions similar to ACE inhibitors, but may have fewer side effects. In one study, patients who took the ARB candesartan (Atacand) had significantly fewer headaches compared to patients who received placebo.

Neurostimulation Devices. Researchers are investigating a transcranial magnetic stimulation (TMS) device to help stop migraines before they occur. The hair dryer-size device is held to the back of the head and delivers quick magnetic pulses. The device is used when a patient experiences the first signs of a migraine. Other types of nerve stimulation devices are also under investigation.

Inhalation Devices. These devices use heat to vaporize a drug so that it can be inhaled into the lungs. Clinical trials are currently testing this device with procholorperazine (Compazine), a tranquilizer drug that is used to treat nausea and vomiting.

Nasal Devices. New types of nasal sprays and powders are being researched. Some of them use capsaicin, the chemical found in cayenne peppers, to help relieve pain.

Skin Patches. The Actyve transdermal patch uses a small battery-powered system to deliver a triptan drug through the skin.

Drugs. New drugs in development include tonabersat (gap junction blocker), trexima (combination triptan and non-steroidal anti-inflammatory drug), and GW274150 (nitric oxide synthase inhibitor).

Resources

www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.clinicaltrials.gov -- Find clinical trials
www.migraineinfo.org -- National Migraine Association

References

Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4;297(13):1443-54.

Lewis DW, Winner P, Hershey AD, Wasiewski WW; Adolescent Migraine Steering Committee. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics. 2007 Aug;120(2):390-6.

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007 Jan 30;68(5):343-9.

Monastero R, Camarda C, Pipia C, Camarda R. Prognosis of migraine headaches in adolescents: a 10-year follow-up study. Neurology. 2006 Oct 24;67(:1353-6.

Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study. Neurology. 2007 May 15;68(20):1694-700.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Chewing Gum Fights Stress?

FitSugar — Mon, 05 Jan 2009 03:00:00 -0800

My favorite candy, chewing gum, not only fights heartburn, but it looks like it may also help conquer stress. Chomping on a piece of gum, and may I add that the gum should definitely be sugar-free, was found to decrease levels of the stress hormone cortisol by 17 percent. In recent laboratory tests, chewing gum also increased alertness and improved performance. It sounds like a winning combination but might be a bit more complicated than unwrapping a stick of gum.

While working your jaw, chewing gum may increase the flow of blood to your brain helping you think more clearly, but it can also tire out the muscles of the jaw and lead to overuse injuries of the joint, like TMJ. For full disclosure, I should mention that the study on gum for stress release was funded by gum maker Wrigley, who is "committed to advancing and sharing scientific research that explores the benefits of chewing gum." While I thoroughly enjoy chewing gum, I think I will also stick to my free and injury-free stress reduction technique, breathing. How about you?

Source

Parkinson's disease

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Levadopa (L-dopa)
Other Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the FDA approved the first skin patch drug for treatment of Parkinson’s disease. Transdermal rotigotine (Neupro) is a dopamine agonist drug that may help improve symptoms of early-stage Parkinson’s disease. The patch is applied daily.
Rivastigimine (Exelon), an Alzheimer’s disease drug, was approved in 2006 for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Drug Withdrawal

In 2007, the FDA withdrew the dopamine agonist pergolide (Permax) from the market due to safety concerns. Several articles published in 2007 in the New England Journal of Medicine indicated that pergolide and a similar drug, cabergoline (Dostinex), are associated with heart valve problems. Cabergoline is not approved in the U.S. for treatment of Parkinson’s disease.

Dietary Supplements

In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine may help slow the progression of Parkinson’s disease. Creatine is a nutritional supplement that is sometimes used to enhance exercise performance.
Coenzyme Q10, an antioxidant dietary supplement, does not help improve Parkinson’s disease symptoms, according to a study published in 2007 in the Archives of Neurology.

Deep-Brain Stimulation

Deep-brain stimulation outperformed drug therapy in a randomized trial comparing these two treatment approaches. In a study published in 2006 in the New England Journal of Medicine, patients who received deep-brain stimulation had better symptom and quality of life improvement than those who were treated with only medications. However, more serious side effects were reported in the deep-brain stimulation group. Deep-brain stimulation is a surgical technique that involves implanting electrodes in a target area of the brain.

Introduction

Parkinson's disease (PD) is a slowly progressive disorder that affects movement, muscle control, and balance. Parkinson's disease is referred to as idiopathic, which means that the cause is unknown. This term distinguishes the primary disease from parkinsonism, which are the symptoms occurring from a known cause. In addition to its effects on motor control, Parkinson's disease is now recognized as a broader condition that can include cognitive and behavioral disturbances, sleep disorders, speech difficulties, and other problems.

Parkinson's disease occurs from the following process in the brain:

PD develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Nerve cells in the substantia nigra send out fibers to the corpus stratia, gray and white bands of tissue located in both sides of the brain.
There the cells release dopamine, an essential neurotransmitter (a chemical messenger in the brain). Loss of dopamine in the corpus stratia is the primary defect in Parkinson's disease.

Dopamine. Dopamine deficiency is the hallmark feature in PD. It is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response. Loss of dopamine negatively affects the nerves and muscles controlling movement and coordination, resulting in the major symptoms characteristic of Parkinson's disease. Dopamine also appears to be important for efficient information processing, and deficiencies may also be responsible for problems in memory and concentration that occur in many patients.

Although it is clear that dopamine deficiency is the primary defect in Parkinson's disease, it is not clear what causes dopamine loss. The culprit is less likely to be a single cause than a combination of genetic and biologic factors, which are triggered by some environmental assault.

Other Changes. The PD disease process also appears to impair nerve endings in the heart to cause dysautonomia-- changes in the autonomic (also called sympathetic) nervous system. Such changes may impair the release of norepinephrine, a hormone that regulates blood pressure, pulse rate, perspiration, and other automatic responses to stress. Evidence suggests this may be responsible for the abrupt drops in blood pressure when standing that occur in PD. Further research is underway to determine if the loss of nerve terminals is confined to the heart or if it affects other organs as well.

Click the icon to see an animation about Parkinson's disease.

Apoptosis and Alpha Synuclein. Important research now suggests that three molecules are critical in the development of inherited PD: alpha synuclein, parkin, and ubiquitin, which all interact in the normal brain. Abnormally high levels of alpha synuclein, which is produced in dopamine-rich nerve cells, may play a central role. Normally, two other molecules, parkin and ubiquitin, are involved in the natural self-destruction of synuclein -- a natural process of programmed cell death called apoptosis. If this process goes awry, for instance, with a defective parkin gene, cell death fails to occur. If synuclein is not eliminated in these cells, it builds up and becomes toxic to dopamine. In such cases, synuclein accumulates in Lewy bodies, the deposits of fibrous tissue found in all patients with PD.

Another protein, beta amyloid, also increases the build-up of synuclein. Beta amyloid is a known factor in Alzheimer's disease, and may help explain the co-existence between Alzheimer's and Parkinson's disease in many patients.

Lewy Bodies. The fibrous deposits known as Lewy bodies are the hallmark signs of Parkinson's disease. They are found in the substantia nigra, the place in the brain where dopamine is first released. It is not clear whether Lewy bodies are the major killers of the nerve cells or whether they are simply a byproduct of the degenerative process. They are found not only in the brains of patients with Parkinson's disease but, in rare cases, may show up in cells in other parts of the body (the heart, intestine), causing severe disabling symptoms. These substances are also present in other diseases that cause dementia, such as Alzheimer's, and can occur in people without neurologic symptoms.

The Mitochondria and Oxygen-Free Radicals. Some research has observed that certain patients with PD have significantly low levels of complex I, an enzyme found in the mitochondria, sausage-like structures that are the primary source of energy within cells. Some theories suggest that low amounts of complex I may make nerve cells vulnerable to the assault of oxygen free radicals (also called oxidants). Oxidants are unstable molecules that bind to other molecules in the body. They are normally produced by the natural chemical processes in the body. If the body is subjected to environmental stresses, however, they can be over-produced. In excess, they can damage any cell, including nerve cells in the brain, and even interfere with their DNA.

NMDA Receptors. Also of interest in PD are processes that occur in an area of the brain called the subthalamic nucleus. Here, receptors known as glutamatergic N-methyl-D-aspartate (NMDA) become persistently overexcited and produce high levels of calcium ions within brain cells. This in turn leads to a cascade of events that trigger oxygen-free radicals and cell damage.

Immune Factors and the Inflammatory Response. An over-responsive immune system triggered by initial damage may also play a role in perpetuating Parkinson's disease. When the immune system becomes overactive, it produces excessive numbers of potent factors called cytokines, which cause inflammation and further injury in brain cells. Important cytokines under investigation are interleukin-1 and tumor necrosis factor.

Specific genetic factors appear to play a strong role in early-onset Parkinson's disease, an uncommon form of the disease. Research from the last several years suggests that multiple genetic factors may also be involved in late-onset Parkinson’s disease. Several important studies, published in 2005, lay the groundwork for potential genetic screening for this disease. Researchers identified the leukine-rich repeat kinase 2 (LRRK2) gene, located on a region of chromosome 12 known as PARK8, as a key gene involved in inherited forms of Parkinson’s. The researchers estimate that a single gene mutation in LRRK2 may be responsible for 5% of inherited Parkinson’s cases and about 2% of isolated cases.

Early Onset PD. The cases of genetic early-onset Parkinson's disease have most often been detected in specific family groups.

Defective genes that regulate the molecules alpha synuclein and parkin, which are important in the PD disease process, may be responsible for a number of early-onset cases. For example, genetic abnormalities the alpha synuclein protein have been detected in some early-onset Parkinson's patients of European descent.
The parkin gene may be the cause of many cases of early-onset Parkinson's in young adults. (Parkinson's cases associated with this mutation tend to progress slowly and respond well to treatment, even after years of symptoms. Dementia is also rare with this form.)

Late Onset PD. Two landmark studies published in the Journal of the American Medical Association provided the first evidence of a genetic link to late-onset Parkinson’s disease. In these 2001 studies, researchers found that regions on chromosomes 5, 6, 8, 9, and 17 were implicated with Parkinson’s. The parkin gene (located on chromosome 6) and the tau gene (located on chromosome 17) were both found in families that had late onset Parkinson’s. Parkin was previously thought to be responsible only for early-onset Parkinson’s, but this research identified it in families that had both early- and late-onset disease forms. These studies also bolstered the theory that Parkinson’s does have a genetic component and is not caused solely by environmental factors. A 2005 study found that a G2019S mutation in the LRRK gene, located on the PARK8 region of chromosome 12, was definitively associated with late-onset Parkinson’s disease in North American and European families.

Environmental toxins, infections, and other triggers can provoke excessive production in the body of oxygen free-radicals, damaging particles that may play a major role in the deterioration of nerve cells that lead to Parkinson's.

Infectious Organisms. Some research has identified immune factors that suggest a viral presence in the Lewy bodies and swollen nerve pathways of Parkinson's brains. Influenza and other potent viruses have long been known to be a cause of parkinsonism. In one well-known example, a major flu epidemic causing encephalitis in the early twentieth century left many of its victims with parkinsonism.

Environmental and Industrial Chemicals. Intense exposure to certain environmental and industrial chemicals is also being studied.

Pesticides and Herbicides. Some evidence implicates pesticides and herbicides as important factors in many cases of Parkinson's disease. A higher incidence of parkinsonism has long been noted in people who live in rural areas, particularly those who drink private well water or are agricultural workers. A large 2000 study found a strong link between high exposure to insecticides and herbicides at home and a 50 - 70% increase in risk of Parkinson's.
Other Chemicals. Intense exposure to other industrial chemicals and metals (manganese, copper, lead, iron, mercury, zinc, aluminum, and others) has also been linked with parkinsonism, a cause that is often reversible. The role of long-term exposure in the development of Parkinson's disease is unclear. High levels of iron content observed in critical parts of the brain in PD are under particular scrutiny.

Most, but not all, Parkinson's victims are elderly. Some studies indicate that the very elderly are not susceptible to the disease, indicating that the aging process itself is not the major player in the disease. Aging does appear to reduce the concentration of dopamine in structures called dopamine transporters, which carry the neurotransmitter back and forth between nerve cells. Some researchers posit that any excessive stress on these transporters might trigger Parkinson's disease in the aging, and more vulnerable, brain.

Symptoms

Parkinson's disease (PD) symptoms often start with tremor, which may occur in the following ways:

Tremors may first be only occasional, starting in one finger and spreading over time to involve the whole arm. The tremor is often rhythmic, 4 - 5 cycles per second, and frequently causes an action of the thumb and fingers known as pill rolling.
Tremors can occur when the limb is at rest or when it is held up in a stiff unsupported position. They usually disappear briefly during movement and do not occur during sleep.
Tremors can also eventually occur in the head, lips, tongue, and feet. Symptoms can occur on one or both sides of the body. In one study, 44% of patients reported experiencing internal tremors lasting less than half an hour, but occurring several times a week.

In younger patients tremor is usually predominant and often suggests a less aggressive form of the disease. Some evidence suggests that tremor in PD may occur from mechanisms in the brain that are different from those that cause other PD symptoms.

A number of PD symptoms involve motor impairment caused by the abnormalities in the brain that regulate movement:

Slowness of motion (bradykinesia) is one of the classic symptoms of Parkinson's disease. Patients may eventually develop a stooped posture and a slow, shuffling walk. The gait can be erratic and unsteady. After a number of years, muscles may freeze up or stall, usually when a patient is making a turn or passing through narrow spaces, such as a doorway.
Intestinal motility (the ability to swallow, digest, and eliminate) may slow down, causing eating problems and constipation.
Muscles may become rigid (akinesia). This symptom often begins in the legs and neck. Muscle rigidity in the face can produce a mask-like, staring appearance.
Motor abnormalities that limit action in the hand may develop in late stages. Handwriting, for instance, often becomes diminutive.
Normally spontaneous muscle movements, such as blinking, may need to be done consciously.

The traditional view of Parkinson's disease is shifting to reflect growing awareness that it is much more than a motor disease. Many non-motor components and their treatments are now under study. The following symptoms should be carefully monitored by doctors and caregivers:

Depression is the most common psychiatric problem associated with PD, affecting about 40% of patients. Because depression is a common problem in older people, it is likely not to be recognized as a symptom.
Anxiety affects about 30% of patients.
Dementia and paranoia are more common than previously understood.
Orthostatic hypotension -- some patients experience a sudden drop in blood pressure when they stand. This can cause dizziness and fainting.
Changes in sensations of temperature, hot flashes, and excessive sweating.
Daytime sleepiness and other sleep disorders are common.

Risk Factors

Parkinson's disease affects about 3% of Americans over 65 years old. Experts estimate that this percentage could double in the next 30 - 40 years. The symptoms of parkinsonism (tremor, gait disturbance, bradykinesia, and rigidity) occur in even more people, estimated to be 8 million over age 65. In a study that included very mild symptoms, parkinsonism occurred in about 15% of people 65 - 74 years of age, about 30% in those 75 - 84, and over half of people older than age 85.

The average age of onset of Parkinson's disease is 55. About 10% of Parkinson's cases are in people younger than 40 years old. Older adults are at higher risk for both parkinsonism and Parkinson's disease. There is some evidence, however, that the risk declines significantly after age 75 and that the very elderly are at low risk.

Some research indicates that men may face up to twice the risk as women. Estrogen may offer some protection for women up until menopause. A 2001 study, for example, reported a higher rate of Parkinson's disease in women who had undergone hysterectomy. Other studies suggest that the disease also progresses more rapidly in men than women. Older women seem to be more at risk for gait disturbance and men for rigidity and tremor.

People with siblings or parents who developed Parkinson's at a younger age are at higher risk for Parkinson's disease, but relatives of those who were elderly when they had the disease appear to have an average risk.

African- and Asian-Americans have a lower risk than Caucasians. Some evidence suggests that non-Caucasians may be more vulnerable to an atypical form of PD, which causes early impairment in thinking and has a poor response to levodopa, the primary PD treatment.

Increasing weight gain in middle age was associated with a higher risk of PD in a 2002 study.

Complications

Parkinson's disease (PD) is not fatal, but it can reduce longevity. The disease progresses more quickly in older than younger patients, and may lead to severe incapacity within 10 - 20 years. Older patients also tend to experience freezing and greater declines in mental function and daily functioning than younger people. If PD starts without signs of tremor, it is likely to be more severe than if tremor had been present. Having other family members with PD does not appear to have any effect on the severity of the disease.

Parkinson's disease can seriously impair the quality of life in any age group. The physical and emotional impact on the family should not be underestimated as the patient becomes increasingly dependent on their support.

Treatment advances are increasingly effective in alleviating symptoms and even slowing progression of the disease. Taking many of the medications over time, however, can produce significant side effects. Newer drugs may help reduce these occurrences.

The negative effect of overall motor and muscle impairment on daily life can be considerable. Some motor complications can be life-threatening.

Disturbed gait and unstable posture are common and serious problems in elderly patients, since they increase the risk for falling and injury. Some studies have suggested that the appearance of these symptoms early in the course of the disease predict a faster decline than having tremor as the predominant symptom.
Swallowing problems (dysphagia). The presence of dysphagia is associated with shorter survival time. Motor impairment of the muscles in the throat not only impairs swallowing but it also poses a risk for aspiration pneumonia.
Constipation is a major problem and occurs both as a result of the disease and a side effect of its treatment. Laxatives, stool softeners, and other medications may be prescribed.
Bladder control and urinary incontinence are also important complications of PD.
Speech problems occur in more than 70% of patients, by some estimates. Speech difficulty can be caused by rigidity of the facial muscles, loss of motor control, and impaired breath control. Tone can become monotonous, words may be repeated over and over, or the rate of speech may even be very fast.

Depression is extremely common, affecting up to 40% of patients with Parkinson's. PD poses multiple threats on the emotional health:

The disease process itself causes changes in chemicals in the brain that affect mood and well-being.
The complications of its symptoms have a profound impact on daily life that can be emotionally devastating without help and support.
Some drug treatments (levodopa combined with a dopamine agonist) can cause compulsive behavior, such as gambling, shopping, and increased sexuality. Patients who have pre-existing tendencies to novelty-seeking behavior, or a family or personal history of alcohol abuse, may be more likely to develop compulsive gambling. Deep brain stimulus (DBS) surgery may also increase the risk for compulsive gambling in patients who have a history of gambling.

Impaired Thinking (Cognitive Impairment). Defects in thinking, memory, language, and problem solving skills may occur early on in untreated patients or late in the course of the disease. Medications may play a role in thinking problems. In one study, for example, patients with PD were slower in detecting associations, although (unlike in Alzheimer's disease) once they discovered them they were able to apply this knowledge to other concepts. After they were taken off medication, however, they had no problems with the tasks.

Dementia. Dementia is three to six times more common in the elderly Parkinson patient than in the average older adult. It is most likely to occur in older patients who have had major depression. PD marked by muscle rigidity (akinesia), rather than tremor, and early hallucinations also increase the risk for dementia. (Visual hallucinations can also occur in about a third of patients from PD medication.) Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia.

A number of other problems associated with Parkinson's disease affect daily life:

Vision Problems. Vision is also affected, including impaired color perception and contrast sensitivity. These problems progress and can impair motor functioning.

Sleep Disorders. Excessive daytime sleepiness and other sleep disorders are common in PD, both from the disease itself and from the drugs that treat it. In general, patients have a 25% higher risk for daytime sleepiness, including suddenly falling asleep, than patients with other neurologic diseases.

Restless legs syndrome, an irresistible urge to move the calves, which often occurs at night, affects many patients. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on. The common connection between RLS and Parkinson's disease may derive from iron deficiencies that can play a role in both conditions.

Many patients also suffer from nighttime leg cramps. And, some of the medications cause vivid dreams as well as waking hallucinations.

Impaired Sexuality. Although Parkinson's disease and its treatments can cause compulsive sexual behavior, the disease can also affect patients' self-esteem and inhibit sexuality. This is an area not often studied but which is important for many patients' well-being. A 2000 study reported that not only did sexual dysfunction occur, but also affectionate touching and expression of feelings were reduced, even though both partners maintained a desire for intimacy.

Worsened Sense of Smell. The sense of smell is impaired in about 70% of patients.

Osteoporosis. Parkinson’s disease may increase the risk for low bone density and osteoporosis. Both men and women are at risk. Experts recommend that patients with Parkinson’s disease get tested for osteoporosis, especially if they have problems with walking.

Diagnosis

It is difficult to diagnose Parkinson's in early stages. The disease is primarily diagnosed by its symptoms, and studies indicate that doctors make an incorrect initial diagnosis of Parkinson's disease in 8 - 35% of cases. Even neurologists have difficulties in correctly identifying the disease.

A medical and personal history should include any relevant symptoms as well as any medications taken, and information on exposure to environmental toxins.

Early Symptoms. Early treatment may help slow progression, so an early diagnosis of Parkinson's is highly desirable. Early symptoms are often mild, however, so Parkinson's disease can be missed, particularly in young adults. Repeated assessment of symptoms over time is important for improving the accuracy of diagnosis. Too often a younger person with Parkinson's may be diagnosed with mental illness, because the doctor associates the disease only with older people.

Parkinson's may be suspected in patients with the following symptoms:

Slowness and difficulty of movement. These are usually the first symptoms. The patient will be asked to walk and to get out of a chair, preferably a deep one. Early gait disturbance, however, often indicates a disease other than Parkinson's disease.
A tremor when their limb is relaxed. (As many as 25% of patients, however, will not have a tremor.)
Symptoms on one side of the body.

Later Symptoms. In later stages of Parkinson's disease, the symptoms are usually unmistakable, and the problem can often be diagnosed using simple physical tests and a medical and personal history.

The loss of smell is associated with loss of dopamine receptors in the brain. “Scratch and sniff” smell tests can help a doctor diagnose Parkinson’s disease. Smell tests can help differentiate Parkinson’s disease from other conditions with similar symptoms. Some patients with a very similar condition called multiple system atrophy will have a good initial response to levodopa, but it is not usually sustained.

Levodopa and apomorphine can confirm a diagnosis of Parkinson’s disease. If patients’ symptoms improve when they take these drugs, they likely have Parkinson’s, ruling out other neurological diseases.

According to 2006 guidelines from the American Academy of Neurology, there is not enough evidence to recommend for or against the use of imaging techniques such as computerized tomography (CT), magnetic resonance imaging (MRI), or positron-emission tomographic (PET) to diagnose PD.

When symptoms resemble Parkinson's disease but have an identifiable cause, the syndrome is known as parkinsonism. People who have parkinsonism, but not Parkinson's disease, often have additional neurologic symptoms. A number of conditions can also have similar or some of these symptoms.

Other Neurologic Conditions. Many medical conditions may cause symptoms of Parkinson's disease:

Hardening of the arteries (arteriosclerosis) in the brain can cause multiple small strokes, which can produce loss of motor control.

Click the icon to see an image of plaque in an artery.

Alzheimer's disease can be very similar. In one study 23% of people with Alzheimer's also met the criteria for Parkinson's disease. The two diseases often coexist, and research suggests that Alzheimer's and Parkinson's disease may sometimes share a common biologic origin, the accumulation of the protein alpha synuclein and Lewy bodies in the brain.
Lewy bodies variant (LBV), also called dementia with Lewy bodies, is a separate disease from both Alzheimer's and Parkinson's disease. It has similar symptoms to both but is marked by early dementia.
Encephalitis caused by influenza has been known to cause parkinsonism.
Primary progressive freezing gait is a progression condition, in which freezing gait occurs at the onset. Other Parkinson-like features, such as slow movement, often develop. Although very similar to PD, this condition does not respond to L-dopa or other PD medications.
Essential tremor, unlike the tremor of Parkinson's disease, often occurs in the head and voice and is usually worse during motion, as opposed to rest.
Progressive supranuclear palsy has similar symptoms, but involves less tremor and earlier rigidity, and it tends to affect both sides of the body symmetrically. Magnetic resonance imaging scans that measure parts of the midbrain may be a reliable method for distinguishing between PD and progressive supranuclear palsy.
Multiple system atrophy (previously called Shy-Drager syndrome) is a degenerative nerve disease that also affects movement and blood pressure and has many of the symptoms of Parkinson's disease. Some research suggests that a trial using the drug apomorphine may help differentiate between the two.
Other problems that may mimic Parkinson's disease include Wilson's disease, thyroid abnormalities, hydrocephalus, tumors, having the fragile X trait (but not the full disorder), and a number of degenerative neurologic diseases.

Drugs. Certain drugs or medications account for about 4% of all cases of parkinsonism. According to some studies, patients who experience drug-induced parkinsonism may actually be at an increased risk of developing Parkinson's disease later in life. A number of drugs can cause these symptoms, including antipsychotic and antiseizure drugs. Anyone with parkinsonism should discuss their medications with their doctor.

The American Academy of Neurology (AAN) recommends the Beck Depression Inventory or the Hamilton Depression Rating Scale to screen for depression in patients with Parkinson’s disease. The AAN recommends the MMSE and CAMCOG tests to screen for dementia. During these tests, the patient answers a series of questions.

Treatment

Drugs, physical therapy, and surgical interventions can manage Parkinson's disease. The goals of treatment for Parkinson's disease are to:

Relieve disabilities
Balance the problems of the disease with the side effects of the medications

Treatment is very individualized for this complicated disease. Patients must work closely with doctors and therapists throughout the course of the disease to customize a program suitable for their particular and changing needs. Patients should never change their medications without consulting their doctor, and they should never stop taking their medications abruptly.

The American Academy of Neurology recommends the following therapies for the initial treatment of Parkinson’s disease:

Levodopa (L-dopa). Levodopa, or L-dopa, has been used for years and is the gold standard for treating Parkinson's disease. The drug increases brain levels of dopamine. It is used in nearly all phases of the disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, a drug that slows the breakdown of levodopa. Levodopa is better at improving motor problems than dopamine agonists but increases the risk of involuntary movements (dyskinesia).

Dopamine Agonists. Dopamine agonist drugs mimic dopamine to stimulate the dopamine system in the brain. These drugs include pramipexole (Mirapex), ropinirole (Requip), bromocriptine (Parlodel), and rotigotine (Neupro). The Food and Drug Administration (FDA) pulled the dopamine agonist pergolide (Permax) from the market in March 2007 over safety concerns that included potentially fatal heart valve damage.

Selegiline (Eldepryl) and rasagiline (Azilect). Selegiline is a monoamine oxidase B (MAO-B) inhibitor that may have some mild benefit as an initial therapy. However, unlike levodopa, it does not slow the progression of Parkinson’s disease. Another MAO-B inhibitor, rasagiline (Azilect), was approved in May 2006. Unlike selegiline, which needs to be taken by mouth twice a day, rasagiline needs to be taken only once a day.

Drug treatments for Parkinson disease do not consistently control symptoms. At certain points during the day, the beneficial effects of drugs wear off, and patients can experience a return of symptoms, such as uncontrolled muscular motor function, difficulty walking, and loss of energy. In 2006, the American Academy of Neurology (AAN) reviewed evidence for the various drugs used to treat “off time.” The AAN found that the following drugs had the strongest evidence for controlling off time symptoms:

Entacapone (Comtan) belongs to a class of drugs called catechol-o-methyl transferase (COMT) inhibitors. COMT inhibitors help prolong the effects of levodopa by blocking an enzyme that breaks down dopamine.
Rasagiline (Azilect) belongs to a class of drugs called monoamine oxidase (MAO) inhibitors. These drugs slow the breakdown of dopamine that occurs naturally in the brain and dopamine produced from levodopa.

The AAN also found good evidence for the dopamine agonists ropinirole (Requip) and pramipexole (Mirapex), and the COMT inhibitor tolcapone (Tasmar). Deep brain stimulation is a surgical treatment that may help improve motor fluctuations in some patients.

Both Levodopa and dopamine agonists can cause involuntary movements (dyskinesia). The AAN has not found any strong evidence to recommend any drug for treating dyskinesia. However, weak evidence suggests that the antiviral drug amantadine (Symmetrel) may help reduce stiffness and improve dyskinesia. There is also weak evidence that deep brain stimulation of the subthalamus area may be helpful.

Conditions associated with motor impairment and other symptoms of Parkinson's disease may require a variety of treatments.

Depression. Although depression is very common in PD, there have been surprisingly few controlled studies. Antidepressants used for PD include tricyclics, particularly amitriptyline (Elavil). Some studies have found that selective serotonin-reuptake inhibitors (SSRIs) -- which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) -- may worsen symptoms of Parkinson's. Doctors should monitor patients taking SSRIs.

Psychotic Side Effects. Studies indicate that clozapine (Clozaril) and quetiapine (Seroquel), antipsychotic drugs used to treat schizophrenia, may be the best drugs for treating psychosis in patients with Parkinson's disease. A similar drug, olanzapine (Zyprexa), should not be used for patients with PD because it can worsen their psychotic symptoms.

Dementia. The cholinesterase inhibitor drugs donepezil (Aricept) and rivastigmine (Exelon) are used to treat Alzheimer’s disease. Studies suggest that these drugs may also help treat dementia associated with Parkinson’s disease. In 2006, rivastigimine was approved for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Daytime Sleepiness. Modafinil (Provigil), a drug used to treat narcolepsy, is proving to be very helpful for patients with sleepiness related to their disease.

Drooling. In search of a simple solution for the problem of drooling, scientists have reported that injections of very small amounts of botulinum toxin effectively reduce saliva production and drooling. In such small amounts the toxin is safe.

Voice Loss. A relatively simple procedure using collagen injections in the neck appears to be a safe and effective method of improving the voice and speech disorders caused by PD. The procedure augments the collagen in the vocal fold and works best in patients who can still initiate speech. A 2001 study reported improvements that lasted from 2 - 7 months in 61% of patients.

Erectile Dysfunction. Sildenafil (Viagra) is proving to be very helpful for men who suffer from impotence from Parkinson's disease. However, the drug may worsen orthostatic hypotension, a side effect of some PD medications.

Eventually, symptoms such as stooped posture, freezing, and speech difficulties may not respond to drug treatment. (Total unresponsiveness is unlikely, however, even after 20 years of treatment.) The following approaches may be tried:

Simply increasing the dose of levodopa or its frequency raises an unacceptable risk of the distressing side effects. Some doctors have tried hospitalizing patients, totally withdrawing the levodopa, and then re-administering it. Benefits were seen for only a few months, however, and there were some dangerous risks to the process of withdrawal, including pneumonia and blood clots in the lungs.

An embolus is a blockage of an artery in the lungs by fat, air, tumor tissue, or blood clot.

Surgical treatments, including deep brain stimulation and pallidotomy, may help some patients.
Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.

Levadopa (L-dopa)

Levodopa, also called L-dopa, which is converted to dopamine in the brain, remains the gold standard for treating Parkinson's disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. Dosages vary, although the preparation is usually taken in three or four divided doses per day. In 2004, the FDA approved a new oral form of carbidopa-levodopa (Parcopa) that dissolves on the tongue.

In general L-dopa has the following effects on Parkinson's disease:

It is most effective against rigidity and slowness.
It produces less benefit for tremor, balance, and gait.

In many patients, levodopa significantly improves the quality of life for many years. If symptoms do not improve after 2 - 3 months, one of the following reasons may account for the failure:

Other neurologic problems may be causing the symptoms.
Some patients have abnormalities in other brain sites that do not respond to L-dopa.
Sometimes patients are so depressed they cannot tell if the drug is beneficial or not. Only a series of physical examinations by the doctor will indicate that the drug is actually helping.

Studies suggest that levodopa may help slow disease progression and protect against brain cell degeneration.

The toxic effects of levodopa with or without carbidopa are considerable.

Physical Side Effects. The physical side effects are as follows:

Low blood pressure. Low blood pressure is a common problem during the first few weeks, particularly if the initial dose is too high. The addition of extra supplements of carbidopa reduces this effect to some degree. The patient should drink lots of fluids and possibly increase salt intake to maintain normal blood pressure.
Arrhythmia. In some cases the drug may cause abnormal heart rhythms.
Gastrointestinal effects. Stomach and intestinal side effects are common even with carbidopa. Taking the drug with food can alleviate the nausea. However, proteins interfere with intestinal absorption of levodopa, and some doctors recommend not eating any protein until nighttime in order to avoid this interference. The drug can also cause gastrointestinal bleeding.
Effects in the lung. Levodopa can cause disturbances in breathing function, although it may benefit patients who have upper airway obstruction.
Hair loss.

Psychiatric and Mental Side Effects. The major adverse effects of the drug are psychiatric. Patients taking levodopa, especially in combination with other drugs, can experience:

Confusion.
Extreme emotional states, particularly anxiety.
Vivid dreams.
Visual and possibly auditory hallucinations. The drug may even unmask dementia that had not been previously noticed.
Effects on learning. L-dopa appears to have mixed effects on learning. It may improve working memory. However, some evidence suggests that it impairs areas of the brain related to other learning functions and social behavior.
Sleepiness and sleep attacks.

Levodopa causes fewer psychiatric side effects than other drugs used for Parkinson's disease, including anticholinergics, selegiline, amantadine, and dopamine agonists. Because psychiatric side effects often occur at night, if they are severe some doctors recommend reducing or stopping the evening dose.

Within 4 - 6 years of treatment with levodopa, the effects of the drug in many patients begin to last for shorter periods of time (called the wearing-off effect) and the following pattern may occur:

Patients may first notice slowness (bradykinesia) or tremor in the morning before the next dose is due.
Less commonly, some experience painful dystonia, muscle spasms that can cause sustained contortions of various parts of the body, particularly the neck, jaw, trunk, and eyes and possibly the feet.
Patients must increase the frequency of levodopa doses. This puts them at risk for dyskinesia (the inability to control muscles), which usually occurs when the drug level peaks. Dyskinesia can take many forms, most often uncontrolled flailing of the arms and legs or chorea, rapid and repetitive motions that can affect the limbs, face, tongue, mouth, and neck. Dyskinesia is not painful, but it is very distressing.
In some people, eventually L-dopa is effective only for 1 - 2 hours and most patients start to experience motor fluctuations. In about 15 - 20% of patients such fluctuations become extreme, a phenomenon known as the on-off effect, which consists of unpredictable, alternating periods of dyskinesia and immobility. Sometimes the symptoms switch back in forth within minutes or even seconds. (The transition may follow such symptoms as intense anxiety, sweating, and rapid heartbeats.)

Reasons for the Wearing-Off Effect. Debate is ongoing about the cause of the wearing-off effect and dyskinesia. Some theories suggested for these effects are:

The disease progresses beyond the ability of levodopa to control it.
Some patients become tolerant to prolonged exposure to dopamine and, at the same time, the disease is progressing.
The brain's own dopamine neurons become incapable of storing dopamine. When the levodopa wears off, little or no natural dopamine remains.
Levodopa itself accelerates the disease by producing oxygen free radicals, unstable particles that increase injuries to the brain and dopamine degradation.

Preventing the Wearing-Off Effect. To reduce the effects of fluctuation and the wearing-off effect, it is important to maintain as consistent a level of dopamine as possible. Unfortunately, levodopa is poorly absorbed and may remain in the stomach a long time. A number of strategies are being developed to take care of these problems:

Some patients take multiple small doses on an empty stomach, crushing the pills and mixing them with a lot of liquid.
A liquid form of Sinemet may produce fewer fluctuations and a prolonged "on" time compared with the tablet.
A prolonged release version of levodopa and carbidopa (Sinemet CR) is also available to control fluctuations for some people. (Some evidence suggests that there is no actual difference in symptom control between the sustained and immediate release forms, but patients on Sinemet CR tend to experience a better quality of life.)

Other Medications

Selegiline (Eldepryl, Movergan, Zelepar), also known as deprenyl, is an antioxidant drug that blocks monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. Until recently, selegiline was the drug most commonly used in early-onset disease and in combination with levodopa for maintenance. A major 2002 study reported, however, that although selegiline delays the need for L-dopa by a few months, it has no effect on long-term progression.

Rasagiline (Azilect), another MAO-B inhibitor, was approved in May 2006 for the initial treatment of Parkinson’s disease. It is used alone during early-stage PD and in combination with L-dopa for moderate-to-advanced PD. Unlike selegiline, which is taken twice a day, rasagiline is taken once a day.

Other Adverse Effects. MAO-B inhibitors may have severe side effects:

One of the most important side effects is orthostatic hypotension, particularly in people taking Sinemet plus selegiline. This condition is a sudden drop in blood pressure that causes dizziness and lightheadedness when a patient stands up. Orthostatic hypotension can also occur with other Parkinson's drugs.
Can cause high blood pressure (hypertension) if combined with drugs that increase serotonin levels -- such drugs include nearly every major antidepressant. Patients suffering from depression and taking selegiline should discuss all treatment options with their doctor.
Can also cause a dangerous increase in blood pressure if patients eat foods rich in the amino acid tyramine. Patients should avoid the following foods while taking selegiline or rasagiline and for 2 weeks after stopping medication: aged cheeses, air-dried meats, pickled herring, yeast extract, aged red wines, draft beers, sauerkraut, and soy sauce

Debate over Mortality Rates. Some major studies have reported higher mortality rates in patients with advanced PD. Such findings may be due to adverse effects on the heart and blood vessels. Although other studies have not reported lower survival rates, some experts believe that, given its modest effects, selegiline may be a poorer drug choice than others, particularly in patients with risk factors for heart disease.

Dopamine agonists stimulate dopamine receptors in the substantia nigra, the part of the brain in which Parkinson's is thought to originate. Dopamine agonists are effective in delaying motor complications during the first 1 or 2 years of treatment.

Newer Dopamine Agonists. The most commonly prescribed dopamine agonists are pramipexole (Mirapex) and ropinirole (Requip). They are used either alone or in combination with L-dopa. Pramipexole appears to work better and have fewer side effects than ropinirole.

Studies still report, however, that L-dopa is superior for improving motor function. In one study, motor function was no different in disease progression among all of the drugs by the third year of treatment. Recent research suggests that L-dopa is better at improving motor disability and dopamine agonists are better at reducing motor complications. L-dopa has a higher risk for dyskinesia side effects than dopamine agonists, but dyskinesia can also occur with dopamine agonists.

Side Effects. Side effects of pramipexole and ropinirole vary but can be severe and include:

Gastrointestinal side effects (nausea and constipation). Nausea can be controlled by drugs, such as domperidone.
Headache
Orthostatic hypotension (sudden drop in blood pressure upon standing up)
Nasal congestion
Nightmares, hallucinations, and psychosis (more severe than with L-dopa for both drugs)
Sudden sleep attacks. These can be very serious, particularly if patients are driving. (Sleep attacks may occur -- although less commonly -- with other PD drugs.)

Other Dopamine Agonists.

Specific dopamine agonists that contain ergot alkaloids include bromocriptine (Parodel), pergolide (Permax), cabergoline (Dostinex), and lisuride (Dopergin). As of 2007, bromocriptine is the only ergot dopamine agonist approved for Parkinson’s treatment in the United States. In January 2007, the New England Journal of Medicine (NEJM) published two studies indicating that pergolide and cabergoline are associated with heart valve damage. In March 2007, due to these safety concerns, the FDA withdrew pergolide from the U.S. market. Cabergoline and lisuride are not approved in the U.S. for Parkinson’s disease treatment but are used for this purpose in other countries. The NEJM studies did not find any heart valve problems associated with bromocriptine or lisuride.
Rotigotine transdermal (Neupro) is a dopamine agonist that is delivered through a skin patch that is changed daily. In 2007, the FDA approved rotigotine transdermal for treatment of symptoms of early Parkinson’s disease. It is the first skin patch approved for Parkinson’s disease. Side effects are similar to those of other dopamine agonists.
Apomorphine is a dopamine agonist used as a "rescue" drug in people experiencing on-off effects severe enough to require going off L-dopa for a few days. In 2004, the FDA approved apomorphine for treating off-time episodes of Parkinson’s disease. Apomorphine is given by injection. Because it causes severe nausea and vomiting, it must be taken with an anti-nausea drug.

Catechol-O-methyl transferase (COMT) inhibitors increase concentrations of existing dopamine in the brain. Entacapone (Comtan, Stalevo) is the current standard COMT inhibitor. (Stalevo combines entacapone and levodopa into a single pill.) It improves motor fluctuations related to the wearing-off effect and has shown good results in improving on time and reducing the requirements for L-dopa. If the patient does not respond to the drug within 3 weeks, it should be withdrawn. No one should withdraw abruptly from these drugs.

Side Effects. Side effects include:

Involuntary muscle movements
Mental confusion and hallucinations
Cramps, nausea, and vomiting
Insomnia
Headache
Urine discoloration (a harmless side effect but should be reported to the doctor)
Diarrhea
Less commonly, constipation, susceptibility to respiratory infection, sweating, dry mouth

Of major concern are reports of a few deaths from liver damage in patients taking the COMT inhibitor tolcapone (Tasmar). The drug has been taken off the market in many countries and is recommended in the U.S. only for patients who cannot tolerate another other drugs. Entacapone does not appear to have the same effects on the liver and does not require monitoring. A 2003 3-year study suggested that the drug is safe and effective over the long term. Still, patients should watch out for symptoms of liver damage, including jaundice (yellowish skin), fatigue, and loss of appetite.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

Anticholinergics were the first drugs used for PD, but have largely been replaced by dopamine drugs. They are generally used only against tremor in the early stages. They are not as effective against bradykinesia and posture problems and may increase the risk for dementia in late stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexy), benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and ethopropazine (Parisdol). Orphenadrine (Norflex) is a drug with anticholinergic properties, but is also a muscle relaxant and does not cause urinary retention.

Side effects of Anticholinergics. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can also increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs cautiously.

Amantadine (Symadine, Symmetrel) stimulates the release of dopamine and may be used for patients with early mild symptoms. It has some benefit against muscle rigidity and slowness and may help some patients in advanced stages who are unresponsive to other drugs. It is less powerful than levodopa and may lose its effectiveness after 6 months. It may also reduce motor fluctuations brought on by levodopa, however, and these benefits appear to persist for at least a year. Large, well-conducted studies are still needed to determine its true benefits and safety.

Side Effects. Side effects are similar to those of anticholinergic drugs and also may include swollen ankles and mottled skin. It can also cause visual hallucinations. Overdose can cause serious and even life-threatening toxicity. Patients with Parkinson's should not withdraw from this drug abruptly. In rare instances, it can cause acute delirium or a life-threatening condition called neuroleptic malignant syndrome. Pregnant or nursing women should not use this drug.

Anticonvulsants. Zonisamide (Zonegran), a drug used to treat epilepsy, is showing promise in treating tremors, motor problems, and involuntary movements in patients with Parkinson’s disease.

Budipine and Other Glutamate Blockers. A number of experimental drugs are being investigated for Parkinson's disease because they block the actions of glutamate, an amino acid that is a particularly potent nerve cell killer. Some of these drugs block a receptor group to glutamate called N-methyl-D-aspartate (NMDA). Investigational NMDA antagonists include remacemide, memantine, riluzole, and budipine.

Stem Cell Transplantation. Scientists are investigating whether transplanting embryonic stem cells into the brain may help treat Parkinson’s disease. Researchers hope that the transplanted stem cells may be able to stimulate dopamine production. However, stem cell transplantation research is still in its very early stage. It will be many years before clinical trials will be conducted in humans.

Surgery

Surgical procedures are recommended for specific patients with advanced Parkinson’s disease who no longer respond to drug treatments. Surgical treatment cannot cure Parkinson's disease, but it may help control symptoms such as motor fluctuations and dyskinesia. Pallidotomy and thalamotomy are older procedures that destroy tissue in certain parts of the brain. Deep brain stimulation, the current standard surgical practice for Parkinson’s disease, has largely replaced the older operations.

In deep brain stimulation (DBS), also called neurostimulation, an electric pulse generator controls symptoms. The generator is similar to a heart pacemaker. It sends electrical pulses to specific regions of the brain. Candidates for surgery are generally patients who have responded well to levodopa drug treatment. Patients who have had PD for fewer than 16 years may experience greater benefit from DBS than patients who have had the disease longer.

Evidence indicates that DBS improves motor function and reduces dyskinesia best when the procedure targets the subthalamic nucleus (STN) of the brain. Many studies demonstrate the effectiveness of STN stimulation. Procedures that target the globus pallidus interna or ventral intermediate nucleus of the thalamus can also sometimes treat rigidity and tremors. However, there is not yet enough evidence to support stimulation of these parts of the brain.

The procedure is performed as follows:

The surgeon implants a tiny pulse generator near the collarbone, which is connected to four electrodes that have been implanted in the target area in the brain.
The generator delivers programmed pulses to this area, which the patient can turn on and off using a magnet held over the skin.
When on, the pulses suppress symptoms. Complications occur in 2 - 4% of operations. The most serious ones are bleeding in the brain and infection. Depression is common.

In a 2006 study of patients with advanced Parkinson’s disease and severe motor symptoms, patients who received DBS had better improvement in symptoms and quality of life than those who received only drug therapy. However, patients in the neurostimulation group had more serious side effects than those who were treated only with medications. Researchers are also studying whether DBS can benefit patients with earlier-stage Parkinson’s disease.

Pallidotomy and thalamotomy are surgical procedures that destroy brain tissue in regions of the brain associated with Parkinson’s symptoms such as dyskinesia, rigidity, and tremor. In these procedures, a surgeon drills a small hole in the patient’s skull and inserts an electrode to destroy brain tissue. Pallidotomy targets the global pallidus area. Thalamotomy targets the thalamus. Because these procedures permanently eliminate brain tissue, most experts now recommend deep brain stimulation instead of pallidotomy or thalamotomy.

Surgical complications may include behavioral or personality changes, trouble speaking and swallowing, facial paralysis, and vision problems. Weight gain after surgery is also common.

Scientists are investigating whether stem cells may eventually help treat Parkinson disease. Experimental surgery has shown promise using fetal brain cells rich in dopamine implanted in the substantia nigra area of the brain. Because the use of embryonic stem cells is controversial, researchers are studying alternative types of cells, including stem cells from adult brains and cells from human placentas or umbilical cords. Studies are also using gene therapies and other advanced treatments for transplanting dopamine-producing cells or nerve-protecting cells into the brain. All of this research is still in preliminary stages.

Lifestyle Changes

No special diets or natural foods have been shown to slow down the progression of Parkinson's disease, but there are some dietary recommendations.

Protein. High levels of proteins compete with levodopa for transport to the brain and reduce its effectiveness. Avoiding protein altogether is not the solution, since malnutrition can result. Most experts now recommend trying to maintain a carbohydrate-to-protein ratio of 7:1 throughout the day. This may be difficult to calculate and some doctors recommend simply keeping proteins to 12% of total daily calories.

As an aid in calculation, food labels indicate proteins in grams. One gram of protein equals four calories. Good control of protein intake may help minimize fluctuations and wearing-off and may allow some patients to reduce their daily levodopa dosage.

Fruits and Vegetables and Increasing Fiber. Eating whole grains, fresh fruits, and vegetables is the best approach for any healthy life. A diet rich in fruits and vegetables may help protect nerve cell function. Many of these foods are also often rich in fiber, which is particularly important for helping to prevent constipation.

Dietary fiber is the part of food that is not affected by the digestive process in the body. Only a small amount of fiber is metabolized in the stomach and intestine, the rest is passed through the gastrointestinal tract and makes up a part of the stool. There are two types of dietary fiber, soluble and insoluble. Soluble fiber retains water and turns to gel during digestion. It also slows digestion and nutrient absorption from the stomach and intestine. Soluble fiber is found in foods such as oat bran, barley, nuts, seeds, beans, lentils, peas, and some fruits and vegetables. Insoluble fiber appears to speed the passage of foods through the stomach and intestines and adds bulk to the stool. It is found in foods such as wheat bran, vegetables, and whole grains. Fiber is very important to a healthy diet and can be a helpful aid in weight management. One of the best sources of fiber comes from legumes, the group of food containing dried peas and beans.

People whose diets have been low in fiber should increase it gradually. It is best to obtain dietary fiber, soluble or insoluble, in the natural form of whole grains, nuts, legumes, fruits, and vegetables. If it proves difficult to do so, psyllium, a grain naturally found in India, is an excellent soluble fiber supplement (Metamucil, Fiberall, Perdiem Fiber). Fluids are particularly important in preventing constipation.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, are proving to have powerful anti-inflammatory effects and may also be nerve protective.

Click the icon to see an image of foods that contain omega-3 fatty acids.

Dairy Products. A 2002 study reported a higher risk for Parkinson's disease in men (but not in women) who consumed high amounts of dairy products. This association was not linked to fats in dairy foods and high intake of calcium or protein from other sources did not increase the risk. A 2005 prospective study of men found that milk consumption in midlife was associated with increased risk of Parkinson’s disease. As with prior research, the researchers did not find that calcium itself carried a risk. They suggested that some unidentified neurotoxic contaminant in milk may be responsible.

Vitamins.

B Vitamins. Most B vitamins play important roles in the brain and central nervous system. Vitamin B6 (pyridoxine) theoretically has benefits for PD because it is necessary in the production and metabolism of dopamine. Folate deficiency may increase toxic effects against dopamine neural pathways, perhaps by increasing levels of homocysteine, an amino acid that may play a destructive role in many diseases, including heart and neurologic disorders. Some evidence suggests that L-dopa elevates homocysteine levels, so folate supplements may be particularly important for patients. Although the major food sources of B vitamins are meats and dairy products, which are high in protein, these vitamins are also found in whole grains and are added as supplements to commercial cereals.

Click the icon to see an image of the benefits of vitamin B6.

Click the icon to see an image of foods that contain vitamin B6.

Click the icon to see an image of foods that contain folate.

Vitamin E. Researchers have investigated antioxidant vitamins, especially vitamin E, for their effect on the brain. Some, but not all, studies have reported slower mental decline and lower risk for Parkinson's and Alzheimer's disease in people who ate large amounts of foods rich in vitamin E. Such foods include vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Vitamin E supplements, however, do not appear to be helpful for slowing disease progression or improving symptoms.

Both smoking and coffee drinking have been associated with lower risk for PD. Researchers are attempting to discover if these substances protect nerve cells. One interesting study suggested that the early disease process in PD produces changes in the dopamine pathway that actually protects an individual from caffeine and nicotine addiction, so that fewer patients have a history of smoking and caffeine. Research is needed to determine why these toxic substances protect against PD.

Smoking and Nicotine Replacement. Cigarette smokers appear to have a 40% lower risk for Parkinson's disease, indicating some protection by nicotine. This finding, of course, is no excuse to smoke, but such protection may help researchers develop new therapies. Studies on nicotine replacement, such as gum or patches, have been conflicting, however, with some short-term studies reporting no benefits. A 2002 study suggested that nicotine replacement may help smokers with early PD, but not nonsmokers.

Coffee Consumption. Studies have indicated that the risk for PD in coffee drinkers is about 30% lower than for non-coffee drinkers. In a 30-year study of Japanese-American men, coffee consumption was associated with a lower risk for Parkinson's disease, and the more coffee they drank, the lower their risk became. Coffee and tea can reduce fluids by increasing urination, however, and so may increase constipation in PD.

Regular use of ibuprofen may reduce the risk of Parkinson’s disease according to research presented at the 2005 annual meeting of the American Academy of Neurology. In this prospective study, people who took at least two ibuprofen tablets per week for at least 1 year lowered their risk of developing Parkinson’s by 35% compared to nonusers or irregular users. For those who took ibuprofen daily, the comparative risk was 38% lower. Other non-steroidal anti-inflammatory drugs (NSAIDS) did not appear to affect disease risk.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following dietary supplements are being studied for treatment of Parkinson's disease:

Creatine. Creatine is a nutritional supplement that is sometimes used to improve exercise performance. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine can slow the progression of Parkinson’s disease. The trial will enroll patients who have been diagnosed with PD within the last 5 years and who have received levodopa therapy for no more than 2 years.

Coenzyme Q10 (Ubiquinone). Coenzyme Q10 (also called ubiquinone) is an antioxidant being studied for the treatment of Parkinson's disease. This enzyme is important for cellular energy, which may be impaired in PD. In one study, patients who took coenzyme Q10 had slower decline in daily activities and mental and motor skills compared to patients on placebo. However, a 2007 study found that small doses of coenzyme Q10 had no effect on improving Parkinson’s symptoms. Researchers are still investigating whether larger doses given over a long period of time may benefit patients.

Exercise early in adult life may help protect against later development of Parkinson’s disease. Exercise is also an important component of rehabilitation. Physical therapy is extremely important and usually includes active and passive exercise, gait training, practice in normal activities, and if needed, hot or cold treatments, water therapy, and electrical stimulation. Exercise is also essential for well-being and helps patients maintain productive years. To date, no specific approach has been proven to be better than others.

Exercise Programs. Exercise programs are defined as passive or active.

Passive exercise, mostly stretching and manipulation of muscles by a physical therapist, is aimed at preventing muscles from shortening. A passive exercise program that begins with slow and gentle exercises and becomes progressively more intense may improve mobility in patients with early and mid-stage Parkinson's disease.
Active exercises are used to help range-of-motion, coordination, and speed. Patients should continually make efforts to practice movement, even simple ones, such as marching in place, making circular arm movements, and raising the legs up and down while sitting. Patients who enjoy sports or the use of exercise equipment should continue with these activities even if their skills diminish, assuming there are no other medical conditions that would prevent participation.

Gait Training. Practicing new methods for standing, walking, and turning may help retain balance. The following tips may be helpful:

Take large steps when walking forward, raising the toes at the forward step, and hitting the ground with the heel.
Take small steps while turning.
When walking or turning, have the legs 12 - 15 inches apart to provide a wide base.
Do not wear rubber or crepe-soled shoes because they grip the floor and may cause the patient to fall forward.
Using devices that keep a rhythmic beat, such a metronome (a simple device used by musicians to keep time), may be very effective, possibly more than music itself, in helping patients to walk faster and take longer steps. One study found that setting a metronome rhythm to about 10% faster than the patient's fastest gait offers significant improvement over walking to no rhythm at all or to a rhythm that matches the gait.

Reducing Muscle Freezing. The patient should practice regular daily activities that simplify actions and reduce the incidence of muscle freezing. Most often, freezing occurs when a patient begins to move or is presented with an obstacle. The following tips may be helpful:

Rock from side to side.
If the legs feel frozen, lift the toes. This simple action may free spasm in some cases.
Hum marching tunes. In fact, music has been shown to help people move and to get out of bed in the morning. Some studies report that wearing a Walkman and turning music on in situations associated with freezing, such as crossing a street, is helpful.
Divide actions into separate events, which may prevent freezing that occurs from trying to coordinate too many physical operations at one time. For instance, when going through a doorway, approach the door, stop at the door, open it, stop, and then walk through the doorway.
A cane equipped with a laser pointer may be helpful, at least temporarily.
Simply being touched by another person can sometimes release the patient (although a patient with PD should never be pulled or pushed).

Sleep Deprivation Therapy. Sleep deprivation therapy may have a role in treating some cases of depression and some studies are finding some benefits on the depression, tremor, and rigidity experienced by patients. Scientists believe that sleep deprivation produces certain anticholinergic effects, which may improve both depression and Parkinson's symptoms.

Mental Tasks. Mental training may increase dopamine in the brain. Some studies indicate that being mentally fit may be as important for patients as being physically fit. Helpful approaches include:

Select and learn new hobbies that require finger and hand mobility, such as sewing, carpentry, fishing, or playing cards.
Practice deep breathing and relaxation exercises. These may help maintain proper speech control, control tremor, and reduce anxiety.
Both the patient and any caregivers should consider psychological therapy and support for depression and loss of motivation. If psychological therapy is too costly, inexpensive support programs and groups are widely available and can be invaluable for the patient and the family.

Speech Therapy. Speech therapy may help those who develop a monotone voice and lose volume, particularly in combination with medications. There are no well-conducted studies comparing specific speech therapies, but the Lee Silverman Voice Treatment (LSVT) appears to be an example of an effective technique. It has five major components:

Focus on the voice ("think loud/think shout")
High effort (pushes patients to overcome limitations)
Intensive treatment (16 sessions in 1 month)
Calibration (learning to know and accept the amount of effort needed to produce normal sound so it becomes automatic)
Quantification (continuous feedback to objectively document success)

LSVT may help swallowing as well as speech.

Equipment and Devices. A number of devices can be helpful for maintaining stability and preventing falls. The following are some examples:

Rails installed where the patient needs support in getting up or down, such as along the bed and in the bathroom.
Walkers with locking wheels. (Walkers do not appear to be helpful for freezing.)
Chairs with straight backs, firm seats, and arm rests.
Firm mattresses and satin sheets or less expensive sheets with high thread counts. (These are useful for helping patients slide out of bed.)

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.apdaparkinson.org -- American Parkinson's Disease Association
www.pdf.org -- Parkinson's Disease Foundation
www.parkinson.org -- National Parkinson Foundation
www.michaeljfox.org -- Michael J. Fox Foundation for Parkinson's Research
www.wemove.org -- Worldwide Education and Awareness for Movement Disorders
www.parkinsonsaction.org -- Parkinson's Action Network

References

Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, et al. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908.

Murata M, Hasegawa K, Kanazawa I. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007 Jan 2;68(1):45-50.

Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007 Jan 4;356(1):29-38.

Schupbach WM, Maltete D, Houeto JL, du Montcel ST, Mallet L, Welter ML, et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology. 2007 Jan 23;68(4):267-71. Epub 2006 Dec 6.

Storch A, Jost WH, Vieregge P, Spiegel J, Grelich W, Durner J, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol. 2007 July;64.

Voon V, Thomsen T, Miyasaki JM, de Souza M, Shafro A, Fox SH, et al. Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol. 2007 Feb;64(2):212-6.

Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology. 2007 Jan 23;68(4):272-6. Epub 2007 Jan 3.

Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med. 2007 Jan 4;356(1):39-46.

Review Date:
6/4/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Rheumatoid arthritis

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Treatment Approaches

Patients with rheumatoid arthritis who do not respond to single-drug therapy often do better when a combination of drugs is used, indicates a review of 23 clinical trials published in 2007 in the Annals of Internal Medicine. However, the researchers were unable to determine which combinations of drugs work best or which individual drugs are more effective than others.
Combination drug treatment is now becoming a standard approach to treating rheumatoid arthritis while it is still in its early stages. Another 2007 Annals of Internal Medicine study indicated that initial combination therapies slow progression of joint damage more rapidly than single-drug therapy but, after several years, all treatment strategies produce benefits.

Fish Oil for Joint Pain

The omega-3 fatty acids found in fish oil may have anti-inflammatory properties that can help relieve joint pain, indicates a 2007 review in Pain. The researchers found that taking omega-3 fatty acids for 3 - 4 months helped reduce joint pain intensity, minutes of morning stiffness, the number of painful or tender joints, and consumption of non-steroidal anti-inflammatory drugs (NSAIDs). Salmon, mackerel, and herring are types of fish that are particularly high in these fatty acids. Fish oil can also be taken through dietary supplements, but these can interact with some types of prescription medications and may not be safe or appropriate for all patients. (Check with your doctor before taking these or any other supplements.)

Introduction

Rheumatoid arthritis (RA) is a chronic disease in which various joints in the body are inflamed, leading to swelling, pain, stiffness, and the possible loss of function.

Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints affected is usually symmetrical, involves the hands and other joints, and is worse in the morning. Rheumatoid arthritis is a systemic (body-wide) disease, involving other body organs, whereas osteoarthritis is limited to the joints. Both forms of arthritis can be crippling.

The process probably develops in the following way:

The disease process leading to rheumatoid arthritis begins in the synovium, the membrane that surrounds a joint and creates a protective sac.
This sac is filled with lubricating liquid called the synovial fluid. In addition to cushioning joints, this fluid supplies nutrients and oxygen to cartilage, a slippery tissue that coats the ends of bones.
Cartilage is composed primarily of collagen, the structural protein in the body, which forms a mesh to give support and flexibility to joints.
In rheumatoid arthritis, an abnormal immune system produces destructive molecules that cause continuous inflammation of the synovium. Collagen is gradually destroyed, narrowing the joint space and eventually damaging bone.
If the disease develops into a form called progressive rheumatoid arthritis, destruction to the cartilage accelerates. Fluid and immune system cells accumulate in the synovium to produce a pannus, a growth composed of thickened synovial tissue.
The pannus produces more enzymes that destroy nearby cartilage, aggravating the area and attracting more inflammatory white cells, thereby perpetuating the process.

This inflammatory process not only affects cartilage and bones but can also harm organs in other parts of the body.

Click the icon to see an image of rheumatoid arthritis.

Causes

Although much has been learned about the process leading to rheumatoid arthritis, researchers have yet to uncover all the factors that lead to this devastating disease. One prevalent theory is that a combination of factors triggers rheumatoid arthritis, including an abnormal autoimmune response, genetic susceptibility, and some environmental or biologic trigger, such as a viral infection or hormonal changes.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight any infections.
In the process the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting off any bleeding blood vessel and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has other special factors that control and limit this inflammatory process.

The Infection Fighters. Two important components of the immune system that play a role in the inflammation associated with rheumatoid arthritis are B cells and T cells, both of which belong to a family of immune cells called lymphocytes.

When macrophages recognize foreign particles entering the bloodstream, they are programmed to ingest them, split them into pieces, and bring specific sections of them (antigens) into contact with the surface of the T cell. These antigens are placed within specialized proteins on the surface of the T cell that signal to a T cell and begin a process of immune system inspection. This process involves the interaction of several proteins on B cells and T cells, which seem to signal back and forth.

If the T cell recognizes an antigen as "non-self," it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion. T cells can be further categorized as killer T cells or helper T cells. Killer T cells directly attack antigens, such as viruses and tumor cells. Helper T cells recognize antigens that are presented to them by macrophages (or other specialized cells), and can stimulate B cells to mount various kinds of attacks on the antigen. They also produce chemicals (cytokines) that can have a more direct role in the inflammatory process.

For reasons that are still not completely understood, both the T cells and the B cells become overactive in patients with RA. In an immune response it is normal for the antibody response to change over time, particularly if the first antibodies that are made do not eliminate the invading particles. Little by little, the types of antibodies being made undergo changes in an attempt to achieve better recognition and a stronger inflammatory response against a recalcitrant invader. In RA, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal repertoire of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Cytokines. Cytokines are very important in the destructive process of rheumatoid arthritis, particularly those known as interleukins (ILs) -- notably IL1 and IL6 -- and tumor necrosis factor (TNF). TNF is now known to be the major cause of joint damage and various systemic manifestations of RA, including weight loss.

Leukocytes. The leukocytes, the other major white blood cells in the body, are also spurred into action by the over-zealous T cells. Leukocytes stimulate the production of key players in the inflammatory process, including leukotrienes, prostaglandins, and nitric oxide.

The Hypothalamic-Pituitary-Adrenal Axis and Stress Hormones. Some research suggests that abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) may contribute to RA. The HPA system includes two parts of the brain (the hypothalamus and the pituitary) and the adrenal gland.

Click the icon to see an image of the adrenal glands.

The HPA axis regulates a person's response to stress, which includes the release of cortisol (an important stress hormones) and DHEA (a weak male hormone). The cytokines interleukin-6 and TNF-alpha normally stimulate a surge in these hormones, which then block further release of the cytokines. Research suggests, however, that in RA, a defective HPA axis responds to the cytokines with a lower-than-normal release of cortisol and DHEA. Without a strong stress response, the cytokine levels remain high and become destructive, causing inflammation.

Genetic factors play some role in RA, but are clearly not the only important factor. The presence of certain genetic mutations, however, may worsen the disease process. It should be pointed out that defective genes not only can be inherited but they may be changed and mutated by environmental or other factors. More research is needed to determine the specific genetic contributions to this disease.

HLA. HLA (human leukocyte antigen) is a genetically regulated molecule that traps part of antigens and presents them on the surface of cells for destruction by antibodies and T cells. It is designed to recognize self- from non-self cells. A number of HLA genetic forms called HLA-DRB1 alleles are referred to as the RA-shared epitope because of their association with rheumatoid arthritis. These genetic factors do not cause RA, but they may make the disease more severe once it has developed. Genetic variations in the HLA region may also predict drug treatment response to etanercept and the disease-modifying anti-rheumatic drug methotrexate.

Lack of Corticotropin-Releasing Hormone. Some people with RA may have a genetic deficiency of a hormone known as corticotropin-releasing hormone (CRH), which produces corticosteroids, hormones that suppress the inflammatory process.

Infections. Although many bacteria and viruses have been studied, no single organism has been proven to be the primary trigger for the autoimmune response and subsequent damaging inflammation. Higher than average levels of antibodies that react with the common intestinal bacteria E. coli have appeared in the synovial fluid of people with RA. Some experts think they may stimulate the immune system to prolong RA once the disease has been triggered by some other initial infection. Other potential triggers include Mycoplasma, parvovirus B19, retroviruses, mycobacteria, and Epstein-Barr virus.

Chemicals. A number of chemicals are being investigated as triggers of rheumatoid arthritis, but it is very difficult to determine causal effects of any specific trigger.

Risk Factors

Rheumatoid arthritis (RA) is an ancient disease. The condition has been identified in skeletons thousands of years old. According to the Arthritis Foundation, RA affects an estimated 2.1 million Americans.

Although the disease can occur at any age from childhood to old age, it usually starts in young adulthood, with onset peaking between the ages of 20 - 45. Still, about 50,000 children may be afflicted with juvenile rheumatoid arthritis.

Women are more likely to have RA than men. (The risk for women is slightly lower if they have been pregnant.) Women are also at higher risk for the severe type 2 rheumatoid arthritis.

Some people may inherit genes that make them susceptible to RA, but a family history of RA does not appear to increase an individual's risk.

Other factors may place certain susceptible individuals at higher risk for developing RA:

Heavy long-term smoking is a very strong risk factor for RA, particularly in patients without a family history of the disease.
Women who have a shorter fertility time (and so lower levels of reproductive hormones) may be at higher risk.
History of blood transfusions.

Most studies have not found any association between silicone breast implants and rheumatoid arthritis or other autoimmune disease (except possibly Sjögren syndrome).

Reports from a Dutch study suggest that hay fever sufferers have a reduced risk of developing rheumatoid arthritis, and, conversely, arthritis patients are less likely to have hay fever.

Symptoms

The hallmark symptom of rheumatoid arthritis is morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis, for instance, usually clears up within half an hour.) Even after remaining motionless for a few moments, the body can stiffen. Movement becomes easier again after loosening up.

Swelling and pain in the joints must occur for at least 6 weeks before a diagnosis of rheumatoid arthritis is considered. The inflamed joints are usually swollen and often feel warm and "boggy" when touched. The pain often occurs symmetrically but may be more severe on one side of the body, depending on which hand the person uses more often.

Although rheumatoid arthritis almost always develops in the wrists and knuckles, the knees and joints of the ball of the foot are often affected as well. Indeed, many joints may be involved, including those in the cervical spine, shoulders, elbows, tips, temporomandibular joint (jaw), and even joints between very small bones in the inner ear. Rheumatoid arthritis does not usually show up in the fingertips, where osteoarthritis is common, but joints at the base of the fingers are often painful.

In about 20% of people with RA, inflammation of small blood vessels can cause nodules, or lumps, under the skin. They are about the size of a pea or slightly larger, and are often located near the elbow, although they can show up anywhere. Nodules can occur throughout the course of the disease. Rarely, nodules may become sore and infected, particularly if they are in locations where stress occurs, such as the ankles. On rare occasions, nodules can reflect the presence of rheumatoid vasculitis, a condition that can affect blood vessels in the lungs, kidneys, or other organs.

Fluid may accumulate, particularly in the ankles. In rare cases, the joint sac behind the knee accumulates fluid and forms what is known as a Baker cyst. This cyst feels like a tumor and sometimes extends down the back of the calf causing pain.

Symptoms such as fatigue, weight loss, and fever may accompany early rheumatoid arthritis. Some people describe them as being similar to those of a cold or flu except, of course, RA symptoms can last for years.

In children, juvenile rheumatoid arthritis, also known as Still's disease, is usually preceded by high fever and shaking chills along with pain and swelling in many joints. A pink skin rash may be present.

Complications

Rheumatoid arthritis is not fatal, but complications of the disease may shorten survival by a few years in some individuals. Although type 2 rheumatoid arthritis is progressive and there is no cure, over time the disease becomes less aggressive, and symptoms may even improve.

Treatments for RA are increasingly effective in slowing this debilitating disease, and some may even prevent initial destruction by aggressively reducing inflammation. If bone and ligament destruction and any deformities have occurred, however, the effects are permanent. It is essential, therefore, to seek a doctor's help as soon as symptoms develop. Side effects of the treatments often contribute to the severity of the disease.

Affected joints can become deformed, and the performance of even ordinary tasks may be very difficult or impossible. According to one survey, 70% of patients with rheumatoid arthritis feel the disease prevents them from living a fully productive life. A 2000 study found that about one-third of people with RA stop working within 5 years of onset of the disease.

Rheumatoid arthritis can affect other parts of the body as well as the joints. Some patients with severe disease may then be at higher risk for complications, such as the following:

Peripheral Neuropathy. This condition affects the nerves, most often those in the hands and feet. It can result in tingling, numbness, or burning.
Muscle problems. Many patients have weakness of the muscles.
Anemia. People with RA may develop anemia, which involves a decrease in the production of red blood cells.
Scleritis and Episcleritis. This is an inflammation of the blood vessels in the eye that can result in corneal damage. Symptoms include redness of the eye and a gritty sensation.
Infections. Patients with RA have a higher risk for infections, particularly from some of the immune-suppressing drugs (corticosteroids, anti-tumor necrosis factors, disease modifying drugs) that they take.
Skin Problems. Skin problems are common, particularly on the fingers and under the nails. Some patients develop severe skin complications that include rash, ulcers, blisters (which may bleed in some cases), lumps under the skin, and other problems. Severe skin disease can reflects a more serious case of RA in general.
Osteoporosis. Osteoporosis, a disorder in which bone density decreases, is more common than average in postmenopausal women with RA. The hipbone is particularly affected. The risk for osteoporosis also appears to be higher than average in men with RA who are over 60 years old.
Lung Disease. Patients with RA are susceptible to chronic lung diseases, including interstitial fibrosis, pulmonary hypertension, and other problems. Both rheumatoid arthritis itself and some treatments may cause this damage.
Kidney. Although rheumatoid arthritis only rarely involves the kidney, many of the drugs used to treat it can damage kidneys.
Vasculitis. Vasculitis involves autoimmune inflammatory abnormalities in very small vessels and can affect many organs in the body. Manifestations of vasculitis include mouth ulcers, nerve disorders, rapid worsening of the lungs, inflammation of coronary arteries, and inflammation of the arteries supplying blood to the intestines.
Heart Disease. Inflammation of the heart muscle itself in the sac around the heart can cause many problems. Mounting evidence suggests that RA can increase the risk for heart disease, possibly because of the inflammatory response in RA, which may also injure arteries and heart muscle tissue. Some studies have reported that people with RA are 30 - 50% more likely to suffer heart vessel blockages and 60 - 70% more likely to die as result than people without RA.
Lymphoma and Other Cancers. Research suggests that patients with RA are four times more likely than healthy patients to develop non-Hodgkin’s lymphoma. There has also been concern that some RA treatments may increase the risk for lymphoma. Studies from 2006 indicate that RA’s chronic inflammatory process may play a role in the development of lymphoma. Researchers found that patients with very severe and long-term RA had a substantially increased risk of developing lymphoma. Other 2006 research suggests that RA drugs, such as biologic response modifiers, do not increase lymphoma risk, although they do increase skin cancer risk.
Periodontal Disease. People with RA may be twice as likely as non-arthritic individuals to have periodontal disease. Chronic inflammation and immune dysfunction are central to both diseases.
Pregnancy. Women with RA have an increased risk for premature delivery. They are also three times more likely than healthy women to develop hypertension during the last trimester of pregnancy.

Juvenile rheumatoid arthritis often resolves before adulthood. Patients who experience arthritis in only a few joints do better than those with more widespread (systemic) disease, which is very difficult to treat. Although it can be very serious, very few people die from this condition.

MAS. Macrophage activation syndrome (MAS) is a life-threatening complication of this disorder and requires immediate treatment with high-dose steroids and cyclosporin A. Parents should be aware of symptoms, which include persistent fever, weakness, drowsiness, and lethargy.

Diagnosis

Rheumatoid arthritis can be difficult to diagnose. Many other conditions resemble it and its symptoms can develop insidiously. Blood tests and x-rays may show normal results for months after the onset of joint pain. Even after rheumatoid arthritis has been diagnosed, it is extremely important to determine whether the course of the disease is benign (type 1) or aggressive (type 2) in order to treat the problem appropriately.

Specific findings or presentation more likely to suggest the diagnosis of rheumatoid arthritis include morning stiffness, involvement of three joints at the same time, involvement of both sides of the body, subcutaneous nodules, positive rheumatoid factor, changes in x-rays.

Various blood tests may be used to help diagnose RA, determine its severity, and detect complications of the disease.

Rheumatoid Factor. In RA, antibodies that collect in the synovium of the joint are known as rheumatoid factor. In about 80% of cases of RA, blood tests reveal rheumatoid factor. It can also show up in blood tests of people with other diseases. However, when it appears in patients with arthritic pain on both sides of the body, it is a strong indicator of type 2 RA. The presence of rheumatoid factor plus evidence of bone damage on x-rays also suggests a significant chance for progressive joint damage.

Erythrocyte Sedimentation Rate Test. An erythrocyte sedimentation rate (ESR or sed rate) measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the patient's blood. The higher the sed rate the greater the inflammation. In addition to rheumatoid arthritis, the sed rate can be high in many conditions ranging from infection to inflammation to tumors. The test is used, then, not for diagnosis, but to help determine how serious the condition is.

C-Reactive Protein. High levels of C-reactive protein (CRP) are also indicators of active inflammation. However, because obesity also increases CRP levels, the doctor should consider a patient’s body mass index when evaluating CRP levels during RA diagnosis.

Anti-CCP Antibody Test. The presence of antibodies to cyclic citrullinated peptides (CCP) can identify RA years before symptoms develop. In combination with the test for rheumatoid factor, the CCP antibody test is the best predictor of which patients will go on to develop severe RA. Used in Europe, the test is now beginning to be used somewhat more commonly in the U.S. U.S. laboratories have not yet developed consistent standards for interpreting the test, however.

Tests for Anemia. Anemia is a common complication. Blood tests are needed often to determine the amount of red blood cells (hemoglobin and hematocrit) and iron (soluble transferrin receptor and serum ferritin) in the blood.

Analyzing the synovial fluid might prove to be helpful in detecting markers of joint destruction, but this is not commonly performed. Some investigational examples include the following:

An enzyme called MMP-3 (matrix metalloproteinase 3) is involved with the degradation of cartilage. Its presence in synovial fluid is strongly associated with progressive joint destruction in patients with chronic RA.
High levels urocortin, a member of the peptide family involved in the stress response, may also be a major player in the RA inflammation.

X-Rays. X-rays generally have not been helpful to detect the presence of early rheumatoid arthritis because they cannot show images of soft tissue. The use of a technique known as dual energy x-ray absorptiometry, however, may be useful in detecting early bone loss in rheumatoid arthritis (2 - 27 months after onset). Evidence of damage on x-rays along with elevated rheumatoid factor is a significant predictor for progressive joint destruction.

Ultrasound. Special ultrasound techniques called power Doppler ultrasonography (PDUS) or quantitative ultrasound (QUS) may be helpful in RA. PDUS may be reliable for monitoring inflammatory activity in the joint. QUS, which is used for osteoporosis, can detect bone loss in fingers, which may prove to be a good indicator of early RA.

Magnetic Resonance Imaging. Specially designed magnetic resonance imaging (MRI) equipment called extremity MRI may be able detect bone erosions in the hands of RA patients where x-rays cannot. Further evaluation is necessary.

Symptoms of rheumatoid arthritis can be mimicked by things as benign as a bad mattress or as serious as cancer. A number of rare genetic diseases attack the joints. Physical injuries, infections, and poor circulation are among the many problems that can cause aches and pains. It would be impossible to discuss in this report the dozens of all conditions with symptoms of joint aches and pains.

Osteoarthritis. Osteoarthritis requires some special mention because it is the most common form of arthritis. It differs from RA in several important respects.

Osteoarthritis usually occurs in older people.
It is located in only one or a few joints. (In fact, osteoarthritis is probably most often confused with rheumatoid arthritis if it affects multiple joints in the body.)
The joints are less inflamed.
Progression of pain is almost always gradual.

Gout. Gout also causes swelling and severe pain in a joint, although most commonly starting in one joint. It is particularly difficult to distinguish chronic gout in older people from rheumatoid arthritis, however, since gout in this population can occur in a number of joints. A proper diagnosis can be made with a detailed medical history, laboratory tests, and detection in the affected joint of a salt called monosodium urate (MSU), which identifies gout.


Disease	Specific Subtypes
Osteoarthritis
Infectious Arthritis	Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis
Postinfectious or Reactive Arthritis	Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease
Crystal Induced Arthritis	Gout and pseudogout
Other Rheumatic Autoimmune Diseases	Systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's Disease (also called juvenile rheumatoid arthritis), Behcet's disease
Other Diseases	Chronic fatigue syndrome, hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis

Treatment

The treatment of rheumatoid arthritis involves medications and lifestyle changes.

Many drugs are used for managing the pain and slowing the progression of rheumatoid arthritis, but none completely cure the disease. Some experts believe that no single drug will ever cure rheumatoid arthritis because of the many factors that affect the disease at various times. The goals of drug treatment for rheumatoid arthritis include:

Reduce inflammation
Prevent damage to the bones and ligaments of the joint
Preserve movement
To be as inexpensive and as free from side effects as possible over the long-term

The drug categories used for RA include:

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are the least potent drugs used for RA. These drugs relieve pain by reducing inflammation, but do not affect the course of the disease.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are the main drugs used for treating rheumatoid arthritis. They slow the progression of the disease. They are much more effective than NSAIDs but also have more side effects. Methotrexate (Rheumatrex, Trexall) is the most widely used of these drugs.
Biologic Response Modifiers (also known as Biologic DMARDs) are often prescribed to patients who have failed to respond to DMARDs. They may be used alone or in combination with DMARDs such as methotrexate. They modify or block destructive immune factors such as tumor-necrosis factor (TNF). Current anti-TNF drugs include infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). Other biologic response modifiers include the interleukin-1 antagonist anakinra (Kineret), the T cell co-stimulation modulator abatacept (Orencia), and rituximab (Rituxan), which targets CD20-positive B cells.
Corticosteroids, or steroids, are powerful anti-inflammatory drugs that are used to quickly reduce inflammation. These drugs include prednisone and prednisolone.

The question of how early and how aggressively to treat RA has been the subject of great debate. Among patients with RA, some will go into remission and remain in remission for the length of their lives even in the absence of treatment, while others will go on to develop active, sometimes severe RA.

Current practice has moved towards treating the disease aggressively while it is in its early stages to help prevent it from reaching a more severe and chronic state. Studies have found less joint damage in patients with early, aggressive treatment, particularly with the use of DMARDs and TNF modifiers in combination with methotrexate. Intensive early dosing of methotrexate may help slow progression of rheumatoid arthritis. Early combination therapy with DMARDs and corticosteroids is also showing good results.

During the first year of treatment, combination therapy appears to reduce the progression of joint deterioration more rapidly and effectively than single drug treatment. In addition, patients who have not been helped by one drug often benefit from a combination of drugs. However, over a longer period of time, it is not clear whether a drug combination approach offers many advantages over single drugs. It is also not certain which combination of drugs works best. Depending on your particular health condition, and how you respond to the drugs prescribed, your doctor may try various treatment strategies.

Medications

Two-thirds of people with RA rank pain as their primary reason for seeking professional help. The most common pain relievers for RA are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil). In 2004, a new NSAID, meloxicam (Mobic) was approved in the U.S. for the management and treatment of rheumatoid arthritis.

Studies suggest that the best times for taking an NSAID may be after the evening meal and then again on awakening. RA symptoms increase gradually during the night, reaching their greatest severity at the time of awakening. Taking NSAIDs with food can reduce stomach discomfort, although it may slow down the pain-relieving effect.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same warning label used for the COX-2 inhibitor celecoxib (Celebrex). This "black box" warning, the FDA's strongest warning, emphasizes the increased risks for cardiovascular events and gastrointestinal bleeding associated with these drugs’ use. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions. In December 2006, the FDA proposed even stronger labeling changes to highlight these drugs’ risk for liver damage as well as alcohol and drug interactions.

Long-term, regular use of NSAIDs can increase the risk for heart attack, especially for people who have a heart condition. Long-term use of NSAIDs is also the second most common cause of ulcers and gastrointestinal bleeding. To reduce the risks associated with NSAIDs, take the lowest dose possible for pain relief.

Other possible side effects of NSAIDs may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Long-term use of NSAIDs is the second most common cause of ulcers. Ulcers caused by NSAIDs are more likely to bleed than those caused by the bacteria Helicobacter pylori.

NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Those at high risk for bleeding include people over age 60, anyone with a history of ulcers of gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

COX-2 Inhibitors (Coxibs). Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of heart problems, skin rashes, and other adverse effects, the FDA re-evaluated the risks and benefits of this drug class. This lead to the removal of rofecoxib (Vioxx) and valdecoxib (Bextra) from the United States market. Celecoxib (Celebrex) is still available, but patients should ask their doctor whether the drug is appropriate and safe for them. In December 2006, the FDA approved celecoxib for the relief of symptoms of juvenile rheumatoid arthritis in patients ages 2 years and older.

Disease-modifying anti-rheumatic drugs (DMARDs) are the standard treatments for RA. They are used either alone or in combination with newer biologic DMARDs.

DMARDs do not have any common properties other than their ability to slow down the progression of rheumatoid arthritis. Many were used for other diseases and were found accidentally to help RA. DMARDs include:

Methotrexate (considered to be the current standard of care)
Leflunomide
Hydroxychloroquine
Sulfasalazine
Gold
Minocycline
Azathioprine
Cyclosporine

Unfortunately, all DMARDs tend to lose effectiveness over time, even methotrexate. Patients rarely use one drug for more than 2 years. Combining DMARDs with each other or with drugs in other categories offers the best approach for many patients. The addition of a corticosteroid to any combination may also be helpful.

All DMARDs may produce stomach and intestinal side effects, and, over the long-term, each poses some risk for rare but serious reactions. (In some cases, however, they may be less harmful than long-term NSAID treatment.)

Methotrexate. Methotrexate (Rheumatrex, Trexall) acts as an anti-inflammatory drug and is now the most frequently used DMARD, particularly for severe disease. It has a faster mode of action than other DMARDs, (it starts working within 3 - 6 weeks), and its effectiveness as a well proven in studies.

Even this drug loses effectiveness, however, when used alone. It may be more effective when used in combination with other DMARDs or other drugs. Recent studies have focused on combining methotrexate with various biological response modifier drugs, especially for treatment of patients with early aggressive arthritis. The combination appears to work better than single drug therapy.

About 20% of patients withdraw from methotrexate because of its side effects. They include nausea and vomiting, rash, mild hair loss, headache, mouth sores, and muscle aches. Methotrexate reduces levels of folic acid (folate) in the body, which can lead to some of these side effects. Doctors may prescribe folic acid supplements to prevent side effects. However, some research suggests that folic acid may interfere with methotrexate’s effectiveness.

Methotrexate is usually given as pills. Patients who need higher doses can take it as an injection. Methotrexate has fewer serious toxic effects than many DMARDs. Although these severe reactions are rare, they may include:

Kidney and liver damage. People at particular risk for liver damage from methotrexate include those with diabetes, obesity, and alcoholism.
Increased risk for infections
Lung disease occurs in up to 5% of people. People who have poor lung function are most at risk.
The drug increases the risk for birth defects and should not be taken by pregnant women. However, methotrexate will not harm a woman’s chance for future healthy pregnancy.

Leflunomide. Leflunomide (Arava) blocks autoimmune antibodies and reduces inflammation. It also may inhibit metalloproteinases (MMP), which are involved in cartilage destruction. It has the following benefits:

It slows disease progression as early as 6 months into treatment.
Comparison studies with methotrexate report a better quality of life with leflunomide, including more energy, greater vitality, and fewer emotional side effects. (Studies comparing their risk for serious adverse effects are mixed. One, for example, showed fewer problems with leflunomide, while another reported identical rates.)

The combination of methotrexate and leflunomide (which has different effects on the immune system) is very effective compared to either drug alone. (This combination poses a risk for liver toxicity and requires monitoring.)

Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury. Everyone taking leflunomide should be monitored regularly, including blood tests for liver function, and anyone with liver problems should not take this drug. Monitoring of serum concentrations of the most active metabolite of leflunomide may help predict treatment response.

Hydroxychloroquine. Hydroxychloroquine (Plaquenil) was originally used for preventing malaria and is now also used for mild, slowly progressive arthritis. It can help relieve pain and improve mobility. It has one of the least toxic profiles of the DMARDs. The downside is that this drug can take up to 6 months to achieve full benefit. It also does not appear to slow disease progression. One study concluded that joint erosion after 2 years was worse than with no DMARD at all.

As with all DMARDs, gastrointestinal complaints are fairly common. This drug used to be associated with eye and vision problems, but with current lower doses this side effect is rare. If vision problems occur, it is usually with people taking very high doses, those with kidney disease, or those over 60 years of age. Still, you should have regular eye exams while taking this drug and notify your doctor if you experience any sudden changes in vision.

Sulfasalazine. Sulfasalazine (Azulfidine) was developed in the 1930s for treating rheumatoid arthritis, but fell into disfavor when gold treatment emerged. It has regained popularity, however, and is now used for both adult and juvenile RA. It works best when the disease is confined to the joints. Symptom relief occurs within 1 - 3 months.

Side effects are common, particularly stomach and intestinal distress, which usually occur early in the course of treatment. (However, serious gastrointestinal side effects, such as stomach ulcers, occur less frequently with sulfasalazine than with NSAIDs.) A coated-tablet form may help reduce side effects. Other side effects include skin rash and headache. Sulfasalazine increases sensitivity to sunlight. Be sure to wear sunscreen (SPF 15 or higher) while taking this drug. People with intestinal or urinary obstructions or who have allergies to sulfa drugs or salicylates should not take sulfasalazine.

Gold. Gold has been a long-standing DMARD for rheumatoid arthritis, although its use has decreased with the development of disease modifying and biologic drugs. Gold is usually administered in an injected form because the oral form, auranofin (Ridaura), is much less effective. There are two injectable forms of gold: Gold sodium thiomalate (Myochrysine) and aurothioglucose (Solganal). It can take 3 - 6 months before injections have an effect on RA symptoms.

Gold injections cause mouth sores in about a third of patients. Skin side effects include itching and rash, which can be severe in some patients. . The most serious side effects of gold injections, while rare, are kidney damage and decreased white blood cell count. Gold injections are not usually given to pregnant women. It is not definite that gold causes birth defects but doctors generally recommend that women use birth control while receiving this drug.

Minocycline. Minocycline (Minocin) is a tetracycline antibiotic that is usually prescribed for patients with mild RA. It can take 2 - 3 months before symptoms begin to improve and up to a year for full benefit. Side effects include upset stomach, dizziness, and skin rash. Long-term use of minocycline can cause changes in skin color, but this side effect usually disappears once the medication is stopped. Minocycline can cause yeast infections in women. Minocycline increases sensitivity to sunlight and patients should be sure to wear sunscreen. In rare cases, minocycline can affect the kidneys and liver.

Azathioprine. Azathioprine (Imuran) suppresses immune system activity. It takes 6 - 8 weeks for early symptom improvement and up to 12 weeks for full benefit. Azathioprine can cause serious problems with the gastrointestinal tract. About 10 - 15% of patients experience nausea and vomiting, often accompanied by stomach pain and diarrhea. (Taking the medication twice daily, instead of once daily, or taking it after eating may help avoid this problem.) Azathioprine can also cause problems with liver function and pancreas gland inflammation, and can reduce white blood cell count.

Cyclosporine. Like azathioprine, cyclosporine (Sandimmune, Neoral) is an immunosuppressant. It is used for people with RA who have not responded to other drugs. It can take a week before symptoms improve and up to 3 months for full benefit. The most serious and common side effects of cyclosporine are high blood pressure and kidney function problems. While kidney function usually improves once the drug is stopped, mild-to-moderate high blood pressure may continue. Cyclosporine can also cause gout or worsen gout in people who have this condition.

Other common side effects include headache, nausea, vomiting, stomach pain and upset, and swelling of hands and feet. About 10% of patients who take cyclosporine develop tremors, increased hair growth, muscle cramps, and numbing or tingling in hands and feet (neuropathy). Swelling of the gums is also common. Patients should practice good dental hygiene, including regular brushing and flossing.

Biologic response modifiers are drugs made from living cells. These drugs target specific components of the immune system that contribute to the joint inflammation and damage that are part of the rheumatoid arthritis disease process.

Currently approved biologic response modifiers include:

Etanercept (Enbrel). Etanercept is an anti-tumor necrosis factor (anti-TNF) drug. Approved in 1998, etanercept was the first biologic response modifier drug for treatment of rheumatoid arthritis. It is also approved for juvenile RA and psoriatic arthritis.
Infliximab (Remicade). Approved in 1999, infliximab is also an anti-TNF drug. It is used in combination with methotrexate.
Adalimumab (Humira). Adalimumab is another anti-TNF drug. First approved in 2002 as a second-line treatment for RA, adalimumab received additional approvals in 2005 as a first-line treatment for RA and psoriatic arthritis. It is used alone or in combination with methotrexate or other DMARDs. It is also showing promising results in clinical trials for juvenile rheumatoid arthritis.
Anakinra (Kineret). Approved in 2001, anakinra targets interleukin-1 (IL-1), another type of immune factor.
Abatacept (Orencia). Approved in 2005 for adults with moderate-to-severe RA who have not responded to DMARD or anti-TNF drugs. Abatacept is known as a T cell co-stimulation modulator. It blocks T cell activation. It is used alone or in combination with other DMARDs aside from anti-TNF drugs.
Rituximab (Rituxan). Approved in 2006, rituximab targets CD20-positive B cells and blocks their activation. It is used in combination with methotrexate for patients with moderate-to-severe RA who have not responded to anti-TNF therapies.

Some of these drugs are used as first-line treatments for RA. Others are used for patients who have not responded to DMARDs or other types of treatment. Depending on the specific drug, they may be used alone or in combination with the DMARD methotrexate. However, biologic response modifiers are not used in combination with each other, as they can lead to serious infections.

As with other rheumatoid arthritis drugs, these drugs do not cure the disease but can help slow progression and joint damage. In recent clinical trials, some patients have achieved remission using methotrexate in combination with infliximab, adalimumab, or rituximab.

Side Effects and Complications. Etanercept, adalimumab, and anakinra are given by injection and may cause pain at the injection site. To prevent injection reactions, patients are sometimes pretreated with betamethasone, a corticosteroid drug, but some research suggests that the steroid does little good. Infliximab, abatacept and rituximab are given by intravenous infusion. Common infusion reactions include headache, nausea, and flu-like symptoms. Because biologic response modifiers affect the immune system, patients who take these drugs have an increased risk for infections.

Other risks associated with these drugs include:

Anti-TNF drugs (etanercept, infliximab, adalimumab) have been associated with sepsis, pneumonia, and tuberculosis; non-melanoma skin cancer, lymphoma, and other malignancies; lupus; heart failure; blood disorders (including aplastic anemia); palmoplantar psoriasis; lung disease; and liver damage.
Anakinra may cause a sudden drop in white blood cells (leukopenia) that increases the risk for infections.
Abatacept should be used cautiously in patients with chronic obstructive pulmonary disorder (COPD) as it may increase the risk for respiratory complications.
Rituximab has been associated with cases of a rare and deadly brain infection called progressive multifocal leukoencephalopathy (PML). It also may cause hepatitis B reactivation, viral infections, and heart rhythm disturbances and other heart problems.

Corticosteroids work rapidly to control inflammation and pain. Long-time use, however, can have severe adverse effects. Still, they are often used under the following conditions:

Oral corticosteroids, such as prednisolone and prednisone (Deltasone, Orasone), are most often used in combination with DMARDs, which significantly enhances the benefits of DMARDs.
Oral corticosteroids are sometimes used in early stage-RA for patients who cannot tolerate NSAIDs. Studies, in fact, suggest that low-dose corticosteroids may significantly slow joint pain when it is the first drug administered and then used for 2 years. (Even low-dose oral steroids have adverse effects on bone density, blood sugar, and weight.)
Higher doses of corticosteroids are used for flareups of vasculitis and severe reactions to medications.
Corticosteroids may also be used during pregnancy to avoid exposure to more toxic drugs.
Daily, low-dose corticosteroids are also needed in some patients to control their rheumatoid arthritis symptoms.
Corticosteroids are sometimes injected directly into joints for relief of flare-ups when only one or a few joints are affected. Experts suggest no more than three or four injections into a specific joint a year. Steroid injections in the joints may be a safe and effective treatment for juvenile rheumatoid arthritis and reduce the need for oral medication.
Corticosteroid pulse therapy (intravenous administration) may work as well as DMARDs.

Side Effects of Oral Corticosteroids. Serious side effects are associated with long-term use of oral steroids. (Low doses may reduce these risks, but they do not eliminate them.) Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, or bisphosphonates (alendronate etidronate, risedronate). Other adverse effects include cataracts, glaucoma, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and, rarely, psychosis. Recent research suggests that prednisone can increase the risk of developing non-melanoma skin cancer.

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. There have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctor measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Biologic Drugs. For many years, therapeutic treatment of rheumatoid arthritis focused on T cell mediation. New research is now examining the role of B cells, which become overactive in autoimmune disease, and how B cell depletion may help to reduce disease activity. Other areas of intense research include interleukin receptor antagonists, which target cytokines involved in the inflammatory process.

Many of the current investigational drugs are monoclonal antibodies (MAbs), biologic drugs that are designed to target specific receptors. Promising candidates in late-stage research include tocilizumab (Actemra), golimumab, denosumab, ocrelizumab, ofatumumab, and certolizumab.

Statins. Some research suggests that compounds derived from statins, the highly regarded cholesterol-lowering drugs, may suppress the inflammation responsible for RA damage.

Stem cell transplantation. Stem cells are the early versions of mature, specialized blood cells. Investigators are reporting that transplantation of donated hemopoietic stem cells, which mature into various blood cells, has induced remission in a few children with severe juvenile rheumatoid arthritis. The procedure is promising in select cases, but it can be highly toxic. More studies are needed to determine risks and benefits for RA patients.

Plasmapheresis. A device called the Prosorba column is used to remove inflammatory antibodies from the patient's blood. Small, short-term studies have shown that this therapy may slow or even halt the progression of the disease in a third to a half of patients. Side effects from the Prosorba column may include anemia, fatigue, itching, fever, a drop in blood pressure, and nausea. Nearly all patients experience an immediate flare-up of joint pain that lasts a few days. Some patients develop infection from the catheter used to remove blood. Long-term studies are needed.

Surgery

Certain surgical techniques may be helpful for people with severe deformities or disabilities.

Arthroscopy. Arthroscopy is performed to clean out bone and cartilage fragments that cause pain and inflammation. It is usually performed on the knee, but it also may be done on the hip:

The surgeon makes a small incision and injects a sterile solution to make the joint swell for easier viewing.
A lighted tube, called an arthroscope (which enables the surgeon to view the joint), is then inserted through another small incision.
Through a third incision, the surgeon trims, shaves, or stitches the damaged tissue. (Arthroscopy is most successful when the removal of cartilage only, and not bone, is involved.)

In many cases, the procedure can be done using local anesthetic, and the patient can go home within a day. In the case of knee operations, patients can resume mild activity in a couple of days, but full recovery can take up to 3 months.

Osteotomy. If only a certain section (the medial compartment) of the knee is damaged and deformed, the surgeon may choose to perform osteotomy:

The knee is opened.
A debridement (removal of damaged tissue) is performed in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.

The procedure is best used in heavier adults who are under 60 years old.

Unicompartmental Knee Arthroplasty. Unicompartmental knee arthroplasty (also called unicondylar knee arthroplasty) may be a useful procedure in some cases of limited damage in the knee. It is intended to relieve pain and preserve function as long as possible before a total knee replacement is necessary. The procedure involves a small incision and insertion of small implants. It retains important knee ligaments, which should preserve more movement than a total knee replacement. The procedure is not widely available and is somewhat controversial, since the implants may not be as reliable as those in total knee replacement.

Synovectomy. Synovectomy is a procedure whereby the diseased joint lining is removed. It is used when more conservative measures fail, particularly in the wrist. Studies are suggesting, however, that with the use of lasers for the procedure, eventually synovectomy may prove to be an alternative to DMARD treatments in reducing symptoms and achieving long-term remission.

Joint Replacement Surgery. Eventually, even after these procedures, rheumatoid arthritis may progress to the point that normal functioning is impossible. In such cases, artificial (prosthetic) replacement joint implants may be considered for knees, hips, or other joints. The prosthesis is usually made of a chromium alloy and plastic and may be attached to the adjoining bones using a cement, polymethyl methacrylate, or the prosthesis may be composed of a porous material that allows bone to grow into and eventually adhere to the device.

Although this procedure has usually been performed in people over 60, implants are now lasting 20 years and more and younger patients with severe disability are finding them useful. Uncemented arthroplasty using porous material is showing particularly good results. Studies on hip replacement, for example, now report that after 10 years, 5% of patients require reoperation and 12% of patients report some pain.

Lifestyle Changes

It is important to maintain a balance between rest (which will reduce inflammation) and exercise (which will relieve stiffness and weakness). Studies have suggested that even as little as 3 hours of physical therapy over 6 weeks will help people with RA, and that these benefits are sustained.

The goal of exercise is to:

Maintain a wide range of motion
Increase strength, endurance, and mobility
Improve general health
Promote well-being

In general, doctors recommend the following approaches:

Start with the easiest exercises, stretching and tensing of the joints without movement.
Next attempt mild strength training. (One study found that people with RA who exercised with machines that use compressed air for gentle resistance experienced less pain and increased muscle tone.)
The next step is to try aerobic exercises. These include walking, dancing, or swimming, particularly in heated pools. Avoid heavy impact exercises, such as running, downhill skiing, and jumping.
Tai chi, which uses graceful slow sweeping movements, is an excellent method for combining stretching and range-of-motion exercises with relaxation techniques. It is of particularly value for elderly RA patients who report significantly less pain after practicing this technique.

While traditional guidelines have restricted RA patients to only gentle exercise, recent research suggests that more intense exercise may not only be safe, but may actually produce greater muscle strength and overall functioning. Common sense is the best guide:

If exercise is causing sharp pain, stop immediately.
If lesser aches and pains continue for more than 2 hours afterwards, try a lighter exercise program for a while.
Using large joints instead of small ones for ordinary tasks can help relieve pressure, for instance, closing a door with the hip or pushing buttons with the palm of the hand.

Many patients with RA try dietary approaches, such as fasting, vegan diets, or eliminating specific foods, that seem to worsen RA symptoms. There is little scientific evidence to support these approaches but some patients report anecdotally that they are helpful.

In recent years, a number of studies have suggested that the omega-3 fatty acids contained in fish oil may have anti-inflammatory properties useful for RA joint pain relief. The best source of fish oil is through increased consumption of fatty fish such as salmon, mackerel, and herring. Fish oil supplements are another option, but they may interact with certain medications. If you are thinking of trying fish oil supplements, talk to your doctor first.

Various ointments, including Ben Gay and capsaicin (a cream that use the active ingredient in chilli peppers), may help soothe painful joints.

Orthotic devices are specialized braces and splints that support and help align joints. Many such devices made from a variety of light materials are available and can be very helpful when worn properly.

A number of specially designed appliances and devices are available to ease daily activities.

Although the influence of stress or emotions on the progression of RA is not fully known, having a history of major depression that persists or reoccurs seems to increase the pain, disability, and fatigue. Stress management alone cannot reduce pain, but it may be very helpful in helping people deal with their condition.

One study found that people with RA reported significant clinical improvement after writing about their pain, stress, or other traumatic experiences. Writing for 20 minutes, just a few days a week, resulted in improvement that lasted for months. One study found that spirituality (defined as "a belief in a power outside oneself and one's own existence," as opposed to the practice of any specific religion) is associated with better health, happiness and well-being among RA patients. (Spiritual healing does not appear to offer any advantages.)

People often turn to alternative therapies or nontraditional remedies to relieve the pain of rheumatoid arthritis. Some alternative procedures, such as acupuncture, massage, relaxation techniques, biofeedback, and hypnosis, are not harmful and may be a useful adjunct to standard treatments.

In a small study, acupuncture reduced pain by a third in 73% of patients, and more than half reported at least a 50% improvement in pain. Patients also reduced their use of pain medications. Research presented at the 2006 American College of Rheumatology annual meeting suggested that both electroacupuncture and traditional acupuncture may help reduce joint tenderness.
Balneotherapy, also known as hydrotherapy or spa therapy, is an ancient form of therapy that involves mineral baths to soothe pain, and some patients have reported relief using such baths.
The NIH is conducting clinical trials to examine whether relaxation response, tai chi, stress management, and cognitive-behavioral therapy can help patients with RA feel better.

Herbal remedies used for RA include boswellia, equisetum arvense (horsetail), devil's claw, borage seed oil, and many others. To date, no evidence supports their efficacy.

Researchers are currently conducting studies in animals to determine if supplements extracted from the turmeric spice can help prevent joint inflammation. The U.S. National Institutes of Health is also conducting a clinical trial to compare the clinical effects of the Chinese herb Tripterygium wilfordii Hook F (TwHF) with the pharmaceutical drug sulfasalazine. TwHF is traditionally used in Chinese medicine for its anti-inflammatory properties.

Resources

www.niams.nih.gov -- The National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation
www.fda.gov/cder/drug/infopage/cox2 -- FDA information on COX-2 inhibitors and NSAIDs
www.clinicaltrials.gov -- Find a clinical trial

References

Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess. 2006 Nov;10(42):iii-iv, xi-xiii, 1-229.

Donahue KE, Gartlehner G, Jonas DE, Lux LJ, Thieda P, Jonas BL, et al. Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. Ann Intern Med. 2007 Nov 19 [Epub ahead of print]

Firestein GS. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii2-22.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM,, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):406-15.

Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1.

Harris ED Jr. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005. O’Dell JR. In: Goldman, ed. Cecil Medicine. 23rd ed. Saunders; 2007.

Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007 Dec 1;370(9602):1861-74.

Smolen JS, Keystone EC, Emery P, Breedveld FC, Betteridge N, Burmester GR,. et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 Feb; 66(2): 143-50.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Stroke

FitSugar — Wed, 08 Oct 2008 17:35:08 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Prognosis
Prevention
Diagnosis
Managing a Stroke
Medications
Surgery
Recovery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Statin Drug Approved for Stroke Prevention

In 2007, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risk of stroke in patients with heart disease.
High-dose atorvastatin may help reduce the risk of recurrent stroke in patients who have had a recent stroke or transient ischemic attack, according to a New England Journal of Medicine study.

Drug Warnings

In 2006, the FDA strengthened the warning label for the anticoagulant drug warfarin (Coumadin) to emphasize its bleeding risks. However, warfarin is still the gold standard treatment for most patients with atrial fibrillation.
Evidence suggests that people at risk for stroke should avoid taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil) and diclofenac (Cataflam). COX-2 inhibitors should only be used as a last resort for pain relief. Try non-drug treatments (physical therapy, hot/cold compresses) first.

Aspirin

In 2007, the American Heart Association (AHA) issued new heart disease prevention guidelines for women. The AHA recommends low-dose aspirin therapy for women over age 65 who are at risk for stroke.
The combination of aspirin and dipyridamole (Aggrenox) may be better than aspirin alone in preventing major stroke in patients who have had a minor stroke, suggests a Lancet study.

Diagnosis

Magnetic resonance imaging (MRI) is better than computed tomography (CT) in detecting whether stroke (especially ischemic stroke) has occurred, indicates an important Lancet study.

Surgery

Carotid endarterectomy appears to be superior to and safer than carotid angioplasty and stenting (CAS) for most patients with artery stenosis (narrowing) of over 60%, suggest several recent studies. Most experts recommend CAS only for patients who have severe stenosis (greater than 70%) and high surgical risk.

Rehabilitation

Constraint-induced movement therapy (CIMT) may help patients who have recently had a stroke regain use of a paralyzed arm. The technique involves repetitive motion exercises while restraining the less functional arm.

Introduction

Blood Flow Blockage. The brain receives about 25% of the body's oxygen, but it cannot store it. Brain cells require a constant supply of oxygen to stay healthy and function properly. Therefore, blood needs to be supplied continuously to the brain through two main arterial systems:

The carotid arteries come up through either side of the front of the neck. (To feel the pulse of a carotid artery, place your fingertips gently against either side of your neck, right under the jaw.)
The basilar artery forms at the base of the skull from the vertebral arteries, which run up along the spine, join, and come up through the rear of the neck.

The Circle of Willis is the joining area of several arteries at the bottom (inferior) side of the brain. At the Circle of Willis, the internal carotid arteries branch into smaller arteries that supply oxygenated blood to over 80% of the cerebrum.

A reduction of, or disruption in, blood flow to the brain is the primary cause of a stroke. Blockage for even a short period of time can be disastrous and cause brain damage or even death.

Click the icon to see an image of the brain.

A stroke is usually defined as two types:

Ischemic (caused by a blockage in an artery)
Hemorrhagic (caused by a tear in the artery's wall that produces bleeding in the brain)

The consequences of a stroke, the type of functions affected, and the severity, depend on where in the brain it has occurred and the extent of the damage.

Ischemic strokes are by far the more common type, causing over 80% of all strokes. Ischemia means the deficiency of oxygen in vital tissues. Ischemic strokes are caused by blood clots that are usually one of three types:

Thrombotic stroke
Embolic stroke
Lacunar stroke

Thrombotic or Large-Artery Stroke and Atherosclerosis. The thrombotic stroke accounts for about 60% of all strokes. It usually occurs when an artery to the brain is blocked by a thrombus (blood clot) that forms as the result of atherosclerosis (commonly known as hardening of the arteries). These strokes are also sometimes referred to as large-artery strokes. The process leading to thrombotic stroke is complex and occurs over time:

The arterial walls slowly thicken, harden, and narrow until blood flow is reduced, a condition known as stenosis.
These now abnormal arteries become vulnerable to injury. Such injuries signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. This process is the first step in the inflammatory response, which may play a significant role in the stroke.
Macrophages literally "eat" foreign debris and become foamy cells that attach to smooth muscle cells of blood vessels, causing them to build up.
The immune system, sensing further harm, releases other factors called cytokines, which attract more white blood cells and perpetuate the whole cycle.

As these processes continue, blood flow slows. In addition, other events contribute to the coming stroke:

The injured inner walls fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity. The arteries become calcified and lose elasticity.
The arteries, now hardened and rigid, become susceptible to tearing. In this event, the thrombus (blood clot) forms.
The blood clot then blocks the already narrowed artery and shuts off oxygen to part of the brain. A stroke occurs.

Embolic Strokes and Atrial Fibrillation. An embolic stroke is usually caused by a dislodged blood clot that has traveled through the blood vessels (an embolus) until it becomes wedged in an artery. Embolic strokes account for about 25% of all strokes and may be due to various conditions:

In about 15% of embolic strokes, the blood clots originally form as a result of a rhythm disorder known as atrial fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart (the atria). Because of the irregular pumping, some blood may remain in the heart chamber where it forms clots, which can then break off and travel to the brain as emboli.
Emboli can originate from blood clots that form at the site of artificial heart valves or as a result of heart valve disorders.
Emboli can also occur after a heart attack or in association with heart failure.
Rarely, emboli are formed from fat particles, tumor cells, or air bubbles that travel through the bloodstream.

Lacunar Strokes. Lacunar infarcts are a series of very tiny, ischemic strokes, which cause clumsiness, weakness, and emotional variability. They are actually a subtype of thrombotic stroke and constitute about 38% of this major group. In some populations, such as among Japanese, they are the most common stroke subtypes. They can also sometimes serve as warning signs for a major stroke.

Silent Brain Infarctions. Many elderly people have silent brain infarctions, small strokes that cause no apparent symptoms. They are detected in between 10 - 38% of elderly patients who undergo imaging tests for problems other than stroke. A 2002 study suggested that they double the risk for future stroke. They also may be major contributors to mental impairment in the elderly. Smokers and people with hypertension are at particular risk.

Transient ischemic attacks (TIAs) are mini-ischemic strokes, usually caused by tiny emboli (clots often formed of pieces of calcium and fatty plaque) that lodge in an artery to the brain. They typically break up quickly and dissolve but they do temporarily block the supply of blood to the brain. The mental or physical disturbances resulting from TIAs generally clear up in less than a day, with nearly all symptoms resolving in less than an hour.

However, experts now advise that a TIA should be taken very seriously and treated as aggressively as a stroke. Both stroke and TIA increase the risk for a subsequent stroke. Moreover, the risk for having another stroke can be as high as 40% within 5 years. The American Heart Association/American Stroke Association recommends these guidelines to prevent a second stroke after TIA:

Lifestyle changes.

Stop smoking
Limit alcohol
Increase exercise (30 minutes a day of moderate physical activity)
Lose excess weight (waist measurements should be no more than 35 inches for women and 40 inches for men; body mass index should be 18.5 - 24.9)

Drug treatments.

Drugs to control cholesterol, high blood pressure, and (for people with diabetes) high blood sugar levels
Antiplatelet therapy such aspirin, dipyridamole, or clopidogrel)

Surgery.

Carotid endarterectomy surgery or carotid artery stenting is recommended for patients with severe (70% or more) carotid stenosis (narrowing or blockage of one or both arteries in the neck)
Endarterectomy or stenting may also be appropriate for some patients with moderate stenosis (50 - 69%)
Endarterectomy and stents are not needed for patients with mild stenosis (less than 50%)

Over 15% of strokes occur from hemorrhage (sudden bleeding) in the brain. In a healthy brain, brain cells called neurons are protected from exposure to blood by the blood-brain barrier, a wall of tiny vessels and structural cells. In a hemorrhagic stroke, however, this barrier is broken.

Hemorrhagic strokes may be categorized by how and where they occur.

Parenchymal, or cerebral, hemorrhage strokes. These strokes occur within the brain and account for about 10% of all strokes. They are most often the result of hypertension exerting excessive pressure on arterial walls already damaged by atherosclerosis. Heart attack patients who have been given drugs to break up blood clots or blood-thinning drugs have a slightly elevated risk of this type of stroke.
Subarachnoid hemorrhagic strokes. This other major hemorrhagic stroke accounts for about 5% of all strokes. This kind of stroke occurs when a blood vessel on the surface of the brain bursts, leakign blood into the subarachnoid space, an area between the brain and the skull. They are usually caused by the rupture of an aneurysm, a weakening in the blood vessel wall, which is often an inherited trait.
Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins. If it occurs in the brain and ruptures, it can also cause a hemorrhagic stroke.

Symptoms

People at risk and partners or caretakers of people at risk for stroke should be aware of the general symptoms. The stroke victim should get to the hospital as soon as possible after these warning signs appear. It is particularly important for people with migraines or frequent severe headaches to understand how to distinguish between their usual headaches and symptoms of stroke.

The American Stroke Association lists the following five warning signs of stroke. PEOPLE SHOULD IMMEDIATELY CALL FOR EMERGENCY ASSISTANCE IF THEY EXPERIENCE ANY OF THESE SYMPTOMS:

Sudden numbness or weakness of the face, arm or leg, especially on one side of the body
Sudden confusion, trouble speaking or understanding
Sudden trouble seeing in one or both eyes
Sudden trouble walking, dizziness, loss of balance or coordination
Sudden, severe headache with no known cause

Research indicates that patients receive faster treatment for stroke if they arrive by ambulance rather than coming to the emergency room on their own.

An easy way to remember the signs of stroke, and what to do, is by the acronym "F.A.S.T." If you think you or someone else is having a stroke, the National Stroke Association's F.A.S.T. test advises:

(F)ACE. Ask the person to smile. Check to see if one side of the face droops.
(A)RMS. Ask the person to raise both arms. See if one arm drifts downward.
(S)PEECH. Ask the person to repeat a simple sentence. Check to see if words are slurred and if the sentence is repeated correctly.
(T)IME. If a person shows any of these symptoms, time is essential. It is important to get to the hospital as quickly as possible. Call 9-1-1. Act FAST.

The symptoms of a transient ischemic attack (TIA) and early ischemic stroke are similar. In the case of a TIA, however, the symptoms should resolve within 24 hours. Symptoms depend on where the injury in the brain occurs. The origin of the stroke is usually either the carotid or basilar arteries.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

Symptoms From Blockage in the Carotid Arteries. The carotid arteries stem off of the aorta (the primary artery leading from the heart) and lead up through the neck around the windpipe and on into the brain. When TIAs or stroke occur from blockage in the carotid artery, which they often do, symptoms may occur in either the retina of the eye or the cerebral hemisphere (the large top part of the brain).

Symptoms include the following:

When oxygen to the eye is reduced, people describe the visual effect as a shade being pulled down. People may develop poor night vision. About 35% of TIAs are associated with temporary lost vision in one eye. Although such events are risk factors for future stroke, they pose a lower risk for a stroke and its complications than more widespread TIA symptoms.
When the cerebral hemisphere is affected, a person can experience problems with speech and partial and temporary paralysis, drooping eyelid, tingling, and numbness, usually on one side of the body. The stroke victim may be unable to express thoughts verbally or to understand spoken words. If the stroke injuries are on the right side of the brain, the symptoms will develop on the left side of the body and vice versa.
Uncommonly, patients may experience seizures.

Symptoms From Blockage in the Basilar Artery. The other major site of trouble, the basilar artery, is formed at the base of the skull from the vertebral arteries, which run up along the spine and join at the back of the head. When stroke or TIAs occur here, both hemispheres of the brain may be affected so that symptoms occur on both sides of the body. The following symptoms may develop:

Temporarily dim, gray, blurry, or lost vision
Tingling or numbness in the mouth, cheeks, or gums
Headache, usually in the back of the head
Dizziness
Nausea and vomiting
Difficulty swallowing
Weakness in the arms and legs, sometimes causing a sudden fall

Such strokes usually occur in the brain stem, which can have profound affects on breathing, blood pressure, heart rate, and other vital functions, but does not affect thinking or language.

Speed of Symptom Onset. The speed of symptom onset of a major ischemic stroke may indicate its source:

If the stroke is caused by a large embolus (a clot that has traveled to an artery in the brain), the onset is sudden. Headache and seizures can occur within seconds of the blockage.
When thrombosis (a blood clot that has formed within the brain) causes the stroke, the onset usually occurs more gradually, over minutes to hours. On rare occasions it progresses over days to weeks.

Click the icon to see an image of carotid dissection.

Click the icon to see an image of stroke.

Cerebral Hemorrhage Symptoms. Symptoms of a cerebral, or parenchymal, hemorrhage typically begin very suddenly and evolve over several hours and include:

Headache
Nausea and vomiting
Altered mental states
Seizures

Subarachnoid Hemorrhage. When the hemorrhage is a subarachnoid type, warning signs may occur from the leaky blood vessel a few days to a month before the aneurysm fully develops and ruptures. Warning signs may include:

Abrupt headaches
Nausea and vomiting
Sensitivity to light
Various neurologic abnormalities. Seizures, for example, occur in about 8% of patients.

When the aneurysm ruptures, the stroke victim may experience:

A terrible headache
Neck stiffness
Vomiting
Altered states of consciousness
Eyes may become fixed in one direction or lose vision
Stupor, rigidity, and coma

Risk Factors

New or recurrent strokes affect about 700,000 Americans every year. Although incidence of stroke has increased, more people are surviving stroke, and the death rate is declining. While age is the major risk factor, people with stroke are likely to have more than one risk factor.

Older Adults. People most at risk for stroke are older adults, particularly those with high blood pressure, who are sedentary, overweight, smoke, or have diabetes. Older age is also linked with higher rates of post-stroke dementia.

Younger Adults. Younger people are not immune, however. About 28% of stroke victims are under age 65.

In most age groups except older adults, stroke is more common in men than in women. However, it kills more women than men, regardless of ethnic groups. It is not clear why women have a higher mortality rate from stroke. The arteries that lead to the brain may be more vulnerable to the effects of plaque build-up in women than in men.

In 2007, the American Heart Association released new heart disease prevention guidelines for women. The new guidelines recommend daily aspirin therapy (75 - 325 mg/day) to help prevent stroke in high-risk women over the age of 65. For older women with a lower stroke risk, the AHA recommends 81 mg of aspirin a day or 100 mg of aspirin every other day. Aspirin does not appear to provide much stroke protection benefit for women under the age of 65.

All minority groups, including Native Americans, Hispanics, and African-Americans, face a significantly higher risk for stroke and stroke death than Caucasians. The risk is also higher in Asian Americans, although stroke rates appear to be declining in this group. The differences in risk among all groups diminish as people age.

The greatest disparity in risk occurs in young adults. Younger African-Americans are two to three times more likely to experience a stroke than their Caucasian peers and four times more likely to die from one. They also face a higher risk for death from heart disease. African-Americans have a higher prevalence of diabetes and hypertension than other groups. However, studies suggest that socioeconomic factors also affect these differences.

People in the southeastern U.S. have had the highest risk for stroke in the country for some years; those at particular risk live in North Carolina, South Carolina, and Georgia. This risk may be shifting westward. High stroke rates are also occurring in the lower Mississippi valley and in Southern California. Socioeconomic differences do not fully explain these higher-risk areas.

Heart disease and stroke are closely tied for many reasons:

Patients with one condition often have risk factors for the other, such as high blood pressure, atherosclerosis (hardening of the arteries), and diabetes.
The risk of stroke increases during surgical procedures involving the coronary arteries, including coronary bypass operations and angioplasty. Coronary bypass poses the greater risk -- about 2 - 5%.
Anti-clotting drugs used for treatment of heart disease and heart attacks slightly increase the risk for hemorrhagic stroke.
A heart attack itself poses a high risk for stroke, which, according to a major 2002 study, is 2.5% in the first 6 months and 5% per year thereafter. In the study, patients with a higher risk (about 4%) for stroke within 6 months of a heart attack tended to be older (over age 75), African-American, or to have a history of a previous stroke, atrial fibrillation, hypertension, diabetes, or peripheral artery disease. Most people at high risk have more than one of these problems.

High Blood Pressure (Hypertension). High blood pressure (known medically as hypertension ) contributes to 70% of all strokes. Researchers have estimated that controlling blood pressure can prevent nearly 40% of strokes.

Two numbers are used to describe blood pressure phases and may affect stroke risk separately:

The systolic pressure (the higher and first number) is measured as the heart contracts to pump out the blood. Evidence suggests that elevated systolic pressure poses a significant danger for heart and stroke emergencies when diastolic is normal, a condition called isolated systolic hypertension. The wider the spread between the systolic and diastolic measurements, the greater the danger.
The diastolic pressure (the lower and second number) is measured as the heart relaxes to allow blood to refill the heart between beats. Abnormally higher diastolic pressure is a strong predictor of heart attack and stroke in most people with hypertension.
Stroke from Low Blood Pressure (Hypotension). Uncommonly, blood pressure that is too low can reduce oxygen supply to the brain and cause a stroke. This can occur from a heart attack, a major bleeding episode, an overwhelming infection, or rarely, from surgical anesthesia or from over-treatment of high blood pressure.

Hypertension is a disorder characterized by chronically high blood pressure. It must be monitored, treated, and controlled by medication, lifestyle changes, or a combination of both.

Click the icon to see an image of the risks of untreated hypertension.

Atrial Fibrillation. About one in six strokes are due to atrial fibrillation. This is a heart rhythm disorder in which the atria (the upper chambers in the heart) beat very quickly and nonrhythmically. The blood pools instead of being pumped out, increasing the risk for formation of blood clots that break loose and travel toward the brain. Atrial fibrillation poses a six-fold increased risk for stroke and may also pose a higher risk for complications after a stroke.

Atrial fibrillation is uncommon in people under 60 years old, but about 6% of adults over age 80 have this heart rhythm disorder. In this patient group, the risk for stroke may be higher or lower with the presence of other risk factors, including having heart failure, high blood pressure, diabetes, and a previous history of stroke, TIA, or rheumatic heart disease. More women than men have AF, but risk for stroke is higher in women with this condition than in men.

Patent Foramen Ovale. Patent foramen ovale (PFO) is a flap-like opening between chambers of the heart. The foramen ovale is always open during fetal development to enhance blood flow to the fetus. It then typically closes after birth when the lungs take over. However, evidence suggests that it remains open in up to 30% of adults. In such cases, blood moves backward (right to left) through this opening when pressure in the right chamber exceeds the left. Large PFOs are a major cause of stroke, particularly in younger adults. Treatments include anti-clotting drugs and procedures for closing the opening.

Atrial Septal Aneurysm. Atrial septal aneurysm is an inborn condition in which part of the atrium (one of the heart chambers) bulges out. Studies indicate that this may pose a slight risk for stroke in young people.

People who smoke a pack a day have almost two and a half times the risk for stroke as nonsmokers. Smoking increases both hemorrhagic and ischemic stroke risk. The risk for stroke may remain elevated for as long as 14 years after quitting, so the earlier one quits the better.

Heart disease and stroke are the leading causes of death in people with diabetes. Diabetes is a strong risk factor for ischemic stroke, perhaps because of accompanying risk factors, such as obesity and high blood pressure. Diabetes does not appear to increase the risk for hemorrhagic stroke. Diabetes is second only to high blood pressure as the main risk factor for stroke. The risk is highest for adults newly diagnosed with type 2 diabetes and patients with diabetes who are younger than age 55. African-Americans with diabetes are at even higher risk for stroke at a younger age.

Studies have also implicated insulin resistance, an important disease mechanism in type 2 diabetes, as an independent factor in the development of atherosclerosis and stroke. With this condition, insulin levels are normal to high, but the body is unable to use the insulin normally to metabolize blood sugar. The body compensates by raising the level of insulin, which in turn increases the risk for blood clots and reduces HDL levels (the beneficial form of cholesterol). Some studies have also reported a worse outcome in patients whose blood sugar levels are high at the time of a stroke.

Obesity may increase the risk for both ischemic and hemorrhagic stroke independently of other risk factors that often co-exist with excess weight, including insulin resistance and diabetes, high blood pressure, and unhealthy cholesterol level. Weight that is centered around the abdomen (the so-called apple shape) has a particularly high association with stroke, as it does for heart disease, in comparison to weight distributed around hips (pear-shape).

Obesity is particularly hazardous when it is one of the components of metabolic syndrome. This syndrome is diagnosed when three of the following conditions are present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high blood pressure, and insulin resistance. Because metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease, people with this syndrome are at increased risk for stroke even before diabetes develops.

Although an unhealthy balance of cholesterol and other lipids (fatty compounds) plays a major role in heart disease, its role in stroke is less clear. Different lipids may have different effects:

Ischemic Stroke. The effects of high total cholesterol and LDL levels on stroke are not clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. HDL (the so-called good cholesterol) may protect against ischemic stroke (although statins have little effect on HDL).

Hemorrhagic Stroke. HDL may reduce the risk for hemorrhagic stroke (bleeding in the brain). People with overall cholesterol levels below 180 mg/dL, however, may be at risk for hemorrhagic stroke, particularly if they also have high blood pressure. This is a far less common stroke, however, than ischemic stroke.

In any case, reducing cholesterol is extremely important in anyone with heart disease and abnormal lipid levels.

Genetics may be responsible for many of the causes of stroke. Studies indicate that a family history of stroke, particularly in one's father, is a strong risk factor for stroke.

Genetics and Subarachnoid Hemorrhage. Genetic factors account for between 7 - 20% of cases of subarachnoid hemorrhage. Ruptured aneurysms that occur in such patients tend to happen at an earlier age, are usually smaller, and are more apt to recur than in those without an inherited condition. A study of people who had suffered subarachnoid hemorrhages found that first-degree relatives of these stroke victims had a high lifetime risk of between 2 - 5%. Some experts recommend screening for aneurysms in people with more than one close relative who suffered a hemorrhagic stroke.

Inherited Disorders that Contribute to Stroke. Some cases of atrial fibrillation may be inherited. Genetic disorders that cause connective tissue disorders are also associated with stroke from hemorrhage; they include polycystic kidney disease, Ehlers-Danlos syndrome type IV, neurofibromatosis type 1, Marfan's syndrome, and moyamoya disease.

Specific Genetic Factors Under Investigation. Specific genetic factors are under investigation. They include:

Inherited deficiencies in protein factors C and S, which inhibit blood clotting, may be responsible for certain cases of stroke in young adults.
A genetic mutation in a factor V Leiden may be related to blood clotting risks.
People who have inherited a gene called apolipoprotein (Apo) E-4 may be at increased risk of stroke. This gene is also associated with Alzheimer's disease.

Stress. One survey revealed that men who had a more intense response to stressful situations, such as waiting in line or problems at work, were more likely to have strokes than those who did not report such distress. In some people, prolonged or frequent mental stress causes an exaggerated increase in blood pressure, which in turn can increase the risk for stroke.

Depression. Depression has also been linked to higher risk for stroke and lower stroke survival rates. In one study, patients with severe depression had a 73% higher risk for stroke, and those with moderate depression had a 25% higher risk than average. The risk for stroke in African-Americans with depression was 160% higher than average.

Studies indicate that migraine or severe headache may be a risk factor for stroke in both men and women, especially before age 50. Overall, between 2 - 3% of ischemic strokes occur in people with a history of migraine. However, in patients under age 45, about 15% of all strokes (and 30 - 60% of strokes in young women) are associated with a history of migraines, particularly migraine with aura. Some evidence suggests that some strokes in these cases may be due to excessive activation of the nervous system and the dehydration from vomiting that occurs during a severe migraine with aura.

The actual risk itself for migraineurs is low, however. In one study, women with migraines had a 2.7% risk of stroke, with the greatest risk between the ages of 45 - 65. Studies suggest specific risk factors for younger women with migraines, particularly those with auras, include taking high-estrogen oral contraceptives (OCs). (Whether progesterone-alone contraceptives carry any risk is unknown.) In migraineurs who take OCs, the risk increases with high blood pressure, smoking, or both.

Inflammation that occurs with various infections has been associated with stroke. One study found that patients hospitalized for stroke were three times more likely than patients without strokes to have recently been exposed to infections, usually mild ones in the respiratory tract.

Varicella Virus. Varicella zoster virus (the virus that causes chicken pox and shingles) has been associated with cerebral vasculitis, a condition in which blood vessels in the brain become inflamed. It is a very rare cause of stroke in children. The virus has also been associated with some cases of stroke in young adults.

Chlamydia Pneumonia. Some investigators suspect that some infections may produce inflammation in the arteries that can lead to stroke over time. (Similar work is underway in heart disease.) Researchers are particularly interested in Chlamydia pneumoniae, a non-bacterial organism that causes mild pneumonia in adults. Chronic infection has been linked with a higher risk for stroke, and evidence of the organism has been observed in thickened inner vessel walls of the carotid arteries in some studies. Chlamydia has also been linked to heart disease.

Periodontal Disease. A number of studies now strongly support an association between periodontal disease and cardiovascular disorders. According to a major analysis, periodontal (gum) disease is associated with a 20% higher risk for ischemic stroke and heart disease. The added risk may be even greater in adults under 65. Recent evidence points to the inflammatory response as the common element.

In 2007, the American Heart Association (AHA) issued a scientific statement encouraging doctors to change the way they prescribe pain relief medication for patients at risk for heart disease or stroke. The AHA recommends that at-risk patients first try non-drug methods of pain relief (physical therapy, exercise, weight loss to reduce stress on joints, and heat or cold therapy). If these methods don’t work, patients should take the lowest possible dose of acetaminophen (Tylenol) or aspirin. COX-2 inhibitors, such as celecoxib (Celebrex), should be the last resort.

In 2005, the FDA warned that all NSAIDs -- with the exception of aspirin -- carry heart risks. In particular, the NSAIDs ibuprofen (Advil, Motrin) and diclofenac (Cataflam, Voltaren) appear to carry increased risks for heart attack and stroke.

A number of medical or physical conditions may contribute to the risk for stroke:

Sleep apnea. This common disorder, in which the throat becomes obstructed during sleep, may contribute to the narrowing of the carotid artery, appearing to increase the risk for stroke three- to six-fold.
Pregnancy. Pregnancy carries a very small risk for stroke, mostly in women with pregnancy related high blood pressure and in those with cesarean delivery. The risk appears to be higher in the postpartum (post-delivery) period, perhaps because of the sudden change in circulation and hormone levels.
Anti-phospholipid antibodies. Nearly 40% of young people with strokes and 10% of all stroke patients have components of the immune system known as anti-phospholipid antibodies that increase the chance for blood clots.
Sickle-cell anemia. People with sickle-cell anemia are at risk for stroke at a young age.
Drug abuse, particularly with cocaine and, increasingly, methamphetamine, is a major factor in the incidence of stroke in young adults. Anabolic steroids, used for body-building and sports enhancement, also increase risk.

Timing. Like heart attack and sudden cardiac death, stroke appears to be more common in the morning hours, perhaps due to a temporary rise in blood pressure at that time. Various studies point to a higher risk for stroke on weekends, Mondays, and holidays. The risk for hemorrhagic stroke may also be higher in the winter, particularly in older people with high blood pressure.

Homocysteine and Vitamin B Deficiencies. Abnormally high blood levels of the amino acid homocysteine, which occur with deficiencies of vitamin B6, B12, and folic acid, may be linked to an increased risk of coronary artery disease and stroke.

Neck Manipulation. Some studies have reported a higher risk for stroke from injury to the carotid artery after neck manipulation by a chiropractor.

Prognosis

A stroke, the third leading cause of death in the U.S., is always serious. In 2004, over 150,000 Americans died of stroke with women accounting for 61% of these stroke deaths. The mortality rates are declining, however. Over 75% of patients survive a first stroke during the first year, and over half survive beyond 5 years.

People who suffer ischemic strokes have a much better chance for survival than those who experience hemorrhagic strokes. Among the ischemic stroke categories, the greatest dangers are posed by embolic strokes, followed by thrombotic and lacunar strokes. Hemorrhagic stroke not only destroys brain cells but also poses other complications, including increased pressure on the brain or spasms in the blood vessels, both of which can be very dangerous. Studies suggest, however, that survivors of hemorrhagic stroke have a greater chance for recovering function than those who suffer ischemic stroke.

Between 50 - 70% of people recover functional independence after a stroke. However, between 15 - 30% of those who survive either an ischemic or hemorrhage stroke suffer some permanent disability. On the encouraging side, one study reported that people who survived for many years after a stroke had a chance for independent living that was about the same as for their peers who had not suffered strokes. The stroke patients even appeared to be less depressed than the comparison group.

The National Institutes of Health (NIH) have devised a scoring system that helps predict the severity and outcome of the stroke by scoring 11 factors (levels of consciousness, gaze, visual fields, facial movement, motor functions in the arm and leg, coordination, sensory loss, problems with language, inability to articulate, and attention). Up to 70% of patients with ischemic strokes who score less than 10 have a favorable outlook after a year, while only 4 - 16% of patients do well if their score is more than 20.

The risk for recurring stroke is highest within the first few weeks and months. The risk is about 14% in the first year and about 5% thereafter, so preventive measures should be instituted as soon as possible. Some specific risk factors for early recurrence include:

Older age
Evidence of blocked arteries (a history of coronary artery disease, peripheral artery disease, ischemic stroke, or TIA)
Hemorrhagic or embolic stroke
Diabetes
Alcoholism
Valvular heart disease
Atrial fibrillation

Prevention

Forty percent of patients who have had a stroke or TIA will suffer a subsequent stroke within 5 years. In 2006, the American Heart Association/American Stroke Association released guidelines for preventing a second stroke. These guidelines recommend:

Quit Smoking. Also avoid exposure to second-hand smoke.

Maintain Weight. People should aim for a BMI index of 18.5 - 24.9. In people who are obese, reducing weight to this level can reduce the risk for stroke by 15% in men and 22% in women. Waist measurements should be no more than 35 inches for women and 40 inches for men.

Exercise. Everyone in normal health should engage in at least moderate physical activity for a minimum of 30 minutes on most -- if not all -- days of the week.

Limit alcohol. No more than 2 drinks a day for men and 1 drink a day for nonpregnant women.

Healthy Diet. Everyone should aim for a diet that contains a healthy balance of fruits, vegetables, grains, fish, nuts, legumes, poultry, lean meat, and low-fat dairy items. Avoid saturated fats and trans fatty acids.

Improve Cholesterol. People with at least two risk factors and a 10-year risk for heart disease or stroke of more than 20% should aim for LDL levels of less than 100 mg/dl. Raising HDL levels is important for people at risk for stroke. Statins are now used in most cases.

Keep Blood Pressure Low. People in normal health should aim for 139/89 mm Hg or less. Patients with certain health problems, such as diabetes, should aim lower.

Control Diabetes. People with diabetes should aim for fasting blood glucose levels of less than 110 mg/dl and hemoglobin A1C of less than 7%. Blood pressure goals should be 130/80 mm Hg or less.

Take Aspirin or Other Antiplatelet Therapy. People at high risk for heart disease should take a low-dose aspirin every day, unless they have medical reasons to avoid aspirin. (As an alternative to aspirin alone, your doctor may prescribe clopidogrel alone or aspirin plus extended release dipyridamole.) Aspirin may help to prevent strokes caused by blockage in the artery (ischemic stroke), but it may slightly increase the risk of strokes caused by bleeding in the brain (hemorrhagic stroke). The American Heart Association recommends aspirin therapy for women over age 65 who are at risk for stroke.

Control Atrial Fibrillation. People with atrial fibrillation should use anticoagulants to reduce their risk of blood clots. Carotid Endarterectomy Surgery or Stenting: Recommended for most symptomatic patients with neck artery stenosis (narrowing or blockage) of more than 70% and some patients with stenosis of 50 - 69%.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for both ischemic and hemorrhagic stroke. For diet plans, the Mediterranean diet may be a particularly good choice for reducing the risk of stroke. [See In-Depth Report #43: Heart-healthy diet.]

Fruits and Vegetables. Studies suggest that people can protect their heart and circulation by eating plenty of fruits and vegetables. Eating at least five servings a day reduces blood pressure and protects against both heart attack and stroke. Important foods include most fruits (especially potassium-rich fruits including bananas, oranges, prunes, and cantaloupes) and vegetables (especially carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, broccoli). Vegetables, such as broccoli and kale, may be specifically protective against a first ischemic and possibly hemorrhagic stroke. Foods such as apples and tea, which are high in food chemicals called flavonoids, may also be very beneficial.

Whole Grains and Nuts. A 2000 study reported a lower incidence in stroke in women who had a high intake of whole-grain foods. Nuts may also be protective.

Calcium, Potassium, and Magnesium. Calcium, magnesium, and potassium serve as electrolytes in the body. They are important in controlling blood pressure and may also have protective effects against stroke:

Some evidence suggests that diets rich in potassium may protect against stroke by 22 - 40%, mostly by reducing blood pressure but also possibly because of other mechanisms. Low potassium levels may increase the risk for stroke in certain people.

A major study reported that calcium intake is associated with a lower risk for stroke in women, which supports an earlier study reporting a lower risk for stroke in men who drank more milk.

Magnesium deficiencies may increase the risk for atrial fibrillation. No evidence yet exists, however, that taking magnesium supplements is protective.

Salt Restriction. Although the effects of salt restriction are not entirely clear, a 2002 study indicated that even a modest reduction in salt intake for more than a month might reduce the risk of death from stroke by 14% in people with high blood pressure and 6% in people with normal blood pressure.

Fats and Oils. The effects of fats and oils on stroke are complex. One study indicated that middle-aged men without heart disease who had the highest intake of monounsaturated or saturated fat (but not polyunsaturated oils) also had the lowest risk for stroke. Monounsaturated oils, obtained in olive and canola oils, may have protective benefits against both heart disease and stroke. Saturated fats, found in animal products, are known risk factors for heart disease. Some studies suggest, however, that low intake of animal protein and saturated fat increases the risk of hemorrhagic stroke.

Other fat compounds that may be stroke protective are omega-3 fatty acids:

Alpha-linolenic acid is found in canola oil, soybeans, and walnuts. One particular benefit against stroke is its ability to help prevent the formation of blood clots.
Omega-3 fatty acids are categorized as docosahexaenoic (DHA) or eicosapentaneoic acids (EPA). They are found in oily fish and nutritional supplements. These compounds have anti-inflammatory and anti-blood clotting effects and may be significantly beneficial to the heart and reduce the risk for stroke. However, people who have implantable defibrillators should not take fish oil supplements because they may worsen heart rhythm problems.

In any case, consuming fish two or three times a week helps the heart.

Folic Acid and B Vitamins. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid and B6 and B12 vitamins and those who received placebo. And, the vitamins seemed to increase risks for patients who had undergone stenting. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Antioxidant Vitamins. The effects of antioxidant vitamins and carotenoids on stroke have been studied extensively. Most studies have found that these vitamins do not help protect against stroke. An important 2001 study reported no protection from stroke with vitamins A or E or beta carotene. A 2005 study in the Journal of the American Medical Association found that vitamin E definitely does not protect women from stroke or heart attack.

Smoking. Everyone should quit smoking.

Alcohol. Mild-to-moderate alcohol use (one to seven drinks a week) is associated with a significantly lower risk for ischemic stroke, although not hemorrhagic stroke. Heavy alcohol use, particularly a recent history of drinking, is associated with a higher risk of both ischemic and hemorrhagic stroke.

Coffee. In healthy people with normal blood pressure, drinking a couple of cups of coffee a day is unlikely to do any harm. Caffeine may actually have nerve-protecting properties that may help stroke survivors. Caffeine drinkers, however, might do better to choose tea, which may have beneficial nutrients, and people with existing hypertension should avoid caffeine altogether (since caffeine may increase the risk for stroke in this group).

Exercise helps reduce the risk of atherosclerosis, which can help reduce the risk of stroke. Experts recommend at least 30 minutes of exercise on most, if not all, days of the week.

Hypertension is a disorder characterized by chronically high blood pressure. It must be monitored, treated, and controlled by medication, lifestyle changes, or a combination of both.

Reducing blood pressure is essential in stroke prevention. Lifestyle measures such as exercise, weight loss, and healthy diets are important for everyone. Drug therapy is recommended for people with hypertension who cannot control their blood pressure through lifestyle changes. Many different types of drugs are used to control blood pressure. They include ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers, and diuretics. Some drugs, such as Hyzaar, combine an angiotensin receptor blocker with a diuretic to both treat high blood pressure and prevent stroke. [See In-Depth Report #14: High blood pressure.]

Statins have become the most important LDL-lowering drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Research increasingly suggests that lowering LDL levels as much as possible is critical for preventing stroke and other heart disease problems. A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. Another study of over 20,000 people with cerebrovascular disease found that patients who took statin therapy for 2 years reduced their risk of ischemic stroke by 25%.

Statins are proven to reduce the risk of stroke in people at increased risk for heart disease. Research suggests that they may also prevent stroke in patients without heart disease. However, current guidelines recommend that statins should be prescribed to patients without heart disease and with normal LDL levels only if diabetes and several heart disease risk factors are also present.

Researchers are also investigating whether statins might be beneficial in preventing a second stroke in patients who have suffered a stroke or transient ischemic attack (TIA). A study published in 2006 in the New England Journal of Medicine indicated that high-dose atorvastatin (Lipitor) therapy may help reduce the risk of stroke recurrence and other heart events for patients who have had a prior stroke or TIA. In 2006, the FDA expanded atorvastatin’s indications to include reducing the risk of fatal and non-fatal strokes in patients with heart disease

[See In-Depth Report #23: Cholesterol.]

Influenza vaccinations may protect patients with a history of heart attack or heart events. A 2002 study further suggested that flu shots might protect against stroke, although possibly not in patients older than age 75.

Treatment for atrial fibrillation always includes drugs (aspirin or warfarin) to prevent clots from forming. In addition to anticoagulants (blood thinners), other approaches may include:

Restoring or maintaining normal heart rhythm. This is accomplished with anti-arrhythmic drug, cardioversion procedures, or surgery to remove the defective area.
Controlling heart rate. Specific drugs are used for this approach.

Important studies report that controlling heart rate may be the preferable approach. In several studies, rhythm control offered no survival advantages and did not protect against ischemic stroke. Therapies aimed at controlling heart rate, furthermore, had fewer complications.

Drugs to Prevent Blood Clots

After a diagnosis of atrial fibrillation, warfarin (an anticoagulant) or aspirin (an antiplatelet) are essential to prevent blood clots. These drugs can reduce the risk for stroke by over 60% in patients with atrial fibrillation.

Warfarin (Coumadin) is the main anticoagulant (“blood thinner”) drug used to prevent strokes in high-risk patients with atrial fibrillation. Warfarin carries a risk for bleeding, but for most patients, warfarin’s benefits far outweigh its risks. The risk for bleeding is highest when warfarin therapy is first started, with higher doses, and with long periods of treatment. Patients at risk for bleeding are usually older and have a history of stomach bleeding and high blood pressure. It is important that patients who take warfarin have their blood checked regularly to make sure that it does not become “too thin.” Blood that is too thin increases the risk for bleeding, while blood that is “too thick” increases the risk for blood clots and stroke. Prothrombin time (PT) and international normalized ratio (INR) tests are used to monitor blood coagulation.
Aspirin is less effective than warfarin, but has a lower risk for bleeding. It is the preferred treatment for younger people with atrial fibrillation and for people who do not have other risk factors for stroke, such as high blood pressure or diabetes. Aspirin is also prescribed for higher risk patients who cannot tolerate anticoagulation therapy.
Researchers are investigating other drugs for preventing stroke and heart problems in patients with atrial fibrillation. These drugs include the antiplatelet medication clopidogrel (Plavix) and the angiotensin receptor blocker irbesartan (Avapro). Recent research indicates that anticoagulants such as warfarin (Coumadin) work better for atrial fibrillation patients than the combination of clopidogrel plus aspirin. Clinical trials are continuing to investigate whether clopidogrel alone is better than aspirin alone.

Restoring and Controlling Heart Rhythm

To initially restore heart rhythm, anti-arrhythmic drugs are usually tried first. If they fail to restore normal rhythm, cardioversion is often effective. (Some experts suggest trying cardioversion first to avoid side effects of the drugs.) Long-term maintenance therapy using anti-arrhythmic drugs may be required.

Electrical Cardioversion. Electrical cardioversion is mild shock therapy and is the current standard treatment used to restore normal heart rhythm. It is conducted as follows:

Anticoagulants (drugs used to prevent blood clotting) should be administered, if possible, at least 3 weeks before the procedure.
During the procedure, the patient must be conscious and, although sedated, can experience some pain from the procedure.

Although the stabilizing effect is usually only temporary, some evidence suggests that a series of cardioversion may succeed in maintaining normal rhythm in young healthy patients without the need for antiarrhythmic medications.

Low-energy implanted cardioverters (Atrioverter, Jewel AF) are being investigated for maintenance. Studies are promising.

Drugs Used for Maintaining Normal Heart Rhythm. For maintaining a stable rhythm, the following drugs may be used. The specific choices typically depend on whether or not the patient has existing heart disease:

For patients with no heart disease, the first choices include sotalol, flecainide, or propafenone, which are often used sequentially. If these fail, then amiodarone or a newer drug dofetilide (Tikosyn) may be tried. Others include ibutilide (Covert) and azimilide. If these drugs are not effective, other drugs tried include quinidine, procainamide, and disopyramide.
In patients with heart disease, amiodarone, dofetilide, or sotalol are commonly used depending on the cause of heart disease.

Amiodarone is more effective than most others and has been thought to be safer than many other similar drugs. Even in low doses, however, there is a high incidence of side effects, including thyroid disorders, neurologic, skin, and eye problems, and abnormally slow heart beats. Many of these drugs carry a small but significant increased risk, however, for a life-threatening arrhythmia called torsades de pointes. People with certain heart conditions should avoid these drugs.

Surgical Procedures for Complex AF. In some difficult cases, surgery may be recommended. The options and candidates depend on other complicating factors. The following are some examples:

AV node ablation involves severing the communication between the atria (the two upper chambers of the heart) and the ventricles (the two lower chambers). A pacemaker is then implanted just under the skin with electrodes leading to the ventricles. This approach is very effective, but it is irreversible and lifelong. Radiofrequency ablation may be an option in some patients.
A more aggressive procedure uses open chest surgery, in which a maze of cuts is made in the atria. As they heal, the scar tissue prevents the heart circuitry from misfiring. This technique controls atrial fibrillation in more than 90% of appropriate candidates. A new procedure is similar but less invasive.

Controlling Heart Rate

Drugs Used to Control Heart Rate. Beta-blockers or calcium channel blockers are used to control heart rate at the onset of atrial fibrillation. Digitalis, an older drug, is not used as often but can be effective in combination with the other drugs.

Diagnosis

Preventing a major stroke in people who experience transient ischemic attacks or small strokes requires determining the source of such attacks. A complete blood count, chest x-ray, and electrocardiogram are usually performed. Discouragingly, a 2001 study reported that over 30% of patients with TIA who called their primary care doctor were neither evaluated nor sent to the hospital within the month after a first event.

Examining the Carotid Artery. The doctor examines the carotid artery to determine if it is severely narrowed. If so, the patient is in danger of a major stroke. (The thickness of the carotid artery is also an important indicator for long-term risks for stroke, as well as heart disease and mortality rates in general.)

The doctor may use a number of approaches to determine the thickness of the artery:

An important clue to a blocked carotid artery is a bruit. This is a whooshing sound caused by blood flow turbulence in the narrowed artery. A doctor may be able to hear a bruit using a stethoscope. Occasionally, even a patient can hear the sound. The presence of a bruit, however, is not necessarily a sign of an impending stroke, nor does the absence of a bruit indicate an unblocked artery.
Carotid ultrasound is a very valuable tool for measuring the width of the artery. At this time, ultrasound is most useful in people between the ages of 40 and 60 years. Severely blocked carotid arteries may distort some measurements, so other tests may be required to confirm the results.
Measuring blood pressure to the eye may also be important in identifying problems in the carotid artery. If blood flow to the eye is reduced, it is likely that the carotid artery is severely narrowed.

Carotid duplex is an ultrasound procedure performed to assess blood flow through the carotid artery to the brain. High-frequency sound waves are directed from a hand-held transducer probe to the area. These waves "echo" off the arterial structures and produce a two-dimensional image on a monitor, which will make obstructions or narrowing of the arteries visible.

Imaging Techniques for TIAs. Several imaging techniques may identify small clots or other indicators of risk in the brain.

Identifying a Stroke Quickly. To save a patient's life, a fast diagnosis of both the presence and type of stroke is critical. Health professionals have devised different tests to help emergency workers quickly identify a person with stroke even before they reach the hospital. For example, an assessment tool called Face, Arms, Speech, Time (FAST) is highly accurate. It involves watching for the following signs:

(F)ACE. Ask the person to smile. Check to see if one side of the face droops.
(A)RMS. Ask the person to raise both arms. See if one arm drifts downward.
(S)PEECH. Ask the person to repeat a simple sentence. Check to see if words are slurred and if the sentence is repeated correctly.
(T)IME. If a person shows any of these symptoms, time is essential. It is important to get to the hospital as quickly as possible. Call 9-1-1. Act FAST.

Determining Ischemia Versus Hemorrhagic Stroke. Once a stroke has been identified, the next important step is to determine as quickly as possible whether it is hemorrhagic or ischemic. Clot-busting drug therapies can be life-saving for ischemic stroke patients, but they are effective only in the first 3 hours. In addition, they cause bleeding and can be lethal if the stroke is caused by a hemorrhage.

A computed tomography (CT) scan is essential for identifying or ruling out hemorrhagic strokes. The goal is to complete the CT examination and obtain and interpret the results within 45 minutes of arrival at the hospital. (An ultrasound technique called transcranial duplex sonography may be sensitive enough to differentiate between hemorrhagic and ischemic strokes if CT scans are not available.)

Certain factors suggest a hemorrhagic rather than ischemic stroke. They include specific symptoms (coma, vomiting, and severe headache), taking anticoagulants, very high systolic blood pressure, or high blood sugar levels in nondiabetics. However, such findings are not conclusive, and a CT scan or MRI is always needed.

Ruling Out Other Disorders. In most cases of stroke, the diagnosis is evident although a number of conditions may cause similar symptoms. These include seizures, infections that cause mental confusion, syncope (fainting), hypoglycemia, and brain tumors.

Magnetic Resonance Imaging (MRI). MRI uses a magnetic field to provide 3-dimensional images of the brain. In 2007, an important Lancet study of emergency room patients clearly indicated that MRI is superior to computed tomography (CT) in assessing whether a stroke has occurred. The MRI appears to work especially well for detecting ischemic stroke (stroke caused by blood clot). In the study, MRI accurately detected presence or absence of acute stroke in 80% of patients compared to 58% for CT. (Acute stroke included both ischemic and hemorrhagic types.) MRI detected acute ischemic stroke in 40% of patients compared to 10% for CT. In addition, MRI detected ischemic stroke within 3 hours of symptom onset (an important timeframe for delivering clotbuster drugs) in 46% of patients compared to only 7% for CT. Both MRI and CT performed similarly for detecting hemorrhagic stroke.

Computed Tomography. A computed tomography (CT) test uses x-ray images to take pictures of the skull and brain. Sometimes a dye is injected into a patient’s veins to enhance image contrast. Although research indicates that MRI is better in determining ischemic stroke, CT still may be useful in diagnosing hemorrhagic strokes.

Ultrasound. Ultrasound may be used in different circumstances. This imaging technique is painless and noninvasive.

Carotid ultrasound (also called Doppler or duplex sonography) can determine blockage in the carotid arteries that could lead to or be causing a stroke.
Transcranial duplex sonography can identify blockage in large arteries in stroke patients and to monitor the effects of thrombolytic therapy.

Cerebral Angiography. Cerebral angiography is an invasive procedure that may be used for patients with TIAs who require surgery. It can also detect aneurysms and monitor thrombolytic therapy. It requires the insertion of a catheter into the groin, which is then threaded up through the arteries to the base of the carotid artery. At this point a dye is injected, and x-rays, CTs, or MRI scans determine the location and extent of the narrowing, or stenosis, of the artery. In people with TIAs the risk of stroke itself increases using this technique, particularly in elderly people with diabetes.

Other Techniques. Other imaging tests, including positron-emission tomography (PET) and single photon-emission computed tomography (SPECT), may also help the doctor identify injuries caused by the stroke.

Electrocardiogram (ECG). A heart evaluation using an electrocardiogram (ECG) is important in any patient with a stroke or suspected stroke. An ECG records the electrical current in the heart muscle.

Echocardiogram. An echocardiogram uses ultrasound to view the chambers and valves of the heart. It is generally useful for stroke patients to identify blood clots or risk factors for blood clots that can travel to the brain and cause stroke. There two are types:

Transthoracic echocardiograms (TTE) view the heart through the chest. It is noninvasive and is the standard approach.
Transesophageal echocardiogram (TEE) examines the heart using an ultrasound tube that the patient literally swallows and passes down the throat. It is uncomfortable and requires sedation. It is typically used to obtain more accurate images of the heart if a TTE has suggested abnormalities, such as atrial fibrillation or patent foramen ovale (PFO).

Patients who have a TIA are at increased risk for a major stroke in the days and weeks that follow. The ABCD² score is a tool that helps doctors predict short-term stroke risk following a TIA. The ABCD² score assigns points for various factors:

Age (over 60 years)
Blood pressure (greater or equal to 140/90 mm Hg)
Clinical features (weakness on one side of the body; speech impairment without weakness
Duration of TIA symptoms (at least 60 minutes)
Diabetes

Based on the number of points, a doctor can identify whether a patient is at low, moderate, or high risk of having a subsequent stroke within 2 days after a TIA. Several 2006 and 2007 studies indicated that the ABCD² score works well in predicting stroke, and can help doctors better decide which patients require hospitalization and emergency care.

Blood Tests. Several blood tests may help predict the risk for a stroke and determine the severity and complications of an existing stroke.

Specific blood tests are important to determine clotting times, to check electrolytes (potassium, calcium, sodium), and to measure factors indicating liver or kidney problems. Kidney tests measure blood proteins that are filtered through the kidneys. These proteins include creatinine and blood urea nitrogen (BUN). A more recent type of kidney test measures the protein cystatin C. Recent research suggests that the cystatin C kidney test may be better at predicting cardiovascular risks in elderly patients.
Blood sugar (glucose) levels are measured. Hyperglycemia (high levels) may indicate a worse outcome for some strokes (although not hemorrhagic or lacunar strokes). Hypoglycemia (low levels) is a common complication of diabetes treatments, and its symptoms may mimic those of a stroke.
A new blood test, the PLAC test, was approved in 2005 to help diagnose people at increased risk for ischemic stroke. The PLAC test measures an enzyme called lipoprotein-associated phospholipase A2 (Lp-PLA2). Patients with high levels of this protein have twice the risk for ischemic stroke as patients with normal levels.

Examination of Spinal Fluid. If the CT scan is negative but the doctor still suspects a subarachnoid hemorrhagic stroke, a spinal tap may be performed. Spinal fluid containing significant amounts of blood will usually confirm a hemorrhagic stroke.

Managing a Stroke

Until recently, the treatment of stroke was restricted to basic life support at the time of the stroke and rehabilitation later. Now, however, treatments can be dramatically beneficial when administered as soon as possible after the onset of the stroke. It is critical to get to the hospital and be diagnosed as soon as possible. There are several steps in the initial assessment and management of a person with a stroke.

If significant symptoms appear in people at risk for stroke, calling 911 is critical (as opposed to calling the family doctor or trying to get the patient to the hospital by car). One study reported that patients who went to the emergency room in an ambulance had a much shorter delay in getting treatment than those who went on their own. Receiving treatment early is critical in reducing the damage from a stroke.

Important diagnostic and evaluation steps are needed for the optimal treatment of a stroke patient:

Determine Whether the Stroke Is Ischemic or Hemorrhagic. As soon as the patient enters the hospital, diagnostic tests, particularly a CT scan, should occur to determine whether the stroke is ischemic or hemorrhagic.

Determine The Need for Thrombolytic Drugs. If the stroke is ischemic, the next step is to determine if the patient would benefit from blood clot-busting drugs (called thrombolytics). The following factors can assist in making this decision:

Estimate the time of onset of the stroke. Time is critical in the decision-making process. Clot-buster drugs do not generally help if given more than 3 hours after stroke onset. Onset is when the patient first experiences any symptoms, even minor impairment. If the patient had a previous TIA that completely resolved before the stroke, however, onset is dated from when the more recent symptoms developed.
Tell the doctor if the patient has been taking any blood-thinning drugs.
Give the doctor a thorough history of any accompanying medical or physical condition and any recent event, such as surgery or injury, which might contribute to the condition.
CT scans will indicate if there are extensive early injuries, which might affect the decision to use these drugs.

The patient should receive treatment to support basic life functions and to reduce stress, pain, and agitation. The following steps are also very important:

Maintain Adequate Delivery of Oxygen. It is very important to maintain oxygen levels. In some cases, airway ventilation may be required. Supplemental oxygen may also be necessary for patients when tests suggest low blood levels of oxygen. Hyperbaric oxygen (which is oxygen administered under pressure) may help specific stroke patients, although it is not recommended for most patients, since there is some risk of significant adverse effects using this approach.

Managing Fever and Lowering Body Temperature (Hypothermia). Fever should be aggressively treated, since strong evidence suggests that its presence predicts a poorer outlook. Some evidence suggests that hypothermia -- reducing body temperature -- might protect nerve cells in stroke patients. Cooling is done through special cooling blankets, ventilators, or infusion of cool fluids. Unfortunately, severe side effects occur with even moderate hypothermia (86°F, 30°C), which can include pneumonia, blood clotting disorders, heart rhythm disturbances, and others.

Maintain Electrolytes. Maintaining a healthy electrolyte balance (the ratio of sodium, calcium, and potassium in the body's fluids) is critical.

Managing Blood Pressure. Managing blood pressure is essential and complicated. Patients with stroke and pressures above 220 (systolic) or 120 (diastolic) should be treated. Lowering blood pressure too quickly can be dangerous, however, in patients with both ischemic and hemorrhagic strokes. In general, experts do not advise aggressively lowering elevated pressures below 220/120 mm Hg in patients unless they have other conditions, such as a heart attack, that require pressure-lowering treatments. In patients who require thrombolytic drugs, blood pressure should cautiously be lowered to 185/110 mm Hg. In most cases, blood pressure declines when these patients become stabilized.

Managing Increased Brain Pressure. Hospital staff should watch carefully for increased pressure on the brain, which is a frequent complication of hemorrhagic strokes. It can also occur a few days after ischemic strokes. Early symptoms of increased brain pressure are drowsiness, confusion, lethargy, weakness, and headache. Medications such as mannitol may be given during a stroke to reduce pressure or the risk for it.

Keeping the top of the body higher than the lower part, such as by elevating the head of the bed, can reduce pressure in the brain and is standard practice for patients with ischemic stroke. However, this practice also lowers blood pressure in general, which may be dangerous for patients with massive stroke.

Monitoring the Heart. Heart attack and arrhythmias are potential complications of ischemic stroke. Patients must be monitored using electrocardiographic tracings.

Controlling Glucose Levels. Elevated blood sugar (glucose) levels can occur with severe stroke and may be a marker of serious trouble. In general, it is advisable to lower glucose levels that are about 300 mg/dL, usually with insulin. It is not clear, however, if glucose-lowering treatments offer any advantage. Excessive lowering of glucose levels can have damaging effects on the brain. Studies are underway to determine the best approach.

Medications

Intravenous Thrombolytics. Clot-busting (thrombolytic) drugs break up existing blood clots. They are among the important treatments for heart attacks, and are now also used for ischemic (not hemorrhagic) stroke. While research has confirmed that early treatment with thrombolytics can greatly increase a stroke patient's chances for recovery, their use has been limited due to the short treatment window (within 3 hours of onset of stroke symptoms). The standard thrombolytic drugs are tissue plasminogen activators (t-PAs). They include alteplase (Activase) and reteplase (Retavase).

The following steps are critical before administering these clot-buster drugs:

Before the thrombolytic is given, a CT scan must first confirm that the stroke is not hemorrhagic. If the stroke is ischemic, a CT scan can also suggest if injuries are very extensive, which might affect the use of thrombolytics.
Thrombolytics must be administered within 3 hours of a stroke to have any effect. According to a 2004 review of clinical trials, best results are achieved if patients are treated with 90 minutes of a stroke. Unfortunately, most stroke patients arrive at the hospital more than 3 hours after an attack and therefore are not eligible for treatment. There is some evidence that t-PA administered with 4 hours may also be effective, but more research needs to be conducted. These findings underscore the critical need for people to go to a hospital immediately if a stroke is suspected.

Thrombolytics carry a risk for hemorrhage, so they may not be appropriate for patients with existing risk factors for bleeding. They should not be used in patients who are experiencing seizures. The drug may be appropriate in more patients than previously thought, however, including older people, those with a history of stroke, and those with high blood pressure. Although older studies cited concern over the safety and effectiveness of t-PA, a 2004 review of clinical trial data found that patients who received t-PA were two times more likely to experience a favorable outcome than those who did not receive this treatment.

Intra-Arterial Thrombolytics. Researchers are investigating thrombolytics injected directly into an artery in the brain. Early studies suggest this approach may allow effective treatment up to 6 hours after a stroke and improve recovery in more patients. The risk for bleeding and hemorrhagic stroke is significantly increased, however.

Fibrin-Depleting Drugs. These drugs deplete the amount of fibrinogen in blood, which in turn reduces the "stickiness" in blood. Such drugs include ancrod and batroxobin (Defibrase), both derived from the venom of poisonous snakes. Some experts believe these drugs might be a possible alternative to thrombolytics. Studies suggest they may modestly reduce the risks for death and disability if given early on. As with all anti-clotting drugs, there is a higher risk for hemorrhage, but it appears to be slight.

Medications that prevent blood from clotting are used to prevent a recurring or second stroke. Anticlotting drugs include antiplatelets and anticoagulants.

Antiplatelet Drugs.Blood platelets are involved in blood clotting. Antiplatelets prevent clotting by blocking the accumulation of platelets. An antiplatelet drug -- most often aspirin -- is given within 48 hours of an ischemic stroke and continued in low doses as maintenance therapy. Studies suggest that antiplatelet therapy can reduce the risk for a second stroke by 25%.

Aspirin. Aspirin is recommended within 48 hours of a first ischemic stroke in doses of 50 - 325 mg. Daily low-dose aspirin may also help prevent a second ischemic stroke. Experts also recommend aspirin combined with the antiplatelet drug dipyridamole (Aggrenox). A 2006 study indicated that aspirin plus dipyridamole may be better than aspirin alone in preventing a heart attack or major stroke in patients who have had a minor ischemic stroke. Patients should not be given an aspirin until a diagnosis of ischemic or hemorrhagic stroke has been determined. Aspirin increases the risk for bleeding in patients with hemorrhagic stroke and can be dangerous.
Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are antiplatelet drugs known as thienopyridines. (Clopidogrel is preferred over ticlopidine because of its better safety record.) Evidence suggests that clopidogrel plus aspirin is better than aspirin alone in reducing blood clots in patients who have carotid artery blockage (carotid stenosis). Other studies indicate that clopidogrel alone may be sufficient for patients who have had a recent ischemic stroke or TIA. A study of over 7,000 of these patients found that adding aspirin to clopidogrel therapy provided no additional benefit and increased the risk of bleeding; therefore, aspirin plus clopidogrel is not usually recommended for most patients who have had an ischemic stroke or TIA. Clopidogrel alone may also be better than aspirin alone in preventing a third stroke or heart attack in high-risk patients.
Glycoprotein IIB/IIIa Inhibitors. Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors are sometimes administered intravenously in the hospital and include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), lotrafiban, and lamifiban. They are being investigated alone or as additions to thrombolytic (clot-busting) drugs.

Anticoagulants.Anticoagulants thin blood and may be useful under certain circumstances.

Warfarin. The anticoagulant warfarin (Coumadin) may not work as well as aspirin in preventing a second stroke in people who have partial artery blockage in the brain (intracranial stenosis). Warfarin is, however, very important in high-risk patients with atrial fibrillation. It may be useful in other situations, such as patients with patent foramen ovale (PFO), those whose stroke followed a heart attack, or in high-risk patients who cannot take antiplatelet drugs.
Heparin. Intravenous heparin, a potent anti-platelet drug, has been used for ischemic stroke since 1941. Although many doctors continue to use it, five out of six major studies have reported no clear protective benefits compared to aspirin with the use of standard heparin or any heparin-like drugs. They also pose a much higher risk for hemorrhagic stroke. Experts now recommend heparins only for preventing thromboembolism in stroke patients at risk for this condition.
Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI is hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaparoid (Orgaran), lepirudin (Refludan), desirudin (Revasc), inogatran, and efegatran. Ximelagatran (Exanta) is new oral drug that is showing great promise for protection against stroke in patients with atrial fibrillation while posing a low risk for bleeding.

All anti-clotting drugs carry a risk for bleeding and a slightly increased risk for hemorrhagic stroke.

It is important that patients control their high blood pressure and LDL (“bad”) cholesterol levels. Various drugs, such as statins, diuretics, and ACE inhibitors, can manage these conditions. People with diabetes should also maintain tight control of their blood sugar levels.

Calcium Channel Blockers. Early administration of calcium channel blockers, such as nimodipine (Nimotop), can improve functional outcome. One of the most common and serious dangers after a subarachnoid hemorrhagic stroke is spasm of the blood vessels near the ruptured site, which closes off oxygen to the brain. Calcium causes contraction of the smooth muscles of the blood vessels; calcium channel blockers are drugs that relax the blood vessels. The drugs work best if they are administered within 6 hours of the stroke. Calcium channel blockers are not useful for ischemic strokes, although they can be used in combinations with blood pressure lowering drugs to prevent them.

Nerve-Protecting Drugs. More than 50 medications have been studied in clinical trials aimed at slowing or preventing the cascading process that destroys nerve cells after a stroke. Many investigative drugs are targeting the excitatory amino acids, such as glycine and glutamate, which are known to destroy nerve cells after a stroke. Although none to date have proven to have any significant benefits, some are showing promise. They include magnesium sulfate, citicoline, ebselen, piracetam, edaravone, albumin, erythropoietin, and NXY-059.

Investigative Drugs for Nerve Regeneration. Scientists used to think that when cells in the brain were destroyed, new ones could not grow to replace them. Researchers have now observed, however, that nerve regrowth (neurogenesis) can occur in the adult human brain. This exciting discovery opens the way for new drugs that might in the future stimulate nerve growth and repair damage done by many neurologic diseases, including stroke. For example, a 2002 study reported nerve regeneration in animals whose brains were treated with the drug inosine. More research is underway.

Surgery

Carotid endarterectomy is a surgical procedure that cleans out and opens up the narrowed carotid artery. It is used in patients at high risk for thrombotic ischemic strokes, which are caused by blockages in the internal carotid artery. It is also sometimes used after a stroke. In such cases, patients have reported improvements in vision, speech, swallowing, functioning of arms and legs, and general quality of life.

There is a risk of a heart attack or stroke from the procedure. Anyone undergoing this procedure should be sure their surgeon is experienced in recent techniques and that the medical center has complication rates of less than 6%. A 2000 study reported that older surgeons had a worse record than younger ones, possibly because they relied on residents or were less likely to adopt new procedures.

Procedure Description. The procedure generally is as follows:

The patient is usually given general anesthesia, although it has been reported that using local anesthetic is just as safe and reduces the cost of the procedure.
A bypass tube is put in place to transport blood around the blocked area during the procedure.
The surgeon scrapes away the plaque on the arterial wall.
The artery is sewn back together, and blood flow is restored.
The patient generally stays in the hospital for about 2 days. There is often a slight aching in the neck for about 2 weeks, and the patient should refrain as much as possible from turning the head during this period.

Endarterectomy is a surgical procedure removing plaque material from the lining of an artery.

Click the icon to see an illustrated series detailing surgery for unblocking carotid arteries.

Determining Who Should Have Surgery. Evidence strongly suggests that most patients with severe stenosis (over 70% of the carotid artery is obstructed) can benefit from either carotid endarterectomy or carotid artery stenting. An experienced surgeon with a good track record is essential. Patients with mild stenosis (less than 50% obstruction) should not have endarterectomy; these patients do better with medications even if they have symptoms. For patients with moderate stenosis (50 - 69%), the decision to perform surgery needs to be determined on an individual basis. When a carotid endarterectomy procedure is recommended, it should be performed within 2 weeks.

Carotid angioplasty and stenting (CAS) is being investigated as a less-invasive alternative to carotid endarterectomy. It is based on the same principles as angiography done for heart disease.

An extremely thin catheter tube is inserted into an artery in the groin.
It is threaded through the circulatory system until it reaches the blocked area in the carotid artery.
The doctor either breaks up the clot or inflates a tiny balloon against the blood vessel walls (angioplasty).
After temporarily inflating the balloon, the doctor typically leaves a circular wire mesh (stent) inside the vessel to keep it open.

This procedure carries a risk for an embolic stroke and other complications. At this time, it is being used in some centers as an alternative to endarterectomy in patients who cannot undergo endarterectomy, especially for patients with severe stenosis (blockage greater than 70%) and high surgical risk. Several studies published in 2006 suggested that CAS should be used only for patients with these types of conditions. One of these trials, EVA-3S, was stopped early because results clearly indicated a higher 30-day risk of death and stroke in patients who underwent CAS. Experts are waiting for results of further trials comparing stenting and endarterectomy.

Hemicraniectomy is surgical removal of a bone patch from the skull to relieve pressure. The bone is stored under sterile conditions and reimplanted a few months latter. It may have be a life-saving option for some patients with severe stroke that has resulted in swelling and injury to a large area in the brain. Studies are showing some benefits for high-risk patients, but more information is needed to determine specific conditions that will respond to this treatment.

Extracranial-intracranial (EC-IC) bypass has been under investigation for decades for ischemic stroke, but has had very mixed results, some extremely negative. With this procedure, a healthy artery in the scalp is rerouted to an area of the brain that was deprived of blood because of a blocked artery. This procedure is now sometimes used for patients with aneurysms. Some experts hope, however, that, in specific cases chosen via careful imaging and using the latest surgical techniques, EC-IC may prove to be helpful for some stroke patients.

Surgical Intervention of the Ruptured Aneurysms. In patients with subarachnoid hemorrhagic stroke, surgery to block off the aneurysm is usually recommended within a few days of the stroke. The standard procedure is to clip the aneurysm and stop bleeding. Alternative approaches are promising.

Surgical Intervention of Unruptured Aneurysms. If an unruptured aneurysm is detected, patients should discuss all options with their doctor, including surgical repair. Unruptured aneurysms occur in between 1 - 8% of the general population, however, and controversy exists over when to operate and on which patients.

In general, the decision rests on the size of the aneurysm, but uncertainty still exists. In one study, for example, the risk of rupture for aneurysms between 10 - 25 mm was quite low -- slightly less than 1% per year for both groups. Aneurysms over 25 mm, however, had a 6% chance of rupturing within a year. Studies have reported that in general, the risk for rupture is between .05 - 2% a year, but recent evidence suggests that the risks may be even less. In one study, even people with a history of subarachnoid hemorrhage had only a 0.5% annual risk for recurrence when aneurysms were small.

Aneurysms can often cause symptoms, however, even if they do not rupture. Patients should discuss their particular risk factors carefully with their doctors. Individuals with arteriovenous malformation, a condition caused by abnormal associations between arteries and veins, should be monitored for the development of an aneurysm.

Clipping the Aneurysm. The standard surgical procedure for treating a ruptured aneurysm is to place a clip across the neck of the aneurysm, which blocks off bleeding. It is usually performed within the first 3 days. Getting to the aneurysm is often extremely difficult. Deep cooling of the body to stop circulation may be used to allow more time for the operation. Procedures that remove large portions of the bone in the skull are being developed to allow fast access. There is a relatively high risk for newly formed aneurysms, particularly after 9 years. Patients may want to discuss follow-up angiography to detect any new aneurysms 9 - 10 years after the procedure.

Transcatheter Embolization for Sealing off the Aneurysm. Transcatheter embolization is a new technique for ruptured and unruptured aneurysms that is proving to be effective, although it is still investigational. The surgeon threads a thin tube through the artery leading to the aneurysm through which materials are passed to plug or obstruct the aneurysm. In one version of this procedure, the following occurs:

A tiny platinum coil is inserted through the tube and positioned into the aneurysm.
An electric charge is passed through the coil to form blood clots.
In this case, blood clots benefit the patient by using the coil as a scaffold and sealing off the aneurysm.

A 2002 study suggested it could be attempted safely in over 95% of patients with unruptured aneurysms. In the study, the procedure eliminated the aneurysm in nearly 90% of the patients. In small trials using the coil with a ruptured aneurysm, only 3.7% of patients suffered a second stroke after 7 months compared to the usual re-rupture rate of 30 - 40%.

Emergency Surgery for Hemorrhagic Strokes. Emergency surgery for a hemorrhagic stroke involves locating and removing large blood clots. In the past, such procedures had little effect on survival. Advances, however, are improving outcomes when surgery is performed very early.

Recovery

After a stroke, patients should take all necessary measures, including medications and lifestyle changes, to prevent another stroke. For those whose stroke was ischemic, aspirin, warfarin, or both will usually be prescribed.

Having a neurologist as the primary doctor after a stroke, rather than some other specialist or primary care doctor, significantly increases the chance for survival. Patients or their families should be persistent in requesting the best care possible during this important early period.

Receiving initial treatment at a stroke unit, instead of a general ward, plays a strong role for better long-term quality of life. Rehabilitation services aimed at patients living at home are also very effective in improving independence. Patients or their families should seek patient advocates or support associations to ensure they receive the right care.

In addition to problems brought on by neurologic damage, stroke patients are also at risk for other serious problems that reduce their chances for survival. They include:

Blood clots in the legs (deep vein thrombosis)
Pulmonary embolism (a blood clot that travels to the lungs)
Pneumonia
Widespread infection
Heart problems
Urinary tract infections (a catheter is sometimes used in the first 48 hours after stroke to help with urinary retention, but if it is left in longer it can cause urinary tract infections)

Measures should be taken to monitor and treat patients for these important problems.

In all, 90% of stroke survivors experience varying degrees of improvement after rehabilitation. The current cost-cutting climate generates pressure to send elderly patients who have had a stroke directly to a nursing home rather than a rehabilitation first. Not all patients, however, need or benefit from formal rehabilitation:

If the stroke is severe, intensive training would not be helpful.
If the stroke is mild, patients often improve on their own.

Positive factors that help predict good candidates for rehabilitation:

A patient should be able to sit up for at least an hour.
The patient should be able to learn and be aware.
Spasticity may be a good sign, because it indicates live nerve action.
Patients who are able to move their shoulders or fingers within the first 3 weeks after having a stroke are more likely to recover the use of their hands than patients who cannot perform these movements. The ability to feel light pressure on the affected hand, however, makes no difference for future hand movement.
Family members or close friends are available to be active participants in the rehabilitation process.

Factors that predict a poor response to rehabilitation:

Dysphagia (the inability to swallow) is associated with a higher mortality rate, possibly because of increased risk for infection and malnutrition. Dysphagic patients are given nutrition using a stomach tube or a feeding tube inserted down through the nose.
Incontinence.
The inability to recognize nonspeech sounds that occur right after a stroke.
A poor hand grip that is still present after 3 weeks is an indicator of severe problems.
Having had very severe seizures after the stroke.

Factors that do not rule out rehabilitation:

About 30% of patients experience aphasia (an impaired ability to speak). However, this disability does not necessarily affect the ability to think. Aphasia can also be temporary.
Although confusion is common among people who have had strokes, partial or even complete recovery is very possible.

Physical therapy should be started as soon as the patient is stable, as early as 2 days after the stroke. Some patients will experience the fastest recovery in the first few days, but many will continue to improve for about 6 months or longer. Because stroke affects different parts of the brain, specific approaches to managing rehabilitation vary widely among individual patients:

Exercise program. Recent guidelines from the Veteran’s Administration recommend that patients get back on their feet as soon as possible to prevent deep vein thrombosis. Patients should try to walk at least 50 feet a day. Assisted devices or bracing are sometimes used to help support the legs. Treadmill exercises can be very helpful for patients with mild-to-moderate dysfunction. Exercise should be tailored to the stroke survivor's physical condition and can include aerobic, strength, flexibility, and neuromuscular (coordination and balance) activities.
Retraining muscles. Stretching and range-of-motion exercises are used to help treat spastic muscles. They can also help patients regain function in a paralyzed arm. There are several approaches. The Bilateral Arm Training with Rhythmic Auditory Cueing (BATRAC) technique involves moving a bar with both arms in a sustained rhythmic pattern. A 2004 study in the Journal of the American Medical Association (JAMA) reported that BATRAC helped patients get back use of their paralyzed arm. Patients had a stroke at least 4 years before participating in the BATRAC study. Another technique, constraint-induced movement therapy (CIMT), involves doing a series of repetitive exercises while the less functional arm is restrained. Research published in 2006 in JAMA indicated that 2 weeks of CIMT can help patients regain arm function. Patients in the CIMT study had experienced a stroke within the prior 3 - 9 months.
Speech therapy and sign language. People who have had a stroke often have aphasia, a brain condition that makes it difficult to speak and understand language. Aphasia can come in many different forms. A person may be unable to speak at all, or just have difficulty saying the right word. Intense speech therapy after a stroke is important for recovery. Some experts recommend 9 hours a week of therapy for 3 months. A 2005 study indicated that a shorter period (3 hours a week for 10 days) also works well. Language skills improve the most when family and friends help reinforce the speech therapy lessons.
Biofeedback techniques combined with physical therapy. This combination has been beneficial in certain cases. Electrical stimulation of the throat, for example, may help patients with dysphagia recover their ability to swallow faster. Stimulation of the wrist and finger is also showing promise for improving motor capabilities.
Swallowing exercise. A promising study reported that swallowing improved when patients performed a simple exercise 3 times a day for 6 weeks. They lay flat and raised their heads three times, holding them up for 1 minute with a 1 minute rest in between. This was followed by 30 consecutive head lifts.
Attention training. Problems with attention are very common after strokes. Direct retraining teaches patients to perform specific tasks using repetitive drills in response to certain stimuli. (For example, they are told to press a buzzer each time they hear a specific number.) A variant of this approach trains patients to relearn real-life skills, such as driving, carrying on a conversation, or other daily tasks.
Occupational training. Occupational therapy is important and improves daily living activities and social participation.

Drug therapy can sometimes help relieve specific effects of stroke:

Dantrolene (Dantrium), tizanidine (Zanaflex), and baclofen (Lioresel) are used to treat spasticity.
Heparin, a blood-thinning drug, is used to prevent blood clots from forming in the veins of the legs (thrombosis).
Some patients experience constant hiccups, which can be very serious. Among the drugs used for this condition are chlorpromazine or baclofen.
Studies have reported that dextroamphetamine or methylphenidate (Ritalin), an amphetamine used in attention deficit disorder, may help patients recover speech and motor skills when combined with physical therapy.

Certain drugs commonly taken for conditions associated with stroke may actually slow recovery. They include drugs used for high blood pressure, including clonidine and prazosin, anticonvulsant drugs, the antipsychotic drug haloperidol, and anti-anxiety drugs such as benzodiazepines.

The Emotional State of the Patients. Strong motivation with the goal of independence after rehabilitation is important for recovery. Unfortunately, depression is very common after a stroke, both as a direct and indirect result of the stroke:

Strokes that affect the right hemisphere in the brain increase the risk for depression.
Patients can become depressed by the changes in their ability to function.
A peculiar stroke-induced condition, known as post-stroke crying or neurologic emotionalism, is a neurologic not a psychologic disorder.

If depression is prolonged, it can interfere with recovery. One study showed that people who suffered strokes and became depressed were three times more likely to die within 10 years than stroke victims who were not depressed. There is a significantly increased risk of suicide in patients with stroke, especially in women and those under age 60.

Antidepressants, particularly fluoxetine (Prozac) and similar so-called SSRI drugs, have been beneficial in relieving post-stroke crying as well as improving recovery in general and mood in particular. Antidepressants may also help restore mental abilities.

Some doctors also recommend tricyclic antidepressants, which include amitriptyline (Elavil) and nortriptyline (Pamelor). In one study nortriptyline (Pamelor) not only improved mood but also had positive effects on mental functioning, suggesting perhaps that some dementia associated with stroke may actually be due to depression. Tricyclics may also be useful for neurologic emotionalism.

Anxiety disorder is also common and debilitating. Some research indicates that many patients suffer from feelings identical to post-traumatic stress syndrome. The two disorders often overlap, but drug treatments for each differ and may offset the other.

Many drugs for psychologic disorders affect the central nervous system and can delay rehabilitation. Skilled professional help is needed to determine the most effective and safest treatments.

The Emotional State of the Caregiver. The caregiver's emotions and responses to the patient are critical. Patients do worse when caregivers are depressed, overprotective, or not knowledgeable about the stroke. Unfortunately, in one study, over half of the caregivers themselves were depressed, particularly if the stroke victims were left with dementia or abnormal behavior.

Resources

www.strokeassociation.org -- American Stroke Association
www.americanheart.org -- American Heart Association
www.stroke.org -- National Stroke Association
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aphasia.org -- National Aphasia Association
www.aan.com -- American Academy of Neurology
www.strokecenter.org/trials -- Stroke Trials Directory

References

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Wolf SL, Winstein CJ, Miller JP, Taub E, Uswatte G, Morris D, et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9months after stroke: the EXCITE randomized clinical trial. JAMA. 2006 Nov 1;296(17):2095-104.

Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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