FitSugar

Eat Yogurt - It's Good For Your Mouth

FitSugar — Tue, 26 Feb 2008 16:00:00 -0800

If you eat yogurt, you'll be happy to know that Japanese research found that it may be keeping your mouth healthy. Eating yogurt and other foods that contain lactic acid such as wheat beer, kefir, and some cottage cheeses are associated with better periodontal health. When adults have periodontal disease, this chronic bacterial infection causes receding gums and tooth loss. Aside from brushing, flossing, and regular cleanings, effective ways to deal with this are limited, so this is great news.

This study found that those who consumed 55 grams or more of yogurt a day, or some other lactic-acid drink, had a significantly lower occurrence of periodontal disease. (That's equal to less than half a 6-ounce container of yogurt). More research needs to be done, because the benefits may have something to do with the lactobacillus bacteria found in yogurt and other lactic-acid foods. Since signs of periodontal disease can show up in your 30s, so it's good to start thinking about ways to prevent it now.

Source

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

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

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

ACTIVE Writing Group on behalf of the ACTIVE Investigators; Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10;367(9526):1903-12.

Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006 Aug 10;355(6):549-59.

Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation. 2007 Mar 27;115(12):1634-42. Epub 2007 Feb 26.

Chalela JA, Kidwell CS, Nentwich LM, Luby M, Butman JA, Demchuk AM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet. 2007 Jan 27;369(9558):293-8.

ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20;367(9523):1665-73.

Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007 Jan 27;369(9558):283-92.

Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA. 2006 Jul 19;296(3):283-91.

Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, et al. Endarterectomy versus stenting in patients with symptomatic severe carotidstenosis. N Engl J Med. 2006 Oct 19;355(16):1660-71.

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.

SPACE Collaborative Group; Ringleb PA, Allenberg J, Bruckmann H, Eckstein HH, Fraedrich G, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006 Oct 7;368(9543):1239-47.

Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.

Tsivgoulis G, Spengos K, Manta P, Karandreas N, Zambelis T, Zakopoulos N, et al. Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study. Stroke. 2006 Dec;37(12):2892-7. Epub 2006 Oct 19.

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.

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.

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.

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

Diabetes - type 1

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Life-Threatening Complicati...
Diagnosis
Dietary Goals and Exercise...
Treatment
Monitoring Tests
Long-Term Complications
Transplantation Procedures...
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Continuous Glucose Meter System

In 2007, the FDA approved the STS-7 System, which monitors glucose levels every 5 minutes during a 7-day period. The STS-7 System, like other continuous glucose meter systems, is designed to be used in combination with traditional fingerstick tests and meters. It does not replace them. But the system can track trends and fluctuation patterns in blood sugar levels that fingerstick tests cannot detect.

Type 1 Diabetes Gene Discovered

In 2007, scientists announced the discovery of a gene that may increase the risk of developing childhood type 1 diabetes.

Anemia Drugs Warning

In 2007, following the publication of several studies in the New England Journal of Medicine, the FDA warned that erythropoiesis-stimulating drugs (used to treat anemia) can increase the risk for blood clots, strokes, and heart attacks when excessive doses are given. The FDA has set new dosing and hemoglobin target levels for these drugs. Anemia is a common complication of end-stage kidney disease.

Cell Transplantation Research

Islet cell transplantation using the Edmonton protocol is a promising treatment for type 1 diabetes, suggests a 2006 study published in the New England Journal of Medicine. The Edmonton protocol involves isolating islet cells from donor pancreases and then injecting the cells into the patient. In the first international multicenter trial of this investigational procedure, 44% of 36 patients were able to temporarily suspend insulin injections, while 28% achieved partial islet function.
Stem cell transplantation using cells harvested and re-infused from the patient’s own body may help increase beta cell function and eliminate the need for insulin injections, according to a small, preliminary study published in 2007 in the Journal of the American Medical Association.

Type 1 Diabetes Prevention Research

Scientists around the world are investigating new ways to prevent type 1 diabetes or at least delay its onset. Experimental preventive measures include treatment with oral insulin and with drugs that may prevent the immune system’s attack on beta cells.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes.

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:

During and immediately after a meal the process of digestion breaks carbohydrates down into sugar molecules (of which glucose is one) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply. (Glucose levels after a meal are called postprandial levels.)
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 20 minutes after a meal insulin rises to its peak level.
Insulin enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (It should be noted that the brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

The pancreas is located behind the liver and stomach. In addition to secreting digestive enzymes, the pancreas secretes the hormones insulin and glucagon into the bloodstream. The release of insulin into the blood lowers the level of blood glucose (simple sugars from food) by enhancing glucose to enter the body cells, where it is metabolized. If blood glucose levels get too low, the pancreas secretes glucagon to stimulate the release of glucose from the liver.

In type 1 diabetes, the disease process is more severe than with type 2 diabetes, and onset is usually in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."
Patients become dependent on administered insulin for survival.

Type 2 diabetes is the most common form of diabetes, accounting for 90% of cases. About 20 million Americans have type 2 diabetes and half are unaware they have it. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that it may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin, and in the beginning this amount is usually sufficient to overcome such resistance.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

Maturity-Onset Diabetes in Youth. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. It accounts for 2 - 5% of type 2 cases.

Gestational Diabetes. An estimated 5% of pregnant women develop a form of type 2 diabetes in their third trimester called gestational diabetes. Gestational diabetes is usually temporary. [See In-Depth Report #60: Diabetes - type 2.]

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta-blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes, and others) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) also increase the risk for diabetes.

Causes

Type 1 diabetes is usually a progressive autoimmune disease, in which the beta cells that produce insulin are slowly destroyed by the body's own immune system. It is unknown what first starts this cascade of immune events, but evidence suggests that both a genetic predisposition and environmental factors, such as a viral infection, are involved.

Islets of Langerhans contain beta cells and are located within the pancreas. Beta cells produce insulin which is needed to metabolize glucose within the body.

Certain factors are thought to be important in this process:

White blood cells called T lymphocytes produce immune factors called cytokines that attack and gradually destroy the beta cells of the pancreas. Important cytokines are interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma.
Specific proteins are also critical in the process. They include glutamic acid decarboxylase (GAD), insulin, and islet cell antigens. These proteins serve as autoantigens. That is, they trigger the self-attack of the autoantibodies on the body's own beta cells.

Progression from the first stage, known as insulitis, to full-blown diabetes can take 7 years or longer. Unfortunately, by the time a person is aware that something is wrong and goes to the doctor with symptoms of type 1 diabetes, about 80 - 90% of the beta cells have been destroyed.

More than half of patients with insulitis do not develop diabetes. Researchers are greatly interested in discovering any factors that prevent the disease.

Researchers have found at least 18 genetic locations, labeled IDDM1 - IDDM18, that are related to type 1 diabetes. The IDDM1 region contains the HLA genes that encode proteins called major histocompatibility complex. The genes in this region affect the immune response. New advances in genetic research are identifying other genetic components of type 1 diabetes. In 2007, scientists announced that they had discovered a gene, KIAA0350, on chromosome 16. Variations in this gene appear to increase the risk of a child developing type 1 diabetes. The research team expects to identify an additional 15 - 20 genes associated with type 1 diabetes.

The odds of inheriting the disease, however, are only 10% if a first-degree relative has diabetes, and even in identical twins, one twin has only a 33% chance of having type 1 diabetes if the other has it. Children are more likely to inherit the disease from a father with type 1 diabetes than from a mother with the disorder.

Genetic factors cannot fully explain the development of diabetes. Over the past 30 years, a major increase in the incidence of type 1 diabetes has been reported in certain European countries, and the incidence has nearly tripled in the northeastern U.S. If genetic factors were the only cause of type 1 diabetes, such an increase in cases would take at least 400 years.

Some researchers believe one or more viral infections may trigger the disease in genetically susceptible individuals. Researchers suggest the following scenario:

An infection introduces a viral protein that resembles a beta-cell protein.
T cells and antibodies are tricked by this resemblance into attacking the beta protein as well as the virus.

Among the viruses under scrutiny are enteric viruses, which attack the intestinal tract. Coxsackieviruses are a family of enteric viruses of particular interest. (One study has suggested that respiratory infection in a child's first year, and not later, may be protective against diabetes, perhaps by priming the immune response so that it is better able to respond later on to other organisms.)

Risk Factors

An estimated 1 million people in the U.S. have type 1 diabetes, with about 30,000 new cases diagnosed each year. It is much less common than type 2, however, consisting of only 5 - 10% of all cases of diabetes. Nevertheless, like type 2 diabetes, the incidence of type 1 diabetes among children and adolescents has been rising over the past few decades. Experts estimate that about 1 in every 400 - 600 children and adolescents has type 1 diabetes. While type 2 diabetes has been increasing among African-American and Hispanic adolescents, the highest rates of type 1 diabetes are found among Caucasian youth.

Type 1 can occur at any age but usually appears between infancy and the late 30s, most typically in childhood or adolescence. Boys and girls are equally vulnerable. Studies report the following may be risk factors for developing type 1 diabetes:

Being ill in early infancy.
Early foods. Some studies have reported that early exposure to cow's milk in infancy and not being breast fed increased the risk for type 1 diabetes. Two studies in 2003 suggested that very early exposure to cereal -- not cow's milk -- plays a role in risk. Any risk from early dietary factors is still very low and likely to affect children who already have a genetically impaired immune response to dietary proteins. Breast milk contains factors that may help regulate the immune response and prevent diabetes in such children. National differences in risk also suggest that not all cow's milk is the same, and some proteins may confer higher risks than others.
Having a parent with type 1 diabetes.
Having an older mother.
Having a mother who had preeclampsia during pregnancy.
Obesity in children has long been linked to a higher risk for type 2 diabetes. Two 2001 studies reported an association between high weight at birth and obesity during childhood as risk factors for type 1 diabetes as well. The common risk factor may be an increase in insulin secretion, which occurs with obesity. This theoretically could overstress the beta cells so that they become susceptible to damage by overactive immune factors (particularly cytokines), and eventually to destruction in children genetically vulnerable to type 1 diabetes.

Until recently, diabetes in children was almost always type 1 diabetes. Of major concern, however, are estimates that between 8 - 45% of new diabetes cases in children are now type 2, most likely because of the increase in childhood obesity. [See In-Depth Report #60: Diabetes - type 2.]

The incidence of type 1 diabetes is higher than average among people with other autoimmune diseases, including Grave's disease, Hashimoto's thyroiditis (a form of hypothyroidism), Addison's disease, multiple sclerosis (MS), and pernicious anemia. Research has raised the possibility that all autoimmune diseases share a common genetic basis. A 2001 study found, for example, that the T-cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Both diseases have been associated with cow's milk protein. Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders or why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

There is a very wide variation in incidence of type 1 among population groups. Type 1 diabetes appears to be most common in people of northern European descent and in specific Mediterranean groups (such as Sardinians). It is less common among Asians and African-Americans. Still, African-Americans with type 1 diabetes are 50% more likely to die from it than Caucasians, mostly due to lower-quality health care.

Symptoms

The process that destroys the insulin-producing beta cells can be long and insidious. At the point when insulin production bottoms out, however, type 1 diabetes usually appears suddenly and progresses quickly. Warning signs of type 1 diabetes include:

Frequent urination (in children, a recurrence of bed-wetting after toilet training has been completed)
Unusual thirst, especially for sweet, cold drinks
Extreme hunger
Sudden, sometimes dramatic, weight loss
Weakness
Extreme fatigue
Blurred vision or other changes in eyesight
Irritability
Nausea and vomiting (acute symptoms)

Children with type 1 diabetes may also be restless, apathetic, and have trouble functioning at school. In severe cases, diabetic coma may be the first sign of type 1 diabetes.

Life-Threatening Complications

Diabetic ketoacidosis (DKA) is a life-threatening complication that develops when insulin stores are depleted. It is almost always caused by noncompliance with insulin treatments. Other contributing factors are lack of health insurance and intentionally reducing insulin levels in order to lose weight. In one study, adolescent girls were at higher risk for ketoacidosis than other groups of children and young people.

Diabetic ketoacidosis often develop as follows:

The process is usually triggered in insulin-deficient patients by a stressful event, most often pneumonia or urinary tract infections. Other triggers include alcohol abuse, physical injury, pulmonary embolism, heart attacks, or other illnesses.
Severely low insulin levels cause excessive amounts of glucose in the bloodstream (hyperglycemia).
Fat breakdown then accelerates and increases the production of fatty acids.

These fatty acids are converted into chemicals called ketone bodies, which are toxic at high levels. Symptoms and complications include:

Nausea and vomiting
Deep and rapid breathing may with frequent sighing
Rapid heartbeat
Cerebral edema, or brain swelling, is a rare but very dangerous complication that occurs in 1% of ketoacidosis cases and results in coma, brain damage, or death in many cases. Research now suggests that the risk for this complication is significantly higher in children with severe ketoacidosis (indicated by low carbon dioxide levels and high nitrogen urea levels), and possibly if they are also treated with bicarbonate to reduce acid levels.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.
If the condition persists, coma and eventually death may occur, although over the past 20 years, death from DKA has decreased to about 2% of all cases.

Life-saving treatment uses rapid rehydration with a salt (saline) solution followed by low-dose insulin and potassium replacement.

Ketoacidosis is a serious condition of glucose build-up in the blood and urine. A simple urine test can determine if high ketone levels are present.

Tight blood sugar (glucose) control increases the risk of low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, occurs if blood glucose levels fall below normal. Hypoglycemia may also be caused by insufficient intake of food, or excess exercise or alcohol. Usually the condition is manageable, but occasionally, it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms.

Risk Factors for Severe Hypoglycemia. Among young patients, the youngest children and boys of any age are at higher risk for hypoglycemia. Specific risk factors for severe hypoglycemia include:

Intensively controlling blood glucose and HbA1c levels
Having long-term diabetes
Being less educated about the condition
Being underinsured
Having psychiatric disorders

Hypoglycemia unawareness. Hypoglycemia unawareness is a condition in which people become insensitive to hypoglycemic symptoms. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Sweating
Trembling
Hunger
Rapid heartbeat

Severely low blood glucose levels can cause neurologic symptoms such as:

Confusion
Weakness
Disorientation
Combativeness
In rare and worst cases, coma, seizure, and death

Preventive Measures. The following tips may help avoid hypoglycemia or prepare for attacks.

Nocturnal hypoglycemia (which occurs during sleep) is a common problem for children, even those on nonintensive insulin therapy. (The risk for hypoglycemia is high in any case in children.) Bedtime snacks are advisable if blood glucose levels are below 180 mg/dL (10 mmol/L). Protein snacks may be best. (The use of the insulin pump may help prevent hypoglycemic episodes.)
Some research has suggested that children (particularly thin children) are at higher risk for hypoglycemia because the injection goes into muscle tissue. Pinching the skin so that only fat (and not muscle) tissue is gathered or using shorter needles may help.
Various insulin regimens are available that can reduce the risk. For example, taking a fast-acting insulin (insulin lispro) before the evening meal may be particularly helpful in preventing hypoglycemia.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who are at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes.

Family and friends should be aware of the symptoms and be prepared:

If the patient is helpless (but not unconscious), family or friends should administer three to five pieces of hard candy, two to three packets of sugar, half a cup (four ounces) of fruit juice, or a commercially available glucose solution.
If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment, possibly including the intravenous administration of a glucose solution.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see an example of a glucagon kit.

Experts have been concerned that the increased incidence of hypoglycemia accompanying strict blood glucose control could cause mental deterioration over time, but a 6-year study has found no evidence of this in adolescents and adults. (The effect on young children, however, is not known.)

Diagnosis

Fasting Plasma Glucose. The fasting plasma glucose (FPG) test is the standard test for diagnosing diabetes. It is a simple blood test taken after 8 hours of fasting. In general, results indicate the following:

FPG levels are considered normal up to 100 mg/dL (or 5.5 mmol/L).
Levels between 100 - 125 mg/dL (5.5 - 7.0 mmol/L) are referred to as impaired fasting glucose or pre-diabetes. These levels are considered to be risk factors for type 2 diabetes and its complications.
Diabetes is diagnosed when FPG levels are 126 mg/dL (7.0 mmol/L) or higher.

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the tests are normal in people who have symptoms or risk factors for diabetes. For example, people who take the test in the afternoon and show normal results may actually have abnormal levels that would be revealed if they are tested in the morning.

Glucose Tolerance Test. The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some experts recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

It first uses an FPG test.
A blood test is then taken 2 hours later after drinking a special glucose solution.

The following results suggest different conditions:

OGTT levels are normal up to 140 mg/dL.
Levels between 140 - 199 mg/dL are referred to as impaired glucose tolerance or pre-diabetes.
Diabetes is diagnosed when OGTT levels are 200 mg/dL or higher.

Both the FPG and OGTT tests require that the patient not eat for at least 8 hours prior to the test.

The oral glucose tolerance test is used to diagnose diabetes. The first portion of the test involves drinking a special glucose solution. Blood is then taken several hours later to test for the level of glucose in the blood. Patients who have diabetes will have higher than normal levels of glucose in their blood.

Test for Glycated Hemoglobin. Another test examines blood levels glycated hemoglobin, also known as hemoglobin A1c (HbA1c). Measuring glycated hemoglobin is not currently used for an initial diagnosis, but it may be useful for determining the severity of diabetes.

The basis for its use as a diagnostic measurement in diabetes is as follows:

Hemoglobin is a protein molecule found in red blood cells. When glucose binds to it, the hemoglobin becomes modified, a process called glycation.
Glycation affects a number of proteins, and elevated levels of glycolated hemoglobin is strongly associated with complications of diabetes.
A glycated hemoglobin level of 1% above normal range identifies diabetes in 98% of patients. Normal HbA1c levels do not necessarily rule out diabetes, but if diabetes is present and levels are normal, the risk for complications is low.

The test is not affected by food intake so it can be taken at any time. A home test has been developed that might make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%.
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Testing for Insulin Resistance. Investigators hope that some day a simple test for insulin resistance will be available to identify people at risk for diabetes. Some research suggests that measuring insulin and triglyceride levels during a fasting period may predict a person's sensitivity to insulin.

Type 1 diabetes is characterized by the presence of a variety of antibodies that attack the islet cells. These antibodies are referred to as autoantibodies because they attack the body's own cells -- not a foreign invader. Blood tests for these autoantibodies can help differentiate between type 1 and type 2 diabetes.

Screening for Heart Disease. All patients with diabetes should be tested for high blood pressure (hypertension) and unhealthy cholesterol and lipid levels and given an electrocardiogram. For cholesterol, people with diabetes should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Blood pressure goals should be 130/80 mmHg or lower. Other tests may be needed in patients with signs of heart disease.

High blood pressure is strongly associated with diabetic nephropathy (kidney disease). In fact, patients with type 2 diabetes who show signs of microalbuminuria typically already have hypertension. Type 1 diabetes patients with microalbuminuria, on the other hand, usually have normal blood pressure readings in the doctor's office. A 2002 study using home monitors, however, found that in patients with type 1 diabetes, high systolic blood pressure during sleep often occurs before development of nephropathy. (Systolic pressure is the first and higher number in a blood pressure reading.) Home blood pressure monitoring, may help identify patients with type 1 diabetes who are at risk for kidney damage.

Click the icon to see an image of an ECG.

Screening for Kidney Damage. The earliest manifestation of kidney disease is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. Microalbuminuria is also a marker for other complications involving blood vessel abnormalities, including heart attack and stroke.

The American Diabetes Association recommends that people with diabetes receive an annual microalbuminuria urine test. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleaning the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 1 diabetes have an annual comprehensive eye exam, with dilation, to check for signs of retina disease (retinopathy). Patients at low risk may need exams only every 2 - 3 years.

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who have loss of sensation in their feet should have a foot exam every 3 - 6 months to check for ulcers or infections.

Screening for Thyroid Abnormalities. Thyroid function tests should be administered.

Dietary Goals and Exercise

The treatment goals for a diabetes diet are:

Achieve near-normal blood glucose levels. People with type 1 diabetes must coordinate calorie intake with medication or insulin administration, exercise, and other variables to control blood glucose levels. New forms of insulin now allow more flexibility in timing meals.
Protect the heart and aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure.
Achieve reasonable weight. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Children, pregnant women, and people recovering from illness should be sure to maintain adequate calories for health.
Manage or prevent complications of diabetes. People with diabetes, whether type 1 or 2, are at risk for a number of medical complications, including heart and kidney disease. Dietary requirements for diabetes must take these disorders into consideration.
Promote overall health.

Overall Guidelines. There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 – 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists
Fats should provide 25 – 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 – 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat

[See In-Depth Report #42: Diabetes diet.]

Weight gain is a potential side effect of intense diabetic control with insulin. Being overweight can increase the risk for health problems. On the other hand, studies suggest that more than one-third of women with diabetes omit or underuse insulin in order to lose weight. Eating disorders have become a serious problem within the general population and are especially dangerous in patients with diabetes. Some evidence suggests that they contribute to about 20% of cases of recurrent ketoacidosis in young women. Ketoacidosis is a significant complication of insulin depletion and can be life threatening.

Aerobic exercise has significant and particular benefits for people with type 1 diabetes. It increases sensitivity to insulin, lowers blood pressure, improves cholesterol levels, and decreases body fat. Because glucose levels swing dramatically during workouts, people with type 1 diabetes need to take certain precautions:

Monitor glucose levels carefully before, during, and after workouts.
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
To avoid hypoglycemia, inject insulin in sites away from the muscles they use the most during exercise.
Before exercising, avoid alcohol and if possible certain drugs, including beta-blockers, which increase the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates, especially in the form of pre-exercise snacks. Skim milk is particularly helpful. They should also drink plenty of fluids.
Good, protective footwear is essential to help avoid injuries and wounds to the feet.

Resistance or high impact exercises should be avoided. They can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet. Because patients with diabetes may have silent heart disease, they should always check with their doctors before undertaking vigorous exercise.

A 2006 study of over 19,000 children with type 1 diabetes found that regular physical activity helps improve blood sugar levels without increasing the risk of severe hypoglycemia. The researchers suggest that doctors recommend regular exercise for pediatric patients with type 1 diabetes.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Treatment

Insulin is essential for strict control of blood glucose levels in type 1 diabetes. Tight blood glucose control is the best way to prevent major complications in type 1 diabetes including those that affect the kidneys, eyes, nerve pathways, and blood vessels. Intensive insulin treatment in early diabetes may even help preserve any residual insulin secretion for at least 2 years.

There are, however, some significant problems with intensive insulin therapy:

There is a higher risk for low blood sugar (hypoglycemia).
Many patients experience significant weight gain from insulin administration, which may have adverse effects on blood pressure and cholesterol levels. It is important to manage heart disease risk factors that might develop as a result of insulin treatment.

A diet plan that compensates for insulin administration and supplies healthy foods is extremely important. [See In-Depth Report #42: Diabetes diet.] Pancreas transplantation eventually may be recommended for patients who cannot control glucose levels without frequent episodes of severe hypoglycemia.

The goal of intensive insulin therapy is to keep blood glucose levels as close to normal as possible. In one major study, even when levels were 40% higher than nondiabetic levels, benefits were still observed.


	Normal	Goal
Blood glucose levels before meals	Less than 110 mg/dL (or 6.1 mmol/L)	90 - 130 mg/dL (or 5 - 7.2 mmol/L)
Bedtime blood glucose levels	Less than 120 mg/dL (6.6 mmol/L)	110 - 150 mg/dL (or 6.1 - 8.3 mmol/L)
Glycated hemoglobin (HbA1c) levels	4 - 6%	Less than 7%
Source: National Diabetes Information Clearinghouse, National Institutes of Diabetes and Digestive and Kidney Diseases.

Standard insulin therapy usually consists of one or two daily insulin injections, one daily blood sugar test, and visits to the health care team every 3 months. For strictly controlling blood glucose, however, intensive management is required. The regimen is complicated although newer insulin forms may make it easier.

There are two components to flexible insulin administration and a number of variations of insulin delivery for accomplishing them:

Basal insulin administration. The basal component of the treatment attempts to provide a steady amount of background insulin throughout the day. Basal insulin levels maintain regular blood glucose needs. Insulin glargine now offers the most consistent insulin activity level, but other intermediate and long-acting forms may be beneficial when administered twice a day. Short-acting insulin delivered continuously using a pump is proving to a very good way to provide basal rates of insulin.
Mealtime insulin administration. Meals require a boost (a bolus) of insulin to regulate the sudden rise in glucose levels after a meal.

In achieving insulin control the patient must also take other steps:

The patient should perform four or more blood glucose tests during the day.
Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
Insulin requirements vary depending on many non-nutritional situations during the day, including exercise and sleep. People are at enhanced risk for low blood sugar during exercise. Some patients experience a sudden rise in blood glucose levels in the morning -- the so-called "dawn phenomenon."
The patient must also maintain a good diet plan and should visit the health care team of doctors, nurses, and dietitians once a month.

Because of the higher risk for hypoglycemia in children, experts recommend that intensive treatment be used very cautiously in children under 13 and not at all in very young children.

Insulin cannot be taken orally because the body's digestive juices destroy it. Injections of insulin under the skin ensure that it is absorbed slowly by the body for a long-lasting effect. The timing and frequency of insulin injections depend upon a number of factors:

The duration of insulin action. Insulin is available in several forms, including: standard, intermediate, long-acting, and rapid-acting.
Amount and type of food eaten. Ingestion of food makes the blood glucose level rise. Alcohol lowers levels.
The person's level of physical activity. Exercise lowers glucose levels.

Fast-Acting Insulin. Insulin lispro (Humalog) and insulin aspart (Novo Rapid, Novolog) lower blood sugar very quickly, usually within 5 minutes after injection. Insulin peaks in about 4 hours and continues to work for about 4 hours. This rapid action reduces the risk for hypoglycemic events after eating (postprandial hypoglycemia). Optimal timing for administering this insulin is about 15 minutes before a meal, but it can be also taken immediately after a meal (but within 30 minutes). Fast-acting insulins may be especially useful for meals with high carbohydrates.

Regular Insulin. Regular insulin begins to act 30 minutes after injection, reaches its peak at 2 - 4 hours, and lasts about 6 hours. Regular insulin may be administered before a meal and may be better for high-fat meals.

Intermediate Insulin. NPH (neutral protamine Hagedorn) insulin has been the standard intermediate form. It works within 2 - 4 hours, peaks 4 - 12 hours later, and lasts up to 18 hours. Lente (insulin zinc) is another intermediate insulin that peaks 4 - 12 hours and lasts up to 18 hours.

Long-Acting (Ultralente) Insulin. Long-acting insulins, such as insulin glargine (Lantus), are released slowly. Insulin glargine matches parts of natural insulin and maintains stable activity for more than 24 hours. Studies suggest that it poses less of a risk for hypoglycemia and weight gain than NPH. It has a higher incidence of pain at the injection site than NPH. Ultralente insulin peaks at 10 hours and lasts up to 20 hours but varies greatly in activity from day to day.

Combinations. Regimens generally include combinations of short and longer-acting insulins to help match the natural cycle. For example, one approach in patients who are intensively controlling their glucose levels uses 3 injections of insulin, which includes a mixture of regular insulin and NPH at dinner. Another approach uses 4 injections, including a separate short-acting form at dinner and NPH at bedtime, which may pose a lower risk for nighttime hypoglycemia than the 3-injection regimen.

Insulin Pumps. An insulin pump can improve blood glucose control and quality of life with fewer hypoglycemic episodes than multiple injections. The pumps correct for the “dawn phenomenon” (sudden rise of blood glucose in the morning) and allow quick reductions for specific situations, such as exercise. Many different brands are available.

The typical pump is about the size of a beeper and has a digital display. Some are worn externally and are programmed to deliver insulin through a catheter in the skin or the abdomen. They generally use rapid-acting insulin, the most predictable type. They work by administering a small amount of insulin continuously (the basal rate) and a higher dose (a bolus dose) when food is eaten.

Many adults, adolescents, and school children use insulin pumps. A 2006 study found that even very young children (ages 2 - 7 years) can successfully use insulin pumps and that the pumps provided better blood sugar control than twice-daily insulin injections.

The catheter at the end of the insulin pump is inserted through a needle into the abdominal fat of a person with diabetes. Dosage instructions are entered into the pump's small computer, and the appropriate amount of insulin is then injected into the body in a calculated, controlled manner.

Learning to use the pump can be complicated, although over time most patients find the devices are fairly easy to use. To achieve good control, patients and parents of children must undergo some training. The patient and doctor must determine the amount of insulin used -- it is not automatically calculated. This requires an initial learning period, including understanding insulin needs over the course of the day and in different situations and knowledge of carbohydrate counting. Frequent blood testing is very important, particularly during the training period.

Insulin pumps are more expensive than insulin shots and occasionally have some complications, such as blockage in the device or skin irritation at the infusion site. In spite of early reports of a higher risk for ketoacidosis with pumps, more recent studies have found no higher risk.

Insulin Pens. Insulin pens, which contain cartridges of insulin, have been available for some time. Until recently, they were fairly complicated and difficult to use. Newer, prefilled pens (Humulin Pen, Humalog) are disposable and allow the patient to dial in the correct amount.

Inhaled Aerosol. In 2006, the FDA approved the first non-injected form of insulin. Exubera is an inhaled form of insulin. It is approved for adults but should not be used by patients who smoke or have quit smoking within the past 6 months. Patients with asthma, bronchitis, or emphysema should also not use inhaled insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

Other Alternative Insulin Delivery Methods. Another promising avenue of investigation for delivering insulin is the use of ultrasound pulses.

Pramlintide (Symlin) is a new type of injectable drug that can help control postprandial hyperglycemia, the sudden increase in blood sugar after a meal. Pramlintide is injected before meals and can help lower blood sugar levels in the 3 hours after meals. Pramlintide is used in addition to insulin for patients who take insulin regularly but still need better blood sugar control. The FDA approved this drug in 2005 for adults with type 1 and type 2 diabetes. Pramlintide and insulin are the only two drugs approved for treatment of type 1 diabetes.

Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Side effects may include nausea, vomiting, abdominal pain, headache, fatigue, and dizziness. Patients with type 1 diabetes have an increased risk of severe low blood sugar (hypoglycemia) that may occur within 3 hours following a pramlintide injection. This drug should not be used if patients have trouble knowing when their blood sugar is low or have slow stomach emptying (gastroparesis).

CD3-Antibodies. A new type of drug called a CD3 antibody is showing promise for helping patients newly diagnosed with type 1 diabetes. In phase II clinical trials, patients received the drug for 6 days. Results from a 2005 trial published in the New England Journal of Medicine indicated that the CD3 antibody helped stimulate the patients’ natural insulin production and decreased their need for insulin drug therapy. The beneficial effects lasted up to 18 months after CD3 treatment. Researchers think that this drug affects the autoimmune response involved in type 1 diabetes and helps preserve the residual beta cell function of the pancreas.

Monitoring Tests

Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to carefully monitor blood glucose levels. In general, patients with type 1 diabetes need to take readings four or more times a day. Patients should aim for the following measurements:

Pre-meal glucose levels of between 90 - 130 mg/dL
Bedtime levels of between 110 - 150 mg/dL

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Finger-Prick Test. A typical blood sugar test includes the following:

A drop of blood is obtained by pricking the finger.
The blood is then applied to a chemically treated strip.
Monitors read and provide results.

Home monitors are about 10 - 15% less accurate than laboratory monitors are and many do not meet the standards of the American Diabetes Association. Most doctors believe, however, that they are accurate enough to indicate when blood sugar is too low.

To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some simple procedures may improve accuracy:

Testing the meter once a month.
Recalibrating it whenever a new packet of strips is used.
Using fresh strips; outdated strips may not provide accurate results.
Keeping the meter clean.
Periodically comparing the meter results with the results from a laboratory.

Supplementary Monitoring Devices. Other devices are available for monitoring blood glucose. These devices are used in addition to traditional fingerstick test kits and glucose meters but do not replace them:

Continuous glucose monitoring systems (CGMS) use a needle-like sensor inserted under the skin of the abdomen to monitor glucose levels every 5 minutes. In 2007, the STS-7 System was approved. Using a disposable sensor, the STS-7 measures glucose levels for up to a week. An alarm will sound if glucose levels are too high or low. The older Minimed system measures glucose over a 72-hour period and has wireless communication between the monitor and an insulin pump.
GlucoWatch is a battery-powered wristwatch-like device that measures glucose by sending tiny electric currents through the skin, a technique called reverse iontophoresis. It is painless and has a warning device when detecting high glucose levels. It takes 2 hours to warm up, and the sensor pads need to be changed every day. Glucowatch measures glucose levels three times per hour for up to 12 hours. About a quarter of the time, the results differ significantly from actual fingerstick tests, however.

Hemoglobin A1c (also called HbA1c , HA1c, or A1C) is measured periodically every 2 - 3 months to determine the average blood-sugar level over the lifespan of the red blood cell. Normal A1C levels should be below 7%. Home tests are also available for measuring A1C.

Urine tests are useful for detecting the presence of ketones. These tests should always be performed during illness or stressful situations, when diabetes is likely to go out of control. The patient should also undergo yearly urine tests for microalbuminuria (small amounts of protein in the urine), a risk factor for future kidney disease.

Long-Term Complications

Type 1 diabetes reduces the normal lifespan by an average of 5 - 8 years. However, survival rates are improving in all ethnic groups and both genders. Longer survival rates are probably due to improvements in monitoring and tighter control of blood glucose. There are two important approaches to preventing complications from type 1 diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. This approach is proving to prevent complications due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
Managing risk factors for heart disease. Blood glucose control helps the heart, but it is also very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

Patients with type 1 diabetes have a 10 times greater risk of heart disease than healthy patients. Heart attacks account for 60% and strokes for 25% of deaths in patients with diabetes. Diabetes affects the heart in many ways:

Both type 1 and 2 diabetes accelerate the progression of atherosclerosis (hardening of the arteries). Diabetes can adversely affect blood lipid levels by lowering HDL ("good cholesterol") and increasing triglycerides. This can lead to coronary artery disease, heart attack, or stroke.
In type 1 diabetes, high blood pressure (hypertension) usually develops if the kidneys become damaged. High blood pressure is another major cause of heart attack, stroke, and heart failure. Children with diabetes are also at risk for hypertension.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions ranges from 15 - 53%.

Click the icon to see an image of the kidney.

Results from the Diabetes Control and Complications Trial (DCCT) prove that intensive blood sugar control reduces the long-term risk of heart disease complications by 50%. The results indicate that intensive blood sugar control is even more important in reducing these risks than blood pressure- and cholesterol-lowering drugs. Original participants in the trial received intensive blood glucose control for 6 years during the 1980s. Researchers continued to follow these patients’ progress during the next 17 years. A follow-up study, published in 2005 in the New England Journal of Medicine, found that the benefits of tight blood glucose control persisted over time and halved the risk of heart attack, stroke, angina, or coronary artery disease.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin reduces the risk for blood clotting and may help protect against heart attacks. In a 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes.

Reducing Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Dozens of anti-hypertensive drugs are available. Most fall into the following categories:

Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
Angiotensin-receptor blockers (ARBs) block angiotensin.
Beta-blockers block the effects of adrenaline and ease the heart’s pumping action.
Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

The American Diabetes Association (ADA) recommends any of these classes of drugs as first-line treatment for hypertension. New research suggests, however, that beta-blockers are less effective at preventing strokes and heart attacks than other types of blood pressure medications. ACE inhibitors are especially helpful for patients with type 1 diabetes as they may help prevent kidney disease (nephropathy).

Many patients require more than one type of drug to control blood pressure. For patients with diabetes who have microalbuminuria, the ADA strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).

Anti-hypertensive drugs that block or reduce angiotensin are the first option for many people with diabetes. Angiotensin is a natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure.

The 2005 landmark Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicated that a thiazide-type diuretic works as well as an ACE inhibitor or CCB for patients with type 2 diabetes and high blood pressure. Compared with ACE inhibitors or CCBs, diuretics appeared to be better at lowering systolic blood pressure and preventing heart failure. In addition, the trial suggested that diuretics are especially helpful for African-Americans, by offering greater protection than ACE inhibitors or CCBS in preventing strokes. [See In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances, including low HDL (“good”) cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor and generics), pravastatin (Pravachol), simvastatin (Zocor and generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels. Recent studies indicate that aggressive high-dose statin therapy may be an important treatment approach for high-risk patients who need to substantially lower their LDL levels. A 2006 study found that patients with diabetes and heart disease who were treated with 80 mg daily of atorvastatin had a 25% lower risk of heart attack and stroke than patients who received a 10 mg daily dose.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms.

Although lowering LDL cholesterol is beneficial, statins are not as effective as other medications -- such as fibrates, niacin, ezetimbe, or bile acid sequesters -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combining a statin with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care.

Fibrates, such as gemfibrozil (Lopid) and fenofibrate (Tricor), are usually the first choice. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, about 30% of patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [See In-Depth Report #23: Cholesterol.]

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Treatment and Prevention of Nephropathy. Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Long-term studies report that strict control of these two conditions produces a 60% reduction in new cases of nephropathy and a delay in progression of the disease. Research indicates that ACE inhibitors are the best class of blood pressure medications for delaying kidney disease and slowing disease progression in patients with type 1 diabetes. Angiotensin-receptor blockers (ARBs) are also very helpful.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally require higher amounts of protein. [See In-Depth Report #42: Diabetes diet.]

Diabetic nephropathy, the leading cause of end-stage renal disease (ESRD), occurs in about 20 - 40% of patients with diabetes. Patients with ESRD have 13 times the risk of death compared to other patients with type 1 diabetes. If the kidneys fail, dialysis is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color. On an encouraging note, a 2005 study in the Journal of the American Medical Association reported that the prognosis of end-stage renal disease has greatly improved during the last 4 decades for patients with type 1 diabetes. The outlook was best for patients who were diagnosed with diabetes at a young age (under 5 years old). In addition, the study found that fewer people with type 1 diabetes are developing ESRD.

Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually require injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. Patients with end-stage kidney disease should be aware of the current controversies surrounding the dosing of these drugs.

In 2006, two important New England Journal of Medicine studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia. In 2007, the FDA issued new warnings on darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). The warnings describe an increased risk for blood clots, strokes, and heart attacks in patients with end-stage kidney disease when these drugs were given at higher than recommended doses. The FDA has set new dosing and hemoglobin target levels for these drugs.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Maintain hemoglobin levels that do not exceed 12 g/dL
Receive frequent blood tests to monitor hemoglobin levels
Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure

[See In-Depth Report #57: Anemia.]

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral (affects nerves in the toes, feet, legs, hand, and arms)
Autonomic (affects nerves that help regulate digestive, bowel, bladder, heart, and sexual function)

Peripheral neuropathy particularly affects sensation. It is a common complication that affects nearly half of people with type 1 or type 2 diabetes after 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Tingling
Weakness
Burning sensations
Loss of the sense of warm or cold
Numbness (if the nerves are severely damaged, the patient may be unaware that a blister or minor wound has become infected)
Deep pain

Autonomic neuropathy can cause digestive problems (constipation, diarrhea, nausea, vomiting), bladder infections, and erectile dysfunction. In some cases, neuropathy may mask angina, the warning chest pain for heart disease and heart attack. Patients with diabetes should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

Blood sugar control is the only treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. A 2005 study also suggested that heart disease risk factors can increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

Pain-Relief Treatment for Peripheral Neuropathy. A number of different drugs are used for peripheral neuropathy pain relief: They include:

Nonprescription analgesics, such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately, tricyclics may cause heart rhythm problems.
Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, a newer type of antidepressant, which was approved in 2004 for treatment of pain associated with diabetic peripheral neuropathy.
The anti-convulsant drug pregabalin (Lyrica) was approved in 2004 for neuropathic pain management. It is classified as a controlled substance (like narcotics), which indicates a potential risk for abuse. Other anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin) and valproate (Depakote).

Treatments under investigation include acetyl-l-carnitine and intravenous alpha-lipoic acid. Patients may also benefit from transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments such as hypnosis, biofeedback, relaxation techniques, and acupuncture have helped some patients manage pain. Doctors also recommend lifestyle measures, such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy.

Erectile dysfunction is also associated with neuropathy. Studies indicate that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms.

Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of patients with diabetes experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations, 50 - 75% of them due to diabetes. The number is increasing as the prevalence in diabetes type 2 rises. According to a 2005 study in the Lancet, every 30 seconds someone in the world receives a lower limb amputation due to diabetes. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. A 2006 study reported that people with diabetes who develop foot infections are 155 times more likely to have an amputation than people who did not develop infections. Foot infections often develop from injuries. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

A 2003 government survey found that those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers. [See In-Depth Report #102: Peripheral artery disease and intermittent claudication.]

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in up to 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Charcot foot is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:

Patients should inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.
When washing the feet, the water should be warm (not hot) and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.
Moisturizers should be applied, but not between the toes.
Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.
Patients should not use medicated pads or try to shave the corns or calluses themselves.
Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of patients with diabetes wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole (LucRo) reduce pressure under the heel and front of the foot by 35 - 65% and may be particularly helpful. Custom-molded boots increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
Shoes should be changed often during the day.
Wear socks, particularly with extra padding (which can be specially purchased).
Patients should avoid tight stockings or any clothing that constricts the legs and feet.
Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
A specialist in foot care should be consulted for any problems.

Click the icon to see an image of foot inspection.

Treating Foot Ulcers in Diabetes. About one-third of foot ulcers will heal within 20 weeks with good wound care treatments. Some treatments are as follows:

Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
Felted foam may be helpful in healing ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, patients who had had ulcers that had not responded to treatment for over 3 months received daily treatments that lasted 90 minutes for 2 weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.
Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Diabetes accounts for 12,000 - 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults ages 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries -- probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.

The early and more common type of this disorder is called nonproliferative or background retinopathy. The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision.
If the capillaries become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These woolly areas may signal the development of proliferative retinopathy. Often there are no symptoms of progressing retinopathy. In this more severe condition, new abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2, although in one study over 20% had signs of retinopathy 6 years after diagnosis. In general, all patients with diabetes should have a yearly eye examination. Patients with no signs of retinal damage or low risk factors for retinopathy may only require screening every 2 - 3 years.

Click the icon to see an animation on diabetic retinopathy.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slow ability to do mental arithmetic.

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5 - 15% during flu epidemics, and they are six times more likely to be hospitalized with complications from flu than nondiabetic patients who have flu. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Diabetes doubles the risk for depression. Furthermore, depression, in turn, increases the risk for hyperglycemia and complications of diabetes, according to one study. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but may help patients control their blood sugar levels.

Diabetes changes bone quality and density, 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 fractures. The best medications for bone loss in patients with diabetes are bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [See In-Depth Report #18: Osteoporosis.]
Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

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

Diabetes increases the risk for other conditions, including:

Hearing loss
Periodontal disease
Carpal tunnel syndrome
Nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH); a particular danger for people who are obese
Colorectal cancer
Uterine cancer

Diabetes and Pregnancy. Both temporary diabetes that occurs during pregnancy (gestational diabetes) and pregnancy in a patient with existing diabetes can increase the risk for birth defects. Studies indicate that high blood sugar levels (hyperglycemia) may affect the developing fetus as soon as it is conceived.

Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes large amounts of insulin. This combination of high fetal blood levels of insulin and glucose can have significant effects:

Excessive fetal weight gain, which can lead to complications during delivery
Birth defects
Breathing problems and delayed lung development
Low blood sugar
Higher future risk for obesity and diabetes

In addition to endangering the fetus, diabetes also presents risks to the pregnant woman, particularly preeclampsia, which is a potentially dangerous condition involving very high blood pressure during pregnancy. Pregnant women with diabetes are also at greater risk for retinopathy.

Some recommendations for preventing complications include:

Intensive blood sugar control during pregnancy may reduce the risk for problems in the infant.
Monitoring blood glucose after meals may protect against preeclampsia more effectively than monitoring before meals.
Aerobic exercise before and during pregnancy can lower glucose levels. (All pregnant women, particularly those with diabetes, should check with their doctors before embarking on a rigorous exercise regimen.)
To prevent birth defects that affect the heart and nervous system, women with diabetes should take a higher dose of folic acid from the time of conception up to week 12 of pregnancy. They should also be checked for any heart problems.
Women with diabetes should have an eye examination during pregnancy and up to a year afterward.

Although there was some concern that short-acting insulin lispro might increase the risk for birth defects, the most recent evidence suggests that it does not. In fact, some experts believe it achieves a better outcome and should be preferred to regular insulin in pregnant women. More research is needed.

Effect on Estrogen. Diabetes appears to blunt some of the effects of estrogen, which may increase the risk for heart disease. Women with diabetes have a higher risk for early menopause, which, in one study, occurred at an average age of about 41 years.

Reproductive Cancers. Women with type 1 diabetes often have lumps in the breast that are benign but which make mammograms difficult to interpret. It is not clear whether these lumps are risk factors for breast cancer. One study indicated that women with diabetes have a higher risk for endometrial cancer and possibly for breast cancer.

Lack of Blood Glucose Control. Control of blood glucose levels is generally very poor in adolescents and young adults. Adolescents with diabetes are at higher risk than adults for ketoacidosis resulting from noncompliance. In a British study of young adults with type 1 diabetes, 15% were already hypertensive, and about half of these young people had signs of kidney damage. Young people who do not control glucose are also at high risk for permanent damage in small vessels, such as those in the eyes.

Self-Destructive Behaviors. One study found that young people with diabetes have a higher than average rate of suicidal fantasies. Although the actual rate of suicide was no higher than that of their nondiabetic peers, such thoughts are strongly associated with self-destructive behavior.

Of particular note, up to one-third of young women with type 1 diabetes have eating disorders and under-use insulin to lose weight. Anorexia and bulimia pose significant health dangers in any young person -- but they can be especially severe in people with diabetes.

Transplantation Procedures

Major advances in islet-cell transplantation are allowing more patients to come off insulin or reduce their use of it.

Major clinical trials are now using a specific islet-cell (also called beta-cell) transplantation procedure called the Edmonton protocol, which usually involves the following steps:

As soon as there are sufficient numbers of islets available for transplantation, the patient is given intravenous antibiotics and oral vitamins E, B6, and A.
A machine isolates islet cells taken from donor pancreases, generally from cadavers. Two or three organs are usually needed in order to supply enough islet cells to have any effect on insulin production. (This is a major limitation of the procedure.)
Once the islets have been isolated, they are injected directly in a major vein in the patient's liver.
The islets are carried to capillaries in the liver where they produce insulin.
Specific drugs, such as tacrolimus, sirolimus, or rapamycin (Rapamume), are used to suppress the immune system. (Unlike immunosuppressant drugs used in other transplantation procedures, these drugs do not contain steroids, which destroy islet cells.) Immunosuppressants are needed for the rest of the patient's life so that the body does not reject these foreign islet cells.
The procedure has to be performed two or more times over a period of 2 - 3 months. This generally requires multiple pancreas donors in order to achieve complete independence from insulin therapy. This is a major limitation to the procedure.

In 2006, the New England Journal of Medicine published the results of the first multicenter trial of the Edmonton protocol. The results indicated that this treatment may benefit some patients with severe type 1 diabetes. Of the 36 patients who underwent the transplant procedure, 44% no longer needed insulin injections a year after the final treatment. However, two-thirds of these insulin-independent patients needed to resume insulin injections within 2 years.

The Edmonton protocol achieved partial islet function in 28% of patients, which helped control hypoglycemic unawareness, a serious complication of diabetes. (In hypoglycemic unawareness, patients no longer recognize the symptoms of severe low blood sugar.) Even though these patients still needed insulin shots, they had better control of their diabetes. Researchers are continuing to work on refining the Edmonton protocol so that its benefits can be more sustainable and long lasting.

A major obstacle for the islet cell transplantation is the need for two or more donor pancreases to supply sufficient islet cells. Unfortunately, there are not enough pancreases available to make this procedure feasible for even 1% of patients. Researchers, then, are looking for alternative sources for islet cells. In one center, for example, researchers used pig islet cells as the donor source in children and did not administer immunosuppressant drugs. Half the children responded well to this approach. Another study reported that select patients may require only one donor.

Other research is focusing on umbilical cord cells, embryonic or adult stem cells, bone marrow transplantation, and other types of cellular therapies. These studies are still in very early stages, but experts predict that there will be major research advances in these fields in the coming years. A small, preliminary study published in 2007 in the Journal of the American MedicalAssociation looked at the effects of autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) in patients newly diagnosed with type 1 diabetes. AHST is an experimental treatment for type 1 diabetes. It involves treating a patient with high doses of drugs to suppress the immune system, then harvesting the patient’s own blood cells and re-infusing them back into the body. In the study, 14 out of 15 patients who underwent AHST were able to stop taking insulin shots.

Whole pancreas transplants and double transplants of pancreases and kidneys are proving to have a good long-term success rate for some patients with type 1 diabetes. The operations help to prevent further kidney damage, and long-term studies indicate that they may even eventually reverse some existing damage. There is some evidence that heart disease and diabetic neuropathy improve after pancreas transplantation (although not retinopathy). One 10-year study reported that survival rate at 10 years was 76%, and two-thirds of the patients had both pancreas and kidney function. Immunosuppressive drugs are needed lifelong with this procedure. Experts generally recommend transplants in cases of end-stage kidney failure or when diabetes poses more of a threat to the patient's life than the transplant itself.

Uncontrolled diabetes causes damage to many tissues of the body, including the kidneys. Kidney damage caused by diabetes most often involves thickening and hardening of the internal kidney structures. Strict blood glucose control may delay the progression of kidney disease in type 1 and type 2 diabetics.

Prevention

Fingerstick blood tests are now available that can test for autoantibodies that identify children who are at high risk for developing type 1 diabetes. At this time, however, there is no way to prevent type 1 diabetes, and all preventive therapies are investigative. Until there are ways to prevent the condition, such screening tests are expensive and provide little value.

Investigational approaches focus on preventing type 1 diabetes or at least delaying it as long as possible. Preventive measures are sometimes defined as primary and secondary:

Primary prevention attempts to preserve all beta cells before the disease process starts.
Secondary prevention aims to deter further beta cell destruction once it has started and before symptoms arise.

For primary prevention, one experimental approach involves oral insulin, which is taken as a pill once a day. Unlike insulin injections that lower blood sugar, oral insulin does not affect blood glucose levels because it is quickly broken down in the digestive system. It may, however, help calm the immune system and prevent its attack on beta cells. Another study is exploring whether docosahexaenoic acid (DHA), an omega-3 fatty acid, can help prevent development of autoimmune type 1 diabetes in newborns who are at high risk for the disease.

Secondary prevention focuses on preserving beta cells and their insulin-producing function. Researchers are exploring several treatments for patients who are newly diagnosed with type 1 diabetes. These experimental therapies include:

Rituximab (Rituxan), a monoclonal antibody drug used for treatment of rheumatoid arthritis and non-Hodgkin’s lymphoma, is being studied in patients with type 1 diabetes for its effects on disrupting the immune system’s attack on beta cells.
Immune-suppressing drugs, such as mycophenolate mofetil (MMF) alone or in combination with daclizumab (DZB), are used to prevent rejection in organ transplantation. Researchers hope that these drugs may be able to slow or stop the autoimmune disease process of type 1 diabetes.
CD3-antibody drug therapy is showing promise in retaining newly diagnosed patients’ natural insulin production and decreasing their need for insulin therapy.

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.jdrf.org -- Juvenile Diabetes Research Foundation
www.nei.nih.gov -- National Eye Institute
www.eatright.org -- American Dietetic Association
www.kidney.org -- National Kidney Foundation
www.diabetestrialnet.org -- Type 1 Diabetes International Clinical Trial Net
www.medicalert.org -- Bracelets or neck chain emblems with personal medical information
www.childrenwithdiabetes.com -- Children with diabetes online community

References

American Diabetes Association (ADA). Standards of medical care in diabetes. VI. Prevention and management of diabetes complications. Diabetes Care. 2007 Jan;30(Suppl 1):S15-24.

Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006 Nov 16;355(20):2071-84.

Hakonarson H, Grant SFA, Bradfield JP, Marchand L, Kim CE, Glessner JT, et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature. Published online 15 July 2007.

SEARCH for Diabetes in Youth Study Group , Liese AD, D'Agostino RB, Hamman RF, Kilgo PD, Lawrence JM, et al. The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006 Oct;118(4):1510-8.

Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30.

Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006 Nov 16;355(20):2085-98.

Skyler JS. Cellular therapy for type 1 diabetes: has the time come? JAMA. 2007 Apr 11;297(14):1599-600.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76.

Writing Group for the SEARCH for Diabetes in Youth Study Group , Dabelea D, Bell RA, D'Agostino RB, Imperatore G, Johansen JM, et al. Incidence of diabetes in youth in the United States. JAMA. 2007 Jun 27;297(24):2716-24.

Review Date:
7/19/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Vitamins

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

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

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

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

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

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

References

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Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2007 May 22; [Epub ahead of print]

Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Feb 21; [Epub ahead of print]

Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev. 2007;31(2):119-28. Epub 2007 Feb 28.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin d deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 ;92(9):3517-22. Epub 2007 May 29.

Clements RH, Katasani VG, Palepu R, Leeth RR, Leath TD, Roy BP, Vickers SM. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72(12):1196-202.

Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566.

Dietary Guidelines for Americans 2005. Dept of Health and Human Services, US Dept of Agriculture. Accessed 10/3/2007.

Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77.

Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation. 2007;116(13):1497-503.

Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2007 Sep 20; [Epub ahead of print]

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Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 2007;137(7):1808-1814.

J.G. Ray, C. Kearon, Q. Yi, P. Sheridan, and E. Lonn, for the Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Randomized Trial of Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. Ann Intern Med. 2007;146(11):761-767.

Kitchin B, Morgan SL. Not just calcium and vitamin D: other nutritional considerations in osteoporosis. Curr Rheumatol Rep. 2007;9(1):85-92.

Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.

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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

Gingivitis

admin — Wed, 03 Sep 2008 17:54:07 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention
References

Illustrations

Tooth anatomy

Gingivitis

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Gingivitis is inflammation of the gums (gingiva).

Alternative Names

Gum disease; Periodontal disease

Causes, incidence, and risk factors

Gingivitis is a form of periodontal disease. Periodontal disease involves inflammation and infection that destroys the tissues that support the teeth, including the gums, the periodontal ligaments, and the tooth sockets (alveolar bone).

Gingivitis is due to the long-term effects of plaque deposits. Plaque is a sticky material made of bacteria, mucus, and food debris that develops on the exposed parts of the teeth. It is a major cause of tooth decay. If you do not remove plaque, it turns into a hard deposit called tartar that becomes trapped at the base of the tooth. Plaque and tartar irritate and inflame the gums. Bacteria and the toxins they produce cause the gums to become infected, swollen, and tender.

Injury to the gums from any cause, including overly vigorous brushing or flossing of the teeth, can cause gingivitis.

The following raise your risk developing gingivitis:

General illness
Poor dental hygiene
Pregnancy (hormonal changes increase the sensitivity of the gums)
Uncontrolled diabetes

Misaligned teeth, rough edges of fillings, and ill-fitting or unclean mouth appliances (such as braces, dentures, bridges, and crowns) can irritate the gums and increase the risk of gingivitis.

Medications such as phenytoin and birth control pills, and heavy metals such as lead and bismuth are also associated with gingivitis.

Many people have gingivitis to a varying degree. It usually develops during puberty or early adulthood due to hormonal changes and may persist or recur frequently, depending on the health of your teeth and gums.

Symptoms

Bleeding gums (blood on toothbrush even with gentle brushing of the teeth)
Bright red or red-purple appearance to gums
Gums that are tender when touched, but otherwise painless
Mouth sores
Swollen gums
Shiny appearance to gums

Signs and tests

The dentist will examine your mouth and teeth and look for soft, swollen, red-purple gums. Deposits of plaque and tartar may be seen at the base of the teeth. The gums are usually painless or mildly tender.

No further testing is usually necessary, although dental x-rays and dental bone measurements may be done to determine whether the inflammation has spread to the supporting structures of the teeth.

See: Periodontitis

Treatment

The goal is to reduce inflammation. The teeth are cleaned thoroughly by the dentist or dental hygienist. This may involve various instruments or devices to loosen and remove deposits from the teeth.

Careful oral hygiene is necessary after professional tooth cleaning. The dentist or hygienist will show you how to brush and floss. Professional tooth cleaning in addition to brushing and flossing may be recommended twice per year or more frequently for severe cases. Antibacterial mouth rinses or other aids may be recommended in addition to frequent, careful, tooth brushing and flossing.

Repair of misaligned teeth or replacement of dental and orthodontic appliances may be recommended. Any other related illnesses or conditions should be treated.

Expectations (prognosis)

The removal of plaque from inflamed gums may be uncomfortable. Bleeding and tenderness of the gums should lessen within 1 or 2 weeks after professional cleaning and careful oral hygiene. Warm salt water or antibacterial rinses can reduce the puffiness. Over-the-counter anti-inflammatory medications will ease any discomfort from a rigorous cleaning.

Healthy gums are pink and firm in appearance. Strict oral hygiene must be maintained for your whole life or gingivitis will recur.

Complications

Recurrence of gingivitis
Periodontitis
Infection or abscess of the gingiva or the jaw bones
Trench mouth

Calling your health care provider

Call your dentist if symptoms of gingivitis are present, especially if you have not had a routine cleaning and examination in the last 6 months.

Call your health care provider if the dentist recommends medical treatment of underlying conditions that contribute to the development of gingivitis.

Prevention

Good oral hygiene is the best prevention against gingivitis because it removes the plaque that causes the disorder. The teeth should be brushed at least twice daily and flossed gently at least once per day. For people who are prone to gingivitis, brushing and flossing may be recommended after every meal and at bedtime. Consult the dentist or dental hygienist for instructions on proper brushing and flossing techniques.

Special appliances or tools may be recommended by the dentist for use by people who are particularly prone to plaque deposits. The use supplements does not replace thorough brushing and flossing. Appliances and tools may include special toothpicks, toothbrushes, water irrigation, or other devices.

Antiplaque or antitartar toothpastes or mouth rinses may be recommended by the dentist or dental hygienist.

Regular professional tooth cleaning is important to remove plaque that may develop even with careful brushing and flossing. Many dentists recommend having the teeth professionally cleaned at least every 6 months.

References

Ferri FF. Ferri’s Clinical Advisor: Instant Diagnosis and Treatment. 2005 ed. St. Louis, Mo: Mosby; 2005:447-448:333.

Marx J. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 5th ed. St. Louis, Mo: Mosby; 2002:898.

American Academy of Periodontology. Parameter on plaque-induced gingivitis. J Periodontol. 2000; 71(5 Suppl): 851-2.

Review Date: 5/28/2008

Reviewed By: Jason S. Baker, DMD, Oral and Maxillofacial Surgeon, Private Practice, Yonkers, New York. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_001056

Periodontitis

admin — Wed, 03 Sep 2008 17:54:08 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention

Illustrations

Gingivitis

Swollen gums

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Periodontitis is inflammation and infection of the ligaments and bones that support the teeth.

Alternative Names

Pyorrhea - gum disease; Inflammation of gums - involving bone

Causes, incidence, and risk factors

Periodontitis occurs when inflammation or infection of the gums (gingivitis) is untreated or treatment is delayed. Infection and inflammation spreads from the gums (gingiva) to the ligaments and bone that support the teeth. Loss of support causes the teeth to become loose and eventually fall out. Periodontitis is the primary cause of tooth loss in adults. This disorder is uncommon in childhood but increases during adolescence.

Plaque and tartar accumulate at the base of the teeth. Inflammation causes a pocket to develop between the gums and the teeth, which fills with plaque and tartar. Soft tissue swelling traps the plaque in the pocket. Continued inflammation eventually causes destruction of the tissues and bone surrounding the tooth. Because plaque contains bacteria, infection is likely and a tooth abscess may also develop, which increases the rate of bone destruction.

Symptoms

Breath odor
Gums that appear bright red or red-purple
Gums that appear shiny
Gums that bleed easily (blood on toothbrush even with gentle brushing of the teeth)
Gums that are tender when touched but are painless otherwise
Loose teeth
Swollen gums

Note: Early symptoms resemble gingivitis.

Signs and tests

Examination of the mouth and teeth by the dentist shows soft, swollen, red-purple gums. Deposits of plaque and calculus may be visible at the base of the teeth, with enlarged pockets in the gums. The gums are usually painless or mildly tender, unless a tooth abscess is also present. Teeth may be loose and gums may be receded.

Dental x-rays reveal the loss of supporting bone and may also show the presence of plaque deposits under the gums.

Treatment

The goal of treatment is to reduce inflammation, eliminate pockets if present, and address any underlying causes. Rough surfaces of teeth or dental appliances should be repaired. General illness or other conditions should be treated.

It is important to have the teeth cleaned thoroughly. This may involve use of various instruments or devices to loosen and remove deposits from the teeth (scaling). Meticulous home oral hygiene is necessary after professional tooth cleaning to limit further destruction. The dentist or hygienist will demonstrate brushing and flossing techniques. It is often recommended that patients with periodontitis have professional tooth cleaning more frequently than twice a year.

Surgery may be necessary. Deep pockets in the gums may need to be opened and cleaned. Loose teeth may need to be supported. Your dentist may need to remove a tooth or teeth so that the problem doesn't get worse and spread to nearby teeth.

Expectations (prognosis)

Some people find the removal of dental plaque from inflamed gums to be uncomfortable. Bleeding and tenderness of the gums should go away within 1 or 2 weeks of treatment. (Healthy gums are pink and firm in appearance.)

You need to follow careful oral hygiene for your entire life or the disorder may return.

Complications

Infection or abscess of the soft tissue (facial cellulitis)
Infection of the jaw bones (osteomyelitis)
Return of periodontitis
Tooth abscess
Tooth loss
Tooth flaring or shifting
Trench mouth

Calling your health care provider

Consult your dentist if signs of gum disease are present.

Prevention

Good oral hygiene is the best means of prevention. This includes thorough tooth brushing and flossing, and regular professional dental cleaning. The prevention and treatment of gingivitis reduces the risk of development of periodontitis.

Review Date: 5/28/2008

Reviewed By: Jason S. Baker, DMD, Oral and Maxillofacial Surgeon, Private Practice, Yonkers, New York. Review provided by VeriMed Healthcare Network

A.D.A.M. Copyright

adam.com

Source Doc: 1_001059

Stress

FitSugar — Wed, 08 Oct 2008 17:35:26 -0700

In This Report

Highlights
Introduction
The Body's Response
Complications
Conditions with Similar Sym...
Treatment
Risk Factors
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Some people are pre-programmed for a heightened response to stress by conditions in the womb. Pregnant women under stress who eat a diet high in protein and low in carbohydrates have babies with higher cortisol levels. Later on, these levels increase in response to stress.
The impact of stress on the heart and circulation system is becoming more clear. Stress causes the body to release inflammatory markers that may worsen heart and circulatory diseases as well as inflammatory disease, such as rheumatoid arthritis. High levels of inflammatory markers are associated with increased risk of heart attack and stroke. Extreme stress can also produce a condition that mimics a heart attack, but is reversible. People under severe stress can experience irregular heart beats that make them susceptible to sudden cardiac death.
Stress also increases the risk of developing type 2 diabetes in women.
Traumatic stress has long been known to cause amnesia, emotional numbness, nightmares, and memory problems. Now it is known that traumatic emotional stress can cause permanent changes in the brain that interfere with the normal way information is accepted, coded, and retrieved.
The good news is that our physical response to stress is increasingly understood. Knowing what occurs at the cellular level may help researchers find more ways to counteract the detrimental physical and emotional effects of stress.

Introduction

Stress affects most people in some way. Acute (sudden, short-term) stress leads to rapid changes throughout the body. Almost all body systems (the heart and blood vessels, the immune system, the lungs, the digestive system, the sensory organs, and brain) gear up to meet the perceived danger.

These stresses could prove beneficial in a critical, life-or-death situation. Over time, however, repeated stressful situations put a strain on the body that may contribute to physical and psychological problems. Chronic (long-term) stress can have real health consequences and should be addressed like any other health concern.

Fortunately, research is showing that lifestyle changes and stress-reduction techniques can help people learn to manage their stress.

People can experience stress from external or internal factors.

External stressors include adverse physical conditions (such as pain or hot or cold temperatures) or stressful psychological environments (such as poor working conditions or abusive relationships). Humans, like animals, can also experience external stressors.
Internal stressors can also be physical (infections, inflammation) or psychological (such as intense worry about a harmful event that may or may not occur). As far as anyone can tell, internal psychological stressors are rare or absent in most animals except humans.

Stressors can also be defined as short-term (acute) or long-term (chronic).

Acute Stress. Acute stress is the reaction to an immediate threat, commonly known as the fight or flight response. The threat can be any situation that is perceived, even subconsciously or falsely, as a danger.

Common acute stressors include:

Noise (which can trigger a stress response even during sleep)
Crowding
Isolation
Hunger
Danger
Infection
High technology effects (playing video games, frequently ringing mobile phones)
Imagining a threat or remembering a dangerous event

Under most circumstances, once the acute threat has passed, levels of stress hormones return to normal. This is called the relaxation response.

Chronic Stress. Frequently, modern life poses ongoing stressful situations that are not short-lived. The urge to act (to fight or flee) must therefore be controlled. Stress, then, becomes chronic.

Common chronic stressors include:

On-going highly pressured work
Long-term relationship problems
Loneliness
Persistent financial worries

The Body's Response

The best way to envision the effect of acute stress is to imagine yourself in a primitive situation, such as being chased by a bear.

In response to seeing the bear, a part of the brain called the hypothalamic-pituitary-adrenal (HPA) system is activated.

Release of Steroid Hormones and the Stress Hormone Cortisol. The HPA systems trigger the production and release of steroid hormones (glucocorticoids), including the primary stress hormone cortisol. Cortisol is very important in organizing systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

Release of Catecholamines. The HPA system also releases certain neurotransmitters (chemical messengers) called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (also called adrenaline).

Catecholamines activate an area inside the brain called the amygdala, which appears to trigger an emotional response to a stressful event. In the case of the bear, this emotion is most likely fear.

Release of Neuropeptide S. The brain releases neuropeptide S, a small protein that modulates stress by decreasing sleep and increasing alertness and a sense of anxiety. This gives the person a sense of urgency to run away from the bear.

Effects on Long- and Short-Term Memory. During the stressful event, catecholamines also suppress activity in areas at the front of the brain concerned with short-term memory, concentration, inhibition, and rational thought. This sequence of mental events allows a person to react quickly, either to fight the bear or to flee from it. It also interferes with the ability to handle difficult social or intellectual tasks and behaviors during that time.

On the other hand, neurotransmitters at the same time signal the hippocampus (a nearby area in the brain) to store the emotionally loaded experience in long-term memory. In primitive times, this brain action would have been essential for survival, since long-lasting memories of dangerous stimuli (such as the large bear) would be critical for avoiding such threats in the future.

The stress response also affects the heart, lungs, and circulation:

As the bear comes closer, the heart rate and blood pressure increase instantaneously.
Breathing becomes rapid, and the lungs take in more oxygen.
The spleen discharges red and white blood cells, allowing the blood to transport more oxygen throughout the body. Blood flow may actually increase 300 - 400%, priming the muscles, lungs, and brain for added demands.

The effect on the immune system from confrontation with the bear is similar to organizing a defensive line of soldiers to potentially critical areas. The steroid hormones reduce the activity in parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be repositioned. These immune-boosting troops are sent to the body's front lines where injury or infection is most likely to occur, such as the skin and the lymph nodes.

As the bear gets closer, fluids are diverted from nonessential locations, including the mouth. This causes dryness and difficulty in talking. In addition, stress can cause spasms of the throat muscles, making it difficult to swallow.

The stress effect moves blood flow away from the skin to support the heart and muscle tissues. This also reduces blood loss in the event that the bear causes a wound. The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Stress shuts down digestive activity, a nonessential body function during short-term periods of hard physical work or crisis.

Once the threat has passed and the effect has not been harmful (for example, the bear has not wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also return to normal.

Complications

In prehistoric times, the physical changes in response to stress were an essential adaptation for meeting natural threats. Even in the modern world, the stress response can be an asset for raising levels of performance during critical events, such as a sports activity, an important meeting, or in situations of actual danger or crisis.

If stress becomes persistent and low-level, however, all parts of the body's stress apparatus (the brain, heart, lungs, vessels, and muscles) become chronically over- or under-activated. Such chronic stress may produce physical or psychological damage over time. Acute stress can also be harmful in certain situations, particularly in individuals with preexisting heart conditions.

Studies suggest that the inability to adapt to stress is associated with the onset of depression or anxiety. In one study, two-thirds of subjects who experienced a stressful situation had nearly 6 times the risk of developing depression within that month.

Some evidence suggests that repeated release of stress hormones produces hyperactivity in the hypothalamic-pituitary-adrenal (HPA) system, and disrupts normal levels of serotonin, the nerve chemical that is critical for feelings of well-being. Some people appear to be more at risk for an overactive HPA system under stress, including those with the personality traits that cause perfectionism. Certainly, on a more obvious level, stress reduces the quality of life by reducing feelings of pleasure and accomplishment. In addition, relationships are often threatened in times of stress.

The full impact of mental stress on heart disease is just coming to light, but the underlying mechanisms are not always clear. Stress can certainly influence the activity of the heart when it activates the automatic part of the nervous system that affects many organs, including the heart. Such actions and others could theoretically affect the heart badly in several ways:

Sudden stress increases the pumping action and rate of the heart, while at the same time causing the arteries to constrict (narrow). This restricts blood flow to the heart. A 2002 study suggested that such actions may be responsible for some cases of acute stress that have been associated with a higher risk for serious heart problems. These problems include heart rhythm abnormalities and heart attacks, and even death in people with heart disease.
Emotional effects of stress alter the heart rhythms, which could pose a risk for serious arrhythmias (rhythm abnormalities) in people with existing heart rhythm disturbances.
Stress causes blood to become stickier (possibly in preparation of potential injury), increasing the likelihood of an artery-clogging blood clot.
Stress appears to impair the clearance of fat molecules in the body, raising blood-cholesterol levels, at least temporarily.
Stress that leads to depression appears to be associated with increased intima-medial thickness, a measure of the arteries that signifies worsening blood vessel disease.
Chronic stress may lead to the production of immune factors called cytokines, although study results vary widely. Cytokines produce an inflammatory response that is now believed to be responsible for damaging the arteries. Such damage contributes to heart disease. New studies indicate that some people under stress may have increased levels of C-reactive protein (CRP), a risk marker for heart attack. Each 1 mg/L increase in CRP has been linked to a 20% increased risk of myocaridal ischemia, a condition that signals poor blood flow to the heart muscle.
Stress causes the body to release inflammatory markers into the bloodstream. These markers may worsen heart disease or increase the risk of heart attack or stroke.
Studies have reported an association between stress and high blood pressure, which may be more pronounced in men than in women. According to some evidence, people who regularly experience sudden spikes in blood pressure (caused by mental stress) may, over time, develop injuries in the inner lining of their blood vessels. In one 20-year study, for example, men who periodically measured highest on the stress scale were twice as likely to have high blood pressure as those with normal stress.

Evidence is still needed to confirm any clear-cut relationship between stress and heart disease. For example, a 2002 study in Scotland found no greater risk for actual heart disease or heart events even in men who reported higher mental stress. In fact, higher stress was associated with fewer heart events. Men with high stress levels did tend to complain of chest pain and to go to the hospital for it more often than those with lower stress. They also went to the hospital more often.

Evidence links stress to heart disease in men, particularly in work situations where they lack control. The association between stress and heart problems in women is weaker, and there is some evidence that the ways women cope with stress may be more heart-protective. In one study, men were more apt than women to use alcohol or eat less healthily in response to stress, which might account for their higher heart risks from stress. Different stressors may affect genders differently. In one study, work stress was associated with a higher risk for heart disease in men, but marital stress -- not work stress -- was associated with more severe heart disease in women with existing heart problems.

A condition called stress cardiomyopathy (or Takotsubo cardiomyopathy) is widely recognized. In this disease, intense emotional or physical stress causes severe but reversible heart dysfunction. The patient experiences chest pain, and EKGs and echocardiograms indicate a heart attack, but further tests show no underlying obstructive coronary artery disease.

Acute emotional stress can create abnormal heartbeats. MRI studies show that asymmetric brain activity may play a role in making a stressed heart susceptible to ventricular arrhythmias by creating electrical instability. In some patients, this can cause sudden cardiac death.

Psychological stress is also recognized as a possible cause of acute coronary syndrome (ACS), a collection of symptoms that signify heart attack or approaching heart attack. In one study of men who suffered ACS at work or up to 2 hours after work, many of the men were found to have anger and negative emotions. A 2007 review of studies on blood qualities, coagulation, fibrinolysis, and platelet reactivity found that high levels of psychological stress are associated with harmful changes to the blood. The research suggests that stress has the potential to trigger ACS, particularly in patients with heart disease. The studies also suggest that the risk is greatest immediately after the stressful incident, rather than during it.

Stress Reduction and Heart Disease. Studies suggest that treatments that reduce psychological distress improve long-term outlook in people with heart disease, including after a heart attack. Evidence indicates that stress management programs may reduce the risk of heart attacks by up to 75% in people with heart disease. Specific stress management techniques may help some problems but not others. For example, acupuncture in one study helped people with heart failure but had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure.

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.

Chronic stress affects the immune system in complicated ways, and may have various results.

Susceptibility to Infections. Chronic stress appears to blunt the immune system's response to infections, and may even impair a person's response to immunizations. Several studies have shown that people under chronic stress have low white blood cell counts and are vulnerable to colds. Once a person catches a cold or flu, stress can make symptoms worse. People who carry the herpes virus or HIV may be more susceptible to viral activation following exposure to stress. Even more serious, some research has found that HIV-infected men with high stress levels progress more rapidly to AIDS when compared to those with lower stress levels.

Inflammatory Response. Some evidence suggests that chronic stress triggers an over-production of certain immune factors called cytokines. In excess levels, these chemicals can have very damaging effects. A recent study found that students unable to cope with stress had high levels of TNF-alpha, an inflammatory cytokine. Such findings may partly explain the association between chronic stress and numerous diseases, including heart disease and asthma.

Whether or not stress causes or aggravates cancer is not entirely clear. One study reported no association between stressful life events and recurrence in women who had been treated for breast cancer. Nevertheless, some animal studies suggest that lack of control over stress (not simply stress itself) had negative effects on immune function and contributed to tumor growth.

That being said, a 2007 study found that stress activates a gene that may cause metastatic cancer, as measured by increasing levels of the marker AGR2.

Although stress reduction techniques have no effect on survival rates, studies show that they are very helpful in improving a cancer patient's quality of life. Stress is also known to be one cause of hyponatremia (low plasma sodium levels) in cancer patients. Fortunately, this imbalance can be corrected with drugs called AVP-receptor agonists, developed for use in heart failure.

The brain and intestines are strongly related, and are controlled by many of the same hormones and parts of the nervous system. Indeed, some research suggests that the gut itself has features of a primitive brain. It is not surprising then that prolonged stress can disrupt the digestive system, irritating the large intestine and causing diarrhea, constipation, cramping, and bloating. Excessive production of digestive acids in the stomach may cause a painful burning.

Irritable Bowel Syndrome. Irritable bowel syndrome (or spastic colon) is strongly related to stress. With this condition, the large intestine becomes irritated, and its muscular contractions are spastic rather than smooth and wave-like. The abdomen is bloated, and the patient experiences cramping and alternating periods of constipation and diarrhea. Sleep disturbances due to stress can make irritable bowel syndrome even worse.

Peptic Ulcers. It is now well-established that most peptic ulcers are either caused by the H. pylori bacteria or the use of nonsteroidal anti-inflammatory (NSAID) medications (such as aspirin and ibuprofen). Nevertheless, studies still suggest that stress may predispose someone to ulcers, or sustain existing ulcers. Some experts estimate that social and psychological factors play some contributing role in 30 - 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. In any case, some experts believe that the anecdotal relationship between stress and ulcers is so strong that attention to psychological factors is still warranted.

Inflammatory Bowel Disease. Although stress is not a cause of inflammatory bowel disease (Crohn's disease or ulcerative colitis), there are reports of an association between stress and symptom flare-ups. One study, for example, found that while short-term (over the previous month) stress did not significantly exacerbate ulcerative colitis symptoms, long-term perceived stress tripled the rate of flare-ups compared to patients who did not report feelings of stress.

Stress can have varying effects on eating problems and weight.

Weight Gain. Often stress is related to weight gain and obesity. Many people develop cravings for salt, fat, and sugar to counteract tension. As a result, they gain weight. Weight gain can occur even with a healthy diet, however, in some people exposed to stress. In addition, the weight gained is often abdominal fat, a predictor of diabetes and heart problems.

The release of cortisol, a major stress hormone, appears to encourage abdominal fat and may be the primary connection between stress and weight gain. Cortisol is a glucocorticoid. These hormones, along with insulin, appear to be responsible for stress-related food cravings. A 2005 study showed that hormonally induced cravings for "comfort foods" may have a biological benefit for managing stress. Eating comfort foods appears to reduce the negative hormonal and behavioral changes associated with stress, which might lessen the impact of stress on an individual. Carbohydrates in particular have been found to significantly increase levels of tryptophan and large neutral amino acids. This produces serotonin, which improves mood and performance under stress.

A 2007 study proposes a "reward-based stress eating" model. In this theory, stress and tasty, high-calorie foods cause the brain to make chemicals called endogenous opioids. These neurotransmitters help protect against the harmful effects of stress by slowing activity of a brain process called the hypothalamic-pituitary-adrenal (HPA) axis, thus weakening the stress response. Repeated stimulation of the reward pathways through stress-induced HPA stimulation, eating tasty food, or both, may lead to changes in the brain that cause compulsive overeating.

Weight Loss. Some people suffer a loss of appetite and lose weight during periods of stress. In rare cases, stress may trigger hyperactivity of the thyroid gland, stimulating appetite but causing the body to burn up calories at a faster than normal rate.

Eating Disorders. Chronically elevated levels of stress chemicals have been observed in patients with anorexia and bulimia. Some studies, however, have not found any strong link between stress and eating disorders. More work is needed to determine if changes in stress hormones are a cause or result of eating disorders.

Chronic stress has been associated with the development of insulin resistance, a condition in which the body is unable to use insulin effectively to regulate glucose (blood sugar). Insulin resistance is a primary factor in diabetes. In the Healthy Women Study, a large population of healthy women was studied for 15 years. Very stressful life events and severe depression greatly increased the risk of developing insulin resistance.

In another study of more than 33,000 Swedish workers, the development of type 2 diabetes was strongly correlated with work stress and low emotional support. However, the effect was seen in women, but not in men.

Stress can also exacerbate existing diabetes by impairing the patient's ability to manage the disease effectively.

Researchers are attempting to find the relationship between pain and emotion, but the area is complicated by many factors, including effects of personality types, fear of pain, and stress itself. A recent study suggests that chronic pain may impair the action of neutrophils, thereby weakening the immune response.

Muscular and Joint Pain. Stress may intensify chronic pain caused by arthritis and other conditions. According to a study on patients with rheumatoid arthritis, however, stress management techniques do not appear to have much effect on arthritic pain. Psychological distress also plays a significant role in the severity of back pain. Some studies have clearly associated job dissatisfaction and depression to back problems, although it is still unclear if stress is a direct cause of the back pain.

Headaches. Tension-type headaches are highly associated with stress and stressful events. Sometimes the headache does not start until long after the stressful event has ended. Additionally, stress can contribute to the development of headaches or cause headaches to occur more often.

Some research suggests that people who suffer from tension-type headaches may have some biological predisposition for translating stress into muscle contractions. Among the wide range of possible migraine triggers is emotional stress (although the headaches often erupt after the stress has eased). One study suggested that women with migraines tend to have personalities that over-respond to stressful situations.

The tensions of unresolved stress frequently cause insomnia, generally keeping the stressed person awake or causing awakening in the middle of the night or early morning. This appears to be due to the fact that stress causes physiological arousal during non-rapid eye movement (NREM) sleep.

Sexual Function. Stress can lead to diminished sexual desire and an inability to achieve orgasm in women. Stress response can cause androgen levels to drop, causing temporary impotence in men. Part of the stress response involves the release of brain chemicals that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis, which can prevent erection.

Premenstrual Syndrome. Some studies indicate that the stress response in women with premenstrual syndrome may be more intense than in those without the syndrome.

Fertility. Stress may even affect fertility. Stress hormones have an impact on the hypothalamus gland, which produces reproductive hormones. Severely elevated cortisol levels can even shut down menstruation. One small study reported a significantly higher incidence of pregnancy loss in women who had both high stress and prolonged menstrual cycles. Another reported that women with stressful jobs had shorter periods than women with low-stress jobs.

Effects on Pregnancy. Old wives' tales about a pregnant woman's emotions affecting her baby may have some credence. Stress may cause physiologic alterations, such as increased adrenal hormone levels or resistance in the arteries, which may interfere with normal blood flow to the placenta. Maternal stress during pregnancy has been linked to a higher risk for miscarriage, lower birth weights, and increased incidence of premature births. Some evidence also suggests that stress experienced by expectant mothers can even influence the way in which the baby's brain and nervous system will react to stressful events. Indeed, one study found a higher rate of crying and low attention in infants of mothers who had been stressed during pregnancy.

Menopause. A drop in estrogen levels during perimenopause and menopause may be responsible for changes in mood precipitated by stress. Estrogen replacement therapy can soften this response to stressful events.

Stress affects the brain, particularly memory, but the effects vary widely depending on whether the stress is acute or chronic.

Effect of Acute Stress on Memory and Concentration. Studies indicate that the immediate effect of acute stress impairs short-term memory, particularly verbal memory. On the plus side, high levels of stress hormone during short-term stress have been associated with enhanced memory storage and greater concentration on immediate events. The difference in effect may be due to how cortisol impacts glucocorticoid receptors in the hippocampus and prefrontal cortex. In a study of 20 men and 20 women, those whose cortisol levels increased in response to unpleasant, emotionally arousing photos had less memory recall later than those whose cortisol levels did not rise.

Effect of Chronic Stress on Memory. If stress becomes chronic, sufferers often experience loss of concentration at work and home, and they may become inefficient and accident-prone. In children, the physiologic responses to chronic stress can clearly inhibit learning. Chronic stress in older people may play an even more important role in memory loss than the aging process. In one study, for example, older adults with low stress hormone levels tested as well as younger adults in cognitive tests; those with higher stress levels tested 20 - 50% lower.

Studies have connected long-term exposure to excess amounts of cortisol (a major stress hormone) to shrinking of the hippocampus, the brain’s memory center. For example, two studies reported that groups who suffered from post-traumatic stress disorder (Vietnam veterans and women who suffered from sexual abuse) displayed up to 8% shrinking of the hippocampus. It is not yet known if this shrinking is reversible.

Allergies. Stress has been related to skin allergies. Some research suggests that stress, not indoor pollutants, may actually be a cause of the so-called sick-building syndrome. Sick-building syndrome produces allergy-like symptoms, such as eczema, headaches, asthma, and sinus problems, in office workers.

Compulsive Hoarding. People with obsessive-compulsive disorder (OCD) and compulsive hoarding are far more likely to have experienced a traumatically stressful event than people with OCD who are not hoarders. Hoarders who have experienced traumatic events have significantly more severe hoarding than those who have not been traumatized. The strongest association with traumatic stress is found in the clutter factor of compulsive hoarding, rather than in difficulty discarding objects.

Chronic Fatigue. Stress increases the risk of developing chronic fatigue syndrome, although studies suggest that high levels of emotional instability may genetically predispose someone to the syndrome.

Skin Disorders. Stress plays a role in worsening numerous skin conditions, including hives, psoriasis, acne, rosacea, and eczema, and is one of the most common causes of eczema. Unexplained itching may also be caused by stress. Evidence suggests that experiencing the stress of a traumatic event (parental divorce or separation, or a severe disease in a family member) before age 2 increases the risk of developing eczema.

Unexplained Hair Loss (Alopecia Areata). Alopecia areata is hair loss that occurs in localized (individual) patches. The cause is unknown, but stress is suspected as a player in this condition. For example, hair loss often occurs during periods of intense stress, such as mourning.

Teeth and Gums. Stress has now been implicated in increasing the risk for periodontal disease, which is disease in the gums that can cause tooth loss.

People under chronic stress often turn to alcohol abuse or tobacco use for relief. The damage these self-destructive habits cause under ordinary circumstances is compounded by the physiological effects of stress itself. Many people also resort to abnormal eating patterns or passive activities, such as watching television. The results of a national survey, released in February 2006, show that: "Americans engage in unhealthy behaviors such as comfort eating, poor diet choices, smoking and inactivity to help deal with stress."

Alcohol affects receptors in the brain that reduce stress. Lack of nicotine increases stress in smokers, which creates a cycle of dependency on smoking. One study indicated that nicotine has calming effects in women but not in men. In fact, in the study, smoking increased aggression in men.

The cycle is self-perpetuating: a sedentary routine, an unhealthy diet, alcohol abuse, and smoking all promote heart disease. They also interfere with sleep patterns, and lead to increased rather than reduced tension levels. Drinking four or five cups of coffee, for example, can cause changes in blood pressure and stress hormone levels similar to those produced by chronic stress. Animal fats, simple sugars, and salt are known contributors to health problems.

Conditions with Similar Symptoms

The physical symptoms of anxiety disorders mirror many symptoms of stress, including:

A fast heart rate
Rapid, shallow breathing
Increased muscle tension

Anxiety is an emotional disorder, however, and is characterized by feelings of apprehension, uncertainty, fear, or panic. Unlike stress, the triggers for anxiety are not necessarily or even usually associated with specific stressful or threatening conditions. Some individuals with anxiety disorders have numerous physical complaints, such as headaches, gastrointestinal disturbances, dizziness, and chest pain. Severe cases of anxiety disorders are debilitating, and interfere with career, family, and social spheres.

Depression can be a disabling condition, and, like anxiety disorders, may result from chronic stress. A 2005 study of Canadian workers found that individuals with a high level of work-related stress are more than twice as likely to experience a major depressive episode, compared with people under less stress. Evidence also suggests that certain people may be genetically susceptible to depression after stressful life events. Depression also mimics some of the symptoms of stress, including changes in appetite, sleep patterns, and concentration. Serious depression, however, is distinguished from stress by feelings of sadness, hopelessness, loss of interest in life, and, sometimes, thoughts of suicide. Acute depression is also accompanied by significant changes in the patient's functioning. Professional therapy may be needed in order to determine if depression is caused by stress, or if it is the primary problem.

Post-traumatic stress disorder (PTSD) is a reaction to a very traumatic event, and it is actually classified as an anxiety disorder. The event that brings on PTSD is usually outside the norm of human experience, such as intense combat or sexual assault. The patient struggles to forget the traumatic event and frequently develops emotional numbness and event-related amnesia. Often, however, there is a mental flashback, and the patient re-experiences the painful circumstance in the form of dreams and disturbing thoughts and memories. These thoughts and dreams resemble or recall the trauma. Other symptoms may include lack of pleasure in formerly enjoyed activities, hopelessness, irritability, mood swings, sleep problems, inability to concentrate, and an excessive startle-response to noise.

Treatment

Perhaps the best general approach for treating stress can be found in the elegant passage by Reinhold Niebuhr, "Grant me the courage to change the things I can change, the serenity to accept the things I can't change, and the wisdom to know the difference." The process of learning to control stress is life-long, and will not only contribute to better health, but a greater ability to succeed in one's own agenda.

Stress can be a factor in a variety of physical and emotional illnesses, which should be professionally treated. Many stress symptoms are mild and can be managed by over-the-counter medications (for example, aspirin, acetaminophen, or ibuprofen for tension headaches; antacids, anti-diarrhea medications, or laxatives for mild stomach distress). A physician should be consulted, however, for physical symptoms that are out of the ordinary, particularly those that get worse or wake a person up at night. A mental health professional should be consulted for unmanageable acute stress or for severe anxiety or depression. Often short-term therapy can resolve stress-related emotional problems.

In choosing specific strategies for treating stress, several factors should be considered.

No single method is always successful: A combination of approaches is generally most effective.
What works for one person does not necessarily work for someone else.
Stress can be positive as well as negative. Appropriate and controllable stress provides interest and excitement and motivates the individual to greater achievement. A lack of stress may lead to boredom and depression.

Stress may play a part in making people vulnerable to illness. A physician or psychologist should be consulted if there are any indications of accompanying medical or psychological conditions, such as heart symptoms, significant pain, anxiety, or depression.

People often succeed in relieving stress for the short term. However, they go back to previous ways of stressful thinking and behaving because of outside pressure, long-held beliefs, or habits. The following are some obstacles to managing stress:

The fight or flight urge: The very idea of relaxation can feel threatening, because it is perceived as letting down one's guard. For example, an over-demanding boss may put a subordinate into a psychological state of fighting-readiness, even though there is no safe opportunity for the subordinate to fight back or express anger. Stress builds up, but the worker has the illusion, even subconsciously, that the stress itself is providing safety or preparedness. For this reason, the employee does nothing to correct the condition.
Many people are afraid of being perceived as selfish if they engage in stress-reducing activities that benefit only themselves. The truth is that self-sacrifice (in the form of not reducing one’s stress) may be inappropriate and even damaging, if the person making the sacrifice is unhappy, angry, or physically unwell.
Some people believe that certain emotional responses to stress, such as anger, are natural and unchangeable features of personality. Research has shown, however, that with cognitive behavioral therapy, individuals can be taught to change their emotional reactions to stressful events.

It is essential to remember that reducing stress and staying relaxed clears the mind, so it can begin appropriate actions to get rid of the stress-ridden conditions.

Although treating stress cannot cure medical problems, stress management can be a very important part of medical treatment. Specific stress reduction approaches may benefit different medical problems. For example, acupuncture in one study helped reduce harmful heart muscle actions in people with heart failure, but it had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure. Stress reduction may improve well-being and quality of life for many patients who are experiencing stress because of severe or chronic medical conditions.

Important Note: Never use stress reduction techniques as the only treatment, or in place of proven treatments, for any medical condition.

Risk Factors

At some point in their lives virtually everyone will experience stressful events or situations that overwhelm their natural coping mechanisms. In one poll, 89% of respondents indicated that they had experienced serious stress in their lives. Some people are simply biologically prone to stress. Many outside factors influence susceptibility as well.

Conditions Most Likely To Produce Stress-Related Health Problems. Conditions that are most likely to be associated with stress and negative physical effects include the following:

An accumulation of persistent stressful situations, particularly those that a person cannot easily control (for example, high-pressured work plus an unhappy relationship)
Persistent stress following a severe acute response to a traumatic event (such as an automobile accident)
Acute stress accompanying serious illness, such as heart disease

Factors That Influence the Response to Stress. People respond to stress differently, depending on different factors:

Early nurturing: Abusive behavior towards children may cause long-term abnormalities in the hypothalamus-pituitary system, which regulates stress.
Personality traits: Certain people have personality traits that cause them to over-respond to stressful events.
Genetic factors: Some people have genetic factors that affect stress, such as having a more or less efficient relaxation response. One study found a genetic abnormality in serotonin regulation that was connected with a heightened reaction of heart rates and blood pressure in response to stress. (Serotonin is a brain chemical involved with feelings of well-being.)
Immune regulated diseases: Certain diseases that are associated with immune abnormalities (such as rheumatoid arthritis or eczema) may actually weaken a response to stress.
The length and quality of stressors: Naturally, the longer the duration and more intense the stressors, the more harmful the effects.

Individuals at Higher Risk for Stress. Studies indicate that the following people are more vulnerable to the effects of stress than others:

Older adults: As people age, achieving a relaxation response after a stressful event becomes more difficult. Aging may simply wear out the systems in the brain that respond to stress, so that they become inefficient. The elderly, too, are very often exposed to major stressors such as medical problems, the loss of a spouse and friends, a change in a living situation, and financial worries. No one is immune to stress, however, and it may simply go unnoticed in the very young and old.
Women in general and working mothers specifically: Working mothers, regardless of whether they are married or single, face higher stress levels and possibly adverse health effects, most likely because they bear a greater and more diffuse work load than men or other women. This has been observed in women in the U.S. and in Europe. Such stress may also have a domino and harmful effect on their children. It is not clear, however, if stress has the same adverse effects on women's hearts as it does on men's.
Less educated individuals.
Divorced or widowed individuals: Numerous studies indicate that unmarried people generally do not live as long as their married contemporaries.
Anyone experiencing financial strain, particularly long-term unemployed and those without health insurance.
People who are isolated or lonely.
People who are targets of racial or sexual discrimination.
People who live in cities.

Children are frequent victims of stress because they are often unable to communicate their feelings accurately. They also have trouble communicating their responses to events over which they have no control. Certain physical symptoms, notably repeated abdominal pain without a known cause, may be indicators of stress in children.

Various conditions can affect their susceptibility to stress.

Low Birth Weight. One study reported that low birth weight and slow growth up until age 7 was related to stress in adulthood.

Parental Stress. Parental stress, especially in mothers, is a particularly powerful source of stress in children, even more important than poverty or overcrowding. In a 2002 study, for example, young children of mothers who were highly stressed (particularly if they were depressed) tended to be at high risk for developing stress-related problems. This was especially true if the mothers were stressed during both the child's infancy and early years. Some evidence even supports the old idea that stress during pregnancy can have adverse effects on the infant's mood and behavior. Older children with stressed mothers may become aggressive and anti-social. One study suggested that stress-reduction techniques in parents may improve their children's behavior.

Gender Differences in Adolescent Stress. Adolescent boys and girls experience equal amounts of stress, but the source and effects may differ. Girls tend to become stressed from interpersonal situations, and stress is more likely to lead to depression in girls than in boys. For boys, however, specific events, such as changing schools or getting poor grades, appear to be the major sources of stress.

A report issued in October 2006 by the American Academy of Pediatrics recommends more unstructured play time for children. The report notes that today’s overscheduled, hurried lifestyle that many children experience is a source of stress and anxiety in some children.

In a 1999 study of 46,000 workers, health care costs were 147% higher in workers who were stressed or depressed than in others who were not. Furthermore, according to one survey, 40% of American workers describe their jobs as very stressful, making job-related stress an important and preventable health hazard.

Several studies are now suggesting that job-related stress is as great a threat to health as smoking or not exercising. Stress impairs concentration, causes sleeplessness, and increases the risk for illness, back problems, accidents, and lost time from work. Work stress can lead to harassment or even violence while on the job. At its most extreme, chronic stress places a burden on the heart and circulation that in some cases may be fatal. The Japanese even have a word for sudden death due to overwork, karoushi.

Not all work stress is harmful. However, studies suggest the following job-related stressors may increase people's -- particularly men's -- health risks:

Having no say in decisions that affect one's responsibilities
Unrelenting and unreasonable performance demands
Lack of effective communication and conflict-resolution methods among workers and employers
Lack of job security
Night-shift work, long hours, or both
Too much time spent away from home and family
Wages not matching levels of responsibility

Reducing Stress on the Job. Many institutions within the current culture, while paying lip service to stress reduction, put intense pressure on individuals to behave in ways that increase tension. Yet, there are numerous effective management tools and techniques available to reduce stress. Furthermore, treatment for work-related stress has proven benefits for both the employee and employer. In one study, at the end of 2 years, a company that instituted a stress management program saved nearly $150,000 in workers compensations costs (the cost of the program was only $6,000). Other studies have reported specific health benefits resulting from workplace stress-management programs. In one of the studies, workers with hypertension experienced reduced blood pressure after even a brief (16-hour) program that helped them manage stress behaviorally.

In general, however, few workplaces offer stress management programs, and it is usually up to the employee to find their own ways to reduce stress. Here are some suggestions:

Seek out someone in the Human Resources department or a sympathetic manager and communicate concerns about job stress. Work with them in a non-confrontational way to improve working conditions, letting them know that productivity can be improved if some of the pressure is off.
Establish or reinforce a network of friends at work and at home.
Restructure priorities and eliminate unnecessary tasks.
Learn to focus on positive outcomes.
If the job is unendurable, plan and execute a career change. Send out resumes or work on transfers within the company.
If this isn't possible, be sure to schedule daily pleasant activities and physical exercise during free time.

It may be helpful to keep in mind that bosses are also victimized by the same stressful conditions they are imposing. For example, in one study of male managers in three Swedish companies, those who worked in a bureaucracy had greater stress-related heart risks than those who worked in companies with social supports.

Caregivers of Family Members. Studies show that caregivers of physically or mentally disabled family members are at risk for chronic stress. One study reported that overall mortality rates were over 60% higher in caregivers who were under constant stress. Spouses caring for a disabled partner are particularly vulnerable to a range of stress-related health threats, including influenza, depression, heart disease, and even poorer survival rates. Caring for a spouse with even minor disabilities can induce severe stress.

Specific risk factors that put caregivers at higher risk for severe stress, or stress-related illnesses, include:

Caregiving wives: Some studies suggest that wives experience significantly greater stress from caregiving than husbands do.
Having a low income.
Being African-American: African-American people tend to be in poorer physical health, and have lower incomes, than Caucasians. They therefore face greater stress as caregivers to their spouses than their white counterparts.
Living alone with the patient.
Helping a highly dependent patient.
Having a difficult relationship with the patient.

Intervention programs that are aimed at helping the caregiver approach the situation positively can reduce stress, and help the caregiver maintain a positive attitude. A 2002 program also demonstrated that moderate-intensity exercise was very helpful in reducing stress and improving sleep in caregivers.

Health Professional Caregivers. Caregiving among the health professionals is also a high risk factor for stress. One study, for example, found that registered nurses with low job control, high job demands, and low work-related social support experienced very dramatic health declines, both physically and emotionally.

People who are less emotionally stable or have high anxiety levels tend to experience specific events as more stressful than others. Some doctors describe an exaggerated negative response to stress as "catastrophizing" the event (turning it into a catastrophe). Nevertheless, a 2003 study of patients with anxiety disorder did not find any differences in actual physical response to stress (heart rate, blood pressure, release of stress hormones) compared to people without anxiety.

The lack of an established network of family and friends predisposes one to stress disorders and stress-related health problems, including heart disease and infections. A study, meanwhile, reported that older people who maintain active relationships with their adult children are buffered against the adverse health effects of chronic stress-inducing situations, such as low income or lower social class. Another study suggested this may be because people who live alone are unable to discuss negative feelings as a means to relieve their stress.

Studies of people who remain happy and healthy despite many life stresses conclude that most have very good networks of social support. One study indicated that support even from strangers reduced blood pressure surges in people undergoing a stressful event. Many studies suggest that having a pet helps reduce medical problems aggravated by stress, including heart disease and high blood pressure.

Lifestyle Changes

A healthy lifestyle is an essential companion to any stress-reduction program. General health and stress resistance can be enhanced by regular exercise, a diet rich in a variety of whole grains, vegetables, and fruits, and by avoiding excessive alcohol, caffeine, and tobacco.

Of interest, a 2003 study suggested that fish oil, which has been associated with a lower risk for heart disease and stroke, may blunt some of the harmful effects of mental stress on the heart.

In one study, high doses of vitamin C reduced stress levels and blood pressure. The doses given were higher than the recommended upper limit of 2,000 mg per day. High doses may cause headaches and diarrhea. Long-term use increases risk for kidney stones and has other adverse effects in specific individuals.

Exercise in combination with stress management techniques is extremely important for many reasons:

Exercise is an effective distraction from stressful events.
Exercise may directly blunt the harmful effects of stress on blood pressure and the heart (exercise protects the heart in any case).

Usually, a varied exercise regime is more interesting, and thus easier to stick to. Start slowly. Strenuous exercise in people who are not used to it can be very dangerous and any exercise program should be discussed with a physician. In addition, half of all people who begin a vigorous training regime drop out within a year. The key is to find activities that are exciting, challenging, and satisfying. The following are some suggestions:

Sign up for aerobics classes at a gym.
Brisk walking is an excellent aerobic exercise that is free and available to nearly anyone. Even short brisk walks can relieve bouts of stress.
Swimming is an ideal exercise for many stressed people, including pregnant women, individuals with musculoskeletal problems, and those who suffer exercise-induced asthma.
Yoga or Tai Chi can be very effective, combining many of the benefits of breathing, muscle relaxation, and meditation while toning and stretching the muscles. The benefits of yoga may be considerable. Numerous studies have found it beneficial for many conditions in which stress is an important factor, such as anxiety, headaches, high blood pressure, and asthma. It also elevates mood and improves concentration and the ability to focus.

As in other areas of stress management, making a plan and executing it successfully develops feelings of mastery and control, which are very beneficial in and of themselves. Start small. Just 10 minutes of exercise three times a week can build a good base for novices. Gradually build up the length of these every-other-day sessions to 30 minutes or more.

Cognitive-behavioral techniques (CBT) are among the most effective ways of reducing stress. A 2005 study found that CBT training can have a long-term impact one’s ability to cope with stress. In the study, participants received CBT training and were exposed to a stressful situation 4 months later. The participants who had received CBT training had significantly less stress-induced cortisol responses compared with individuals who had received no stress management training. This effect was observed in both men and women, although the CBT had a greater effect on men. CBT may be particularly helpful when the source of stress is chronic pain or a chronic disease. In fact, in a study of patients with HIV, CBT was more helpful than support groups for improving well-being and quality-of-life.

A typical CBT approach includes identifying sources of stress, restructuring priorities, changing one's response to stress, and finding methods for managing and reducing stress.

Identifying Sources of Stress. One key component in most CBT approaches is a diary that keeps an informal inventory of daily events and activities. While this exercise might itself seem stress producing (and yet one more chore), it need not be done in painstaking detail. A few words accompanying a time and date are usually enough to serve as reminders of significant events or activities.

The first step is to note activities that put a strain on energy and time, trigger anger or anxiety, or precipitate a negative physical response (such as a sour stomach or headache).

Also note positive experiences, such as those that are mentally or physically refreshing or produce a sense of accomplishment.

After a week or two, try to identify two or three events or activities that have been significantly upsetting or overwhelming.

Questioning the Sources of Stress. Individuals should then ask themselves the following questions:

Do these stressful activities meet my goals or someone else's?
Have I taken on tasks that I can reasonably accomplish?
Which tasks are under my control and which ones aren't?

Restructuring Priorities: Adding Stress Reducing Activities. The next step is to attempt to shift the balance from stress-producing to stress-reducing activities. Eliminating stress is rarely practical or feasible, but there are many ways to reduce its impact.

Consider as many relief options as possible. Examples include:

Listen to music. Music is an effective stress reducer in both healthy individuals and people with health problems. In one study, for example, students who listened to a well-known gentle classical piece of music during a stressful task had reduced feelings of anxiety, heart rate, and blood pressure.
Take long weekends or, ideally, vacations.
If the source of stress is in the home, plan times away, even if it is only an hour or two a week.
Replace unnecessary time-consuming chores with pleasurable or interesting activities.
Make time for recreation. This is as essential as paying bills or shopping for groceries.
Own a pet. In a study of people with high blood pressure, pet owners had much lower blood pressure increase in response to stress than non-owners. Note that owning a pet was beneficial only for people who like animals to begin with.

Discuss Feelings. The concept of communication and letting your feelings out has been so excessively promoted and parodied that it has nearly lost its value as good psychological advice. Nevertheless, feelings of anger or frustration that are not expressed in an acceptable way may lead to hostility, a sense of helplessness, and depression.

Expressing feelings does not mean venting frustration on waiters and subordinates, boring friends with emotional minutia, or wallowing in self-pity. In fact, because blood pressure may spike when certain chronically hostile individuals become angry, some therapists strongly advise that just talking, not simply venting anger, is the best approach, especially for these people.

The primary goal is to explain and assert one's needs to a trusted individual in as positive a way as possible. Direct communication may not even be necessary. Writing in a journal, writing a poem, or composing a letter that is never mailed may be sufficient.

Expressing one's feelings solves only half of the communication puzzle. Learning to listen, empathize, and respond to others with understanding is just as important for maintaining the strong relationships necessary for emotional fulfillment and reduced stress.

Keep Perspective and Look for the Positive. Reversing negative ideas and learning to focus on positive outcomes helps reduce tension and achieve goals. The following steps, using an example of a person who is alarmed at the prospect of giving a speech, may be useful:

First, identify the worst possible outcomes (forgetting the speech, stumbling over words, humiliation, audience contempt).
Rate the likelihood of these bad outcomes happening (probably very low or that speaker wouldn't have been selected in the first place).
Envision a favorable result (a well-rounded, articulate presentation with rewarding applause).
Develop a specific plan to achieve the positive outcome (preparing in front of a mirror, using a video camera or tape recorder, relaxation exercises).
Try to recall previous situations that initially seemed negative but ended well.

Use Humor. Research has shown that humor is a very effective mechanism for coping with acute stress. Keeping a sense of humor during difficult situations is a common recommendation from stress management experts. Laughter not only releases the tension of pent-up feelings and helps keep perspective, but it appears to have actual physical effects that reduce stress hormone levels. It is not uncommon for people to recall laughing intensely even during tragic events, such as the death of a loved one, and to remember this laughter as helping them to endure the emotional pain.

Relaxation Methods. Since stress is here to stay, everyone needs to develop methods to promote the relaxation response, the natural unwinding of the stress response. Relaxation lowers blood pressure, respiration, and pulse rates, releases muscle tension, and eases emotional strains. This response is highly individualized, but there are certain approaches that seem to work.

Combinations are probably best. For example, in a study of children and adolescents with adjustment disorder and depression, a combination of yoga, a brief massage, and progressive muscle relaxation effectively reduced both feelings of anxiety and stress hormone levels. A 2005 study of organ transplant recipients showed that training in meditation and gentle yoga led to significant improvements in quality of sleep and lessened anxiety and depression.

No one should expect a total resolution of stress from these approaches, but if done regularly, these programs can be very effective.

Acupuncture. Some evidence suggests that acupuncture may also be helpful. It might even improve some physical factors associated with stress and health problems. For example, in a study of heart failure patients, acupuncture improved stress-related heart muscle activity, which could be an important benefit in these patients. However, acupuncture had no effect on stress-related blood pressure or heart rate.

Hypnosis. Hypnosis may also benefit some people with severe stress. In one study of patients with irritable bowel, stress reduction by hypnosis correlated with improvement in many bowel symptoms.


*Deep Breathing Exercises.* During stress, breathing becomes shallow and rapid. Taking a deep breath is an automatic and effective technique for winding down. Deep breathing exercises consciously intensify this natural physiologic reaction and can be very useful during a stressful situation, or for maintaining a relaxed state during the day.	Inhale through the nose slowly and deeply to the count of 10. Make sure that the stomach and abdomen expand, but the chest does not rise. Exhale through the nose, slowly and completely, also to the count of 10. To help quiet the mind, concentrate fully on breathing and counting through each cycle. Repeat five to 10 times, and make a habit of doing the exercise several times each day, even when not feeling stressed.
*Muscle Relaxation.* Muscle relaxation techniques, often combined with deep breathing, are simple to learn and very useful for getting to sleep. In the beginning it is useful to have a friend or partner check for tension by lifting an arm and dropping it. The arm should fall freely. Practice makes the exercise much more effective and produces relaxation much more rapidly. Small studies have reported beneficial effects on blood pressure in patients with high blood pressure who use this technique.	After lying down in a comfortable position without crossing the limbs, concentrate on each part of the body. Maintain a slow, deep breathing pattern throughout this exercise. Tense each muscle as tightly as possible for a count of five to 10, and then release it completely. Experience the muscle as totally relaxed and lead-heavy. Begin with the top of the head and progress downward to focus on all the muscles in the body. Be sure to include the forehead, ears, eyes, mouth, neck, shoulders, arms and hands, fingers, chest, belly, thighs, calves, and feet. Once the external review is complete, imagine tensing and releasing internal muscles.
*Meditation.* Meditation, used for many years in Eastern cultures, is now widely accepted in this country as a relaxation technique. The goal of all meditative procedures, both religious and therapeutic, is to quiet the mind (essentially, to relax thought). Small studies have suggested that regular meditation can benefit the heart and help reduce blood pressure. Better research is needed, however, to confirm such claims. Some recommend meditating for no longer than 20 minutes in the morning after awakening and then again in early evening before dinner. Even once a day is helpful. Note: Meditating before going to bed may cause some people to wake up in the middle of the night, alert and unable to return to sleep. New practitioners should understand that it can be difficult to quiet the mind, and should not be discouraged by lack of immediate results. Several techniques are available. A few are discussed here. The only potential risks from meditating are in people with psychosis, in whom meditating may trigger a psychotic event.	Mindfulness Meditation. Mindfulness is a common practice that focuses on breathing. It employs the basic technique used in other forms of meditation. Sit upright with the spine straight, either cross-legged or sitting on a firm chair with both feet on the floor, uncrossed. With the eyes closed or gently looking a few feet ahead, observe the exhalation of the breath. As the mind wanders, simply note it as a fact and returns to the "out" breath. It may be helpful to imagine your thoughts as clouds dissipating away. Transcendental Meditation (TM). TM uses a mantra (a word that has a specific chanting sound but no meaning). The person meditating repeats the word silently, letting thoughts come and go. In one study, TM was as effective as exercise in elevating mood. Mini-Meditation. The method involves heightening awareness of the immediate surrounding environment. Choose a routine activity when alone. For example: While washing dishes, concentrate on the feel of the water and dishes. Allow the mind to wander to any immediate sensory experience (sounds outside the window, smells from the stove, colors in the room). If the mind begins to think about the past or future, or fills with unformed thoughts or worries, redirect it gently back. This redirection of brain activity from your thoughts and worries to your senses disrupts the stress response and prompts relaxation. It also helps promote an emotional and sensual appreciation of simple pleasures already present in a person's life.
*Biofeedback.* Biofeedback is a technique that measures bodily functions, like breathing, heart rate, blood pressure, skin temperature, and muscle tension. By watching these measurements, you can learn how to alter these functions by relaxing or holding pleasant images in your mind.	During biofeedback, electric leads are taped to a subject's head. The person is encouraged to relax using methods such as those described above. Brain waves are measured and an audible signal is emitted when alpha waves are detected, a frequency which coincides with a state of deep relaxation. By repeating the process, subjects associate the sound with the relaxed state and learn to achieve relaxation by themselves.
*Massage Therapy.* A 2005 report that reviewed data from multiple studies showed that massage therapy decreases cortisol levels. Another 2005 study showed that massage from a stable romantic partner can reduce physiological responses to a subsequent stressful event. In the study, women who received instructed shoulder-neck-massage from their partners before being exposed to stress had lowered cortisol responses, and smaller heart rate increases after the stressful event. Interestingly, massage was more beneficial than receiving social support from the partner, indicating the power of physical touch in managing stress. Several massage therapies are available.	Many massage techniques are available, such as the following: Swedish massage is the standard massage technique. It uses long smooth strokes, and kneading and tapping of the muscles. Shiatsu applies intense pressure to the same points targeted in acupuncture. It can be painful, but people report deep relaxation afterward. Reflexology manipulates acupuncture points in the hands and feet.

Some people who experience chronic stress seek herbal or natural remedies. It should be strongly noted, however, that just as with standard drugs, so-called natural remedies can cause problems, sometimes serious ones.

Probiotics. Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria. They do so through various mechanisms, such as excreting certain acids (for example, lactate, acetate) that inhibit harmful bacteria. They may also compete with them for nutrients. Stress reduces levels of these bacteria. Research even suggests that probiotics may help maintain remission in patients with IBD. In one small study, people suffering from stress and exhaustion significantly reduced their stress symptoms and gastrointestinal complaints when they took a probiotic supplement for 6 months. The specific bacteria that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Aromatherapy. The smell of lavender has long been associated with a calming effect. In a Japanese study, 14 women who were put in a room with a lavender scent experienced reduced mental stress. Several aromatherapies are now used for relaxation. Use caution, however, as some of the exotic plant extracts in these formulas have been associated with a wide range of skin allergies.

Valerian. Valerian is an herb that has sedative qualities and may reduce stress and associated physical effects. This herb is on the FDA's list of generally safe products. Of note, however, the herb's effects could be dangerously increased if it is used with standard sedatives. Other interactions and long-term side effects are unknown. Side effects include vivid dreams. High doses of valerian can cause blurred vision, excitability, and changes in heart rhythm.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, however, 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 numerous 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.

Special Warning on Kava. Kava has been commonly used to reduce anxiety and stress. It is now highly associated with liver injury and even liver failure in a few cases. Experts now strongly warn against its use.

People seeking relief from stress should be wary of things that promise a quick cure, or plans that include the purchase of expensive treatments. These treatments may be useless and sometimes even dangerous.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.nami.org -- National Alliance for the Mentally Ill
www.nmha.org -- National Mental Health Association
www.amtamassage.org -- American Massage Therapy Association
www.cognitivetherapynyc.com -- American Institute for Cognitive Therapy
www.aabt.org -- Association for the Advancement of Behavior Therapy
www.healthyminds.org -- The American Psychiatric Association
www.naswdc.org -- The National Association of Social Workers
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.stress.org -- The American Institute of Stress

References

Ginsburg KR and the Committee on Communications and Committee on Psychosocial Aspects of Child and Family Health. Clinical Report: The Importance of Play in Promoting Healthy Child Development and Maintaining Strong Parent-ChildBonds.Last accessed on 17 October, 2006.

Dallman MF, Pecoraro NC, la Fleur SE. Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Behav Immun. 2005;19:275-280.

Wang J. Work stress as a risk factor for major depressive episode(s). Psychol Med. 2005;35:865-871.

Hammerfald K, Grau M, et al. Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects-A randomized controlled trial. Psychoneuroendocrinology. 2005 Sep 22; epub ahead of print.

Kreitzer MJ, Gross CR, Ye X, et al. Longitudinal impact of mindfulness meditation on illness burden in solid-organ transplant recipients. Prog Transplant. 2005;15:166-172.

Field T, Hernandez-Reif M, Diego M, et al. Cortisol decreases and serotonin and dopamine increase following massage therapy. Int J Neurosci. 2005;115:1397-1413.

Ditzen B, Neumann I, Bodenmann G, et al. Romantic Partner Interaction Reduces Endocrine and Autonomic Stress Responses in Women. New Research Abstracts, Annual Meeting of the American Psychiatric Association. Washington, D.C. 2005. Abstract NR140.

Review Date:
10/16/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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