FitSugar

Indoor Smokeless Cigarettes?

FitSugar — Wed, 24 Oct 2007 14:30:00 -0700

Smoking, thank goodness, is banned in most public places because second-hand smoke is a known health hazard. So crowds of smokers hang out on the streets puffing away since they are banned from doing so indoors. Well, what if cigarettes were smokeless? One UK nightclub, celebrity hangout Chinawhite, in London's Soho district, is trying out these new smokeless cigarettes. Made in China, the manufacturer says the invention has no harmful side-effects because there is no smoke or tar.

How does it work? This six-inch white plastic stick uses a battery-powered atomizer to create realistic puffs of "smoke," while the tip glows red when you suck. It gives a smoker the smoking experience and the nicotine high without the use of tobacco. Each cigarette contains one filter, which provides enough nicotine for 350 puffs, or about 30 cigarettes.

The thing is though, it may be cutting down on secondhand smoke, but the smoker is still getting the nicotine. There's some talk that these e-cigs may even give the user more nicotine than an average cigarette. They're also a lot more expensive, around $208 for the starter kit, and you have to continue to buy replacement cartridges.

What do you think about these smokeless cigarettes? Since they create no smoke, do you think they should be allowed in places such as restaurants, bars, buses, meetings, public buildings, and airplanes?

Source

Sweet Potatoes: Not Just For Thanksgiving

FitSugar — Thu, 29 Mar 2007 03:00:00 -0700

I think sweet potatoes have gotten a bad rap because of their high carb content. They shouldn't be overlooked because they are one of the most nutritious foods you can eat. Not only that, they are a great option if you're craving something sweet.

Want to know why they're so good for you?

They're bursting with healing antioxidants due to their high levels of vitamins A and C. Antioxidants work in your body to help eliminate free radicals which are the chemicals that damage cells and are associated with the development of conditions like colon cancer. These vitamins are also anti-inflammatory, so they can help reduce the severity of certain conditions like asthma and arthritis.
They're low in calories and have no fat.
They are labeled as a low-glycemic index food, by virtue of their slow digestion and absorption, produce gradual rises in blood sugar and insulin levels, and have proven benefits for health.
They are also high in vitamin B6, manganese, copper, potassium, and iron.
Eating sweet potatoes with their high vitamin A content may help save your life if you or someone you love is a smoker. A common carcinogen in second-hand smoke known as benzopyrene induces vitamin A deficiency. If you aren't getting enough of this vitamin, you could increase your chances of developing emphysema. A diet rich in vitamin A can help prevent it.

Fit's Tips: When you go to a restaurant, choosing sweet potato fries is a healthier choice than regular French fries, but they're still deep-fried. To get your fill of the nutritious goodness in sweet potatoes, bake them whole (don't cut or poke them) in the oven at 400 for 40 minutes to an hour. If you love the fry idea, but don't want all the fat, just cut them up (leave the skins on), drizzle a little olive oil over them, and bake in a pan. Mmmmmm.

What Do You Think of This Commercial About Second-Hand Smoke?

FitSugar — Sun, 11 Feb 2007 13:43:48 -0800

Non-small cell lung cancer

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

About 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke, according to a 2006 Surgeon General report.
Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Advexin is in Phase II clinical trials for NSCLC.
Studies are finding that NSCLC tumors in people who never smoked have a much higher rate of epithelial growth-factor receptor (EGFR) mutations. EGFR helps new blood vessels grow to feed tumors. This discovery may help tailor future treatments to specific patient populations. It also helps explain why some newer treatments seem effective mostly in patients who never smoked.

Treatment News:

Video-assisted thoracic surgery (VATS) is a new, less-invasive surgical technique that uses a thin tube containing a miniature camera and surgical instruments. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients, in the treatment of early stage non-small cell lung cancer (NSCLC).
Bevacizumab, a monoclonal antibody, was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.
Gefitinib (Iressa), a drug that targets EGFR, proved disappointing in final clinical trials. However, erlotinib (Tarceva), a drug that targets a different part of the EGFR molecule, has shown benefits. Erlotinib is now approved as a second-line chemotherapy to treat patients with locally advanced or metastatic NSCLC after a previous course of chemotherapy failed.

Introduction

Although lung cancer accounts for only 13% of all cancers, it is among the most lethal, accounting for over 28% of all cancer deaths. It is more deadly than colon, breast, and prostate cancers combined. An estimated 160,390 people will die from lung cancer in 2007. Death rates have been declining in men over the past decade, and they have now stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air; only 10% is solid tissue.

Air is carried from the trachea (the windpipe) into the lung through flexible airways called bronchi.
Like the branches of a tree, the bronchi in turn divide into over a million smaller airways called bronchioles.
The bronchioles lead to grape-like clusters of microscopic sacs called alveoli.
In each adult lung, there are about 300 million of these tiny alveoli. A thin membrane makes up the alveoli sacs. Oxygen and carbon dioxide pass through this membrane to and from capillaries.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues).

Some experts believe all primary lung cancers come from a single common malignant (cancerous) stem cell that, as it copies itself, can develop into any one of these cancer types in different individuals.

In addition, cancers in the lung may have spread from other primary sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location; for example, "breast cancer with lung metastases."

Non-small cell lung cancers are categorized into three types: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. These separate types are grouped together because, in early stages before the cancers have spread, they all can be treated surgically.

Squamous Cell Carcinoma. Squamous cells are formed from reserve cells, which are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.

Click the icon to see an image of squamous cell carcinoma.

When squamous cell cancer metastasizes, it may travel to the bone, adrenal glands, liver, small intestine, and brain.

Squamous cell carcinoma is nearly always caused by smoking and used to be the most common cancer. It still makes up 25 - 40% of all lung cancers.

Adenocarcinoma. Adenocarcinomas usually arise from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung. In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 30 - 50% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women. In fact, a 2000 European study showed that nearly 34% of the women with lung cancer under investigation had adenocarcinoma, compared to 26.4% who had squamous cell carcinoma, and 22.3% with small cell lung cancer. Adenocarcinoma is also increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in recent decades in this lung cancer type may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into the lungs, thereby possibly increasing the risk for adenocarcinoma.

The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. Other common locations it spreads to include the other lung, the liver, the adrenal glands, and bone.

Click the icon to see an image of adenocarcinoma.

Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.

Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 20% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.

Click the icon to see an image of large cell carcinoma.

Small cell lung cancer may, like squamous cells, be derived from reserve cells or other cells in the epithelium. It causes 15 - 25% of all lung cancers; without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.

Click the icon to see an image of small cell carcinoma.

Causes

Cigarette Smoke. Smoking causes 87% of lung cancer deaths, accounting for 30% of all cancer deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:

In general, chronic exposure to nicotine may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.

The smoke is the most dangerous component of the cigarette. Chemicals formed during smoking trigger genetic mutations that lead to cancer. When people inhale cigarette smoke, they bring into their lungs tar that includes over 4,000 chemicals, some of which are carcinogenic (cancer-causing). Other inhaled chemicals in cigarette smoke that may increase the risk for cancer include cyanide, benzene, formaldehyde, methanol (wood alcohol), acetylene (the fuel used in torches), and ammonia. Smoke also contains nitrogen oxide and carbon monoxide, both of which are harmful gases.
Nicotine itself may be a hazard. A 2000 laboratory study suggested that the human body might be converting inhaled nicotine into a chemical called aminoketone, which has been linked to the formation of tobacco-related lung cancer. A 2001 study reported that nicotine triggered new blood vessel growth, which could, in theory, promote growth of any existing tumors. A study published in 2005 found that nicotine was responsible for disabling a gene that induces the death of cancer cells in lung tumors. Whether or not these studies apply to long-term use of nicotine replacement products (such as patches), or to cigarette smoking, is still unclear. The studies should certainly not discourage people from using nicotine replacement methods for quitting. However, these studies may indicate that people should not use these devices on a long-term basis.

Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon may be responsible for between 10% and 14% of lung cancer deaths, making it, after smoking, the second leading cause of this cancer.

Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. In one study, 53.8% of cigarette smokers, 66.7% of marijuana smokers, and all of those subjects who smoked both substances showed evidence of precancerous changes in the lungs.

There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts). A 2001 study estimated that it would cause an additional 8 deaths from lung cancer out of every 10,000 people or soldiers who were highly exposed to this substance. The study was based on a mathematical model, however, and the issue is not settled.

Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.

Click the icon to see an image of the tobacco plant.

Genetic mutations that cause cancer generally occur in two types of genes:

Tumor-suppressor genes, which prevent cells from endlessly copying themselves
Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in an uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. When normal, the tumor-suppressor genes are involved in cell repair and healthy copying of the cell. When they are damaged or blocked, out of control cell production can occur, leading to cancer. About 10% of the population may carry a gene that protects against lung cancer, by reducing levels of BPDE.
Chemotherapy resistance genes: Tumors that contain the p53 mutation may also be more resistant to chemotherapy.
Rb Mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
Mutations to the FHIT gene: Another potentially important mutation may be an abnormality in the FHIT gene. This mutation causes the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other carcinogens.

Symptoms

Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of malignant cells to other organs.

Early symptoms may include the following:

Frequent bouts of pneumonia, or pneumonia that does not clear up in a normal period of time
Coughing (particularly coughing up blood)
Weight loss
Fever
Shortness of breath
Chest pain

Later-stage symptoms include the following:

Shortness of breath: This common symptom is the result of cancer that has spread in the lung and the pleura, the membrane covering the lung.
Superior vena cava syndrome: In some cases, tumor growth or spreading of the cancer presses against the superior vena cava, a large vein that returns blood from the upper part of the body to the heart. When this happens, a condition called superior vena cava syndrome may occur, leading to obvious swelling in the arms and face.
Trouble swallowing: The esophagus is the pipe that takes food from the mouth to the stomach. The cancer may spread to or press against the esophagus, interfering with swallowing and nutrition.
Hoarseness: Cancer can damage the nerves that control the voice box, causing hoarseness.
Pancoast syndrome: Damage to the brachial plexus, a group of nerves branching from the neck, can cause pain, weakness, or numbness in the arm or hand (Pancoast syndrome).
Bronchoalveolar lung cancer may produce very large amounts of mucus.
Hypercalcemia: Some lung cancers produce substances that remove calcium from bone and release it into the bloodstream, causing a condition called hypercalcemia. Patients with this disorder can experience nausea, vomiting, constipation, weakness, and fatigue.

Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.

Risk Factors

Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. In 2007, lung cancer is expected to strike up to 213,380 Americans, and about 160,390 are expected to die from it.The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing.

Smoking appears to be the primary risk factor in 85 - 90% of lung cancers. About 15% of all people who smoke develop lung cancer. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.

An elevated risk for lung cancer can persist for more than 20 years after quitting smoking, although the risk drops significantly even in the first year after quitting. And, there are benefits to quitting smoking even for people who are well into middle age.


Quitting Age	Percentage
30	2%
40	3%
50	6%
60	10%

Second-Hand Smoke. The Environmental Protection Agency has classified second-hand smoke as a carcinogen (cancer-causing chemical). Exposure to second-hand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.

There may be some ethnic differences in lung cancer risk. For example, African-Americans face a risk that is two to four times higher than that in Caucasians, regardless of smoking status. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.

In China, an estimated one third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. A 2001 study reported that the lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.

People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes One study suggests that people with intense or prolonged exposure to radon in their homes do indeed face the same risk as miners exposed to similar levels of radon. A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for awhile in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend many hours to days in basements with detectable but moderate levels should consider taking protective measures.

Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer in smokers. With better protective measures, these rates are expected to fall in the future.

Other chemicals that put workers at risk for lung cancer include:

Arsenic (insecticide and herbicide sprayers, tanners, oil refinery workers)
Chloromethyl methyl ether (workers exposed to certain polymers, water repellents, or products using chloride and formaldehyde)
Chromium compounds (workers using certain alloys, paints, pigments, and preservatives)
Depleted uranium (soldiers exposed to weapons during battlefield conditions)
Crystalline silica

By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, a 2000 study suggests that agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals and may have cancer-preventing effects on the immune system.

Exposure to Smoke from Grills. Grilling and high-heat frying emit chemicals called heterocyclic amines, which are known to be carcinogenic. A 2000 study of Chinese women found that smokers who stir-fried meat daily and inhaled cooking fumes had a higher risk of lung cancer than did those who stir-fried meat less frequently. No higher risk was found among nonsmokers.

Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies, including a major analysis of vital statistics in 2002, have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, present in polluted air. The risk, if any, is very small.

A family history of lung cancer may play a role in increasing susceptibility to this disease. In one study, people who had parents or siblings with respiratory tract cancers had a 30% higher risk for lung cancer, compared to people without a family history. Women with mothers or sisters with lung cancer had triple the risk. A higher risk occurred in both smokers and nonsmokers. There was no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appeared to contribute to the danger in these individuals.

Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.

Lifestyle Changes

Quitting improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. It should be noted, however, that it can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to a fully healthy condition in which the risk for lung cancer is as low as for nonsmokers. Quitting is extremely difficult. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.

The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and incremental reduction.

At this time perhaps the most effective method for quitting is a combination of the following:

Nicotine replacement products that reduce withdrawal symptoms and cravings.
The antidepressants bupropion (Zyban) or nortriptyline (Pamelor, Aventyl), which reduce emotional effects and cravings associated with withdrawal, and improve abstinence rates.
Professional counseling or support organizations that may be effective, in addition to the medication, in helping people maintain abstinence.

[See In-Depth Report #41: Smoking.]

While people are in the process of quitting (and afterwards), they should maintain as healthy a lifestyle as possible.

Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may be protective against lung cancer in both smokers and non-smokers. Some studies have reported protection from specific plant chemicals (phytochemicals), such as the following:

Isothiocyanates. These chemicals are found in cruciferous vegetables (broccoli, cauliflower, and Brussels sprouts). They may help block the effects of carcinogens in smoke, suppress tumor growth, and inhibit growth-promoting steroid hormones.
Flavonoids. Major sources are apples, grapefruit, onions, red wine, and tea. In one study on flavonoids, apple eaters had the lowest cancer risk, 68% less than those who ate fruit infrequently. In another, those who ate relatively more onions, apples, and white grapefruit had less than half the lung cancer risk as people who ate relatively small amounts of these foods. Flavonoids are also found in soybeans, berries, broccoli, carrots, citrus fruits, eggplant, peppers, squash, and tomatoes. Specific flavonoids in dark chocolate may be protective against lung cancer (but not other cancers).
Lycopene. Lycopene is found in tomatoes, which have been associated with a lower risk for lung cancer. Cooking the tomatoes appears to increase the potency of lycopene.
Cryptoxanthin. Some studies suggest that eating foods rich in cryptoxanthin, a yellow-orange pigment, reduces the risk for lung cancer. Foods with high amounts of cryptoxanthin include pumpkin, corn, papaya, red bell peppers, tangerines, oranges, and peaches. More research is needed in this area, however.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Some evidence suggests the genistein (a type of isoflavone) in soy may have properties that are protective against lung cancer.

Click the icon to see an image of phytochemicals.

Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that the benefits come from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.

Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). Of interest was a 2002 study reporting that women who had a high intake of cheese had a lower risk of lung cancer. Despite these intriguing pieces of information, the ability of these substances to protect against lung cancer remains controversial, and discontinuation of smoking remains the best advice.

Click the icon to see an image of fats and oils.

Vitamin Supplements. Even with a healthful diet, smoking reduces the levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any protection from antioxidant supplements, including vitamins E, A, or beta carotene.

In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and beta carotene supplements may have harmful effects. A 2000 study, for example, reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. The strongest studies to date on negative effects of antioxidant supplements have reported 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. In other words, antioxidants may actually be harmful in people who already harbor cancer cells. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years prior to developing the disease. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

Trace Element Supplements. Trace elements may be important in cancer risk and prevention.

Selenium appears to inhibit cell production and may have other anti-cancer properties. A few studies have reported some protection with selenium. However, a major 2002 analysis supports previous work, indicating that taking selenium helps only people who are deficient to begin with.

Click the icon to see the benefits of selenium.

Zinc may prove to be more important than selenium. Some research suggests that zinc may help protect smokers by blocking cadmium. Smokers have higher levels of cadmium in their body, and there may be a link between cadmium and a higher risk for lung cancer. Some laboratory studies have indicated that zinc might help protect against tumor progression. There is no evidence that taking zinc supplements will reduce the risk for lung cancer, however.

A 2003 study reported a lower risk in lung cancer in men and women who were physically active. Both moderate and intensive exercises were associated with protection.

People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. Methods for removing radon include installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs) both block cyclooxygenase (COX) enzymes. NSAIDs block COX-1 and 2, and coxibs selectively block COX-2. Evidence now strongly suggests that the COX-2 enzyme plays a role in blood vessel growth (angiogenesis) that can feed lung cancers.

NSAIDs. NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). These agents inhibit COX-2, but they also target another COX enzyme. Studies are now reporting an association between regular use of aspirin or other NSAIDs and a reduced risk for non-small cell lung cancer.

COX-2 Inhibitors. The COX-2 inhibitors are more recent forms of NSAIDs. Currently, only celecoxib (Celebrex) is still on the market. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market due to their high risk of causing strokes and heart attacks. Because they target the COX-2 enzyme specifically, researchers are focusing on these drugs for a possible role in treating lung cancer and preventing recurrence.

Diagnostic Tests

Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. Regular screening for lung cancer using x-rays is therefore not currently recommended.

Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms, the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed.

The use of helical CT for early screening is still controversial. Studies of CT scans in smokers suggest that early screening will detect about 2% of lung cancers, most of these in early stages. In the studies, 62 - 82% of the patients with stage 1A cancer (when the tumor has not spread yet) were still alive at 5 years. Neither study, however, was controlled (compared with other groups, such as non-smokers). The survival figures were likely to be higher than in actual practice.

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

Evidence regarding the survival benefits of early detection is not clear. Many experts are highly opposed to widespread screening for lung cancer. Some evidence, for example, suggests that lung cancer cells in non-small cell lung cancer are often very aggressive at microscopic levels (before a tumor is formed). If this were true, the cancer would be highly likely to have already spread, long before it was visible with CT scans. Moreover, some studies have found no association between tumor size at the time of diagnosis and survival times. On the other hand, some suspicious areas detected by CT scans may actually be innocent, and these patients might be more likely to die from aggressive treatments than from the disorder itself.

It should also be noted that about 98% of suspicious areas seen on CT scans turn out to be benign. Even after rescreening, many scans will show suspicious areas that turn out to be harmless but will require invasive and expensive biopsies. Additional experience with CT scans, however, may allow experts to better determine which abnormalities are likely to be benign.

High-risk individuals who are still interested in early screening with CT scans should ask their doctor about available clinical trials.

Computed tomography is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Other imaging tests, however, may be useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).

Positron Emission Tomography. Positron emission tomography (PET), specifically a technique known as FDG/PET, is the most accurate noninvasive test for detecting early lung cancer. It is also the best imaging technique for staging lung cancers, not only those located in the lungs, but also those that have spread, particularly into the space between the two lungs (the mediastinum). With this imaging test, the patient is first injected with a specially formulated liquid sugar (called FDG), and then viewed with a machine that records energy given off by tumor cells.

PET is expensive and not widely available. However, its supporters suggest that it may prevent many unnecessary surgeries by identifying patients whose cancer has advanced past the stage at which surgery is helpful. There is some evidence that FDG/PET scan can detect a metabolic (processing) response to treatments that may help predict the outlook for the patient.

Scintigraphy. Scintigraphy is an imaging procedure in which patients are administered low-level radioactive agents that bind to cancer cells, which then can be tracked by special cameras to reveal the cancer cells' location and intensity. Agents selected are those that can best bind successfully with specific tumor types. For example, a 2001 study of the binding agent 111In-DOTA-LAN demonstrated excellent results in identifying non-small cell lung tumors. This study further suggests the possibility of using such highly-targeted binding agents as lung cancer treatments.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone metastases that can be associated with lung cancer.

Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.

Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of computed tomography scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA) or endoscopic ultrasound-guided needle aspiration (EUS-NA). Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 -10% risk for bleeding or collapsed lung with needle aspiration.

Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber-optic tube to view the area:

The procedure requires general anesthesia.
The surgeon passes surgical instruments and a fiber-optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.

Bronchoscopy. To locate cancer that develops in the central areas and major airways of the lung (usually squamous or small cell cancer), bronchoscopy is typically performed. The procedure is done as follows:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The doctor inserts a bronchoscope, a hollow flexible tube often containing a fiber-optic light source, into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the doctor to see the windpipe and major airways. In a procedure called fluorescence bronchoscopy, the doctor injects the patient with a drug that makes cancer tissue appear red when exposed to laser light from the bronchoscope.
The surgeon removes specimens for biopsy, ideally combining techniques to include cutting tissue, brushings, and a washing process called bronchoalveolar lavage (BAL). BAL involves injecting saline through the bronchoscope into the lung and then immediately suctioning the fluid back through the hollow tube of the bronchoscope; the fluid is then analyzed in the laboratory. Both brushing and washing procedures may be very valuable additions.

Advances in this procedure, such as laser-induced fluorescence endoscopic bronchoscopy, may improve early detection of cancer.

Bronchoscopy is usually very safe, but complications can occur; they include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

Mediastinoscopy. Mediastinoscopy uses a tube inserted between the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet metastasized.

Sputum Analysis for Presence of Cancer Cells. Some experts are now recommending an analysis of coughed-up sputum as a useful and cost-effective measure for identifying cancer cells, particularly those located in central areas of the lung. However, although sputum analysis appears to be as accurate as any other screening test currently conducted, it may miss cancers such as adenocarcinoma, which form in mucus-producing cells typically in the outer portion of the lungs. If a sputum analysis does not show cancer cells, but other signs of lung cancer are present, including blood in the sputum and suspicious areas on x-rays, other tests are performed.

Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some biomarkers may prove to reveal the presence of cancer cells before they are evident on CT scans or other imaging tests. For example, genetic mutations, notably K-ras and p53, can now be detected in cells found in sputum, or cells taken during bronchoscopy. Such mutations occur only with cancerous changes and may enable early detection. Other markers that prove to be important for predicting aggressive cancers are high levels of matrix metalloproteinase (MMP9) and vascular endothelial growth factor (VEGF), which are compounds involved with angiogenesis (the process in which blood vessels serving the tumor develop).

As part of the doctor's initial examination, patients may have a pulmonary function test to evaluate lung health and capacity. In addition, since the heart and lungs are often involved in complications following lung cancer surgery, the doctor may be especially interested in taking a complete history of those systems in patients who might need surgery.

Staging Systems

Tests to Determine Cancer Stage. After diagnosing non-small cell lung cancer, the doctor makes treatment choices by determining the cancer's stage (how large the tumor is and how far the cancer has spread). To stage the cancer and determine other aspects of the disease, a number of tests are conducted:

The cancer cells are examined microscopically for size, shape, and other configurations.
Computer tomography (CT), magnetic resonance imaging (MRI), or both, are used to scan the lung and perhaps other locations, such as the liver, upper abdomen, and brain, to determine the extent of the disease.

Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the general condition of the patient. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain, while bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might reveal the presence of other tumors. Also, according to a 2000 review, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.

In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several regions of the body. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies.

To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.

The TNM categories then determine the stage (numbered 0 to IV), indicating how advanced the cancer is.

TNM stands for Tumor, regional lymph Nodes, and Metastasis (cancer spread beyond the original tumor).

T refers to the size and extension of the tumor itself. In TX and T0, the tumor is indicated by cancer cells in sputum or lung samples but cannot be seen. Tis: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading. In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway.

In T2, the tumor has one or more of the following features:

It is greater than 3 cm
It involves the main airway
It is 2 cm or more away from the ridge (the carina) at the lowest part of the windpipe
It has invaded the pleura
It is associated with collapsed lung tissue (atelectasis) or swelling that blocks part (but not all) of the lung

In T3, a tumor of any size has directly invaded any of the following:

Chest wall
Diaphragm
The membrane covering organs and structures in the chest
The outer wall of the membrane around the heart (pericardium)

In addition, one or more of the following conditions are present:

The tumor is in the main airway, less than 2 cm away from the carina, but is not in the trachea (windpipe).
The tumor is associated with a collapsed lung or swelling that blocks the entire lung.

In T4, the tumor has invaded any of the following:

The area between the lungs (mediastinum)
The heart
The great vessels (the blood vessels that carry blood from the heart)
Carina, trachea, or esophagus
Main portion of the spine

In addition, one or both of the following occurs: separate tumors are present in the same lobe; the tumor is accompanied by an increased amount of fluid between the pleural membrane and the lung.

N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes. In stage N0, the regional lymph nodes are still cancer-free.

In N1, the cancer has spread to the nearest lymph nodes around the airways, to the hilum (a central zone in the lung where blood and lymph vessels enter), or both. The tumor has extended directly into lymph nodes within the lung. In N2, the cancer has spread to lymph nodes in the middle of the chest that are still next to the affected lung, to the nodes below the carina, or to both regions.

In N3 the cancer has spread to lymph nodes in the middle of the chest that are next to the opposite lung, to the hilum in the opposite lung, to lymph nodes in nearby or opposite muscle tissue, or to lymph nodes above the collar bone.

M Stages refer to metastasis. In M0, metastasis has not occurred.

In M1 distant metastasis has occurred. This includes the presence of a separate tumor in a different lobe.

Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:

The presence of respiratory symptoms
A tumor larger than 3 cm
High numbers of blood vessels in the tumor

Researchers are always looking for more accurate ways to determine a treatment and outlook for lung cancer. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help determine how aggressive a cancer is likely to be, and what the best treatment approach is.

If the cancer is still localized, surgery can produce 5-year survival rates of up to 75% in stage I patients and up to 50% in stage II patients. Unfortunately, very few patients are diagnosed at such early stages. In locally advanced stages, the standard treatment is concurrent radiation and chemotherapy. However, even with this approach average survival times are less than 2 years. Even if an initial tumor has been surgically removed or irradiated, cancer recurrence rates are very high. The risk for recurrence is lower in smokers who quit after treatment.

On an encouraging note, advances in therapies for later stage lung cancer are now offering some hope for improving survival. Still at this time, the mortality rate for lung cancer is still extremely high, and reports of improved response or survival rates using drugs or combinations of therapies do not mean cures. Ultimately, the patient must weigh a diminished quality of life using aggressive treatments against a chance for a modestly prolonged life.

Surgical Procedures

Surgery is performed in the following circumstances:

The surgical removal of an entire lobe or parts of a lung is the primary treatment for eligible patients in early stages of cancer. Recurrence is high after surgery, although the new tumor is often operable.
Some patients with stage IIIA cancer may also benefit from surgery. The intent at this stage is to extend survival time, rather than cure the disease.
Surgery is not out of the question in rare cases of metastasis when the cancer appears in a single operable location, such as the brain.

Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.

The type of surgery depends on the amount of lung or other tissue that needs to be removed.

Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung; consequently, they preserve almost normal breathing function after the operation.

Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient's lung function must be adequate before undergoing this procedure. The operation carries an overall mortality rate of 3 - 5%, with older patients having the highest risk.

Click the icon to see an illustrated series detailing surgery to remove diseased lobes of the lung.

Pneumonectomy. Pneumonectomy removes the entire lung. The procedure itself carries a mortality rate of 5 - 8%, with the oldest patients having the greatest risk. In such patients, recurrence almost always occurs.

Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in late stages of the disease.

Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that employs a thin tube containing a miniature camera and surgical instruments. It requires much smaller incisions than open surgery and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those following conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I NSCLC treated with VATS were comparable to those in patients treated with traditional open chest surgeries.

Laser Surgery. Laser surgeries allow removal of minimal amounts of lung tissue and are proving useful for improving symptoms in stage II and IIIA patients. They may also be beneficial in treating cancers that have spread to the throat, obstructing it.

Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Serious side effects include bleeding in the lungs. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.

Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact and is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.

Electric Cauterization. Electric cauterization, the use of electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.

Back Surgery. Spinal cord compression is a common cause of pain in patients with advanced lung cancer. Because such patients can live for a year or longer, some research indicates that back surgery followed by radiation therapy can significantly improve the quality of life for many of these patients.

Radiation Treatments

In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.

Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. In these cases, the 5-year survival rate is about 20%, and the cancer is likely to recur. Survival rates may be higher or lower, depending on the tumor size. In general, treatment with radiation therapy alone shows less benefit with larger tumors. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. Nevertheless, a recent study confirmed earlier results that show that radiation therapy by itself is as effective as surgery in patients who are unable or unwilling to have surgery for early stage non-small cell lung cancer.

Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. At this time, concurrent radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are showing promise.

Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung functions, or in those with metastasized cancer. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, the superior vena cava syndrome, coughing up blood, and symptoms caused by brain metastases. Radiation, in these cases, is not generally used with the intention of reducing mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.

Delaying radiation therapy until symptoms develop does not appear to reduce survival times or impair quality of life compared to starting it right away, in patients with minimal or no symptoms.

Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may be used to deliver powerful, highly targeted radiation to specific areas in the brain. Some trials are investigating using radiation to the head to prevent metastasis to the brain.

The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread:

External-Beam Radiation. External-beam radiation therapy focuses a beam of radiation directly on the tumor. It is generally used for metastasized cancer.
Brachytherapy. Brachytherapy involved the implantation of radioactive seeds through thin tubes directly into the cancer sites. Brachytherapy may be used for lung cancers that have spread to the throat and caused obstruction. High-dose-rate brachytherapy may also have some value for patients with inoperable tumors in the central region of the lung.

Hyperfractionated radiotherapy gives smaller than standard doses a number of times a day (usually two or three). This allows doctors to use a higher cumulative dose over the whole course of treatment. It is not as useful as therapy by itself, but should be combined with chemotherapy to have any survival benefits.

Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses per day but uses standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART is proving to extend survival rates of patients with localized cancer over that of standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems. A modification in which treatment is suspended for 2 days out of 7 may help reduce this effect.

Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation designed to closely match the specific targeted organs or tissues. This allows significantly higher doses to attack the cancer while reducing the risk to healthy cells. In a 2003 report, 3-year survival rates in stage IIIA patients were nearly 60%, and nearly half the patients experienced no side effects.

Stereotactic body radiotherapy, an advance on conformal radiation, uses a body frame and an abdominal press to immobilize the patient's body and limit breath movement. This allows a more accurate delivery of high-energy radiation. The technique is still investigational.

Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or the lungs (pneumonitis). Infection is also a danger.

The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications. Investigators are also studying drugs, notably amifostine, which appear to help reduce throat and lung inflammation caused by radiation, without reducing its cancer-fighting effects.

Treatment Options by Stages

In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.

Treatment Options. Surgical removal of the tumor, if one can be located, allows identification of its stage and often results in cure.

Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers and only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.

Treatment Options:

Surgery, often a limited procedure, where only part of a lobe is removed from the lung.
In patients who cannot be treated surgically, consider photodynamic therapy, cryotherapy, or brachytherapy.

In stage I, the cancer has reached higher layers of the lung but has not spread into the lymph nodes or beyond the lung.

General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should undergo partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients, who have radiation or chemotherapy in addition to surgery, have higher survival rates. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. An analysis of studies using chemotherapy in addition to surgery or radiotherapy, however, indicated benefits in survival. The overall 5-year survival rates for early stage-cancer are in the range of 30 - 50%. Patients should consider clinical trials for prevention of recurring (returning) cancer after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.

Stage IA (T1, N0, M0). The 5-year survival rates for stage IA patients after successful treatment can be as high as 80%. Treatment options are:
- Lobectomy or sometimes pneumonectomy (removal of one lung)
- Wedge or segment removal, particularly in patients with poor lung function who cannot withstand lobectomy
- Radiation in selected patients whose condition is inoperable (for example, frail patients with T1 tumors); 5-year survival rates can be equal to those with surgery, between 32 - 60%
- Clinical trials of adjuvant chemotherapy following surgery

Stage 1B (T2, N0, M0). Stage IB survival rates after treatment can be better than 60%. Treatment options are:
- Lobectomy or sometimes pneumonectomy; wedge or segment removal, particularly patients with poor lung function
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy; studies are promising)
- Clinical trials for radiation treatments in selected patients whose condition is inoperable
- Clinical trials of chemotherapy before, after, or during radiation treatments

In stage II the cancer cells have spread to nearby lymph nodes.

General Treatment Options. Surgery, usually removal of a lobe (lobectomy) or one lung (pneumonectomy), is the treatment of choice. Five-year survival rates associated with stage II surgery can vary. A 2000 review of existing research places the numbers as high as 40 - 50%, but notes that they can drop to 25% and below if the cancer has spread beyond the immediate lymph nodes.

Patients whose cancer is inoperable may consider radiation treatments. In patients who can complete treatment, 5-year survival rates average 20 - 30%, with higher rates for stage IIA. Patients should consider clinical trials for prevention of recurring cancer after primary treatment. To date, however, supplementing surgical treatment with radiation or chemotherapy does not appear to prolong survival rates.

Stage IIA (T1, N1, M0). Survival rates can be as high as 60%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before, after, or during radiation treatments
- Clinical trials of chemotherapy to reduce tumor size before surgery (induction therapy)
Stage IIB (T2, N1, M0) or (T3, N0, M0). Survival rates can be over 40%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy)
- Clinical trials of chemotherapy before, after, or given at the same time as radiation treatments

In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.

General Treatment Options. Generally, the treatment of choice for stage III tumors is radiation and sometimes surgery, chemotherapy, or combinations of all three.

Combination approaches may be significantly more effective than single treatments. For example, of particular interest is a treatment approach that starts with chemotherapy and radiation, given at the same time, followed by surgery. In one study, 5-year survival in stage III patients treated this way was nearly 50%.

Stage IIIA (T1, N2, M0) or (T2, N2, M0) or (T3, N1, M0) or (T3, N2, M0).
- Surgery, if the tumor and affected lymph nodes can be completely removed. Consider platinum-based chemotherapy or radiation therapy after surgery.
- Radiation treatment plus platinum-based chemotherapy, given at the same time, is an option for those in otherwise good health. This regimen should be followed by surgery, if possible.
- Consider clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation.
- Consider other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs.
Stage IIIB (Any T, N3, M0) or (T4, Any N, M0). Some patients may consider surgery if there is no lymph node involvement (T4, N0), and tumor can be removed. Surgery is not an option for other patients with stage IIIB cancer. Treatment options are:
- Radiation alone, usually for symptom control; it may improve survival in certain patients, such as those with lymph node involvement above the collar bone
- Chemotherapy alone
- Concurrent (given at the same time) cisplatin-based chemotherapy plus radiation, sometimes followed by surgery if possible
- Clinical trials using induction chemotherapy alone to shrink tumors, which may then be treated with surgery or radiation
- Clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation
- Other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs

In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.

Treatment Options are:

Combination of two- or three-drug chemotherapies that include platinum-based drugs and newer agents; the best patient candidates are those in otherwise good health, who have a limited number of distant metastasized sites. Chemotherapy is not recommended for patients who are too ill
External-beam radiation for symptom relief
Paclitaxel or gemcitabine as a single medication
Other clinical trials
If metastasized cancer involves only one or two areas in the brain, it may respond to surgery followed by radiation to the brain

Recurring or additional new tumors occur, usually in the lung again, in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.

Treatment Options are:

Radiation for symptom control
Chemotherapy with or without bevacisumab (Avastin)
If the cancer spread to only one site in the brain, it may respond to surgery, followed by whole-brain radiation. Extended disease-free survival is possible. If the brain tumor is not operable, it is treated with radiation. Even if cancer returns in the brain (in 50% of cases), treating it again is possible in many patients, if the disease has not spread elsewhere
Laser therapy or interstitial radiation for tumors inside the airways
Stereotactic radiosurgery (in a few selected patients)

Chemotherapy Treatments

Chemotherapy is the use of drugs given by mouth or by injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the use of supportive care.

Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin, a monoclonal antibody) and platinum-based chemotherapy is also a first line treatment choice for such patients, if the cancer is the non-squamous type

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine or its derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them. Gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer (NSCLC), is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

If you are currently taking gefitinib, do not stop taking it without talking to your doctor.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic NSCLC, who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some trials suggest that they can be reduced by giving the drugs for shorter durations, without loss of cancer-killing effects. Common side effects include the following:

Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate drugs, and in most patients who take drugs that are more powerful. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, achieved either a major or complete reduction in nausea and vomiting.
Anemia: Anemia, an abnormally low number of red blood cells, is common in lung cancer. Treatments include transfusions or injections of erythropoietin, an agent that causes more red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur and may vary depending on the specific drugs. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. White blood cell count can improve with the addition of a type of drug called granulocyte colony-stimulating factor (filgrastim and lenograstim).
Liver and kidney damage: Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy, with or without chemotherapy.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based agents: A simple skin test is under investigation that may identify people with a potential allergic response.

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer seen for the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel, when docetaxel is given every 21 days, but not when it is given weekly.

Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers, then, are interested in medications that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that NSCLC tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating NSCLC in people who have never smoked.

Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trial results have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is administered orally and has very low toxicity (rash and diarrhea are common).

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any survival benefits in patients with advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to extend the time to recurrence, the overall duration of survival, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates, compared to a sequential approach (separate cycles following each other). Chemotherapy and radiation treatments given at the same time are more toxic, however.

Other approaches use even more intensive multi-modal therapy. For example, some trials use radiation therapy with chemotherapy, followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.

There are many painkilling medications available. Research shows that aggressive pain relief can help patients manage cancer treatment symptoms (in addition to pain) better. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief, and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a deadly overdose.

Investigative Agents

According to a 2001 article, of the nearly 500 cancer drugs currently in development, 58 of them (about 13%) are aimed at fighting lung cancer. Only the number of breast cancer drugs exceeded that percentage. Unfortunately, none to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.

Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Trastuzumab (Herceptin) and cetuximab (Erbitux) are MAbs under investigation for lung cancer. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.

All three of these MAbs block epidermal growth factor. These agents are of particular interest for patients who have cancers that produce too much of the protein called HER2. These agents show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, the disease-free survival time in patients with advanced NSCLC is longer when adding bevacizumab to platinum-based chemotherapy.

Antisense oligonucleotides are drugs being used to block molecules that result in too many cells that cause cancers. LY900003 (Affinitak), for example, targets an enzyme called PKC-alpha, which promotes tumor growth. Early studies with Affinitak showed some promising results. However, a 2003 study found no difference in survival when patients received Affinitak in combination with platinum-based chemotherapy, compared to patients receiving chemotherapy alone.

Genasense (G3139, oblimersen) blocks Bcl-2. Bcl-2 is a protein that is expressed in abnormally high amounts in some cancers. This antisense drug is also under investigation.

Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. In one early study, 60% of patients experienced partial or total tumor shrinkage when the agent was used in combination with radiation therapy. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Three of the stabilized patients remained stable for over 9 months. One patient had a partial response to Advexin. The only side effect of the multiple doses given was a passing fever that disappeared within 24 hours. Advexin is in Phase II clinical trials for NSCLC.

Vaccines use inactivated genetic materials from cancer cells, such as defective p53 or ras genes, to cause a highly targeted immune response to attack the cancer.

Retinoids are vitamin A-like antioxidant chemicals that help repair cell damage and appear to support growth of lung cells. A number of retinoid-like agents (retinal palmitate, TAC-101, 23-cis-retinoic acid, N-acetyl-cysteine) are being studied for the treatment or prevention of lung cancer.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.cancercare.org -- Cancer Care
www.lungusa.org -- The American Lung Association
www.asco.org -- American Society of Clinical Oncology
www.alcase.org -- Alliance for Lung Cancer
www.lungcancer.org -- Joint project of Cancer Care and the Oncology Nursing Society
www.nccn.org -- National Comprehensive Cancer Network
www.lungcanceronline.org -- Lung cancer information
www.epa.gov/iaq/radon -- National radon information
www.clinicaltrials.gov -- Find clinical trials
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:1690-1701.

American Cancer Society. Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society; 2006.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga.: American Cancer Society; 2007:34.

Janne PA. Non-small Cell Lung Cancer in Never-smokers: A Biologically and Clinically Distinct Type of Lung Cancer. In: ASCO 2007 Educational Book. Meeting of the American Society of Clinical Oncology, Chicago, Ill.: June 1-5, 2007.

Kagawa S, Fujiwara T, Saijo Y, et al. A multicenter phase I study of adenoviral p53 (ADVEXIN) in Japanese patients with advanced non-small cell lung cancer. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 2564.

Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006 Jul 10;166(13):1359-67.

National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Available online.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 1.2007. Available online.

Tarceva [Package Insert]. Melville, NY: OSI Pharmaceuticals; 2005.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. List of Approved Oncology Drugs with Approved Indications. In: Oncology Tools. Available online.

U.S. Preventive Services Task Force. Lung cancer screening. Ann Int Med. 2004;140:738-739.

Xin M, Deng X. Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10781-9.

Review Date:
8/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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

Smoking and smokeless tobacco

admin — Thu, 04 Sep 2008 18:50:51 -0700

Overview

Alternative Names
Information
References

Illustrations

Tobacco and vascular disease

Tobacco and chemicals

Tobacco and cancer

Secondhand Smoke and Lung Cancer

Respiratory cilia

Tobacco health risks

HEALTH GUIDE REFERENCE FROM A.D.A.M

Alternative Names

Second-hand smoke; Cigarette smoking; Cigar smoking; Pipe smoking; Smokeless snuff; Tobacco use; Chewing tobacco

Information

Tobacco is a plant grown for its leaves, which are smoked, chewed, or sniffed for a variety of effects. It is considered an addictive substance because it contains the chemical nicotine.

In addition to nicotine, tobacco contains over 19 known cancer-causing chemicals (most are collectively known as "tar") and more than 4,000 other chemicals. These include acetone, ammonia, carbon monoxide, cyanide, methane, propane, and butane.

Over 38 million people in the United States have successfully quit smoking. Yet there are still around 50 million Americans who smoke. The majority say they would like to quit.

And, while the number of cigarette smokers in the United States has dropped over recent years, the number of smokeless tobacco users has steadily risen. This trend is likely related to the false belief that smokeless tobacco is safe. It is NOT. Smokeless tobacco carries many of the same health risks as cigarettes. Some people who want to stop smoking, but who still crave the nicotine, turn to smokeless tobacco wrongly thinking that they are doing something good for themselves.

THE EFFECTS OF NICOTINE

Nicotine acts as both a stimulant and depressant on your body. It increases your bowel activity, saliva, and bronchial secretions. It stimulates the nervous system and may cause tremors in the inexperienced user, or even convulsions with high doses.
After stimulation, there's a phase that depresses the muscles in your airways. As a euphoric agent, nicotine causes relaxation from stressful situations.
On average, tobacco increases your heart rate 10 to 20 beats per minute, and it increases your blood pressure reading by 5 to 10 mmHg (because it constricts the blood vessels).
Nicotine may also cause sweating, nausea, and diarrhea. Nicotine elevates the blood level of glucose (blood sugar) and increases insulin production. Nicotine also tends to enhance platelet aggregation, which may lead to blood clots.
Nicotine temporarily stimulates memory and alertness. People who use tobacco frequently depend on it to help them accomplish certain tasks at specific levels of performance. Nicotine also tends to be an appetite suppressant. (For this reason, fear of weight gain also influences the willingness of some people to stop smoking.)

Finally, tobacco is highly addictive. It is considered mood and behavior altering. Tobacco is believed to have an addictive potential comparable to alcohol, cocaine, and morphine.

HEALTH RISKS

There are many reasons to quit using tobacco. Knowing the serious health risks may help motivate you to quit. When used over a long period, tobacco and related chemicals such as tar and nicotine can increase your risk of:

Blood clots, which may lead to aneurysms and strokes
Cancer (especially in the lung, mouth, larynx, esophagus, bladder, kidney, pancreas, and cervix)
Coronary artery disease, including angina and heart attacks
Decreased ability to taste and smell
Delayed wound healing
High blood pressure
Lung problems such as emphysema and chronic bronchitis
Pregnancy-related problems, including miscarriage, premature labor, low birth weight, and risk for sudden infant death syndrome ( SIDS)
Tooth and gum diseases

You have the same risks if you use smokeless tobacco (chewing tobacco, snuff, etc.) for a long time. In addition, smokeless tobacco users have a 50 times greater risk for mouth cancer than those who do not use such products.

SECONDHAND SMOKE

Those who are regularly around the smoke of others (secondhand smoke) have a higher risk of:

Coronary artery disease
Lung cancer
Sudden and severe reactions, including those involving the eye, nose, throat, and lower respiratory tract

Infants and children that are exposed regularly to secondhand smoke are at risk of:

Asthma
Infections, including virus-caused upper respiratory infections, ear infections, and pneumonia
Lungs that do not work as well (poor lung function)
Sudden infant death syndrome (SIDS)

TIME TO QUIT

There are a lot of ways to quit smoking and many resources to help you. Family members, friends, and coworkers may be supportive or encouraging, but the desire and commitment to quit must be your own.

Most people who have been able to successfully quit smoking made at least one unsuccessful attempt in the past. Try not to view past attempts to quit as failures, but rather as learning experiences.

Feel ready to quit? Here are some tips:

List the reasons you want to quit. Include both short- and long-term benefits.
Ask your health care provider for help. Find out whether prescription medications might help. Also ask about nicotine patches, gum, and sprays.
Ask your family, friends, and coworkers for support.
Set a quit date, and get rid of all of your cigarettes by that date.
Quit completely -- cold turkey.
Get more exercise. It relieves the urge to smoke.
Learn self-hypnosis from a qualified practitioner. This helps some people.
Make a plan about what you will do, instead of smoking, when stressed or other times you have the urge for tobacco. Be as specific as possible.
Avoid smoke-filled settings and situations in which you are more likely to smoke.

Like any addiction, quitting tobacco is difficult, particularly if you are acting alone. If you join smoking cessation programs, you have a much better chance of success. Such programs are offered by hospitals, health departments, community centers, and work sites.

The best quit-smoking programs combine multiple strategies, including peer support and ways to overcome potential relapse situations. Counseling by telephone can be a very helpful reinforcement, even as effective as face-to-face counseling.

Short-term use of the antidepressant medication bupropion (Wellbutrin, Zyban), along with a quit-smoking program, may increase your success. Bupropion requires a prescription from your health provider and should not be used if you have a history of seizures or kidney failure.

If you aren't successful the first time, simply look at what occurred or what didn't work, develop new strategies, and try again. Many attempts are often necessary to finally "beat the habit."

THE BENEFITS OF QUITTING

Within 20 minutes of quitting - your blood pressure and pulse rate drop to normal and the temperature of your hands and feet increases to normal.
Within 8 hours of quitting - your carbon monoxide levels drop and your oxygen levels increase, both to normal levels.
Within 24 hours of quitting - your risk of a sudden heart attack decreases.
Within 48 hours of quitting - nerve endings begin to regenerate and your senses of smell and taste begin to return to normal.
Within 2 weeks to 3 months of quitting - your circulation improves and walking becomes easier; even your lung function increases up to 30%.
Within 1 to 9 months of quitting - your overall energy typically increases and symptoms like coughing, nasal congestion, fatigue, and shortness of breath diminish; also, the small hairlike projections lining your lower airways begin to function normally. This increases your lungs' ability to handle mucus, clean the airways, and reduce infections.
Within 1 year of quitting - your risk of coronary heart disease is half that of someone still using tobacco.
Within 5 years of quitting - the lung cancer death rate decreases by nearly 50% compared to one pack/day smokers; the risk of cancer of the mouth is half that of a tobacco user.
Within 10 years of quitting - your lung cancer death rate becomes similar to that of someone who never smoked; precancerous cells are replaced with normal cells; your risk of stroke is lowered, possibly to that of a nonuser; your risk of cancer of the mouth, throat, esophagus, bladder, kidney, and pancreas all go down.

WHEN TO CONTACT A MEDICAL PROFESSIONAL

Call your doctor if you are a smoker and:

You want an individual health risk profile
You want to learn about methods to stop tobacco use
You are pregnant, planning a pregnancy in the future, or using birth control pills
You have symptoms of specific diseases associated with tobacco use (even if you are a nonsmoker exposed to secondhand smoke)

Other resources include local chapters of the American Lung Association and the American Cancer Society. Both organizations have a wide range of resource materials and comprehensive smoking cessation programs.

References

Metz CN. Metabolism and biochemical effects of nicotine for primary care providers. Med Clin North Am. 2004; 88(6): 1399-1413, ix.

Anderson JE. Treating tobacco use and dependence: an evidence-based clinical practice guideline for tobacco cessation. Chest. 2002; 121(3): 932-941.

Parkes GT. Effect on smoking quit rate of telling patients their lung age: the Step 2 quit randomised controlled trial. BMJ. 2008: 336 (7644): 598-600.

Review Date: 6/19/2008

Reviewed By: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Source Doc: 1_002032

Another Reason to Quit Smoking: Third-Hand Smoke

FitSugar — Wed, 07 Jan 2009 14:30:00 -0800

I've heard of first-hand smoke, the smoke you inhale directly from a tobacco product, and there's also second-hand smoke, the smoke that is given off by the burning end of a cigarette, pipe, or cigar. Now research shows there's another type of smoke that can cause harm - third-hand smoke. It's the invisible toxic gasses and particles that linger in the air, carpet, curtains, clothes, and hair long after a cigarette stops burning. Running a fan or opening a window don't get rid of third-hand smoke, and studies show that it poses the same cancer dangers and other health risks as first- and second-hand smoke. Watch the video below to hear more.

If you're interested in hearing more about third-hand smoke, check out this New York Times article.

Chronic obstructive pulmonary disease

FitSugar — Wed, 08 Oct 2008 17:35:32 -0700

Overview

Signs and Symptoms
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Chronic obstructive pulmonary disease (COPD) is the term used to describe chronic lung conditions that cause severe shortness of breath and obstruct the airways in your lungs. Usually it refers to chronic bronchitis or emphysema, but can also encompass asthmatic bronchitis (bronchial asthma). All of these diseases cause the air sacs and tubes in your lungs to become blocked.

With chronic bronchitis, a constant cough that produces mucus causes bronchial tubes to become inflamed and, eventually, scar tissue to form in the lungs, which doesn't allow in as much oxygen as you need. With emphysema, the walls of your lungs lose their elasticity – they can't compact to allow you to exhale. People with COPD can have either or both of these diseases.

The main risk factor for COPD is smoking. There is no cure for COPD, and while treatments may help control symptoms, they can't undo the damage to the lungs. The most important thing you can do to prevent COPD or to stop the damage from getting worse if you have it is not to smoke.

Signs and Symptoms

Ongoing cough, often with phlegm that may be hard to "bring up"
Shortness of breath, especially during exercise
Production of increased mucus
Difficulty exhaling
Wheezing
Frequent respiratory infections

Causes

Smoking is the No. 1 cause of COPD. It can also be caused by exposure to pollutants or toxic chemicals. One rare form is inherited (see Risk Factors).

Risk Factors

Smoking - the longer you smoke and the more packs of cigarettes you smoke, the higher your risk. People who smoke pipes and cigars, and those who are exposed to large amounts of second-hand smoke, also have greater risk
Genetics - people with a a rare hereditary disorder called alpha-1 anti-trypsin deficiency lack an enzyme that normally helps protect the lungs from damage
Being over age 50
Exposure to toxic chemicals such as silica or cadmium
Working around industrial smoke, excessive dust, or other air pollutants (for example, miners, furnace workers, and grain farmers)

Diagnosis

Your doctor will listen to your chest for wheezes and decreased breath sounds. He or she will also look for signs of that you are having trouble breathing, like flaring of your nostrils and contracting of the muscles between your ribs. Your respiratory rate (number of breaths per minute) may be elevated.

Your doctor may order tests to determine your lung function. The most common such test is spirometery, where you'll be asked to blow into a tube connected to a machine called a spirometer. The spirometer measures how much air you have in your lungs, and can help detect COPD before your symptoms become obvious.

Your doctor may also order a chest X ray will to look for over-expanded (hyperinflated) areas in the lungs; a CT scan to check the severity of your COPD; an examination of your sputum; or a blood test to measure the levels of oxygen and carbon dioxide in your blood.

Preventive Care

If you smoke, quit.
If you have COPD, avoiding respiratory infections is very important. Your doctor will recommend that you receive an influenza vaccine (flu shot) each year and a pneumococcal vaccine to protect you from pneumonia.
Eating foods rich in antioxidants, magnesium and other minerals, and omega-3 fatty acids (including fruits, vegetables, and fish) may help lower your risk for COPD.

Treatment Approach

Not smoking is the key to preventing COPD or stopping it from getting worse. Treatment varies depending on the severity of the disease. Your doctor may talk with you about lifestyle changes you can make to help relieve the symptoms of COPD, such as exercising and eating a healthy diet. Support groups or therapy (see Mind/Body Medicine) can help make it easier to live with the condition.

Lifestyle

Quitting smoking is crucial. Other lifestyle measures you can take include dietary changes and exercise as described below.

Diet

People with COPD often lack essential nutrients in their bodies. Low levels of antioxidants and certain minerals including vitamins A, C, and E, potassium, magnesium, selenium, and zinc are associated with having COPD and may contribute to poor lung function. Eating lots of fruits, vegetables, and whole grains is recommended to get the nutrients you need.

Exercise

Although it may seem odd to recommend exercise when you have trouble breathing, exercise does in fact help many people with COPD. By strengthening your legs and arms and improving endurance, you may be able to breathe better. Walking, for example, is a good exercise to build endurance. Talk to your doctor and/or respiratory therapist about how to build up slowly and safely. Attending a comprehensive pulmonary rehabilitation is the best way to learn exercise and safe breathing techniques (see below).

Breathing

There are breathing exercises (for example, a pursed lip technique, breathing from the diaphragm, or using a breathing device called a spirometer twice a day) that may help improve lung function. You can also learn which breathing and relaxation techniques work best when you are short of breath. Talk to your doctor about working with a respiratory therapist in order to learn such exercises.

Medications

There are several types of medications used to control symptoms.

Bronchodilators - increase airflow by opening airways and help make it easier to breathe

Corticosteroids - reduce inflammation; either inhaled with an inhaler or taken by mouth, they are usually used to treat moderate to severe COPD

Leukotriene modifiers - help prevent inflammation and swelling in airways, and reduce mucus

Antibiotics - used to treat respiratory infections

Surgery and Other Procedures

When flare-ups are severe, requiring hospitalization, you may need supplemental oxygen. At later stages of the disease, many people with COPD need continuous oxygen at home.

Lung reduction surgery, in which a surgeon removes damaged parts of your lung to create more space for remaining lung tissue to work better, and lung transplant is sometimes performed for severe cases of COPD.

Nutrition and Dietary Supplements

Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider. Be sure to talk to your physician about any supplements you are taking or considering taking.

N-acetylecysteine (NAC, 400 to 1,200 mg per day) - NAC is a modified form of a dietary amino acid that works as an antioxidant in the body. Several studies using it to treat COPD indicate that it may help relieve symptoms by acting as an antioxidant to reduce oxidative stress on the lungs (damage caused by free radicals, particles that harm cells and DNA). Although not all the studies agree, some suggest that taking NAC can reduce the number of attacks of severe bronchitis.
Magnesium - People with COPD often have low levels of magnesium. Magnesium deficiency may be associated with poor nutrition (often a problem for people with COPD), or it may be caused by some drugs taken to manage COPD. Magnesium is important for normal lung function, and one study found that giving intravenous (IV) magnesium to people who were having an acute flare-up of COPD helped them breathe easier and reduce the number of days they spent in the hospital. It isn’t known, however, whether taking magnesium orally would have the same effect. Your doctor may recommend checking your magnesium level through (a simple blood test) if you have COPD and taking magnesium supplements if your levels are low. Magnesium can lower blood pressure and cause diarrhea. Talk to your doctor before taking magnesium supplements.
L-carnitine - A few studies suggest that L-carnitine may help people with COPD increase their exercise tolerance.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, contain active substances that can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care and only under the supervision of a practitioner knowledgeable in the field of herbal medicine. Also, be sure to talk to your physician about any herbs that you are taking or considering taking.

Eucalyptus (Eucalyptus globulus) - is frequently used in cough drops and acts as an expectorant, which means that it loosens phlegm in your lungs. A combination of eucalyptus, a kind of citrus oil, and an extract from pine (called essential oil monoterpenes) has been studied for respiratory problems. In one study, essential oil monoterpenes appeared to help prevent acute flare-ups of chronic bronchitis.
Ginseng (Panax ginseng, 100 mg per day) - One study suggested that taking ginseng helped people with COPD improve their exercise tolerance and lung function, but more studies are needed to see if there is any real benefit.
Lobelia (Lobelia inflata) - Also called Indian tobacco, lobelia has a long history of use as an herbal remedy for respiratory problems including bronchitis. It is an effective expectorant, meaning that it helps clear mucus from your lungs. However, lobelia can be toxic and should only be used under a doctor’s supervision.
Mullein (Verbascum densiflorum, 3 g per day) - Mullein is an expectorant, meaning it helps clear your lungs of mucus. Traditionally, it has been used to treat respiratory illnesses and coughs with lung congestion. However, it has not been studied for COPD.

Acupuncture

Preliminary studies suggest that acupuncture may help relieve shortness of breath in those with COPD. More research is needed.

If you are trying to quit smoking, acupuncture can help you break the habit.

Mind/Body Medicine

COPD is a difficult disease to live with, and joining a support group where members share common experiences and problems can help relieve stress of the disease.
Yoga and tai chi use deep breathing techniques and meditation, and may be helpful for someone with COPD. Talk to your doctor to see whether they are right for you.
Relaxation techniques may help reduce anxiety and shortness of breath associated with COPD.

Other Considerations

If you have COPD, you are prone to respiratory infections. Your health care provider will most likely tell you to get a flu shot every year and a pneumococcal vaccine once in your lifetime.

Prognosis and Complications

COPD is considered a chronic illness. Whatever damage there is to your lungs will not improve. If you stop smoking, the damage is likely to not get worse. If you continue to smoke, however, your lungs and lung function will continue to deteriorate.

Potential complications of COPD include:

Abnormally high pressure in the lungs called pulmonary hypertension
Enlargement of the heart and heart failure, leading to excessive fluid and weight gain
Abnormal rhythms of the heart
Dependence on mechanical ventilation (a respirator) and/or oxygen therapy
Pneumothorax (collapsing of part of the lung due to air leaking from the lung)
Pneumonia and other infections
Eventually, weight loss and wasting can occur

Supporting Research

Ambrosino N, Palmiero G, Strambi SK. New approaches in pulmonary rehabilitation. Clin Chest Med. 2007 Sep;28(3):629-38, vii. Review.

Behera D. Yoga therapy in chronic bronchitis. J Assoc Physicians India. 1998;46(2):207-208.

Booker R. Chronic obstructive pulmonary disease. Part two--management. Nurs Times. 2007 May 1-7;103(18):28-9.

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, Mass: Integrative Medicine Communications; 1998:423, 468.

Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000:118-123, 139-148, 233-239, 244-248.

Bourjeily G, Rochester CL. Exercise training in chronic obstructive pulmonary disease. Clin Chest Med. 2000;21(4):763-781.

Britton J, Pavord I, Richards K, Wisniewski A, Knox A, Lewis S. Dietary magnesium, lung function, wheezing, and airway hyperactivity in a random adult population sample. Lancet. 1994; 344:357–362.

Britton JR, Pavord ID, Richards KA, et al. Dietary antioxidant vitamin intake and lung function in the general population. Am J Respir Crit Care Med. 1995;151(5):1383-1387.

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Review Date:
12/21/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Heart attack and acute coronary syndrome

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Symptoms
Prognosis
Risk Factors
Diagnosis
Treatment
Medications
Surgery
Rehabilitation
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2006, the FDA approved the use of clopidogrel (Plavix) for patients who have had a STEMI heart attack and who will not be having angioplasty. A STEMI is a very severe type of heart attack caused by sudden and total artery blockage.

Angioplasty and Stents

Surgery with angioplasty and stents that is performed more than 3 days after a heart attack offers no advantage over standard drug therapy for clinically stable patients, indicates an important 2006 New England Journal of Medicine study. Experts recommend that this procedure be performed to open blocked arteries within 12 hours of a heart attack.

Drug-Coated Stents

Drug-coated stents may be better than bare metal stents for patients who have had a STEMI heart attack, suggest several New England Journal of Medicine studies. However, recent research has raised concern that these types of stents increase the risk for blood clots.
Patients who have a drug-coated stent must take aspirin and clopidogrel (Plavix) for at least 1 year after the stent is inserted, according to an important 2007 advisory from the American Heart Association (AHA). The combination of these drugs can help prevent blood clots.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs such as acetaminophen (Tylenol), ibuprofen (Advil) should be used with caution by patients who have had a heart attack:

In 2007, the AHA warned that NSAIDs (with the exception of aspirin) and COX-2 inhibitors increase the risk of heart attack and stroke. The AHA is recommending that doctors change the way they prescribe these pain relievers for patients who have or are at risk for heart disease.
A 2006 Journal of the American Medical Association study suggested that the prescription NSAID diclofenac (Cataflam) carries a higher risk for heart attack than other NSAIDs.

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. In order to perform the arduous 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).

Coronary artery disease is the most common cause of heart attacks. 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. A full-blown heart attack occurs when blood flow to the myocardium is blocked and tissue death occurs from loss of oxygen, severely damaging the heart. The medical term for heart attack is myocardial infarction. [See In-Depth Report #3: Coronary artery disease.]

Click the icon to see an image of atherosclerosis.

Heart attack (or myocardial infarction) is the most serious outcome of atherosclerosis. It 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 an acute myocardial infarction.

Angina is the primary symptom of coronary artery disease and is typically experienced as chest pain. There are two kinds of angina:

Stable Angina is predictable chest pain that can usually be managed with lifestyle measures and medications, such as low-dose aspirin.
Unstable angina is a much more serious situation than stable angina that is often an intermediate stage between stable angina and a heart attack. Unstable angina is part of a condition called acute coronary syndrome.

Acute coronary syndrome (ACS) is a severe and sudden heart condition that requires aggressive treatment, but has not developed into a full blown heart attack. Acute coronary syndrome includes:

Unstable angina. Unstable angina is a much more serious situation than stable angina. It is often an intermediate stage between stable angina and a heart attack.
NSTEMI (non ST-segment elevation myocardial infarction). This condition, also called non Q-wave myocardial infarction, is diagnosed when blood tests and ECGs suggest a developing heart attack. The injury in the arteries is less severe than with a full-blown heart attack.

Symptoms

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

In people with known heart disease, any unusual chest pain or other symptoms of heart attack that do not clear up with medications are signals to go to the hospital. The degree of pain and the specific symptoms before a heart attack vary greatly among individuals. Onset 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. Other common symptoms of a heart attack include:

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

Uncommon 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 are symptoms that are more likely to be due to causes other than a heart event:

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

The presence of these symptoms, however, 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% to a third of all episodes. High on the list of other causes of chest pain are the following:

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.
Anxiety attacks
Gastrointestinal disorders (gallstone attacks, peptic ulcer disease, hiatal hernia, heartburn)
Asthma
Spasm in the coronary artery
Abnormalities of the heart muscle itself
Rupture of the aorta, collapsed lung, acute inflammation of the heart, or a blood clot in the lung
Hyperthyroidism
Anemia
Vasculitis (a group of disorders that cause inflammation of the blood vessels)
Exposure to high altitudes (rare)

Immediately call 911 or the local emergency number.

If patients have been previously diagnosed with angina, they should take one nitroglycerin dose either as an under-the-tongue tablet or in spray form at the onset of symptoms. They should take another dose every 5 minutes up to three doses or when the pain is relieved, whichever comes first.

It should be noted, however, that only 20% of heart attacks occur in patients with long-standing angina.

Anyone who has heart disease or risk factors for it and experiences heart attack symptoms should immediately 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 who experience chest pain should go immediately to the nearest emergency room, preferably traveling by ambulance. They should not drive themselves.

Prognosis

Each year, an estimated 650,000 Americans will suffer a first heart attack, and 450,000 will have a recurrent episode. Currently, half of the men and 63% of the women who died of heart disease had no warning prior to their fatal attacks.

Heart attacks may be rapidly fatal, evolve into a chronic disabling condition, or lead to full recovery. The long-term prognosis for both length and quality of life after a heart attack depends on its severity and the preventive measures taken afterward.

About 88% of patients under age 65 who experience a heart attack can expect to return to work. About 12,600,000 Americans who have had heart attacks, angina, or both are alive today. However, within 6 years of a heart attack, 18% of men and 35% of women have a recurrent attack. And, about 22% of men and 46% of women develop heart failure.

Although no tests can absolutely predict whether another 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 adherence to medical treatments. Two-thirds of patients who have suffered a heart attack, however, do not take the necessary steps to prevent another.

Higher Risk Individuals. A heart attack is always more serious in certain people:

Elderly (particularly those who are thinner)
People with a history of heart disease or risk factors for heart disease
People with heart failure
People with diabetes
People on long-term dialysis

Women are more likely to die after a heart attack than men. The risk is highest in younger women (although in the younger population, the risk for having a first heart attack and then dying from it is very low). It is still unclear why heart attacks are more severe in this group.

Factors Occurring at the Time of a Heart Attack That Increase Severity. The presence of other conditions during a heart attack can contribute to a poorer outlook:

Arrhythmias (disturbed heart rhythms). A dangerous arrhythmia called ventricular fibrillation is a major cause of short-term death from heart attack. Such arrhythmias are more likely to occur within the first 4 hours and are associated with a high mortality rate. Patients who are successfully treated, however, have the same long-term prognosis as those who do not experience such arrhythmias.
Signs of severe physical damage to the heart may indicate a poorer outlook.
Shock. This very dangerous condition is associated with very low blood pressure, reduced urine levels, and cellular abnormalities. Shock occurs in about 7% of heart attacks. The incidence has not declined over recent years, although its survival rates have improved.
Heart block, also called atrioventricular (AV) block, is a condition in which the electric conduction of nerve impulses to specialized muscles in the heart is slowed or interrupted. Although heart block is dangerous, it can be treated effectively with a pacemaker, and it rarely causes any long-term complications in patients who survive it.

Heart attacks and acute coronary syndrome pose a high risk for stroke. According to a major 2002 study, the risk for stroke after heart attack 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 were older (over age 75), African-American, had a history of stroke, atrial fibrillation, hypertension, diabetes, or peripheral artery disease. Most people who fall into these categories have more than one of these risk factors.

Risk Factors

About 25% of all Americans have one or more risk factors for heart disease, increasing their risk for heart attack. Most risk factors for heart disease are related to lifestyle. Some risk factors, (such as age, gender, and ethnicity) cannot be changed. Nevertheless, overall risks can be reduced with healthy lifestyle changes. [See In-Depth Report #3: Coronary artery disease.]

The American Heart Association's 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 new 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 second-hand smoke.

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

Take Aspirin. People at high risk for heart disease 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 of less than 7%.

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

The approach for managing acute coronary syndrome involves lifestyle changes and medications. Experts have come up with a mnemonic device (ABCDE) for remembering the factors that are fundamental for management of acute coronary syndrome:

A. Antiplatelets, anticoagulants, and ACE inhibitors

B. Blood pressure and beta-blockers

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

D. Diet and diabetes control

E. Exercise and education

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 are more likely to have angina than men are. 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 are to die after a heart attack. Evidence suggests that this is because women tend to be older and sicker than men at the time of a first attack. A 2002 study indicated, however, that with early aggressive treatment women with acute coronary syndrome do as well or better than men with the same condition and treatments.

Ethnicity. Of all major ethnic groups, 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.

Timing of Heart Attack. A 2007 study suggested that patients who are admitted to a hospital on a weekend are less likely to receive aggressive heart attack treatment and less likely to survive than patients who are treated on a weekday. However, no one can predict when a heart attack will occur. The most important point is to get treatment quickly, regardless of the day of the week. And, if you think you having a heart attack, call an ambulance -- or have someone call for you -- to ensure prompt treatment. Do not drive yourself.

Cholesterol. Cholesterol is a white, powdery substance that is found in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many 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. [See In-Depth Report #23: 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)	OptimalGoal(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 an 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.

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 Blood Pressure Ranges table.]

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.) [See In-Depth Report #14: High blood pressure.]


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. It should be strongly noted that 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, in any case, has other effects (hypertension, increase in inflammation) that pose major risks to the heart.

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, in any case. And diabetes itself poses a significant risk for high cholesterol levels and heart disease. [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 several effects that benefit the heart and circulation, including improving cholesterol and lipid levels, reducing inflammation in the arteries, assisting weight loss programs, and 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.

Some studies suggest that people may gain the greatest heart protection benefit from the total daily amount of energy they expend, rather than from the length of a single exercise session. 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) can put 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 high density lipoprotein).
Blood clotting problems.
Impaired nerve function (neuropathy), which can also damage the heart. In fact, some experts estimate that the mortality rates from neuropathy-related heart conditions ranges from 15 - 53%.

Patients 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.]

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 either protect or hurt the heart. Experts generally agree on the following heart-smart recommendations:

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables.
Avoid saturated fats (found mostly in animal products) and trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats, particularly omega-3 fatty acids (found in vegetable and fish oils).
In selecting proteins, choose soy, legumes, poultry, and fish over meat. Fat free and low fat dairy products (skimmed milk, yogurt) are also healthy choices.
Controlling weight, quitting smoking, and exercising are essential companions of any diet program.

After starting any heart healthy diet, it generally takes an average of 3 - 6 months before any noticeable reduction in cholesterol occurs, although some people have reported better levels in as few as 4 weeks. An intensive program may be necessary to achieve significant improvements in cholesterol levels and to reduce other heart risk factors. [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 impair a patient's response to medication for heart disease. Although people with heart disease may certainly become depressed, this does not explain entirely the link between the two problems. The data now suggest that depression itself may be a true risk factor for heart disease as well as its increased severity. Several studies have suggested that depression has biologic effects on the heart, including blood clotting and heart rate. A study in 2001, 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. A 2002 study reported a higher risk for heart failure in women -- although not in men -- with depression. The more severe the depression, the more dangerous to the health, although even mild depression, including feelings of hopelessness, experienced over many years, may harm the heart, even in people with no early signs of heart 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 on the Heart. By contrast, heavy drinking harms the heart; 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.

In 2005, the FDA warned that all nonsteroidal anti-inflammatory drugs (NSAIDs) -- with the exception of aspirin -- carry heart risks. NSAIDs and COX-2 inhibitors may increase the risk for death in patients who have experienced a heart attack. The risk is greatest at higher dosages, but not necessarily for length of time. According to a 2006 Danish study of heart attack survivors, patients do not need to take NSAIDs for long periods of time to be at risk.

NSAIDs include nonprescription drugs like ibuprofen (Advil, Motrin) and prescription drugs like diclofenac (Cataflam, Voltaren). Celecoxib (Celebrex) is currently the only COX-2 inhibitor that is available in the U.S. It has been linked to cardiovascular risks such as heart attack and stroke. Patients who have had heart attacks should talk to their doctors before taking any of these drugs.

A 2006 comprehensive report from the U.S. Agency for Healthcare Quality and Research indicated that both NSAIDs and COX-2 inhibitors pose similar risks for heart attacks. The report found that one particular NSAID, naproxen (Aleve, Naprosyn), may present less risk of heart attack for some patients, but other studies have contradicted this finding. A 2006 Journal of the American Medical Association study suggested that diclofenac (Voltaren, Cataflam) poses a higher risk for heart attack than other NSAIDs.

In 2007, the American Heart Association issued a scientific statement encouraging doctors to change the way they prescribe pain relief medication for patients with or who are at risk for heart disease. The AHA recommends that 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.

Anemia. Anemia has adverse effects on the heart and increases the severity of cardiac conditions, including heart failure and heart attacks.

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. 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.

Pregnancy Complications. Although women of child-bearing age are generally at low risk of heart attack, pregnancy can increase the risk for women with certain health conditions. Pregnant women who have diabetes, high blood pressure, or coronary artery disease are at greater risk of having a heart attack than healthy pregnant women. Smoking can increase the risk of heart attack during pregnancy by eight times. Pregnant women who are over 40 years old are at much greater risk than younger women.

Diagnosis

When a patient comes to the hospital with chest pain, the following diagnostic steps are usually taken to determine any heart problems, and, if present, their severity.

The patient will report all symptoms so that a health professional can rule out either a non-heart problem or possible other serious accompany conditions.
An electrocardiogram (ECG) reading is taken, which records the waves made the heart. It is the key tool for determining if heart problems are causing chest pain and, if so, how severe they are.
Blood tests showing elevated levels of certain factors (troponins and CK-MB) indicate heart damage. (The doctor will not wait for results, however, before administering treatment if a heart attack is strongly suspected.)
Imaging tests, including echocardiogram and perfusion scintigraphy, help rule out a heart attack if there is any question.

An electrocardiogram (ECG or EKG) measures and records the electrical activity of the heart. 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:

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 two major pumping chambers in the heart.)
T and U. These waves follow the ventricular contractions.

Click the icon to see an image of a normal sinus rhythm.

Doctors use a term called the P-Q or P-R interval, which is the time taken for an electrical impulse to travel from the atria to the ventricle.

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

Elevated ST Segments: Heart Attack. Elevated ST segments are strong indicators of a heart attack in patients with symptoms and other indicators. They suggest that an artery to the heart is blocked and that the full thickness of the heart muscle is damaged. When this finding coincides with a heart attack, the condition is sometimes referred to as either as a Q-wave myocardial infarction or a STEMI (ST-segment elevation myocardial infarction). STEMI heart attacks are very severe and usually have complete artery blockage. ST-elevations are strong indicators for aggressive treatments (thrombolytic drugs or angioplasty) to reopen blood vessels. (ST segment elevations do not always mean the patient has a heart attack. Also, some patients do not have elevated ST segments. Other factors are important in making a diagnosis.)

Non-Elevated ST Segments: Angina and Acute Coronary Syndrome. A depressed or horizontal ST wave suggests some blockage and the presence of a heart disease, even if there is no angina present. It occurs in about half of patients with other signs of a heart event. This finding, however, is not very accurate, particularly in women, and can occur without heart problems. In such cases, laboratory tests are needed to determine the extent, if any, of heart damage. In general, one of the following conditions may be present:

Stable Angina (blood test results or other tests show no serious problems and chest pain resolves). Most patients with angina can go home. (Between 25 - 50% of people who have angina or silent ischemia have normal ECG readings.)
Acute Coronary Syndrome (ACS). This 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) -- also referred to as non Q-wave myocardial infarction. 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.

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 an exercise stress test, to detect the location and extent of heart muscle damage.

Nuclear ventriculography (also known as a radionuclide test) uses radioactive materials called tracers to make heart chambers and blood vessels visible. The procedure is noninvasive. It is a reliable measure of severe heart events and can help identify if damage has occurred from a heart attack. A radioactive isotope such as thallium (or technetium) is injected into the patient's vein. The radioactive isotope attaches to red blood cells and passes through the heart in the circulating blood. The isotope can then be traced through the heart using special cameras or scanners. The images may be combined with an electrocardiogram. The patient is tested while resting, then tested again during an exercise stress test. 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.

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 cardiac catheterization.

Click the icon to see an image of dye injected into the coronary arteries.

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.

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.

Tests that measure kidney function can help predict which patients are at greatest risk of heart attack, stroke, or death from heart disease. Kidney tests measure proteins in the blood 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.

When heart cells become damaged, they release different enzymes and other molecules into the blood stream. 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 markers 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 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 the 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.

Treatment

Treatment options will depend on whether the patient has angina, acute coronary syndrome, or a full-blown heart attack.

Patients who are diagnosed with acute coronary syndrome (ACS) may be at risk for a heart attack. ACS refers to either unstable angina or NSTEMI (non ST-segment elevation myocardial infarction). 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.

Doctors use a patient's medical history, various tests, and the presence of certain factors to help predict which ACS patients are most at risk for developing a more serious condition. The degree of chest pain itself is not necessarily useful for determining the actual damage in the heart.

Depending on how severe the condition is, the patient is then given either medical treatments or more invasive approaches, such as angioplasty. Some experts believe that even if patients with ACS are only given drug therapy, they should still be transferred to centers equipped for angioplasty.

Early supportive treatments are similar for patients who have ACS or those who have had a heart attack.

Oxygen. Oxygen is almost always administered right away, usually through a tube that enters through the nose. The patient is given aspirin if one was not taken at home.

Medications for Relieving Symptoms.

Nitroglycerin. Most patients will receive nitroglycerin after a heart attack, usually under the tongue. Nitroglycerin decreases blood pressure and dilates the blood vessels around the heart, increasing blood flow. Nitroglycerin may be given intravenously in certain cases (recurrent angina, congestive heart failure, or high blood pressure). Some evidence suggests that intravenous administration may help reduce long-term heart muscle changes that can occur after a heart attack. (Patients with very low blood pressure or severely slow heart rate will not receive nitroglycerin.)
Morphine. Morphine not only relieves pain and reduces anxiety but also dilates blood vessels, aiding the circulation of blood and oxygen to the heart. Morphine can decrease blood pressure and slow down the heart. In patients in which such effects may worsen their heart attacks, other drugs such as meperidine (Demerol) or nalbuphine (Nubain) may be used.

Anticlotting Medications. Appropriate anticlotting medications are started immediately in all patients.

Aspirin (antiplatelet drug) should be taken immediately after a heart attack. It can be either swallowed or chewed, but chewing provides more rapid benefit. If the patient has not taken an aspirin at home, it will be given at the hospital.
Clopidogrel (a stronger antiplatelet drug) is usually given along with other anticlotting drugs. It is sometimes used in place of aspirin.
Heparin (an anticoagulant) is usually given to moderate- to high-risk patients. Low-molecular weight heparin (LMWH), such as enoxaparin, is now recommended over standard heparin. Fondaparinux (Arixtra) is another type of blood thinner that is showing promise for treating patients with STEMI (ST-elevation myocardial infarction), a severe type of heart attack. Fondaparinux may also be better than enoxaparin for patients with acute coronary syndrome (ACS).
Glycoprotein IIb/IIIa inhibitors (antiplatelet drugs), most often tirofiban, are added for patients undergoing angioplasty. These drugs include tirofiban (Aggrastat) and abciximab (ReoPro). They are also beneficial for nonsurgical patients with ACS, notably NSTEMI (non ST-segment elevation myocardial infarction).

After a heart attack, clots form in the injured artery within 4 - 6 hours in 90% of patients. Opening a clotted artery as quickly as possible is the best approach to improving survival.

The standard medical and surgical solutions for opening arteries are:

Angioplasty, also called percutaneous coronary intervention (PCI), is standard procedure for opening the arteries. Coronary artery bypass graft (CABG) is sometimes used as an alternative to angioplasty. Angioplasty should be performed no later than 12 hours after a heart attack.
Thrombolytics are known as blood-clot-busting drugs and are the standard medications used to open the arteries. They are administered as soon as possible in centers where angioplasty is not available or in patients who are not good candidates for angioplasty.

The best candidates for either thrombolytic therapy or angioplasty are:

Adults younger than 75 years old with elevated ST segments or indications of bundle branch block (an ECG reading showing an interruption in the electrical pathway within the heart).
Patients whose symptoms occur within 12 hours of treatment.

Specific Candidates for Emergency Angioplasty. Most patients who meet the criteria for either thrombolytic drugs or angioplasty do better with angioplasty (although only in centers equipped to do this procedure).

Good candidates for angioplasty include:

Elderly patients (including those over age 75) who meet the criteria for both approaches tend to do better with angioplasty than thrombolytic therapy
Patients with diabetes who meet the criteria for both approaches
Patients under age 75 who go into shock, provided that angioplasty can be performed within 18 hours of shock (There is no advantage for patients over 75 who are in shock.)

As with thrombolytic treatments, angioplasty is most effective when performed within 12 hours of symptoms, and the sooner the better. Unfortunately not all communities have centers experienced in the procedure. The experience of the medical center's staff is critical for optimal benefits, and not all surgeons are experienced in angioplasty. However, the procedure is becoming increasingly available, and overall mortality rates are improving over time with angioplasty. Patients or their families should be sure their surgeon has performed at least 75 of these procedures and that the medical center has performed at least 200.

Specific Candidates or Non-Candidates for Thrombolytics. People who meet the criteria for either thrombolytics or angioplasty may benefit from thrombolytic drugs even if they have high-risk conditions such as diabetes, high systolic blood pressure less than 180 mm Hg, or a history of heart attack.

Several studies report that women do worse after thrombolytic therapy. Evidence indicates, however, that they are generally older and have more serious medical conditions when they seek treatment. One study also reported that women were given these drugs an average of 14 minutes later than men were. Women on thrombolytic therapy still do better than those not given these drugs. The bottom line is that thrombolytic therapy is life-saving, and appropriate candidates, regardless of age or gender, should not be denied this therapy.

Thrombolytics should be avoided or used with great caution in the following patients:

People older than age 75 -- a 2000 study suggested that their risk of death was 38% higher than patients in their age group who were not given therapy; a higher risk exists in such older patients even if they are otherwise healthy.
Patients with elevated ST segments whose symptoms have continued beyond 12 hours
Pregnant women
People who have experienced recent trauma (especially head injury) or invasive surgery
People with active peptic ulcers
Patients who have been given prolonged CPR
Current users of anticoagulants

Thrombolytics should not be used in the following patients:

Patients who have experienced any recent major bleeding
Patients with low ST segments
Patients with a history of stroke
Patients with uncontrolled high blood pressure

After a heart attack, the patient may need a number of different medications, depending on their risk factors for a future heart attack:

Beta-blockers reduce the oxygen demand of the heart by slowing the heart rate and lowering arterial pressure. They have been proven to help improve survival in patients who have had a heart attack.
Angiotensin converting enzyme (ACE) inhibitors should be given on the first day to all patients, unless there are medical reasons for not taking them.
Calcium channel blockers may provide relief in patients with unstable angina whose symptoms do not respond to nitrates and beta blockers. They are also useful for patients with Prinzmetal's angina.
Statins. Statins are important cholesterol lowering drugs that are beneficial for patients who have experienced a heart attack. They may also have heart-protective properties that go beyond lowering cholesterol.
Atropine. Atropine may be given for a very low heart rate (bradycardia) or signs of atrioventricular (AV) block, in which electric conduction of nerve impulses to specialized muscles in the heart is slowed or interrupted.

Severely ill patients, particularly those in cardiogenic shock (a dangerous condition that includes a drop in blood pressure and other abnormalities) or with heart failure, will be monitored closely and stabilized. Oxygen is administered, and fluids are given or replaced when it is appropriate to either increase or reduce blood pressure. Such patients may be given dopamine, dobutamine, or both. Other treatments depend on the specific condition.

Heart failure. Intravenous furosemide may be administered. Patients may also be given nitrates, and ACE inhibitors, unless they have a severe drop in blood pressure or other conditions that preclude them. Clot-busting drugs or angioplasty may be appropriate and life-saving in many of these patients, although heart failure patients are less likely to be given these treatments.

Cardiogenic Shock. A procedure called intra-aortic balloon counterpulsation (IABP) is proving to help these patients when used in combination with thrombolytic therapy. IABP involves inserting a catheter containing a balloon, which is inflated and deflated within the artery to boost blood pressure. Left ventricular assist devices and early angioplasty might be considered.

An important study published in 2006 in the Journal of the American Medical Association indicated that early surgical intervention is important for patients who have cardiogenic shock. The study found that patients who had angioplasty or bypass surgery within 6 hours of a heart attack complicated by shock had greatly improved odds for long-term survival compared to patients who received intensive medical therapy with clot-busting drugs.

An arrhythmia is a deviation from the heart's normal beating pattern caused when the heart muscle is deprived of oxygen and is a dangerous side effect of a heart attack. A very fast or slow rhythmic heart rate often occurs in patients who have had a heart attack, and is not usually a dangerous sign.

Premature beats or very fast arrhythmias called tachycardia, however, may be predictors of ventricular fibrillation. This is a lethal rhythm abnormality, in which the ventricles of the heart beat so rapidly that they do not actually contract but quiver ineffectually. The pumping action necessary to keep blood circulating is lost.

Preventing Ventricular Fibrillation. People who develop ventricular fibrillation do not always experience warning arrhythmias, and to date, there are no effective drugs for preventing arrhythmias during a heart attack.

Potassium and magnesium levels should be monitored and maintained.
Intravenous beta-blockers followed by oral administration of the drugs may help prevent arrhythmias in certain patients.

Treating Ventricular Fibrillation.

Defibrillators. Patients who develop ventricular arrhythmias are given electrical shocks with defibrillators to restore normal rhythms. Some studies suggest that implantable cardioverter-defibrillators (ICDs) may prevent further arrhythmias in heart attack survivors of these events who are at risk for further arrhythmias. Patients with ICDs should not take fish oil supplements, as they may increase the risk of ventricular fibrillation.
Antiarrhythmic Drugs. Antiarrhythmic drugs include lidocaine, procainamide, or amiodarone. Amiodarone or another antiarrhythmic drug may be used afterward to prevent future events.

Managing Other Arrhythmias. People with an arrhythmia called atrial fibrillation have a higher risk for stroke after a heart attack and should be treated with anticoagulants such as warfarin (Coumadin). Other rhythm disturbances called bradyarrhythmias (very slow rhythm disturbances) frequently develop in association with a heart attack and may be treated with atropine or pacemakers.

[For more information on atrial fibrillation, ICDs, and pacemakers see In-Depth Report #45: Stroke.]

Medications

Thrombolytic, also called clot-busting or fibrinolytic, drugs are now mainstays in the early treatment of many patients with heart attacks. These drugs dissolve the clot, or thrombus, responsible for causing artery blockage and heart-muscle tissue death.

The standard thrombolytic drugs are recombinant tissue plasminogen activators or rt-PAs. They include alteplase (Activase) and reteplase (Retavase). Both are similar in effectiveness, although reteplase is easier to administer. Tenecteplase (TNKase), a newer drug, can be delivered more rapidly than alteplase, and to date, survival rates are similar. Streptokinase (Kabikinase, Streptase) is sometimes used but is somewhat less effective that the others.

The sooner that thrombolytic drugs are given after a heart attack, the better. The benefits of thrombolytics are highest within the first 3 hours. They can still help if given within 12 hours of a heart attack.

A thrombolytic drug, such as alteplase or tenecteplase, is typically given by IV along with heparin, an anticoagulant drug. (Heparin, like aspirin, cannot destroy existing blood clots but can prevent clots from reforming after they are broken up.) Enoproxin, a form of heparin called low-molecular weight heparin, may be more beneficial than standard heparin.

Other anticlotting drugs are being tested in combination with thrombolytic drugs for emergency treatment following a severe heart attack. Several 2005 studies have indicated that the antiplatelet drug clopidogrel (Plavix) can help prevent arteries from reclosing, and a second heart attack, when given along with aspirin and thrombolytic drugs. The studies evaluated patients who received thrombolytic drugs for treatment of STEMI (severe heart attacks with complete artery blockage).

Hemorrhagic stroke, usually occurring during the first day, is the most serious complication of thrombolytic therapy, but fortunately it is rare. Streptokinase given without heparin poses the lowest risk (although it is also less effective than other regimens in restoring blood flow). In general, the mortality rate from bleeding is only 3 in 1,000 patients treated with thrombolytics, whereas 39 patients in 1,000 would die without these clot-busting drugs. Recent evidence suggests that the survival benefits of thrombolytic therapy, particularly in combination with aspirin, last for years.

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.

Anti-platelet 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 drug. It is the most common anti-clotting drug and nearly anyone with heart disease is advised to take it daily in low dose.
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), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are used with angioplasty and stent placement. They are proving to be helpful for ACS patients with NSTEMI (non ST-segment elevation myocardial infarction).

Anticoagulants. Anticoagulants thin blood. They include:

Heparin
Fondaparinux (Arixtra)
Warfarin (Coumadin)
Direct thrombin inhibitors such as argatroban (Novastan), danaparoid (Orgaran), and lepirudin (Refludan)

How Anti-Clotting Drugs Are Used For Heart Attacks. Unlike the thrombolytic (clot-busting) drugs, which are used to break up blood clots during a heart attack, anti-clotting drugs are used to prevent blood clots from forming in the first place. Such drugs are sometimes used along with thrombolytics, immediately after a heart attack, and also as on-going maintenance to prevent a heart attack.

Aspirin is given immediately, and heparin is usually started during or at the end of the thrombolytic infusion.
Clopidogrel (Plavix) is given along with aspirin, heparin, and thrombolytic (“clot busting”) drugs as emergency treatment following a heart attack and to prepare for angioplasty surgery. In 2006, the FDA approved clopidogrel for patients who have had a STEMI heart attack and who are not going to have angioplasty. Clopidogrel is also helpful for patients with acute coronary syndrome. A 2006 study suggested that clopidogrel plus aspirin may not work better than aspirin alone in preventing a first heart attack. However, many studies show that clopidogrel is an important treatment for patients who have already had a heart attack. Clopidogrel and aspirin may reduce the risk of a second heart attack by 30%. The combination of clopidogrel (or ticlopidine) and aspirin is essential for patients who have a drug-eluting stent. In 2007, the American Heart Association recommended that patients with drug-eluting stents take this drug combination for at least 1 year after the stent is inserted to reduce the risks of blood clots.

All of these drugs pose a risk for bleeding. [See In-Depth Report #03: Coronary artery disease.]

Beta-blockers reduce the oxygen demand of the heart by slowing the heart rate and lowering pressure in the arteries. They are effective for reducing deaths from heart disease. These drugs include propranolol (Inderal), carvedilol (Coreg), bisoprolol (Zebeta), acebutolol (Sectral), atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol-XL), and esmolol (Brevibloc).

Administration During a Heart Attack. The beta-blocker metoprolol is given through an IV within the first few hours of a heart attack to reduce the destruction of heart tissue. However, a study suggests that emergency intravenous use of metoprolol may increase the risk of cardiac shock.

Prevention After a Heart Attack. Beta-blockers taken by mouth are also used on a long-term basis (“maintenance therapy”) after a first heart attack to help prevent future heart 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 not abruptly stop taking these drugs. The sudden withdrawal of beta-blockers can rapidly increase heart rate and blood pressure. The doctor may want the patient to slowly decrease the dose before stopping completely.

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 risk 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.

A 2006 review of studies indicated that early, intensive therapy with statins can help reduce the risk of death, unstable angina, and revascularization (surgery to restore blood flow) for patients with acute coronary syndrome. The review indicated that statins work best when they are prescribed within 14 days of hospitalization for acute coronary syndrome. The researchers found that the effect of statins began about 4 months after starting drug therapy and that benefits lasted up to 2 years.

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.

Angiotensin converting enzyme (ACE) inhibitors are important drugs for treating patients who have had a heart attack, particularly for patients at risk for heart failure. These drugs are commonly used to treat hypertension and are recommended as first-line treatment for people with diabetes and kidney damage.

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 inhibitor together is safe.

Magnesium has blood-thinning properties and may help open blood vessels. It is important to correct any magnesium deficiencies in patients (such as those who are taking diuretics).

Flu Shots. Influenza vaccinations may help protect patients against another heart attack during flu season.

Antibiotics. Researchers have investigated antibiotics for treating patients with heart disease and past infection of the bacteria Chlamydia pneumoniae. Results from several large-scale clinical trials, published in 2003 in the Journal of the American Medical Association (JAMA) and presented in 2004 at the European Society of Cardiology annual meeting, suggest that antibiotic treatment provides no benefit in preventing heart attack or other cardiac events 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.

Stem Cell Therapy. Researchers are investigating whether infusions of adult stem cells can help improve outcomes in patients who have a heart attack. Results from three small trials, published in 2006 in the New England Journal of Medicine, suggested that stem cell therapy may have some benefits in improving heart function. None of the studies reported treatment complications. Research presented at the 2007 American College of Cardiology annual meeting discussed intravenous stem cell therapy with Provacel (a commercial stem cell preparation). In the small study, patients who received Provacel had fewer adverse events (such as arrhythmia) and improved heart, lung, and overall function compared to patients who received placebo. Patients in the study received a Provacel infusion within 10 days of having a heart attack.

Surgery

Percutaneous coronary intervention (PCI), also called angioplasty, and coronary artery bypass graft surgery are the standard operations for opening narrowed or blocked arteries. They are known as revascularization procedures.

Emergency angioplasty is the standard procedure for heart attacks. It should be performed within 12 hours of a heart attack. Clot-buster drugs can help prevent damage, but must be given with 1 hour of a heart attack.
Coronary bypass surgery is typically used as elective surgery for patients with blocked arteries. It may be used after a heart attack if angioplasty or thrombolytics fail or are not appropriate. It is usually not performed for a few days to allow recovery of the heart muscles.

Click the icon to see an illustrated series detailing a heart bypass surgery.

Percutaneous coronary intervention (PCI), also called angioplasty, involves procedures such as percutaneous transluminal coronary angioplasty (PTCA) that help open the blocked artery. A typical angioplasty procedure involves the following steps:

Click the icon to see an image of an angioplasty.

The cardiologist threads a narrow catheter (a tube) containing a fiber into the blocked vessel.
The cardiologist opens the blocked vessel using balloon angioplasty, in which a tiny deflated balloon is passed 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.
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.
To keep the artery open afterwards, doctors use a device called a coronary stent, an expandable metal mesh tube that is implanted during angioplasty at the site of the blockage.
Once in place, the stent pushes against the wall of the artery to keep it open. Stenting is improving results in patients with heart attack who have emergency angioplasty. It also significantly prevents reclosure and reduces heart attack rates in patients with ACS.

Experts recommend that appropriate patients receive angioplasty and stenting within 90 minutes after having a heart attack and no later than 12 hours following an attack. Although some hospitals have been performing angioplasty and stenting for up to a month following a heart attack, a landmark 2006 study found that delayed surgical intervention is not helpful for most patients. The Occluded Artery Trial (OAT), published in the New England Journal of Medicine, reported that balloon angioplasty and stenting failed to prevent heart complications in patients who received the procedure 3 – 28 days after a heart attack. The trial compared angioplasty to medications (aspirin, ACE inhibitors, beta-blockers, statins, clopidogrel).

Experts are now recommending delayed angioplasty and stenting only for patients who are unstable or who continue to have chest pain following a heart attack. This procedure may also be appropriate for patients who cannot tolerate beta-blocker drugs, which are commonly prescribed to help improve survival after a heart attack.

Complications occur in about 10% of patients (about 80% within the first day). Serious side effects include heart attack and the need for additional surgery. Best results occur in hospital settings with experienced teams and backup. Women who have angioplasty after a heart attack have a higher risk of death than men.

Reclosure and Blockage During or Shortly after Angioplasty. Reclosure of the artery often occurs during or shortly after angioplasty. A number of anticlotting drugs are used to reduce this risk. Clopidogrel (Plavix) is often given along with aspirin and thrombolytic drugs (such as abciximab) in the days before angioplasty surgery, to help prevent heart attack or stroke following surgery. Research suggests that abciximab (ReoPro) is especially helpful for patients with acute coronary syndrome.

Prevention of Restenosis. Narrowing or reclosing of the artery (restenosis) occurs within a year of angioplasty in many angioplasty patients, often requiring a repeat operation. In restenosis, the narrowing of the artery is usually due to scarring, not blood clots. Drug-eluting stents, which are coated with sirolimus (Rapamune) or paclitaxel (Taxol), can help prevent restenosis. Several 2006 studies indicated that this type of stent may be better than a bare metal stent for patients who have experienced a STEMI heart attack. However, because drug-eluting stents reduce arterial tissue growth, they can increase the risks of blood clots.

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. [See In-Depth Report #03: Coronary artery disease.]

Click the icon to see an illustrated series detailing balloon angioplasty.

Coronary artery bypass graft surgery (CABG) is the alternative elective procedure to angioplasty for opening blocked arteries in patients with severe angina, particularly those who have two or more blocked arteries. It is a very invasive procedure, however:

The chest is opened, and the blood is rerouted through a lung-heart machine.
The heart is stopped during the procedure.
Segments of veins or arteries taken from elsewhere in the patient's body are fashioned into grafts, which are used to reroute the blood. The blood vessel grafts are placed in front of and beyond the blocked arteries, so the blood flows through the new vessels around the blockage.

Mortality rates with this procedure after a heart attack are much higher (6%) than when it is used electively (1 - 2%). How or when it should be used after a heart attack, then, is controversial. A 2002 study attempted to determine which patients are at highest risk for poor results from CABG after a heart attack. The study found higher risks for women, patients over age 75, and those with heart failure or other severe heart problems.

Rehabilitation

Lifestyle measures, particularly dietary factors, are equally important in preventing heart attacks and must be strenuously adhered to.

Physical rehabilitation is extremely important after a heart attack. It has been associated with a 25% reduction in mortality rates at 3 years. Rehabilitation may include:

Leg exercises may start as early as the first day. The patient usually sits in a chair on the second day, and begins to walk on the second or third day.
Most patients undergo low-level exercise tolerance tests early in their recovery. One study suggests that exercise testing within 3 days after a relatively minor attack may allow patients to go home earlier.
After 8 - 12 weeks, many patients, even those with heart failure, benefit from supervised exercise programs. Health professionals should provide the patient with schedules for low-level aerobic home-activity. Strength (resistance) training is also important. Tai Chi, a Chinese martial art, appears to be very beneficial and safe for people after a heart attack. It should be noted that the risk for serious heart events during rehabilitation is very low.

Patients generally return to work in about 2 months, although timing can vary depending on the severity of the condition.

Sexual activity after a heart attack carries a very low risk and is believed to be safe, particularly in people who had exercised regularly before the attack. In any case, the feelings of intimacy and love that accompany healthy sex can help offset depression, a far greater risk for a future attack.

Major depression affects between 15 - 23% of patients with ACS or heart attacks. Many studies suggest that depression is a major predictor for increased mortality in both women and men. (One reason may be that depressed patients are less likely to comply with their heart medications.)

Psychotherapeutic techniques, especially cognitive behavioral therapies, are very helpful. Doctors have been reluctant to prescribe antidepressant drugs after ACS or a heart attack because older antidepressants tended to have adverse effects on the heart. Newer antidepressants may be safer. Studies on sertraline (Zoloft), one of the selective serotonin reuptake inhibitor (SSRI) antidepressants, have not reported harmful effects for patients who have had a heart attack. It is not yet clear if other SSRIs are equally safe and effective.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.acc.org -- American College of Cardiology
www.americanheart.org -- American Heart Association

References

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.

Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1222-32.

Chou R, Helfland M, Peterson K, Dana T, Roberts C. Comparative Effectiveness and Safety of Analgesics for Osteoarthritis. Comparative Effectiveness Review No. 4. (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-02-0024.) Rockville, MD: Agency for Healthcare Quality and Research. September 2006.

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.

Gislason GH, Jacobsen S, Rasmussen JN, Rasmussen S, Buch P, Friberg J, et al. Risk of death or reinfarction associated with the use of selectivecyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation. 2006 Jun 27;113(25):2906-13. Epub 2006 Jun 19.

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.

Hulten E, Jackson JL, Douglas K, George S, Villines TC. The effect of early, intensive statin therapy on acute coronary syndrome: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Sep 25;166(17):1814-21.

Hochman JS, Lamas GA, Buller CE, Dzavik V, Reynolds HR, Abramsky SJ, et al. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med. 2006 Dec 7;355(23):2395-407. Epub 2006 Nov 14.

Hochman JS, Sleeper LA, Webb JG, Dzavik V, Buller CE, Aylward P, et al. Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction. JAMA. 2006 Jun 7;295(21):2511-5.

Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8.

Kostis WJ, Demissie K, Marcella SW, Shao YH, Wilson AC, Moreyra AE. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med. 2007 Mar 15;356(11):1099-109.

Laarman GJ, Suttorp MJ, Dirksen MT, van Heerebeek L, Kiemeneij F, Slagboom T, et al. Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. N Engl J Med. 2006 Sep 14;355(11):1105-13.

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.

Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1199-209.

McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase2. JAMA. 2006 Oct 4;296(13):1633-44. Epub 2006 Sep 12.

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.

Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1210-21.

Spaulding C, Henry P, Teiger E, Beatt K, Bramucci E, Carrie D, et al. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med. 2006 Sep 14;355(11):1093-104.

Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation. 2006 Jun 20;113(24):2803-9. Epub 2006 Jun 12.

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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

Diabetes - type 2

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Screening Tests
Treatment
Lifestyle Changes
Medications
Long-Term Complications
Emergency Complications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

Sitagliptin (Januvia), the first in a new class of diabetes drugs called DPP-4 inhibitors, was approved in 2006.
Janumet, a 2-in-1 pill that contains both sitagliptin and metformin, was approved in 2007.
These drugs are taken by mouth and may be more convenient for patients than exenatide (Byetta), a similar drug. DPP-4 inhibitors do not cause weight gain and may pose a lower risk for hypoglycemia than some other diabetes drugs.

Drug Safety Alert

Rosiglitazone (Avandia) may significantly increase the risk for heart attack, indicates a review published in the Journal of the American Medical Association. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Rosiglitazone and a similar drug, pioglitazone (Actos), are known to significantly increase the risks for heart failure. There is also evidence that these drugs increase the risk for bone fracture.

Anemia Drugs Warning

Patients with anemia associated with end-stage kidney disease, especially those on dialysis, should be aware of new warnings concerning dosing target levels of erythpoiesis-stimulating drugs. In 2007, the FDA warned that darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) can increase the risk for blood clots, stroke, and heart attacks when excessive doses are given. The FDA has defined target hemoglobin levels and recommends that patients who receive these drugs have frequent blood tests. Patients should also report to their doctors any unusual symptoms.

Genetics Research Breakthroughs

Scientists have now identified 10 genes that are associated with increased risk for type 2 diabetes. Six of these genes were discovered in 2006 and 2007.

Diabetes and Pre-Diabetes

About 20 million Americans have type 2 diabetes, and an additional 54 million have pre-diabetes. According to a 2007 study by the U.S. Centers for Disease Control, the prevalence of type 2 diabetes has been increasing by 5% each year since 1990. Rising rates of obesity may be one factor.
For people with pre-diabetes, lifestyle changes, such as losing weight, appear to work as well as drug treatment in delaying the progression to diabetes, according to a 2007 British Medical Journal study.

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 noninsulin-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 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 down carbohydrates into sugar molecules (including glucose) 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.
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 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. (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 is where the hormone insulin is produced. Insulin is used by the body to store and utilize glucose.

Type 2 diabetes is the most common form of diabetes, accounting for 90 - 95% of cases. 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. 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.

In type 1 diabetes, the disease process is more severe 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. [See In-Depth Report #9: Diabetes - type 1.]

Click the icon to see an image of the pancreas.

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Polycystic ovaries are highly associated with 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 hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) are associated with or increase the risk for diabetes.

Causes

Type 2 diabetes is caused by a complicated interplay of genes, environment, insulin abnormalities, increased glucose production in the liver, increased fat breakdown, and possibly defective hormonal secretions in the intestine. The recent dramatic increase indicates that lifestyle factors (obesity and sedentary lifestyle) may be particularly important in triggering the genetic elements that cause this type of diabetes.

The characteristic features of most patients with type 2 diabetes are:

Insulin resistance in muscle cells
Normal or even excessive levels of insulin (to compensate for this resistance), eventually followed by a drop in insulin production

In addition, researchers are trying to determine the factors that might promote insulin resistance:

Both obesity and insulin resistance at different phases are marked by elevated levels of free fatty acids and the hormones resistin and leptin. It is not known yet if elevated levels are simply a product of obesity or play some causal role in diabetes.
Insulin resistance is associated with a chronic low inflammatory response, which involves a number of immune factors, such as TGH-beta 1 and C-reactive protein. Such factors can cause damage over time and may be responsible for the association between insulin resistance and heart disease.

Type 2 diabetes has a genetic component. In 2006 and 2007, major breakthroughs in genetic research identified six new genes associated with type 2 diabetes. Ten genes have now been positively confirmed as increasing the risk for type 2 diabetes: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, IGF2B2, CDKAL1, CDKN2A, CDKN2B, and FTO.

Most of these genes play a role in regulating insulin action, including the processes that occur in the pancreas’ insulin-producing beta cells. The FTO gene increases the risk for obesity, which itself is a risk factor for type 2 diabetes. These genes appear to cluster around three genetic regions that include a number of chromosomes. Scientists hope that future research will help uncover how genes influence the progression from pre-diabetes to diabetes, and how lifestyle and medical intervention may help delay or prevent this process.

Risk Factors

Nearly 21 million Americans have diabetes; up to 95% of these cases are type 2. In addition, 26% of Americans age 20 and older (and 40% of Americans age 65 and older) have impaired fasting glucose, a pre-diabetes condition that increases the risk for diabetes. According to the American Diabetes Association, 54 million people have pre-diabetes, bringing a total of 75 million Americans who either have diabetes or are at risk of developing it.

Historically, type 2 diabetes usually developed after the age of 40, but it is now also increasing in children. The prevalence of diabetes in the U.S. has increased by 5% each year since 1990, and experts believe that obesity is the major factor behind this dramatic growth rate. Given the current epidemic of obesity, experts estimate that over a third of all people born in 2002 will eventually develop diabetes. Furthermore, the dramatic increase in diabetes is occurring worldwide as American lifestyles become global. Evidence strongly suggests that healthy lifestyles can prevent most cases of type 2 diabetes. People with pre-diabetes can substantially lower their risk by losing weight through diet and exercise.

Healthy adults age 45 and older should get tested for diabetes. Patients who are younger than age 45 and who are overweight or have other risk factors should also ask their doctors about testing. According to the National Institutes of Health, the following are major risk factors for diabetes and pre-diabetes:

Age 45 or older
Family history of diabetes
Overweight
Inactive lifestyle (exercise less than 3 times a week)
African-American, Hispanic/Latin American, American Indian and Alaska Native, Asian-American, or Pacific Islander ethnicity
High blood pressure (140/90 mm/Hg or higher)
HDL (“good”) cholesterol less than 35 mg/dL or triglyceride level 250 mg/dL or higher
Have had diabetes during pregnancy (gestational diabetes) or have given birth to a baby that weighed more than 9 pounds
Polycystic ovary syndrome (metabolic disorder that affects female reproductive system
Acanthosis nigricans (dark, thickened skin around neck or armpits)
History of disease of blood vessels to the heart, brain, or legs
Diabetes test history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)

Obesity is the number one risk factor for type 2 diabetes. It is estimated that 80 - 95% of the current dramatic increases in type 2 diabetes are due to obesity. Excess body fat appears to play a strong role in insulin resistance, but the way the fat is distributed is also significant. Weight concentrated around the abdomen and in the upper part of the body (apple-shaped) is associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Waist circumferences greater than 35 inches in women and 40 inches in men have been specifically associated with a greater risk for heart disease and diabetes. (People with a "pear-shape" -- fat that settles around the hips and flank -- appear to have a lower risk for with these conditions.) However, obesity does not explain all cases of type 2 diabetes. It is also common among people in countries where weights tend to be low, such as Asia or India.

Metabolic Syndrome. A set of conditions referred to as metabolic syndrome (also called Syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome.

Between 25 - 33% of patients with type 2 diabetes have family members with diabetes. Having a first-degree relative with the disease poses a 40% risk of developing diabetes. One study reported that people with diabetic family histories have a higher risk for developing the disease at an earlier stage and with more severe features. Because families share many lifestyle features (eating and exercise habits) it is difficult to determine when genetics or environment play the major role. When clusters of type 1 and type 2 diabetes appear within families, genetic factors should be strongly suspected.

The risk for type 2 diabetes varies among population groups. Diabetes also seems to pose higher or lower risks for specific complications among ethnic groups. Genetic and socioeconomic factors, or both, seem to be involved in some ethnic differences, but in most cases the observed increase in ethnic groups in Americans is due to changes in traditional lifestyles.

African-Americans. African-American men have twice the risk of developing type 2 diabetes as Caucasian men. African-Americans with diabetes are also at higher risk for amputations than Caucasians. This is most likely due to a higher incidence of high blood pressure and smoking as well as poorer health care in African-Americans. Genetic factors may also play a role. For example, there is some evidence that African-Americans process insulin in the liver differently from Caucasians, which may make them more susceptible to diabetes when other risk factors are present.
Native Americans. The Pima tribe in Arizona has an incidence of type 2 diabetes that is 19 times higher than that of the white population. The risk for diabetic complications among young Pima adults is also very high. Other Native American tribes in North America are also at high risk for type 2 diabetes. The association between diet and diabetes among this population remains critical, however, in assessing the reason for their higher risk. For example, Pimas who live in Mexico exercise more and eat less fat (but consume more calories) than Pima tribes in Arizona. Mexican Pimas have a prevalence of diabetes of only 6%, while half of their Arizona Pima neighbors have diabetes.
Hispanic Americans. The rate of type 2 diabetes is also very high among Mexican-Americans, approximately double that for Caucasians. This group may also be at higher risk for heart problems than other ethnic groups with diabetes.
Asian-Americans. Overweight Asian-Americans and Pacific Islanders are at increased risk for developing type 2 diabetes. The risk for some Asian ethnic groups (such as Native Hawaiians and Filipinos) is twice that of Caucasians.

Smoking increases the risk for diabetes. According to a 2006 study, smokers are more than twice as likely to develop diabetes as people who have never smoked. Another 2006 study found that exposure to second-hand cigarette smoke also increases the risk for diabetes in non-smokers.

Low birth weight is now a recognized risk factor for type 2 diabetes and heart disease in adulthood. The reasons are unclear, although studies suggest it may represent a genetic factor. Studies have observed that babies of fathers with type 2 diabetes and of women who later developed type 2 diabetes tend to weigh less than babies of parents without diabetes. Such studies suggest that some parents may have some specific gene that affects insulin factors, putting both themselves and their children at risk for future diabetes. Theoretically, such a gene might also affect insulin factors in the developing fetus, causing low birth weight. (Of note, mothers of very high-weight babies are also at risk for diabetes -- although in these cases it is most often associated with gestational diabetes.)

Obesity-Related Type 2 Diabetes in Children. Until recent years, diabetes in children was almost always type 1 (an autoimmune disease). Between 1982 - 1994, however, the incidence of type 2 diabetes in children increased 10-fold. By 1996, a study reported that a third of all new diabetes cases in children were type 2. This increase parallels the rising epidemic in childhood obesity that has occurred both in the U.S. and worldwide, notably Europe and Japan. In some areas of Japan, type 2 diabetes has now become the dominant form of diabetes in children and adolescents. Obesity in children is also related to abnormalities in cholesterol, blood pressure, and insulin levels in adults. Administering glucose tolerance tests in overweight children may be helpful in identifying those at high risk for diabetes.

Maturity-Onset Diabetes in Caucasian 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. (This form of type 2 diabetes is not associated with obesity.)

An estimated 5% of pregnant women develop a form of type 2 diabetes, usually temporary, in their third trimester called gestational diabetes.

Gestational diabetes is diabetes that first appears during pregnancy. It usually develops during the third trimester of pregnancy. After delivery, blood sugar (glucose) levels generally return to normal, although 25% of these women develop type 2 diabetes within 15 years.

Who Gets Gestational Diabetes? Estimates for the prevalence of gestational diabetes are generally about 4%. Some studies, however, have suggested significantly higher rates. In one German study, 13% of pregnant women were diagnosed with this form of diabetes, including many who did not have any risk factors.

A pregnant woman's risk factors include:

Family history of diabetes
African-American, Hispanic, Asian, or Pacific Islander ethnicity
Overweight
Older than 25 years
Gestational diabetes with past pregnancy
Having given birth to a child weighing over 9 pounds
Diagnosis of pre-diabetes

Who Should Be Tested for Gestational Diabetes? A number of expert groups recommend that all pregnant women be tested for gestational diabetes between their 24th - 28th week. Pregnant women at high risk for diabetes should be tested earlier. The only women who do not need to be tested are those at very low risk. Generally they have the following characteristics:

Under 25 years old
Normal weight
No first-degree relatives with diabetes
Not belonging to high-risk ethnic groups

Effect of Diabetes on the Fetus. Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes high level of insulin. Studies indicate that such conditions may affect the developing fetus as soon as it is conceived, placing the unborn child at risk for:

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

Effect of Diabetes on the Pregnant Woman. In addition to endangering the fetus, diabetes also presents risks to the pregnant woman.

The most serious potential complications from gestational diabetes are high blood pressure during pregnancy, a condition called preeclampsia that is potentially dangerous. Because gestational diabetes increases the size of the fetus, it is also increases the likelihood that a woman will require a Cesarean delivery. Gestational diabetes also increases the risk that a woman will later develop type 2 diabetes.

How Is Gestational Diabetes Managed? Some suggestions for preventing complications include:

In most cases, increases in glucose levels can be managed with diet and exercise. Aerobic exercise before and during pregnancy may lower glucose levels and help protect women at risk or those who have gestational diabetes. (Any pregnant woman should check with her doctor before embarking on a vigorous exercise regimen.)
If a woman with gestational diabetes cannot control her glucose with lifestyle measures, she is usually given insulin.

The placenta provides the fetus with oxygen and nutrients and takes away waste, such as carbon dioxide, via the umbilical cord.

Polycystic Ovary Syndrome. Polycystic ovary syndrome (PCOS) is a condition that affects about 6% of women and results in the ovarian production of high amounts of androgens (male hormones), particularly testosterone. It appears to be an important cause of many menstrual disorders. Women with PCOS are at higher risk for insulin resistance, and about half of PCOS patients also have diabetes.

Click the icon to see an image of polycystic ovary syndrome.

Schizophrenia. While no definitive association has been established, research has suggested an increased background risk of diabetes among people with schizophrenia. In addition, many of the new generation of antipsychotic medications may elevate blood glucose levels. Patients taking antipsychotic medications (such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, ziprasidone) should receive a baseline blood glucose level test and be monitored for any increases during therapy.

Depression. According to a 2007 study, adults who have severe clinical depression may have a greater risk of developing type 2 diabetes than those who have never experienced depressive symptoms.

Hepatitis C. Patients with hepatitis C have a higher incidence of type 2 diabetes. The reasons for this are unclear.

Symptoms

Type 2 diabetes usually begins gradually and progresses slowly. Symptoms in adults include:

Excessive thirst
Increased urination
Fatigue
Blurred vision
Weight loss
In women, vaginal yeast infections or fungal infections under the breasts or in the groin
Severe gum problems
Itching
Erectile dysfunction in men
Unusual sensations, such as tingling or burning, in the extremities

Symptoms in children are often different:

Most children are obese or overweight
Increased urination is mild or even absent
Many children develop a skin problem called acanthosis, which is characterized by velvety, dark colored patches of skin

Screening Tests

There are no clear-cut guidelines for when to screen for diabetes. Some experts recommend that everyone over age 45 be tested regularly for diabetes, although others do not feel this necessary in people without symptoms or risk factors. In fact, early screening may identify some people with impaired glucose levels that would eventually normalize. Such people might be treated unnecessarily with medications that pose a risk for high blood sugar (hypoglycemia).

Still, given the risk for serious complications with diabetes and the potential value of early treatments, most experts recommend that all adults over 45 be screened and that younger adults be screened if they have one or more of the following conditions:

A weight that is 20% more than ideal body weight
Risk factors for heart disease (high blood pressure, unhealthy cholesterol levels -- especially for patients with low HDL cholesterol and high triglyceride levels
A close relative with diabetes
A high-risk ethnic group background
In women, having delivered a baby weighing over 9 pounds or having a history of gestational diabetes

Some experts recommend that children over age 10 should be tested for type 2 diabetes (even if they have no symptoms), if they are overweight and have at least two of the above mentioned risk factors.

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

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 test is 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 were tested in the morning.

A 2005 study suggested that even people with FPG levels in the high end of the normal range (high 90s) may be at increased risk for developing type 2 diabetes. Obesity further increases this risk. Patients with FPG levels in the upper 90s should strive to exercise and lose weight to help lower their FPG levels.

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 considered 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 require that the patient not eat for at least 8 hours prior to the test.

Test for Glycated Hemoglobin. Tests for blood levels of glycated hemoglobin, also known as hemoglobin A1c (HbA1c), are not currently used for an initial diagnosis, but they are useful for determining the severity of diabetes. Some experts think this test can help predict complications in people who have FPG levels between 110 - 139, which are above normal but do not indicate full-blown 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 glycosylation.
Glycosylation affects a number of proteins, and elevated levels of glycolated hemoglobin are 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.

Screening for Heart Disease. All patients with diabetes should be tested for 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.

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.

Screening for Kidney Damage. The earliest manifestation of kidney damage is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. About 20% of type 2 patients show evidence of microalbuminuria upon diagnosis of diabetes. (However, not all people with type 2 diabetes eventually develop kidney disease.) Microalbuminuria typically shows up in patients with type 2 diabetes who have high blood pressure.

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 cleansing the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 2 diabetes get an initial comprehensive eye exam by an ophthalmologist or optometrist shortly after they are diagnosed with diabetes, and once a year thereafter. (People at low risk may need follow-up exams only every 2 - 3 years.) The eye exam should include dilation to check for signs of retinal disease (retinopathy).

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 be sure to have a foot exam every 3 - 6 months to check for ulcers or infections.

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

Treatment

Pre-diabetes precedes the onset of type 2 diabetes. People who have pre-diabetes have fasting blood glucose levels that are 100 - 125 mg/dL -- higher than normal, but not yet high enough to be classified as diabetes. (Pre-diabetes used to be referred to as “impaired glucose tolerance.”) Pre-diabetes greatly increases the risk for diabetes.

Treatment of pre-diabetes is very important. Research shows that lifestyle and medical interventions can help prevent, or at least delay, the progression to diabetes. While insulin-regulating drugs such as metformin (Glucophage) and acarbose (Precose) are sometimes prescribed, evidence indicates that lifestyle changes can be at least as effective as drug therapy. The most important lifestyle treatment for people with pre-diabetes is to lose weight through diet and regular exercise. Even a modest weight loss of 10 - 15 pounds can significantly reduce the risk of progressing to diabetes.

Because people with pre-diabetes have a higher risk for heart disease and stroke, diet and exercise are also very important for heart health, as is quitting smoking. It is also important to have your doctor check your cholesterol and blood pressure levels on a regular basis. Your doctor should also check your fasting blood glucose levels every 1 - 2 years.

The major treatment goals for people with type 2 diabetes are:

Treat all conditions that place the patients at risk for heart disease and stroke, which are the major killers of people with type 2 diabetes.
Control blood glucose levels. The goal is to achieve fasting blood glucose levels of less than 110 mg/dL and glycolated hemoglobin (HbA1c) levels of less than 7%. The objective is to reduce complications in small blood vessels and the nerve damage associated with diabetes.

An intensive multi-pronged approach is critical for reducing complications and improving survival rates in patients with diabetes. Intensive therapy includes:

Healthy lifestyle changes: Regular exercise; heart-healthy diet; quitting smoking.
Controlling blood sugar levels. Monitor blood sugar and hemoglobin HbA1C levels. Oral anti-hyperglycemic drugs such as metformin are first-line drug treatments. Insulin may eventually be needed.
Heart-protective drugs. These medications include various drugs to control high blood pressure (ACE inhibitors, diuretics, others) and cholesterol (statins, fibrates). Controlling high blood pressure is a proven factor in reducing mortality rates. Aspirin may help prevent blood clots and heart attack.

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions. Treating children with type 2 diabetes depends on the severity of the condition at diagnosis. Metformin is approved for children. Formerly, only insulin was approved for treating children with diabetes.

Lifestyle Changes

A simple heart-healthy diet with weight control and exercise is important for people with pre-diabetes and may be sufficient for some people with type 2 diabetes. Some patients may be able to control their blood sugar with lifestyle measures and not need medication. Even for patients who do need to take drugs, lifestyle plays an essential role in controlling diabetes. Lifestyle changes can be difficult to initiate and sustain, however. Patients should surround themselves with a solid network of doctors, dietitians, family, and friends who understand both their condition and their needs.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. High fiber foods help improve blood glucose levels. Whole grain cereals, which are rich in both fiber and magnesium, may also help reduce the risk for diabetes.
Limit saturated fats (found mostly in animal products) to less than 7% of total daily calories and avoid trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart-healthy food choice.
Weight control, quitting smoking, and exercise are essential components of any diet program.

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

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.

[For detailed information, including diabetic exchange lists and carbohydrate counting, see In-Depth Report #42: Diabetes diet.]

Being overweight is the number one risk factor for type 2 diabetes. Even modest weight loss can help prevent type 2 diabetes from developing. It can also help control or even stop progression of type 2 diabetes in people with the condition and reduce risk factors for heart disease. Patients should aim to lose weight if their body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Unfortunately, not only is weight loss difficult to sustain, but many of the oral medications used in type 2 diabetes cause weight gain as a side effect. For obese patients who cannot control weight using dietary measures alone, weight-loss drugs, such as orlistat (Xenical) or sibutramine (Meridia), may be helpful. Orlistat may have specific benefits for people with diabetes. It may not only help achieve weight but also improve glucose, cholesterol, and lipid levels. In 2007, the FDA approved a non-prescription form of orlistat (alli). [See In-Depth Report #53: Obesity.]

Sedentary habits, especially TV watching, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercise. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself.

For improving glycemic control, the American Diabetes Association recommends at least 150 minutes per week of moderate-intensity physical activity (50 - 70% of maximum heart rate) or at least 90 minutes per week of vigorous aerobic exercise (more than 70% of maximum heart rate). Exercise at least 3 days a week, and do not go more than 2 consecutive days without physical activity.

Strength Training. Strength training, which increases muscle and reduces fat, is also helpful for people with diabetes who are able to do this type of exercise. The American Diabetes Association recommends performing resistance exercise three times a week. Build up to three sets of 8 - 10 repetitions using weight that you cannot lift more than 8 - 10 times without developing fatigue. Be sure that your strength training targets all of the major muscle groups.

Exercise Precautions. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.
Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure.

[See In-Depth Report #29: Exercise.]

According to the American Diabetes Association, people with diabetes should aim for preprandial (before eating) plasma glucose levels of 90 - 130 mg/dL and postprandial (after eating) plasma glucose levels less than 180 mg/dL. Hemoglobin A1C levels should be less than 7%.

Measuring Blood Glucose. In patients being treated with insulin or insulin-producing or sensitizing drugs, it is important to monitor blood glucose levels carefully to avoid hypoglycemia. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend measuring blood levels only once or twice a day. For patients who have become insulin-dependent, more intensive monitoring is necessary. Usually, a drop of blood obtained by pricking the finger is applied to a chemically treated strip. The glucose level is read on a standard meter or a small, portable digital display device. For patients who have trouble controlling hypoglycemia (low blood sugar) or fluctuating blood sugar levels, continuous glucose sensor monitors are also available. In 2007, the FDA approved the STS-7 System, which continuously measures glucose levels for up to 7 days through a sensor inserted beneath the skin of the abdomen. Continuous glucose sensor monitors do not replace fingerstick glucose meters and test strips, but are used in combination with them. [See In-Depth Report #9: Diabetes - type 1.]

Measuring Hemoglobin A1C. 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.

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 research suggests that not getting enough sleep may impair insulin use and increase the risk for obesity. More research is needed, but it is always wise to improve sleep habits.

Medications

The American Heart Association now recommends that patients should aim for the following test results for intensive control of glucose levels:

Fasting plasma glucose concentrations below 110 mg/dL.
Glycolated hemoglobin (HbA1c) levels of less than 7%. Controlling HbA1c is the most important factor for reducing the risk of complications in patients with diabetes. According to one 2000 study, a 1% reduction in people with elevated glycolated hemoglobin levels lowers the risk for complications by 21%.

Evidence clearly supports strict glycemic control for reducing complications in the nervous system and blood vessels that occur in both type 1 and type 2 diabetes. Research shows that tight glucose control can help prevent heart disease and complications.

Managing risk factors for heart disease and stroke, particularly strict control of blood pressure, may be more important for improving survival than strict control of blood glucose levels for some patients. Such goals also seem to be more attainable for many patients with type 2 diabetes.

Oral Anti-Hyperglycemic Drugs. Many oral anti-hyperglycemic drugs are available to help patients with type 2 diabetes control their blood sugar levels. Most of these drugs are aimed at using or increasing sensitivity to the patient's own natural stores of insulin. Metformin is the only drug to date that achieves lower mortality rates. Oral type 2 diabetes drugs include:

Biguanides (metformin). Metformin increases tissue sensitivity to available insulin. Metformin also has beneficial effects on cholesterol, blood pressure, and clotting factors. It does not cause weight gain or hypoglycemia. Diarrhea and digestive problems are the most common side effects. Metformin produces lower mortality rates than other drugs, including insulin, and should be considered as first-line therapy for most patients with type 2 diabetes.
Sulfonylureas (glyburide, glipizide, glimepiride, repaglinide). Stimulate insulin secretion but can cause hypoglycemia more than other drugs.
DPP-4 inhibitors (sitagliptin). Also called gliptins, DPP-4 inhibitors were first approved in 2006 and are the newest class of oral diabetes drugs. Like metformin, they do not cause weight gain and have low risks for hypoglycemia.
Meglitinides (repaglinide, nateglinide). Stimulate insulin secretion. These newer drugs are better than sulfonylureas in controlling glucose spikes after meals.
Thiazolidinediones (pioglitazone and rosiglitazone). Reduce insulin resistance. These drugs improve cholesterol levels and may reduce the risk for blood clots. However, they can cause swelling from fluid build-up, which can worsen heart failure or even precipitate it. They may also injure the liver.
Alpha-glucosidase inhibitors (acarbose and miglitol). Slow intestinal absorption of carbohydrates. Have only modest effects on diabetes and have gastrointestinal side effects. Can slightly raise HDL (“good”) cholesterol levels.
Combinations of these drugs, particularly with metformin, are often used to increase effectiveness.

A 2007 review in the Annals of Internal Medicine compared these various classes of medications. The review found that older drugs -- such as metformin and sulfonylureas -- are less expensive than and work as well as newer diabetes drugs. In particular, the review cited metformin as a safe and effective drug because it does not cause weight gain or too-low blood sugar. Metformin can also help lower LDL (“bad”) cholesterol.

Injectable Anti-Hyperglycemic Drugs. In 2005, the FDA approved two new injectable drugs to help patients improve blood sugar control:

Exenatide (Byetta). Exenatide is the first drug in a new class of drugs called incretin mimetics. It lowers blood glucose levels by increasing insulin secretion. Exenatide is used in combination with oral antihyperglycemics, such as metformin or a sulfonylurea drug.
Pramlintide (Symlin). Pramlintide is a first-in-class drug that is a synthetic form of the hormone amylin. The drug is meant for patients who take insulin but still have difficulty controlling their glucose levels.

Insulin Replacement. Insulin replacement may be required when natural insulin reserves are depleted. It is typically started in combination with an oral drug. Eventually, some patients may need to go on full insulin replacement. In addition to injectable forms of insulin, an inhaled insulin product (Exubera) is now available.

Metformin (Glucophage) is a biguanide, which works by reducing glucose production in the liver and by making tissues more sensitive to insulin. Many experts recommend it as a first choice for most patients with type 2 diabetes who are insulin resistant, particularly if they are overweight. Metformin achieves lower mortality rates from diabetes and all causes than other drugs. In one comparison study, it achieved the lowest mortality rates (8%) compared to insulin (28%), a sulfonylurea (16%), and a thiazolidinedione (14%). Combinations with insulin-secreting drugs, other insulin-sensitizing drugs, or insulin itself are particularly effective.

Metformin does not cause hypoglycemia or add weight, so it is particularly well-suited for obese patients with type 2 diabetes. (In some studies, in fact, patients lost weight.) Metformin also appears to have beneficial effects on cholesterol and lipid levels and may help protect the heart. Some research has suggested that it significantly reduces the risk for heart attack. It is also the first choice for children who need oral drugs and is proving to be very effective for women with polycystic ovary syndrome and insulin resistance.

Side Effects. Side effects include:

A metallic taste
Gastrointestinal problems, including nausea, and diarrhea
Interference with absorption of vitamin B12 and folic acid, (which are important for protection against heart disease)
Rare reports of lactic acidosis, a potentially life-threatening condition, particularly in people with risk factors for it. Major studies, however, found no greater risk with metformin than with any of the other drugs used for type 2 diabetes.

Certain people should not use this drug, including anyone with heart failure or kidney or liver disease. It is rarely suitable for adults over age 80.

Sulfonylureas are oral drugs that stimulate the pancreas to release insulin. They are also first-line oral drugs. For adequate control of blood glucose levels, the drugs should be taken only 20 - 30 minutes before a meal. A number of brands are available, including chlorpropamide (Diabinese), tolazamide (Tolinase), acetohexamide (Dymelor), glipizide (Glucotrol), tolbutamide (Orinase), glyburide (Micronase), glimepiride (Amaryl), and repaglinide (Prandin).

Most patients can take sulfonylureas for 7 - 10 years before they lose effectiveness. Combinations with small amounts of insulin or with other oral anti-hyperglycemic drugs (such as metformin or a thiazolidinedione) may extend their benefits. A combination of glyburide and metformin in one pill (Glucovance) is available. Glucovance may be particularly beneficial for patients with unhealthy cholesterol levels and poor control of their blood sugar levels. Some doctors recommend the combination as first-line treatment.

An encouraging 2000 study of patients with severe type 2 diabetes reporting that combinations of insulin with either chlorpropamide or glipizide achieved better glucose control over the long term than insulin alone.

Side Effects and Complications. In general, sulfonylureas should not be used by women who are pregnant or nursing or by individuals who are allergic to sulfa drugs. Side effects may include:

Weight gain (some sulfonylureas, such as glimepiride, may produce less weight gain than others)
Water retention
Although sulfonylureas pose a lower risk for hypoglycemia than insulin does, the hypoglycemia produced by sulfonylureas may be especially prolonged and dangerous. The newer sulfonylureas, such as glimipiride, have much less risk of hypoglycemia than older sulfonylureas.
Some sulfonylureas may pose a slight risk for cardiac events.

Sulfonylureas interact with many other drugs, and patients should be sure to inform their doctor of any medications they are taking, including alternative or over-the-counter drugs.

Meglitinides stimulate beta cells to produce insulin. They include repaglinide (Prandin), nateglinide (Starlix), and mitiglinide. These drugs are rapidly metabolized and short-acting. If taken before every meal, they actually mimic the normal effects of insulin after eating. Patients, then, can vary their meal times with this drug. (Nateglinide appears to work more quickly and is shorter-acting than repaglinide). These drugs may be particularly helpful in combination with metformin or other drugs. They may also be a good choice for people with potential kidney problems.

Side Effects. Side effects include diarrhea and headache. As with the sulfonylureas, repaglinide poses a slightly increased risk for cardiac events. (Newer drugs, such as nateglinide, may pose less of a risk.) People with heart failure or liver disease should use them with caution and be monitored.

Thiazolidinediones, also known as peroxisome proliferator-activated receptor (PPAR) agonists, include rosiglitazone (Avandia) and pioglitazone (Actos). They improve insulin sensitivity by activating certain genes involved in fat synthesis and carbohydrate metabolism. These drugs are usually taken once or twice per day; however, it may take several days before the patient notices any results from them and several weeks before they take full effect. Thiazolidinediones are usually taken in combination with other oral drugs or insulin.

Side Effects. Thiazolidinediones can have serious side effects. They tend to increase fluid-build up, which can cause or worsen heart failure in some patients. Combinations with insulin increase the risk. They should not be used by patients with existing heart failure and should be used cautiously in those with risk factors for heart failure.

In 2007, a study published in the New England Journal of Medicine (NEJM) raised serious concerns that rosiglitazone may increase the risk of heart attack. The study reviewed 42 clinical trials of rosiglitazone. Results suggested that patients who took rosiglitazone were 43% more likely to have a heart attack, and 64% more likely to die from overall heart causes, than patients with diabetes who did not take the drug. A subsequent interim analysis in the NEJM found that while rosiglitazone was definitely associated with increased risk of heart failure, the data were insufficient to determine if the drug increases heart attack risk. The FDA has concluded that rosiglitazone may increase the risk of heart attack and will likely restrict its use. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.

Thiazolidinediones may cause more weight gain than other diabetes medications or insulin. Any patient who experiences sudden weight gain, water retention, or shortness of breath should immediately call their doctor. These drugs have also been linked to increased risks for bone fracture.

There have been rare reports of rosiglitazone causing or worsening diabetic macular edema. This is an eye condition associated with diabetic retinopathy that causes swelling in the macular area of the retina. Symptoms include blurred vision and decreased color sensitivity. Most patients who had this side effect also had swelling in the feet and legs (peripheral edema). The condition resolved or improved when patients stopped taking the drug.

Thiazolidinediones can also cause liver damage. Patients who take these drugs should have their liver enzymes checked regularly.

Alpha-glucosidase inhibitors, including acarbose (Precose, Glucobay) and miglitol (Glyset), reduce glucose levels by interfering with the absorption of starch in the small intestine. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease. Some evidence suggests that early use of these drugs may reduce heart risk factors, including high blood pressure. A 2002 study of acarbose suggested that these drugs may possibly delay the development of type 2 diabetes in high-risk individuals. Alpha-glucosidase inhibitors are not as effective alone as other single oral drugs, but combinations, such as with metformin, insulin, or a sulfonylurea, increase their effectiveness.

Side Effects. These medications need to be taken with meals. Unfortunately, about a third of patients stop taking the drug because of flatulence and diarrhea, particularly after high-carbohydrate meals. The drug may also interfere with iron absorption.

Alpha-glucosidase inhibitors do not cause hypoglycemia when used alone, but combinations with other drugs do. In such cases, it is important that the patient receive a solution that contains glucose or lactose, not table sugar. This is because acarbose inhibits the breakdown of complex sugar and starches, which includes table sugar.

Incretin mimetics belong to a new class of drugs that help improve blood sugar control. Incretins include glucagon-like peptide-1 (GLP-1) inhibitors and DDP-4 inhibitors.

In 2005, the FDA approved exenatide (Byetta), the first GLP-1 inhibitor drug. Exenatide is an injectable drug that is a synthetic version of the hormone found in the saliva of the Gila monster, a venomous desert lizard. Exenatide is injected twice a day, 1 hour before morning and evening meals. It is prescribed for patients with type 2 diabetes who have not been able to control their glucose with metformin or a sulfonylurea drug. It can be taken in combination with these drugs or alone.

Side Effects. Exenatide stimulates insulin secretion only when blood sugar levels are high and so has less risk for causing low blood sugar (hypoglycemia) when it is taken alone. However, the risk for hypoglycemia increases when exenatide is taken along with a sulfonylurea drug. There does not appear to be a risk for hypoglycemia when exenatide is used along with metformin. Other side effects may include nausea, vomiting, and diarrhea.

A 2005 study compared exenatide to insulin for improving glucose control in patients taking metformin and a sulfonylurea. Both insulin and exenatide worked well for glucose control. Patients lost weight with exenatide and gained weight with insulin. However, patients who received exenatide had significantly more problems with nausea, vomiting, and diarrhea than those who received insulin.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, also called gliptins, are the second class of incretin drugs. In October 2006, the FDA approved the first DPP-4 inhibitor -- sitagliptin (Januvia). It can be used alone or in combination with metformin or a thiazolidinedione drug. In April 2007, the FDA approved Janumet, which combines sitagliptin with metformin in one pill. Other DPP-4 drugs being studied include vildagliptin (Galvus) and saxagliptin.

DPP-4 inhibitors work in a similar way to GLP-1 inhibitors. However, unlike exenatide, which is given by injection, DPP-4 inhibitor drugs are taken as pills by mouth.

Like exenatide, DPP-4 inhibitors do not cause weight gain, have low risks for hypoglycemia, and have few severe side effects. The most common side effects include upper respiratory tract infection, sore throat, and diarrhea.

Insulin replacement is the best treatment for strict control of blood glucose and is required once natural insulin reserves are depleted. Because type 2 diabetes is progressive, most patients eventually require insulin, typically starting it in combination with an oral anti-hyperglycemic drug. However, when a single oral drug fails to control blood sugar it is not clear whether it is better to add insulin replacement or to add a second or third oral drug.

Some experts advocate using insulin as early as possible for optimal control. However, in patients who still have insulin reserves, there is concern that extra natural insulin will have adverse effects. Low blood sugar (hypoglycemia) and weight gain are the main side effects of insulin therapy. Some research suggests that insulin may also cause heart complications. A 2006 study reported that insulin therapy increases the risk of developing high blood pressure (hypertension). It is still not clear if insulin replacement improves survival rates compared to oral drugs, notably metformin.

One approach is to combine insulin with metformin, which achieves blood glucose control without added weight gain. Newer forms of insulin analogues, such as glargine, may be especially helpful for people with type 2 diabetes and reduce the risk for hypoglycemia.

Fortunately, studies to date have not reported any adverse cardiac effects in patients with type 2 diabetes who take insulin. In fact, insulin has been associated, in some cases, with improvement in heart risk factors. More research is needed to clarify these important issues.

Forms of Insulin. Experts are working toward administering insulin so that it closely mimics the daily pattern of insulin, which responds to blood sugar levels by surging after meals and then falling to a steady base level afterward. To achieve this, doctors may use two insulin types:

Fast-Acting Insulins for Surges. Insulin lispro and aspart are fast-acting insulins. They mimic insulin's response to food intake. They are taken before meals, and their short action reduces the risk for hypoglycemia afterward.
Slower Insulins for Base Levels. Intermediate forms (including NPH and lente) and long-acting forms (glargine, ultralente) were developed to provide a steady level of insulin throughout the day. To date, glargine (Lantus) seems to be the most successful in achieving this goal in type 2 diabetes.

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. Clinical trials indicate that Exubera can provide sustained blood sugar control over a 2-year period. Patients in the trials who took Exubera experienced half as much weight gain as those who took injected insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

In a 2005 trial, Exubera improved blood sugar control when it was added to or substituted for combination oral drug therapy (sulphonylurea and thiazolidenedione). However, as with other forms of insulin, Exubera caused more hypoglycemia and weight gain than the oral anti-hyperglycemic drugs.

Pramlintide (Symlin) is a new type of injectable drug that may help patients who take insulin but still need better blood sugar control. The FDA approved this drug in 2005. Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Pramlintide is used in combination with insulin to lower blood sugar levels in the 3 hours after meals.

[See In-Depth Report #9: Diabetes - type 1.]

Sodium Glucose Uptake Transporter 2 (SGLT-2) Inhibitors. SGLT-2 inhibitors are a new class of drug being investigated for treatment of type 2 diabetes. Preliminary trials for two of these drugs, dapagliflozin and serglifozin, have shown promising results in helping improve blood glucose control. The drugs are being tested in combination with metformin.

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.

Long-Term Complications

Patients with diabetes have higher mortality rates than people who do not have diabetes regardless of sex, age, or other factors. Heart disease and stroke are the leading causes of death in these patients. All lifestyle and medical efforts should be made to reduce the risk for these conditions.

People with type 2 diabetes are also at risk for nerve damage (neuropathy) and abnormalities in both small and large blood vessels (vascular injuries) that occur as part of the diabetic disease process. Such abnormalities produce complications over time in many organs and structures in the body. Although these complications tend to be more serious in type 1 diabetes, they still are of concern in type 2 diabetes. All people with diabetes should aim for fasting blood glucose levels of less than 110 mg/dL and hemoglobin HbA1C of less than 7%.

There are two important approaches to preventing complications from diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. Tight blood glucose and HbA1c control can 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. Control of blood glucose also helps the heart, but its benefits occur over time. It is very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

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 speed 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. According to a 2007 study, the risk of stroke doubles within 5 years of type 2 diabetes diagnosis.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions range between 15 - 53%.
Women with diabetes are at particularly high risk for heart problems. A 2007 study indicated that while progress has been made in reducing mortality rates among men with diabetes, women with diabetes continue to face a high risk of death from heart disease and overall causes.

Tight blood sugar control may help protect blood vessels and reduce the risk for blood clotting. It is still not known whether intensive control will have a major protective effect on the heart, however. People with diabetes must be sure to use other measures as well to protect the heart.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin (75 - 162 mg/day) reduces the risk for blood clotting and may help protect against heart attacks and heart disease. 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.

Controlling 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. 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 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.

Several 2006 studies suggested that anti-hypertensive drugs may increase the risk of developing diabetes. One study found more risk for thiazide diuretics and beta-blockers than ACE inhibitors and CCBs. Another study indicated that the ACE inhibitor ramipril had a lower risk of causing diabetes in African-Americans than a CCB or beta-blocker. A 2007 review in the Lancet also found a higher risk for new-onset diabetes with beta-blockers and diuretics, a medium risk with CCBs, and the lowest risk with ARBs and ACE inhibitors.

Research in this subject is important for patients with pre-diabetes who have high blood pressure. Results of future research may help doctors decide which treatment is most appropriate for patients with high blood pressure who are at high risk for diabetes. [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, generics), pravastatin (Pravachol), simvastatin (Zocor, 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 the standard 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 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. Combinations of statins 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. Research presented at the 2007 annual meeting of the American Diabetes Association suggested that statins and fibrates may also help reduce the risk of developing peripheral neuropathy, the diabetes-associated nerve damage that can lead to loss of sensation in the feet.

Gemfibrozil (Lopid) and fenofibrate (Tricor) are usually the first choice for fibrate drugs. 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.

Prevention and Treatment 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. ACE inhibitors and ARBs, two classes of blood pressure medications, are very helpful for preventing or slowing the progression of diabetic kidney disease.

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 occurs in about 20 - 40% of patients with diabetes and is the leading cause of end-stage renal disease. 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.

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. Dosing target levels of erythropoiesis-stimulating drugs are controversial, especially for patients with chronic kidney disease. 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 with 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.

Another controversy surrounding erythropoiesis-stimulating drugs concerns their overuse at dialysis centers. A 2007 study in the Journal of the American Medical Association suggested that large, for-profit dialysis centers tend to administer higher-than-appropriate doses of these drugs compared to nonprofit facilities. The study suggested that for-profit centers are giving higher doses for financial, not medical, reasons.

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.]

Click the icon to see an image of the pancreas and kidneys.

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 chest pain warning 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.

Prevention of Neuropathy. Patients with type 2 diabetes should receive regular screenings for loss of sensation in feet and other signs of neuropathy. A 2007 study suggested that statin and fibrate drugs, which are used to control cholesterol, may help protect against diabetic peripheral neuropathy.

Pain Relief 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. Evidence shows 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 about 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 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.

People with diabetes are prone to foot problems because the disease can cause damage to the blood vessels and nerves, which may result in decreased ability to sense trauma to the foot. The immune system is also altered, so that the patient cannot efficiently fight infection.

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

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 age 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, such as primary-open angle glaucoma (POAG). The risk for POAG is especially high for women with type 2 diabetes. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina in the eye 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.

Click the icon to see an animation on diabetic retinopathy.

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 diabetes, although in one study over 20% had signs of retinopathy 6 years after diagnosis. Patients who are newly diagnosed with type 2 diabetes should get a comprehensive eye examination, including dilation. 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.

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 slower 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, according to one study, depression, in turn, increases the risk for hyperglycemia and complications of diabetes. 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

Emergency Complications

People with diabetes who need to intensively control glucose levels are at risk for low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, develops if blood sugar levels fall below normal. It may also be caused by insufficient intake of food, excess exercise, or alcohol intake. The condition is usually manageable, but occasionally it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms. Mild hypoglycemia is common among people with type 2 diabetes, but severe episodes are rare, even among those who are taking insulin. Still, all patients who intensively control blood sugar (glucose) levels should be aware of warning symptoms.

Risk Factors for Severe Hypoglycemia. People at highest risk for severe hypoglycemia are those who intensively control blood glucose and also have one or more of the following conditions:

Long-term diabetes
Less education on their condition
A previous history of severe hypoglycemia
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 hypoglycemia 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:

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
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 also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who use medications that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

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, including intravenous administration of glucose.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see a glucagon kit.

Diabetic ketoacidosis (DKA) is a life-threatening complication caused by insulin depletion. Until recently, it was a complication almost exclusively of type 1 diabetes. In such cases, it is nearly always due to noncompliance with insulin treatments. However, DKA is being reported increasingly in type 2 diabetes, especially among Hispanic- and African-Americans. It is not clear what causes total insulin depletion in these patients. Researchers are trying to learn which individuals are at particular risk.

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 may include:

Nausea and vomiting
Abnormally deep and rapid breathing with frequent sighing
Rapid heartbeat
If the condition persists, coma and, eventually, death, may occur; however, over the past 20 years, death from DKA has decreased to about 2% of all cases.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.

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

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.americanheart.org -- American Heart Association
www.kidney.org -- National Kidney Foundation
www.nei.nih.gov -- National Eye Institute
www.medicalert.org -- Medic Alert
www.eatright.org -- American Dietetic Association
http://limaye.ecri.org -- Limaye Center

References

American Diabetes Association (ADA). Standards of medical care in diabetes. IV. Prevention/delay of type 2 diabetes. Diabetes Care. 2007 Jan;30(Suppl 1):S7-8.

American Diabetes Association (ADA). Standards of medical care in diabetes. V. Diabetes care. Diabetes Care. 2007 Jan;30(Suppl 1):S8-15.

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.

Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 July 11;298:194-206.

Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7.

Bolen S, Feldman L, Vassy J, Wilson L, Yeh H-C, Marinopoulos S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007 Jul 17; 147(6). [Epub ahead of print]

Carnethon MR, Biggs ML, Barzilay JI, Smith NL, Vaccarino V, Bertoni AG, et al. Longitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med. 2007 Apr 23;167(:802-7.

Charbonnel B, Karasik A, Liu J, Wu M, Meininger G; Sitagliptin Study 020 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006 Dec;29(12):2638-43.

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.

Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007 Jan 20;369(9557):201-7.

Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006 Jul 20;355(3):241-50.

Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. Epub 2007 Apr 12.

Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007 Feb 10;334(7588):299. Epub 2007 Jan 19.

Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006 Mar;38(3):320-3. Epub 2006 Jan 15.

Gregg EW, Gu Q, Cheng YJ, Narayan KM, Cowie CC. Mortality trends in men and women with diabetes, 1971-2000. Ann Intern Med. 2007 Jun 18; [Epub ahead of print]

Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, et al. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. N Engl J Med. 2007 Jul 5;357(1):28-38. Epub 2007 Jun 5.

Jeerakathil T, Johnson JA, Simpson SH, Majumdar SR. Short-term risk for stroke is doubled in persons with newly treated type 2 diabetes compared with persons without diabetes: a population-based cohort study. Stroke. 2007 Jun;38(6):1739-43. Epub 2007 May 3.

Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M. Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes: a retrospective cohort study using survival analysis. Diabetes Care. 2007 Apr;30(4):878-83.

Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology. 2006 Jul;113(7):1081-6. Epub 2006 Jun 6.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71. Epub 2007 May 21.

Psaty BM, Furberg CD. Rosiglitazone and cardiovascular risk. N Engl J Med. 2007 Jun 14;356(24):2522-4. Epub 2007 May 21.

Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007 May 14;167(9):956-65.

Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007 Jun 1;316(5829):1341-5. Epub 2007 Apr 26.

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.

Thamer M, Zhang Y, Kaufman J, Cotter D, Dong F, Hernen MA. Dialysis facility ownership and epoetin dosing in patients receiving hemodialysis. JAMA. 2007 Apr 18;297(15):1667-74.

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

Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007 Jun 1;316(5829):1336-41. Epub 2007 Apr 26.

Review Date:
7/31/2007
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.

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 occurrence of such conditions in combination with PAD often signals more severe forms of heart or circulatory disease.

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

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Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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