Coronary Heart Disease and Angina

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CORONARY ARTERY DISEASE AND ANGINA

WHAT IS CORONARY ARTERY DISEASE?

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

The Process of Atherosclerosis

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

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

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

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

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

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

Inflammatory Response. For the arteries to harden there must be a persistent reaction in the body that causes on-going harm. Researchers now believe that this reaction is an immune process known as the inflammatory response.

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

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

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

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

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

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

Angina

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

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

Angina itself is not a disease. Much evidence exists, in fact, that onset of angina less than 48 hours before a heart attack may be protective, possibly by conditioning the heart to resist the damage resulting from the attack.

Angina may be experienced in different ways and can be mild, moderate, or severe:

It is often reported as a dull, heavy pressure that may resemble a crushing object on the chest.
Pain often radiates to the neck, jaw, or left shoulder and arm.
Less commonly, patients report mild burning chest discomfort, sharp chest pain, or pain that radiates to the right arm or back.
Sometimes a patient experiences shortness of breath, fatigue, or palpitations instead of pain.
The intensity of the pain does not always relate to the severity of the medical problem. Some people may feel a crushing pain from mild ischemia, while others might experience only mild discomfort from severe ischemia.
Some people have also reported a higher sensitivity to heat on the skin with the onset of angina.
Angina can also be precipitated by large meals, which place an immediate demand upon the heart for more oxygen.

Stable Angina. Stable angina is predictable chest pain. Although less serious than unstable angina, it can be extremely painful. It is usually relieved by rest and responds well to medical treatment (typically nitroglycerin).

Any event that increases oxygen demand can cause an angina attack. Some typical triggers include the following:

exercise,
cold weather,
emotional tension, or
large meals.

Angina attacks can occur at any time during the day, but a high proportion seems to take place between the hours of 6:00 AM and noon.

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

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

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

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

HOW SERIOUS IS CORONARY ARTERY DISEASE?

Coronary artery disease is the leading killer in America of both men and women, responsible for nearly 460,000 deaths in 1998, about 20% of all deaths. On the positive side, mortality rates from heart attack have declined by over 26% between 1988 and 1998. (Because of the aging population, however, the actual number fell by only about 10%). When the necessary lifestyle changes are enacted in combination with appropriate medical or surgical treatments, a person suffering angina and heart disease has a good chance of living a normal life.

Determining the Degree of Severity

In general, in patients with coronary artery disease, the presence of one of three of the following syndromes suggests different degrees of severity.

Stable Angina. This condition can usually be managed with life-style measures and medications, such as low-dose aspirin.

Acute Coronary Syndromes. These syndromes are severe and sudden heart conditions that require aggressive treatment but have not developed into a full blown heart attack. Acute coronary syndromes include the following:

Unstable angina.
Non Q-wave myocardial infarction. (This latter condition is diagnosed when blood tests and ECG suggest a developing heart attack. In such cases, injury in the arteries appears to be less severe than with a full-blown heart attack).

Heart Attack. The full blown heart attack occurs with severe damage to the heart, which blocks oxygen. [See Box Indications of a Heart Attack.]

Indications of a Heart Attack

ANYONE WHO BELIEVES THEY ARE HAVING A HEART ATTACK SHOULD NOT HESITATE TO CALL THE EMERGENCY MEDICAL SYSTEM.

Any unusual chest pain or angina symptoms that does not clear up with medications is a signal to go to the hospital in people with known heart disease.

Common Heart Attack Symptoms

Some signs to watch out for are as follows:

Pain experienced as a crushing weight against the chest, which is 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 even be numb.
Chest pain, usually precipitated by exercise or stress, that does not clear up when medications are taken or when resting.
Mild chest pain with unexplained fatigue and ill health. Depression may be present. In patients with known heart disease, such symptoms have sometimes been reported within a month of a heart attack.

It should be noted, however, that degree of pain and the specific symptoms before a heart attack vary greatly among individuals.

Some people may feel severe pain; others might feel only a tingling sensation. Some people may only have a sense of fullness, squeezing, or pressure in the chest.)
A feeling of indigestion or heartburn is common, as are nausea and vomiting.
Some people report a great fear of impending death, a phenomena known as angor animi.

Atypical Symptoms in Specific Populations

About one-third of all heart attack patients do not have chest pain at all, putting them at much higher risk for a misdiagnosis. Women and the elderly are particularly more likely to have atypical symptoms (although they can certainly have classic heart attack symptoms as well.)

A 2000 study suggested that heart attacks might go undiagnosed in people over 65 who do not have a history of angina or heart failure. Any older person with signs of weakness, rapid heart beat, difficulty in breathing, and signs of a sudden drop in blood pressure should be tested for a heart event.
Symptoms of angina in women are also often not typical. 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 the same symptom in men. Because of these reasons, women are less likely than men to be tested aggressively for serious heart problems when they enter the emergency room.

Actions Taken at the Onset of Symptoms

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

For angina patients, take one nitroglycerin dose either as an under-the-tongue tablet or in spray form at the onset of symptoms. Take another dose every five minutes up to three doses or when the pain is relieved, whichever comes first.

Call 911 or the local emergency number. This should be the first action taken if angina patients continue to experience chest pain after taking the full three doses of nitroglycerin. Anyone who has heart disease or risk factors for it and experiences heart attack symptoms should contact emergency services. It should be noted that only 20% of heart attacks occur in patients with long-standing angina.

The patient should chew an aspirin and be sure that emergency health providers are informed of this so an additional dose isn't given.

Chest pain sufferers should go immediately to the nearest emergency room, preferably traveling by ambulance. They should not drive themselves.

WHAT ARE THE RISK FACTORS FOR CORONARY ARTERY DISEASE AND HOW CAN THEY BE MANAGED?

About 12.4 million Americans currently have heart disease and 1.1 million people are expected to have a serious heart event this year. An estimated 25% of all Americans have one or more risk factors for heart disease. Most risk factors for heart disease are related to lifestyle and environmental factors. Over the past decades, heart disease declined in both men and women as they quit smoking and improved dietary habits. This rate, however, has stabilized in recent years, most likely because of the dramatic increase in obesity in the US and other industrialized nations. There have also been minimal changes in other risk factors, including smoking, sedentary behavior, and blood pressure control. Some risk factors cannot be changed, including age, gender, and genetics. Nevertheless, their effects can still be modified with healthy lifestyle changes.

Reducing Multiple Risk Factors. The risk for heart disease increases with multiple risk factors, importantly unhealthy cholesterol or lipid levels, diabetes, obesity, smoking, and hypertension. Conversely, risk plummets in the absence of multiple risk factors. For example, a 1999 study found that men and women of all ages who had none of these risk factors had a risk of dying from heart attack that was between 77% and 92% lower than those with one or more of them. (The people with no risk factors also had a lower risk for stroke and cancer.) Conversely, a 2000 study reported that patients who aggressively pursued a healthy lifestyle (low-fat diet, stress management, smoking cessation, moderate aerobic exercise) significantly reduced their risk for heart attack, cardiac surgery, and death.

Nonmodifiable Risk Factors

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, ten to fifteen more years of heart-disease free life than do men, but as women age, they catch up to men. Women, in fact, are more likely to have angina than men are. The American Heart Association reported in 2001 that four million women had angina compared to 2.3 million men. Younger women with heart disease often do not have the same symptoms as their male counterparts do and may be less likely to be diagnose correctly. Studies are now suggesting, however, that the overall higher mortality rates and the less aggressive treatments in women with heart disease appear to be due to their older agent and sicker condition than their male peers at the time of a heart event. (Interestingly, one 1999 study found that although, indeed, women with unstable angina were treated less aggressively than men, when their risk factors were compared head to head, men actually had a worse long-term outcome.)

Genetic Factors . Genetics are involved in increasing the likelihood of developing important risk factors (eg, diabetes, obesity, and high blood pressure). One genetic variant called apolipoprotein E4 (ApoE4) affects cholesterol levels, particularly those associated with heart disease. A 1999 study suggests that it may be a significant risk factor for coronary artery disease in early middle age. (The presence of this variant may also be associated with increased risk for Alzheimer's disease.)

Ethnicity

African Americans. In a 1998 analysis, although mortality rates from coronary artery disease declined between 1987 and 1994 in both Caucasians and African Americans, they did not decline significantly in African Americans. 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.) African Americans face a number of biologic and social dangers to their hearts:

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

Other Groups. 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.

Cholesterol and Other Lipids

Cholesterol. High cholesterol levels are strong risk factors for heart disease, particularly when the harmful type known as low-density lipoprotein (LDL) cholesterol is elevated. The higher the cholesterol, the greater the risk. For example, according to a 2000 study, men with cholesterol levels over 240 mg/dl have a risk that is 2.15 to 3.63 times higher than those whose cholesterol is below 200. A number of studies have now demonstrated that reducing LDL and total cholesterol levels and boosting HDL levels have improved survival and prevented heart attacks. [ See Table Cholesterol Goals.] Only 40% of people with high cholesterol levels actually die of heart disease, however, and experts cannot yet define which people are most at risk from high cholesterol levels.

Triglycerides. Triglycerides are made up of fatty acid molecules and are the basic chemicals in animal and plant fats. Evidence now suggests that these molecules may be major trouble-makers for the heart. Some evidence also suggests that high triglycerides are risk factors for heart disease on their own regardless of cholesterol levels.

Cholesterol Goals
Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
200 mg/dl or less. (One study suggested that the ideal cholesterol goal for older people is between 200 and 220. There is a heart risk below and above these levels.)	160 mg/dL or less. (People with two or more risk factors for heart disease should aim for LDL levels of 130 mg/dl or below. People with existing heart disease should aim for LDL levels of below 100 mg/dl.*)	35 mg/dL or more. (Some experts suggest higher goals, 45 for men and 50 for women, with everyone aiming for about 60.)	200 mg/dL or less. (Evidence is suggesting that levels over only 100 may predict an increased risk for heart disease.)
*Risk factors for heart disease include a family history of heart problems, smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dl.

Other Lipids. Elevated levels of other fatty molecules (lipids) are also now thought to be important indicators of heart disease risk. They include lipoprotein (a) and apolipoprotein A-1 and B. Apolipoprotein B, for example, may actually turn out to be a very accurate indicator of heart disease risk in women. ApoE4, a genetic form of another apolipoprotein, is associated with Alzheimer's disease and is also under investigation for a role in heart disease. [For more information, see the Reports #23, Cholesterol and #43, Heart Healthy Diet .]

High Blood Pressure

High blood pressure, or hypertension, has long been a proven cause of coronary artery disease. Blood pressure is categorized as:

Optimal (below 120/80 mm Hg).
Normal (between 120/80 and 130/85 mm Hg).
High normal (between 130/85 and 139/89). (Some studies indicate that high normal puts one at higher risk for heart events and stroke, although others suggest this risk exists primarily in people with diabetes.)
Hypertension, or high blood pressure (140/90). [For more information, see the Report #14, High Blood Pressure .]

Obesity and Overweight

Obesity is related to hypertension, diabetes, abnormal cholesterol levels, and lack of exercise, all conditions contributing to heart attack risk. Obesity in children is a greater risk for future heart trouble than a family history of heart disease. People who are overweight in middle age may still not completely reduce their risk for coronary artery disease later in life, even if they lose excess weight. Abdominal obesity (the "beer belly") poses a particular risk. Obesity is determined by measurement of body fat, not merely body weight.

People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The current best single gauge for body fat is a measurement called body mass index (BMI). It is derived by a series of calculations:

Multiply one's weight in pounds by 703.
Divide that answer by one's height in inches.
Divide that answer once again by height in inches. The resulting number is the BMI.

Current federal and WHO guidelines define overweight as a BMI of 25 to 29.9 and obesity as a BMI of 30 or greater.

[For more information, see the Report #53, Weight Control and Diet .]

Sedentary Lifestyle and Exercise

People who are sedentary are almost twice as likely to suffer heart attacks as are people who exercise regularly. Regular moderate aerobic exercise benefits the heart in many ways. For instance, brisk walking has the following advantages:

Lowers the heart rate and blood pressure.
Raises HDL ("good") cholesterol.
Lowers blood sugar levels.
Opens up the blood vessels and, in combination with a healthy diet, may improve blood clotting factors.
Reduces stress and improves mood.

Some studies suggest that for the greatest heart protection, it is not the duration of the exercise that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise. Even elderly people with unstable angina or who had a previous heart attack can benefit from a structured exercise program. Exercises that train and strengthen the chest muscles may also prove to be very important for patients with angina.

It should be noted that sudden strenuous exercise (such as snow shoveling and mowing lawns) puts such 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 the Report #29, Exercise.]

Diabetes and Insulin Resistance

Heart attacks account for 60% and strokes for 25% of deaths in all diabetics. A 1998 study reported that people with type 2 diabetes and no history of heart disease have the same seven-year risk for a heart attack as nondiabetics with heart disease.

Long-term insulin resistance, even without type 2 diabetes, appears to have significant damaging effects on the heart. This condition occurs when insulin levels are normal to high but the body is unable to use the insulin to regulate metabolism of blood sugar and to store it for energy. In such cases, the body compensates by increasing insulin levels (hyperinsulinemia), which in turn increases triglyceride levels and reduces HDL cholesterol. Normally, insulin stimulates the release of two substances, endothelin and nitric oxide, that are important in keeping arteries elastic and open. Insulin resistance may cause an imbalance in these substances. [For more information, see the Reports #9, Diabetes: Type I or #60, Diabetes: Type II .]

Smoking

Smokers in their thirties and forties 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.

Specific Effects on the Heart. Its damaging effects on the heart are multifold:

Smoking lowers HDL levels (the so-called good cholesterol) even in adolescents.
It causes deterioration of elastic properties in the aorta, the largest blood vessel in the body, and increases the risk for blood clots.
It increases the activity of the sympathetic nervous system (which regulates the heart and blood vessels).
Tobacco smoke may increase cardiovascular disease in women through an effect that reduces estrogen levels.

Effects of Second-Hand Smoke. Studies continue to confirm the dangers of second-hand smoke. Regular exposure to passive smoke is now estimated to increase the risk of heart disease in the nonsmoker by between 25% and 91%, causing 30,000 to 60,000 deaths each year. [For more information, see the Report Smoking.]

Eating Habits

Eating habits can be protective or dangerous to the heart. Although the best diet is not clear for each individual, avoiding saturated fats and trans-fatty acids is recommended for everyone. [ See Box Dietary Factors and Heart Disease]

Dietary Factors and Heart Disease

Diet plays an important role in the health of the heart. There is no single diet that suits everyone, but a few general observations can be made. [ For detailed dietary information, see the report Heart Healthy Diet .]

Fats

Experts now believe that fats can have both harmful and beneficial effects. Whether harmful or beneficial they are still high in calories:

Harmful Fats. Reducing consumption of saturated fats and trans-fatty acids is the first essential step in managing cholesterol levels through diet.

Saturated Fats. Saturated fats are found predominantly in animal products, including meat and dairy products. They are strongly associated with higher cholesterol levels. Although certain fatty acids in saturated fats called stearic acids may have some benefits, there is no simple method for defining foods that contain them, so, in general, saturated fats should be avoided. (The so-called tropical oils (palm, coconut, and cocoa butter) are [also high in saturated fats. Evidence] is lacking, however, about their effects on the heart. The countries with the highest palm-oil intake, Costa Rica and Malaysia also have much lower heart disease rates and cholesterol levels than Western nations.)
Trans-fatty Acids. Trans-fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They may be particularly dangerous for the heart and may pose a risk for certain cancers. Some experts believe that these partially hydrogenated fats are even worse than saturated fats because they both increase LDL and reduce HDL cholesterol levels and may have harmful effects on the linings of the arteries. One study of 80,000 nurses reported that women whose total fat consumption was 46% of total caloric intake had no greater risk in general for a heart attack than did those for whom fat represented 30% of calories consumed. Women whose diets were high in trans-fatty acids, however, had a 53% increased risk for heart attack compared to those who consumed the least of those fats. Hydrogenated fats are used in stick margarine and in many fast foods and baked goods, including most commercially produced white breads. (Liquid margarine is not hydrogenated and is recommended.) The FDA has now required that food labels include information on trans-fatty acids.

Beneficial oils: Public attention has mainly focused on the possible benefits of small amounts of monounsaturated and polyunsaturated fats found in vegetables oils. Researchers are most interested, however, in the smaller fatty-acid building blocks contained in these oils called essential fatty acids. Three important fatty acids are the essential fatty acids omega-3, omega-6, and omega-9.

Omega-3 fatty acids: They are further categorized as alpha-linolenic acid and docosahexaenoic and eicosapentaneoic acids.

Docosahexaenoic (DHA) and Eicosapentaneoic (EPA) Acids. Fish oils, which contain docosahexaenoic (DHA) and eicosapentaenoic acids (EPA), have anti-inflammatory and anti-blood clotting effects and may be significantly beneficial to the heart. DHA is the most unsaturated of all fatty acids. These fatty acids may reduce triglyceride levels and have modest positive effects on HDL. In patients with high triglyceride levels, but not in others, omega 3 fatty acids may increase LDL. Overall cholesterol levels are not affected. DHA appears to have specific benefits on blood pressure. The International Society for the Study of Fatty Acids and Lipids, in fact, recommends fish oil supplements for heart protection. Omega-3 fatty acids in fish may reduce risks for other disorders, including stroke, rheumatoid arthritis, asthma, ulcerative colitis, and some types of cancers.

Alpha-linolenic Acid . Alpha-linolenic acid is a plant precursor of DHA, which means the body can convert it to DHA. Sources include canola oil, soybeans, flaxseed, and certain nuts and seeds (walnut, flax, chia and sometimes pumpkin seed). Studies have been positive about the effects on the heart of these oils or foods containing these oils.

Omega-6 polyunsaturated fatty acids. Sources are corn, safflower, soybean, and sunflower oil. PUFA oils containing omega-6 fatty acids constitute most of the oils consumed in the US. Some omega-6 fatty acids are important for health. There is some association with a higher risk for certain cancer and some chronic diseases with diets high in omega-6 fatty acids, however.
Omega-9 monounsaturated fatty acids: Sources are canola and olive oil. Extra virgin olive oil has been associated with lower blood pressure and a 2000 study reported that it may have specific benefits for people with diabetes type 2. Of concern is a small study reporting higher concentrations of LDL in subjects consuming an olive-oil rich diet compared to those on a sunflower or rapeseed oil rich diet.

Research suggests that our current Western diet contains an unhealthy high ratio (10 to 1) of omega-6 to omega-3 fatty acid. Omega-9 fatty acids may also contain chemicals that block harmful factors found in omega-6 fatty acids. Researchers are finding then that the most benefits may be found in mixture of all three fatty acids found in both poly- and monounsaturated oils, but in modest amounts that do not add too many calories.

Carbohydrates

Meals overly rich in carbohydrates tend to set off angina attacks, possibly because they raise insulin levels. One study suggested, in fact, that in women, sugar may pose an even higher risk for heart disease than fats do. Whole grains and fresh fruits and vegetables (particularly dark-colored ones), however, are very important. They are rich in fiber, vitamins, and other important nutrients that are heart-protective. Natural chemicals in cooked tomatoes, garlic, nuts, apples, onions, wine, and tea also appear to offer protection for the heart.

Protein

Meat and Fish. For heart protection, one 1999 study suggested that it didn't matter if you chose fish, poultry, beef, or pork as long as the meat was lean. (Saturated fat in meat is the primary danger to the heart.) The fat content of meat varies depending on the type and cut. It is best to eat skinless chicken or turkey; the leanest cuts of pork (loin and tenderloin), veal, and beef are nearly comparable to chicken in calories and fat and their effect on LDL and HDL levels. It should be noted, however, that even chicken and lean meat do not improve cholesterol levels, and, in terms of cardiac health, fish is a more desirable choice. Much evidence suggests that eating fish two or three times a week, particularly oily fish (such as salmon, halibut, swordfish, and tuna) is protective.

Soy. Soy is proving to be a particularly excellent source of protein. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. A number of studies have indicated that subjects that consume about 40 grams of soy protein each day reduce LDL and triglycerides and increase HDL. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits. (Tablets of individual isoflavones found in soy, however, do not appear to offer any advantages.)

Antioxidant Vitamins and Supplements

Vitamin E. Vitamin E may prevent blood clots and the formation of fatty plaques and cell proliferation on the walls of the arteries. Experts have hoped that supplements of this vitamin prove to be protective. However, few studies have offered any strong support for these hopes. One major 2000 study, for example, reported that patients who took a natural vitamin E at 400 IU for four to six years did not gain any protection against cardiovascular disease. Different vitamin E compounds, such as gamma tocopherol or tocotrienol, may prove to have benefits that the standard synthetic supplements (dl alpha tocopherol) do not, but more research is needed.

Vitamin C. Although in the laboratory, vitamin C has positive effects on blood vessels, there is no proof that supplements of vitamin C offer any actual protection against heart disease. And there is some evidence that high doses may even speed up existing damaging processes in the arteries.

B Vitamins. Several important studies have demonstrated a link between deficiencies in the B vitamins folic acid (folate), B6, and B12 and elevated blood levels of an amino acid homocysteine, a possible risk factor for atherosclerosis. Folic acid is particularly potent in reducing homocysteine levels, and folate deficiencies are associated with a higher risk from heart disease. (Green vegetables and legumes, enriched cereals and grains, and orange juice are rich in folate.) It is not clear yet if taking folate supplements and reducing homocysteine levels will actually protect against heart disease. Major studies are under way and small studies are promising. [ See Homocysteine under Emerging Risk Factors .]

Another important B vitamin is niacin (Vitamin B3), which improves cholesterol and triglyceride levels.

Note: Studies are continuing to indicate that high doses of antioxidants supplements, such as vitamins C, E, and beta carotene, may have pro-oxidant effects that can actually harm the arteries and incur other damage. [For more information, see the Report, Vitamins, Carotenoids, and Phytochemicals .]

Stress and Psychologic Factors

Stress. Incidents of acute stress have been associated with a higher risk for serious cardiac events, such as heart rhythm abnormalities and heart attacks, and even death from such events in people with heart disease. Most studies have focused on the negative effects of stress on the hearts of men, particularly from work, but a 2000 study reported that marital stress (but not work stress) also hurts women's hearts. Stress may have actual negative physical effects on the heart. [ See the Report #31, Stress .]

Depression. In one 30-year study, men who were clinically depressed had a greater risk for heart disease and heart attack than men who were not depressed. This higher risk lasted for decades. The more severe the depression, the more dangerous to the health. Some studies have indicated that even mild depression, including feelings of hopelessness, experienced over many years, may harm the hearts in people with no early signs of heart disease. A number of studies have suggested that depression has biologic effects on the heart, including blood clotting and heart rate. . Depression may even impair a patient's response to medication for heart disease. (On the other hand hardening of the arteries in the brain may cause depression, so depression may simply be a marker of severe heart disease.)

Anger and Hostility. There have been some reports of an association between angry temperaments and heart disease. According to a 2000 study on Army personnel, however, psychologic factors (including depression, anxiety, hostility, and stress) did not appear to have any effect on hardening of the arteries, the primary cause of coronary artery disease. And, another 2000 study suggested that anger itself posed no higher risk to the heart, although outwardly expressed anger plus low social support did appear to predict progression of heart disease. [ See the Report #8, Depression.]

Alcohol

The effects of alcohol on heart disease varies depending on consumption. Evidence strongly suggests that light to moderate alcohol consumption (one or two drinks a day) protects the heart, even in people with type 2 diabetes. The benefits are strongest in people at high risk for heart disease and may be fairly small in those at low risk.

One drink is defined as the following:

1.25 fluid ounces (fl oz) of 80-proof spirits (such as bourbon, Scotch, vodka, gin, etc.)
1 fl oz of 100-proof spirits.
4 fl oz of wine.
12 fl oz of beer.

No one recommends that nondrinkers start using alcohol for health reasons or that regular drinkers increase their intake. Large amounts of alcohol can raise blood pressure, trigger irregular heartbeats, and damage the heart muscle. Binge drinkers have a significantly higher risk for a cardiac emergency.

Emerging or Possible Risk Factors

Homocysteine. Abnormally high blood levels of the amino acid homocysteine are strongly linked to an increased risk of coronary artery disease and stroke. Homocysteine may harm the lining of the arteries and reduce blood flow. Excessive levels occur with deficiencies of vitamins B6, B12, and folic acid. Some experts believe that high levels of homocysteine are only indicators, not causes, of heart disease. However, studies are noting a strong association between this compound and heart disease. For example, a 2000 study reported that lower homocysteine levels after taking folic acid and vitamin B12 were associated with more open blood vessels and improved blood flow.

Infectious Agents. Some microorganisms and viruses have been under suspicion for triggering the inflammation and damage in the arteries that contributes to heart disease. The primary suspect has been Chlamydia pneumoniae (a non-bacterial organism that causes mild pneumonia in young adults). This is based on the following:

High levels of antibodies against C. pneumoniae have been associated with a higher risk for heart events.
C. pneumoniae has been detected in plaques in the arteries of patients with heart disease.
Animals inoculated with the organisms have developed hardening of the arteries.

Many people, however, have been infected with C. pneumoniae and some studies have found no evidence that it increases the risk for heart disease. In any case, until better studies are conducted, experts do not recommend antibiotics to treat heart disease even in patients with evidence of C. pneumoniae .

Other organisms under investigation include H. pylori (the bacteria responsible for peptic ulcers), and the viruses herpesvirus and cytomegalovirus.

Periodontal (Gum) Disease. Some studies have reported a 1.5- to four-fold risk for heart disease in people with peridontal disease. In one, 85% of heart attack patients had periodontal disease compared to 29% of people with periodontal disease and no heart problems. Periodontal disease has also been associated with stroke.

Iron Overload. Iron overload (high levels of iron in the blood) has been associated with coronary artery disease in animals. Results of studies on high iron levels in people, however, have been mixed. In a 2000 study of people with high iron levels, for example, Caucasian men had no higher mortality risk, but women had a higher death rate from heart disease and African American men had higher mortality rates from all causes. And a 2001 study reported that blood donations (which reduce iron levels) had no protective effect on heart disease. Most studies have been conducted on Caucasian men, and none have provided clear proof one way or the other on the effects of iron on the heart in any group.

Inflammatory Factors. An immune response that produces inflammation and damage in the arteries (possibly triggered by infection or other factors) is now strongly associated with heart disease. Specific inflammatory factors involved in the process may include those called C reactive protein and fibrinogen.

Elevated levels of C-reactive protein strongly predict future heart attacks in patients with existing heart disease, particularly unstable angina. Some studies have even suggested that the protein itself may directly play a role in damage to heart muscles. Nevertheless, high levels of C-reactive protein may simply be a by-product of processes involved in heart disease, such as obesity or smoking, rather than an independent predictor or cause of heart disease.
High levels of fibrinogen, a protein that is a central participant in the clotting process, is also a potential indicator of heart disease.

Oral Contraceptives. Some women who took early forms of oral contraceptives, particularly if they smoked, had high blood pressure, or both, have a higher risk for heart attack and stroke. Newer forms pose a much lower risk. And, in fact, a 2001 study found no higher risk for a heart attack in women using newer, low-dose OCs .

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 is often accompanied by snoring and short, gasping wakefulness. Many risk factors are associated with both stroke and sleep apnea (obesity, high blood pressure, a risk for blood clots, and narrowing of the arteries). These factors may also increase the risk for heart attacks. In one 2001 study, researchers observed that the higher the number of apneas a patient had, the higher his risk for heart attack.

Conditions Associated with Heart Disease

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

Factors Before Birth and In Infancy. Low weight at birth and in the womb has been associated with later heart disease in a few studies. Some suggest, however, that this may just reflect poor nutrition in the mother, which appears to affect life-long risk. A 2000 British study reinforced the idea that pre-birth or other early events have little significant effect on heart disease risk in later life.
Seasonal Differences. More deaths from heart disease occur in December and January and fewest in the summertime. Although lower temperatures and snow shoveling may play a role in some cases, more winter deaths have been reported even in warm regions. Holiday stress or fewer daylight hours have been suggested as other reasons for these higher winter rates.
Physical Characteristics. Male pattern baldness, hair in the ear canals, and creased earlobes are associated with a higher risk for heart disease in white males. (Interestingly, in African American men, of these factors, only creased earlobes were associated with a higher risk in one study.)
Air Pollution. A 2000 study suggested that air pollution is linked to a higher risk of death from heart disease as well as lung disease and all other causes.

WHAT ARE THE TESTS FOR AN INITIAL DIAGNOSIS OF CORONARY ARTERY DISEASE?

There are many tests are available to diagnose possible heart disease. The choice of which (and how many) tests to perform depends on factors such as the patient's risk factors, history of heart problems, and current symptoms.

Usually the tests begin with the simplest and may progress to more complicated ones. Specific tests depend on the patient's particular condition and the physician's assessment. Some of these tests are noninvasive, that is, they don't involve inserting needles, instruments, or fluids into the body.

Cholesterol

Physicians will routinely check for unhealthy cholesterol levels. Other tests being investigated for indications of risk include blood tests for homocysteine, the protein albumin, and blood clotting factors, especially fibrinogen.

Electrocardiograms

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

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 the contraction of the ventricles (the two major pumping chambers in the heart.)
T and U. These waves follow the ventricular contraction.

Physicians will 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.

Stress Test

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

The patient walks on a treadmill or rides a stationary bicycle. Exercise continues until the heart is beating at least 85% of its maximum rate or until heart rhythm abnormalities, angina, fatigue, or other symptoms of heart trouble occur.
For patients who cannot exercise, the physician may administer dobutamine or dipyridamole, also called persantine. These are drugs that simulate the stress of exercise.
An ECG is used to monitor heart rhythms during a stress test. (An echocardiogram or more advanced imaging technique may also be used to visualize the actions of the heart and blood flow.)
Failure to reach the target heart rate may be a sign of a risk for heart attack and angina in people with coronary artery disease or even a predictor for coronary artery disease in people without a current problem.
Unfortunately, only about 65% of patients are diagnosed correctly using an ECG alone and the accuracy is even worse for women. (Using an echocardiogram may be a more accurate procedure for women.) About 10% of healthy patients, particularly younger people, will have abnormal test results (false positive).
More than 25% of patients stop exercising before they reach their own maximum limits because of fear of a heart event. Patients should be reassured that the activities performed in the test under the guidance of a professional are safe.

Echocardiograms

An echocardiogram is a noninvasive test that uses ultrasound images of the heart. This test is more expensive than an ECG, but it can be very valuable, particularly when used with a stress test, to detect the location and extent of heart muscle damage.

Radionuclide Imaging

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

Diagnosing or determining the severity of unstable angina when less expensive diagnostic approaches are unavailable or unreliable.
Determining the severity of chronic coronary artery disease.
To assess the success of surgeries for coronary artery disease.
To diagnose a heart attack.

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

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

Myocardial Perfusion (Blood Flow) Imaging Test (also called the Thallium Stress Test). This radionuclide test is used to determine blood flow to the heart muscles and is a reliable measure of severe heart events.

It is typically used with an exercise stress test.
Before starting to exercise, an intravenous line is inserted into the patient's hand and ECG wires are hooked up to the chest.
The patient then either exercises or is given a drug to induce exercise-like stress.
About a minute before the patient is ready to stop exercising, the physician administers thallium 201 (or more often now, sestmibi), a radioactive tracer, into the intravenous line.
Immediately afterward the patient lies down and heart scans are performed, usually with a planar scintigraphy or with SPECT.
The scanned images will reveal whether radioactive thallium is taken up by heart muscle cells or not. Heart muscle tissue that does not take up the tracing element is most likely damaged and so blocks the flow of blood (along with the tracing element).
If the scan detects damage, more images are taken three or four hours later.
Damage due to a prior heart attack will persist when the heart scan is repeated. Injury caused by angina, however, will have resolved by that time.

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

The technique may employ two different approaches:

First-pass radionuclide angiography. This technique measures blood flow through the vessels and chambers of the heart.
Gated blood pool imaging (also equilibrium radionuclide angiography, MUGA, gated or radionuclide ventriculography). This technique provides information on blood flow in the heart and also pumping action during rest and exercise.

Investigative Advanced Noninvasive Imaging Techniques

Magnetic Resonance Imaging. A very promising investigative approach using magnetic resonance imaging (MRI) and a contrast material (an injected dye) can provide images of the entire thickness of the heart muscle instead of just the surface. It is proving to be accurate enough to allow prediction of which patients might benefit most from surgical procedures. This approach is unlikely to be widely available for some time.

Computed Tomography (CT) Scans. Advanced techniques used in computed tomography (CT) scans are very promising.

Helical multislice computed tomography (MSCT) angiography is able take pictures of the entire heart in one millimeter slices in the time it takes for a patient to hold one breath. Studies are suggesting that it is highly accurate in detecting the degree of artery stenosis (narrowing).
Electron beam computed tomography (EBCT) scans (also called ultrafast computed tomography (CT) scans) are so fast that they can freeze the motion of the heart. Scans from EBCT reveal deposits of calcium on the arterial walls, indicators of current and future coronary artery disease.

Such procedures are very expensive and still investigative.

Angiography

Angiography is an invasive test that may be performed on patients who have very incapacitating angina that does not respond to medical therapy.

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.

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% to 30% of patients who have this procedure have normal results.

Ruling out Other Causes of Symptoms

Other Conditions that Cause Chest Pain. Many conditions may cause chest pain. High on the list are the following:

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

WHAT ARE THE GENERAL GUIDELINES FOR MANAGING CORONARY ARTERY DISEASE AND ANGINA?

Managing Coronary Artery Disease

The approach for managing coronary artery disease involves lifestyle changes and possibly medications, surgery, or both:

Lifestyle changes are essential for improving outcome in anyone with heart disease.
Drug therapy is effective for the treatment of stable angina and for slowing progression of coronary artery disease.
Unstable angina may require surgical intervention in addition to the therapies given for stable angina.

Managing Angina

Experts have come up with a mnemonic device (ABCDE) for remembering ten factors that are fundamental for angina management:

A. Aspirin and antianginal drugs.

B. Blood pressure and beta-blockers.

C. Cholesterol and cigarettes.

D. Diet and diabetes.

E. Exercise and education .

WHAT ARE THE DRUGS USED TO PREVENT BLOOD CLOTS IN CORONARY ARTERY DISEASE?

Anti-Clotting Agents

Anti-clotting agents that inhibit or break up blood clots are used at every stage of heart disease. They are generally either anti-platelet agents or anticoagulants. Investigators are also studying combinations of anti-clotting agents, which may be useful in patients with severe heart disease. All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

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

Aspirin. Aspirin is an antiplatelet agent. It is the most common anti-clotting drug and nearly anyone with heart disease is advised to take it daily in low dose.
Glycoprotein IIb/IIIa Inhibitors. These potent blood-thinning agents include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are being used after surgery angioplasty and stent placement. [ See Angioplasty and Coronary Stents , below. ] Other benefits are not yet clear.
Thienopyrindines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are potent oral platelet inhibitors.

Anticoagulants. Anticoagulants help thin blood and include the following:

Heparin. Standard and low-molecular weight heparin (enoxaparin, dalteparin, tinzaparin)
Warfarin (Coumadin).

Aspirin

Aspirin is known as a nonsteroidal anti-inflammatory agent (NSAID). It inhibits blood platelets, which are major clotting factors, from sticking together to form a blood clot. A daily low-dose aspirin is usually the first choice for preventing heart attacks in people with stable angina or those with risk factors for a first heart attack. Aspirin alone has been reported to reduce risk of death from heart attack by 25% to 50%. Some investigators are attempting to determine patient subgroups that might particularly benefit from aspirin. A 2000 study has suggested that aspirin works less well in patients with high cholesterol levels. Side Effects. Side effects for anyone from prolonged use of aspirin may include gastrointestinal ulcers and bleeding. (There may be a slight increased risk for bleeding-related strokes, which are very uncommon, however. Furthermore this risk may be outweighed by protection against the more common stroke, which is caused by artery blockage.) Interactions with Other Drugs. Of great concern is research suggesting that NSAIDs, which include aspirin, ibuprofen (Advil), and naproxen (Aleve), interfere with diuretics and ACE inhibitors, which are important heart and blood pressure medicines. (A 2000 report has also suggested that taking ibuprofen (Advil) right before taking an aspirin may inhibit aspirin's benefits on the heart.) Recent use of NSAIDs, in fact, have been associated with a higher risk of hospitalization in heart failure patients, especially those taking diuretics or ACE inhibitors. It is not clear, however, whether interactions with ACE inhibitors would preclude taking both at the same time in patients with coronary artery disease.

Thienopyrindines

Clopidogrel (Plavix, Iscover) is an oral platelet inhibitors called a thienopyrindine. It is showing significant benefits for patients with heart disease. A 2001 report on a major study of patients with acute coronary syndromes found a lower incidence of heart attacks, stroke, and death from heart disease in patients taking clopidogrel compared to those taking aspirin. Clopidogrel is also more effective than either aspirin or ticlopidine for reducing the incidence of a heart attack after angioplasty. Ticlopidine (Ticlid) is another effective thienopyrindine, but has largely been replaced by clopidogrel because of dangerous blood disorders, particularly thrombocytopenia.

Anticoagulants

Standard (Unfractionated) Heparin. Heparin is an anticoagulant. The standard (called unfractionated) heparin has been used alone or in combination with aspirin for managing unstable angina. It must be intravenously administered and monitored with frequent blood test for signs of bleeding.

Low-Molecular Weight Heparin. Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep) are drugs known as low-molecular weight heparins (LMWHs). They require injections but do not need continuous monitoring of the blood, as standard heparin does. Patients may even be able to self-administer LMWHs as people with diabetes do insulin. Studies are finding that they are very effective for unstable angina and are outperforming standard heparin in patients.

Warfarin. Warfarin (Coumadin) is an oral anticoagulant. It prevents clots by inhibiting vitamin K. It is particularly beneficial for preventing blood clots in patients with atrial fibrillation (very fast and irregular heart beats). It is most often used after a heart attack. In such cases it is as effective alone as in combination with aspirin. (Using it alone also reduces the risk for bleeding.) Low-dose warfarin is also being studied as an alternative to aspirin for prevention of heart attacks. Warfarin therapy must be monitored with frequent blood tests.

Glycoprotein IIb/IIIa Inhibitors

Glycoprotein IIb/IIIa inhibitors thin blood by blocking platelets (clotting factors in the blood).

Intravenous IIb/IIIa Inhibitors. Those under investigation are administered intravenously in the hospital and are being used for acute situation, not for management of day-to-day angina. Examples of these drugs include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. Studies on their benefits have been mixed, which depend on how they are used.

Many studies are finding that these agents are very beneficial when used along with angioplasty with coronary stent placement. [ See Angioplasty and Coronary Stents under What Are the Surgical Treatments for Angina and Coronary Artery Disease? .]
One major trial with abciximab reported no additional benefits at all compared to placebo (a dummy pill) when used alone for patients with acute coronary syndromes (unstable angina or non-Q-wave myocardial infarction, a condition showing heart damage but not enough for a full-blown heart attack). In fact, patients who took it had poorer results than those on placebo, particularly after taking it for a long time. Studies in 2000 on tirofiban and eptifibatide, however, reported that early use did reduce the incidence of recurrent adverse heart events in patients with acute coronary syndromes. (It is not yet clear if they have any positive effect on long-term survival rates compared to more conservative treatments).
A 2000 study suggested that tirofiban may be particularly useful for patients with diabetes and acute coronary syndrome.

Certain patients (eg, thin, elderly, nonwhite, with more than one heart risk factor) taking a glycoprotein IIb/IIIa receptor antagonist may be at high risk for thrombocytopenia, a drastic reduction in platelets that can cause severe bleeding, after taking these drugs.

Oral IIb/IIIa Inhibitors. Oral IIb/IIIa inhibitors (called super-aspirins) have been under investigation. Many of these agents were withdrawn, however, after reports of significantly high mortality rates, often from sudden death (not from actual heart attacks) and high rates of major bleeding. Studies continue on two oral IIb/IIIa inhibitors, roxifiban and cromafiban, which have different properties from the other oral agents. Some experts believe, however, that studies using any oral IIb/IIIa inhibitors should be stopped.

Other Anti-Clotting Agents

Hirudin. Bivalirudin (Angiomax) is a drug derived from hirudin, a natural substance derived from the saliva of leeches. Hirudin can cause major bleeding episodes, however, and studies have been disappointing. Other Anticoagulants. Other anticoagulants include argatroban (Novastan) and danaparoid (Orgaran).

WHAT ARE THE OTHER DRUGS USED FOR ANGINA AND CORONARY ARTERY DISEASE?

Nitrates

Nitrates have been used in the treatment of angina for over a hundred years. These drugs release nitric oxide, thereby relaxing the smooth muscles in blood vessels. Many nitrate preparations are available; the most commonly used are nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates can be absorbed from the gastrointestinal tract (oral tablet), skin (ointment or patch), and from under the tongue (sublingual tablet or spray). Rapid Acting Nitrates. Rapid-acting nitrates are used to treat acute attacks. Nitroglycerin is the most widely agent for this purpose. It can be administered under the tongue (sublingually or as a spray) or pocketed between the upper lip and gum (buccally) and can relieve angina within minutes. The procedure for taking nitroglycerin during an attack is as follows:

At the onset of an angina attack, the patient administers one sublingual or buccal tablet or one metered dose of the spray.
If the pain is not relieved within five minutes the patient takes a second dose; a third can be taken after another five minutes if symptoms persist.
If pain continues after a total of three doses in 15 minutes, the patient should go to the nearest emergency room at once.
Nitroglycerin is very volatile so its potency can be easily lost. A patient should take the follow precautions:
Keep no more than 100 tablets on hand stored in their original container.
When first opened, the cotton filler should be discarded, and the cap screwed on tightly immediately after each use.
A supply should always be kept close at hand in case of an attack, with the rest kept in a cool dry place.

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

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

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

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

Common side effects of nitrates include headaches, dizziness, nausea and vomiting, blurred vision, fast heartbeat, sweating, and flushing on the face and neck. Low blood pressure and dizziness can be relieved by lying down with the legs elevated. Note: These effects can be significantly worsened by alcohol, beta-blockers, calcium channel blockers, sildenafil (Viagra), and certain antidepressants. Your doctor may prescribe medicines to lessen these side effects. Contact your doctor if these side effects are persistent or severe.
Serious side effects requiring immediate medical help include fever, joint or chest pain, sore throat, skin rash (especially on the face), unusual bleeding or bruising, weight gain, and swelling of the ankles.

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

Beta-Blockers

Beta-blockers reduce the oxygen demand of the heart by slowing the heart rate and lowering arterial pressure. They are now well known for reducing deaths from heart disease. Beta-blockers do not stop angina attacks, but used preventively, they reduce their frequency and the dependency on nitrates. They may also be beneficial for people with silent ischemia. (Beta-blockers are less useful for the treatment of Prinzmetal's angina.)

Specific Beta-blockers. Beta-blockers include propranolol (Inderal), labetalol (Normodyne, Trandate), acebutolol (Sectral), atenolol (Tenormin), metoprolol (Toprol-XL, Lopressor), and bisoprolol (Zebeta). Carvedilol (Coreg), a newer agent known as a nonselective beta-blocker, appears to be as safe as the older beta-blockers and may prove to have additional advantages. A nasal spray form of propranolol appears to be very beneficial in helping to reduce exercise-induced angina attacks.

Side Effects. Side effect include the following:

Some beta-blockers lower HDL cholesterol (the beneficial cholesterol) by about 10%. The effect is most marked in smokers.
Fatigue and lethargy are the most common neurologic side effects. Some people experience vivid dreams and nightmares, depression, and memory loss.
Exercise capacity may be reduced.
Other side effects may include cold extremities, asthma, decreased heart function, gastrointestinal problems (eg, heartburn, gas, diarrhea, or constipation), and sexual dysfunction.
Dizziness and lightheadedness, especially when getting up from a lying down position.

If side effects occur, the patient should call a physician, but it is extremely important not to stop the drug abruptly. Angina, heart attack, and even sudden death have occurred in patients who discontinued treatment without gradual withdrawal.

Statins and Other Cholesterol and Lipid-Lower Agents

A number of agents are available for lowering cholesterol and other dangerous fat molecules (lipids). They include the following:

Statins, resins, and the drug probucol target LDL cholesterol. Statins and are now the first choice for most people who require lipid-lowering therapy.
Fibrates and niacin (also known as vitamin B3 and nicotinic acid) reduce triglycerides and increase HDL. (In one recent report, for example, the use of niacin plus a statin stopped progression of coronary artery disease completely.)

In spite of the obvious benefits of many of these agents, according to one study, only 37% of patients with recent heart attacks and high cholesterol levels were given any drugs to lower cholesterol. [For information on other cholesterol-lowering agents see the Report, Cholesterol, Other Lipids, and Lipoproteins .]

Statin Drugs. Statins may have significant benefits for heart patients. Statins are proving to reduce the risk for heart attacks even in some people with normal or below-normal cholesterol. Studies in 2000 and 2001 suggest that patients with normal cholesterol but signs of inflammation in the arteries (as indicated by blood tests showing high levels of C-reactive protein) may benefit from statins.

The statins include two groups:

So-called natural statins, including lovastatin (Mevacor), pravastatin (Pravachol), and simvastatin (Zocor). The natural statins are generally administered once a day; they should be taken in the evening because most cholesterol synthesis occurs between midnight and 3 AM. If more intensive treatment is required, a second morning dose may be administered.
Newer statins are fluvastatin (Lescol) atorvastatin (Lipitor), and rosuvastatin (Crestor). Some are taken twice a day. The newer agents may reduce LDL more effectively at equal doses to the natural statins, but more research is needed to confirm this.

All are effective and safe and all are approved for lowering LDL. Although only some statins are yet to be approved for prevention of heart disease and stroke, studies are showing similar benefits among all of them. Any differences are currently under investigation. Because of their positive record and apparent long-term safety, and obvious heart benefits, manufacturers are urging approval for over-the-counter status.

Candidates. Statins are the most effective drugs for the treatment of high cholesterol and are now strongly recommended as the first choice for most patients with high cholesterol levels, particularly the following:

Patients with diabetes, existing heart disease, or both.
Older women with heart disease. (Hormone replacement therapy had been the treatment of choice for many of the patients, but is no longer recommended.) [ See Warning Box Note on Hormone Replacement Therapy.]

The use of statins for children and adolescents with unhealthy cholesterol levels is considered safe, at least in teenage boys, but long-term studies are needed to confirm their value and safety in all children.

Adverse Effects. The statins tend to be better tolerated than other cholesterol-lowering drugs. In many studies the side effects reported were nearly the same as those taking placebo (inactive agents). Those reported include gastrointestinal discomfort, headaches, skin rashes, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet). Statins can affect the liver, so periodic liver function tests should be administered. Statins should never be taken by anyone with liver problems or by women during pregnancy or breast-feeding. [See also Note on Withdrawal of Cerivastatin (Baycor).]

Withdrawal of Cerivastatin (Baycol)

One statin, Baycol, was withdrawn from the market because of reports of death from rhabdomyolysis, severe muscle damage that can lead to kidney failure. People at highest risk were those who were taking high doses and who also took gemfibrozil. Rhabdomyolysis has occurred rarely with other statins but has never before been associated with deaths.

Combinations and Interactions with Other Drugs and Substances. Statins can be used in combinations with other cholesterol lowering agents, including bile acid-binding resins, nicotinic acid, and fibrates, for a more wide-spread effect on other lipids. Use with certain other drugs, however, including nicotinic acid and fibrate, may increase the risk for muscle weakness or pain. (Other drugs that may have the same effect are cyclosporin, macrolide antibiotics, or certain antifungals.) Grapefruit juice may increase their potency.

Calcium Channel Blockers

Calcium channel blockers reduce heart rate and slightly dilate the blood vessels of the heart, thereby decreasing oxygen demand and increasing oxygen supply. They can be considered for some patients with angina who cannot take either beta-blockers or nitrates or if symptoms are not well controlled by these agents. Most calcium channel blockers used in the US may be categorized into three groups based upon different chemical structures.

The Dihydropyridines. These include nifedipine (Adalat, Procardia), amlodipine (Norvasc), nicardipine (Cardene), felodipine (Plendil), and others. These agents selectively target the smooth muscles, which line blood vessels, and have more powerful actions on opening arteries than verapamil or diltiazem. Within the group, some agents have more benefits than others do for patients with angina.

Long-acting nifedipine (Adalat) and newer calcium channel blockers (amlodipine and nicardipine) may have advantages for patients with coronary artery disease. For example, a 2000 study suggested that Adalat may even improve blood vessel function in patients with coronary artery disease. And a 2000 study on amlodipine reported fewer cases of unstable angina and a reduced need for surgical procedures than with placebo and no higher mortality rates from heart events. Nicardipine is short-acting and may have particular benefits for Prinzmetal's angina.

Short-acting nifedipine has been associated with severe and even dangerous side effects, including an increase in heart attacks and sudden death and many physicians have stopped using it.

Verapamil (Calan, Isoptin). This agent may be helpful for some patients with angina because it reduces oxygen demand in the heart muscles. However, some of its effects can cause heart failure in patients with heart dysfunction. Side effects include slow heart beats.
Diltiazem (Cardizem, Tiazac). This calcium blocker improves blood flow through vessels in the heart but is not as powerful an artery opener as the dihydropyridines. It has a low incidence of side effects.

These agents should be taken with food or milk. It should be noted that drinking grapefruit juice or eating grape fruit with these drugs could increase their effects, sometimes to toxic levels.

Overdose can cause dangerously low blood pressure and slow heart beats. It should be noted that there is no evidence that any calcium channel blockers improve survival rates. And, some studies have questioned their safety, particularly large doses of nifedipine. Patients with heart failure have a higher risk for death with these agents and should not take them. No one taking any calcium channel blocker should withdraw abruptly because such action could dangerously increase the risk of high blood pressure.

Angiotensin Converting Enzyme Inhibitors

Angiotensin converting enzyme (ACE) inhibitors are important agents. They are used in hypertension and currently recommended as first-line treatment for people with diabetes and kidney damage, for some heart attack survivors, and for patients with heart failure. Now, an important 2000 study that tested ramipril (Altace) has suggested that other patients might benefit from it. In the study, patients at high risk for heart disease who took ramipril significantly lowered their risk for heart attack, stroke, complications of diabetes, and death. Such patients had either coronary artery disease, a history of stroke, or diabetes plus at least one other heart risk factor, such as high blood pressure, unhealthy cholesterol levels, or smoking. (Ramipril had no effect on angina, however.) It is not yet known if these benefits apply to other ACE inhibitors, such as captopril (Capoten), enalapril (Vasotec), lisinopril (Prinivil, Zestril), and fosinopril.

Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. Of great concern is research suggesting that aspirin (and other so-called NSAIDs) increases the risk for heart failure in patients taking ACE inhibitors. [ See What Are the Drugs Used to Prevent Blood Clots in Coronary Artery Disease?.]

Note on Hormone Replacement Therapy

In spite of estrogen's actions that appear to be heart-protective, the overall effects on the heart from hormone replacement therapy, with or without progestin, is not clear. Although early studies in the mid 1990s reported reductions in heart disease in postmenopausal women who took estrogen replacement, more recent studies have been negative, particularly in women with existing heart disease.

In July 2001, the American Heart Association sent out an advisory regarding the use of HRT in postmenopausal women. These guidelines state that women with heart disease, or women who have a heart attack while on HRT, should stop the therapy. In addition, they recommend that doctors should no longer tell women that hormone replacement therapy has any cardiovascular benefits. Whether HRT prevents heart disease at all is the subject of two ongoing large trials. Data from these trials is expected within the next five years. [For more information see the Report Menopause, Estrogen Loss, and Their Treatments .]

Experimental Drugs

Gene Therapy and Angiogenesis. Agents known as growth factors are being investigated for their ability to grow new blood vessels. Those being tested are genetically engineered forms of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF [GenerX]). Early clinical trials are promising, but there are some concerns. Animal studies have reported tumor growth with the use of these agents (although these growths did not become cancerous). These treatments also use inactivated viruses to deliver the drugs to the heart, which is also of some concern. So far, however, they appear to be safe in humans.

Nicorandil. Nicorandil, know as a potassium channel activator, has anti-ischemic and anti-arrhythmic properties and may be a useful add-on for patients who need aggressive treatment. Severe mouth sores have been reported in some patients with long-term use.

Antibiotics. The antibiotics prescribed for Chlamydia pneumoniae are being investigated for prevention of heart attacks in patients with heart disease and evidence of infection. A two year 2000 study found no significant effect for these treatments. A 2001 study, however, on heart attack patients reported that antibiotics were associated with a lower risk for a second heart attack.

Testosterone Patches. Testosterone is associated with a higher risk for heart disease in men. Nevertheless, a small study using low-dose testosterone patches suggested the hormone may help reduce angina.

WHAT ARE THE GENERAL GUIDELINES FOR SURGICAL TREATMENTS FOR ANGINA AND CORONARY ARTERY DISEASE?

Candidates for Surgery

To date, surgery is usually recommended for patients who have the following conditions:

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

Whether surgery should be used as early treatment for mild angina is controversial. Studies have been mixed on the long-term survival rates in patients who had drug versus surgical treatments. In general, experts believe there is no harm in choosing drug treatments first and angioplasty if symptoms persist.

Choosing Angioplasty or Bypass

A number of invasive techniques are available for treating coronary artery disease. The two standard surgical procedures are the following:

Coronary artery bypass grafting (commonly called bypass).
Percutaneous transluminal coronary angioplasty (commonly called angioplasty). (Angioplasty is now commonly performed with stent placement .)

Each of these procedures is described below.

Studies have generally reported similar effectiveness in the two procedures, although angioplasty requires repeat procedures for opening the blood vessels. The decision usually depends on individual conditions. Patients considering surgery should discuss all options and risks with their physician. No surgical procedure cures coronary artery disease, and patients must continue to rigorously maintain a healthy life-style and continue any necessary medications.

Considerations for Choosing Angioplasty with Stent Placement. Angioplasty has the following advantages for most patients:

It is less invasive than bypass.
It is initially less expensive. (Although the postoperative need for more medications and the high risk for repeat procedures to reopen the artery may reduce the long-term difference in cost between the two procedures.)

It has the following disadvantage:

The blood vessels close up (restenosis) in a large minority of patients and require additional procedures. (New blood thinning agents and radiation treatments may help to significantly reduce restenosis rates.)

Considerations for Choosing Bypass. Bypass is usually the appropriate procedure in patients with the following conditions:

Three or more blocked arteries.
A left main artery narrowed by 50% or more.
A very long diseased portion of the artery.
Diabetes. (In fact, some experts believe angioplasty should rarely, if ever, be used for these patients.)
Being elderly.

Considerations for Specific Groups.

Women have higher mortality rates than men after surgery no matter what procedure, perhaps because they tend to be older and sicker when they have a heart operation. One study of bypass patients, however, indicated that simply being female was a risk factor for higher mortality regardless of age or health status.
A 2000 study reported that African American men had higher mortality rates (3.3%) from bypass procedures than Caucasian men (2.64%). It is not clear whether these differences were due to genetic or socioeconomic causes. (There were no differences between women in these two groups, but overall mortality rates in women were higher than in men (over 4.4%). It should be noted that mortality rates were still low in both groups and should not preclude bypass surgery.

Other Procedures

In addition to angioplasty and bypass procedures, a number of other procedures are available or under investigation for coronary artery disease. They include the following:

Atherectomy.
Myocardial Laser Revascularization.
Enhanced External Counterpulsation (EECP).

WHAT IS CORONARY ARTERY BYPASS GRAFT SURGERY (CABG)?

The Procedure

Coronary artery bypass graft surgery (CABG) is very invasive and involves the following processes:

The chest is opened and the blood is rerouted through a lung-heart machine.
The heart is stopped during the procedure.
Large blood vessels supply the grafts, which are used to reroute the blood. The blood vessel grafts are transplanted in front of and beyond the blocked arteries, so the blood flows through the new vessels around the blockage.
The traditional grafts use two arteries in the chest and a long vessel called the saphenous vein from the leg. Grafts taken from three arteries (two in the chest wall plus one from the abdomen) may prove to be more successful than the standard grafts. Bypass operations that use these three arteries are very complicated, however, and only skilled surgeons should undertake them.
Most people are hospitalized for at least a week and do not return to full activity for at least two months.

Complications

Under the best circumstances, bypass surgery carries about a 1% operative mortality rate and the average is 3%. Complications include the following:

Atrial Fibrillation. Atrial fibrillation (very fast and irregular heart beats) occurs after CABG.

Blood Clots. Blood clots may form in the new graft, closing it up or narrowing the treated vessel over time. Therapy with aspirin and other anti-clotting drugs help keep the graft open and working properly. The anti-platelet agent clopidogrel is proving to be particularly effective. For long-term prevention of closure as well as slowing progression of atherosclerosis, aggressive use of cholesterol-lowering drugs may be more beneficial than the standard anti-clotting drugs.

Of some concern are studies reporting a decline in mental function five years after bypass surgery. It is not known, however, if patients with bypass procedures tend to have other higher risk factors for mental decline (being older or sicker than those who choose angioplasty). Long-term studies are underway.

Minimally Invasive Bypass

Minimally invasive bypass (also called buttonhole or keyhole bypass) surgeries are exciting advances in basic bypass surgery that are currently being tested with good success for patients with disease in single vessels.

One uses a four-inch incision, and the surgeon works on the front of the heart while it is beating slowly. It is used just for bypasses with one or two arteries.
In another, the heart is stopped, and the patient is put on a machine that reroutes the blood through a device that keeps it oxygenated. Fiberoptic scopes and instruments are passed through a number of finger-sized incisions and the surgeon works on all sides of the heart guided by a video image from a tiny camera inserted through a four-inch incision.
Some advanced heart centers now employ robotic systems, which allow the surgeon to perform extremely delicate maneuvers on tiny vessels through pencil-size incisions. They are not yet used for the whole bypass process.

Early results show that minimally invasive bypass procedures will be less expensive, require a shorter hospital stay, and be a significant improvement over conventional coronary artery bypass surgery. To date, they are performed only in a few medical centers for select candidates.

WHAT ARE ANGIOPLASTY AND CORONARY STENTS?

Percutaneous transluminal coronary angioplasty (PTCA), usually simply called angioplasty, involves opening the blocked artery. A typical angioplasty procedure follows the following steps:

The surgeon threads a narrow catheter (a tube) containing a fiber optic camera directly to the blocked vessel.
The physician opens the blocked vessel using balloon angioplasty , in which the surgeon passes a tiny deflated balloon through the catheter to the vessel.
The balloon is inflated to compress the plaque against the walls of the artery, flattening it out so that blood can once again flow through the blood vessel freely.
In order to keep the artery open afterwards, surgeons now commonly employ a device called a coronary stent, which is an expandable metal mesh tube that is implanted during angioplasty at the site of the blockage. (A stent is being increasingly used as the initial opening device after a heart attack instead of balloon angioplasty.)
Once in place, the stent pushes against the wall of the artery to keep it open. (A number of studies are reporting fewer future heart attacks and restenosis in patients who receive stents compared with those who had angioplasty alone.)
Complications occur in about 10% of patients (about 80% within the first day). Serious ones include heart attack and the need for additional surgery. Outcomes are better in hospital settings with experienced teams and backup.

Stenting is now used in the majority of angioplasty procedures. Studies report high survival rates with the use of stents, including their use with multiple blood vessels. Most, but not all, patients are suitable candidates for stents.

Recuperation

Angioplasty is less invasive than bypass surgery, requiring only one night in the hospital. Recuperation takes about a week. It should be pointed out the chest pain after the procedure is very common and usually due to problems other than ischemia. Mild chest pain is even more common when a stent is used, possibly because the artery is stretched.

Reclosure and Blockage During or Shortly after Angioplasty and Prevention

Reclosure of the artery during or shortly after angioplasty often occurs. A number of anti-clotting agents are used to help prevent this, although they are not wholly protective because reclosure in some cases is due to other, unknown causes.

Aspirin and Other Blood Thinners. Aspirin and anticoagulants (heparin, coumarin) are most often used during and after the operation. Aspirin plus the anti-platelet agents clopidogrel or, less preferably, ticlopidine are also helpful in preventing reclosure.

Glycoprotein IIb/IIIa Inhibitors. These powerful agents block platelets (clotting factors in the blood) and are proving to be very effective for preventing reclosure, often when administered in combination with heparin or aspirin. Examples include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), and tirofiban (Aggrastat). Results suggest that when used with angioplasty and coronary stenting, all these agents reduce complications and the risk for recurrent heart events within the first 30 days of the procedure. This aggressive treatment combination is showing particular value when used within 4 and 48 hours of symptom onset. No comparison trials have been conducted between abciximab and eptifibatide. Abciximab in this setting may be more effective than tirofiban. [ See Anti-Clotting Agents under What Are the Drug Treatments for Angina and Coronary Artery Disease? , above .]

Artery Narrowing (Restenosis) Within a Year of Angioplasty

Narrowing or reclosing of the artery (restenosis) occurs within a year of angioplasty in a large minority of angioplasty patients, often requiring a repeat operation. The narrowing of the artery in this case is not due to blood clots and so anti-clotting agents are not useful. Theories for the cause of restenosis include the following:

The release of large amounts of oxidants (damaging unstable particles) at the surgical site may activate damage in certain white blood cells, which causes overgrowth in smooth muscles in the blood vessels.
Some experts argue that other activities, such as scarring, may remodel and narrow the blood vessels.

Prevention of Restenosis

A number of approaches, mostly investigative, have been developed to prevent restenosis after angioplasty.

Coronary Artery Brachytherapy. Radiation treatment called coronary artery brachytherapy can inhibit cell growth in the arteries that may be responsible for restenosis. Two devices (Gamma One, Novoste Beta-Cath System) have been approved for delivering radiation to the arteries in a previously placed coronary stent. After any blockage in the stent has been removed, a tube with an inflatable balloon is inserted. The radiation delivery device is then temporarily inserted. Both devices are showing excellent results in preventing restenosis. There are still many outstanding safety issues with these treatments, however, that will only be answered with long-term use. It should be noted that once radiation is performed, stents cannot be replaced again.

Medications. A number of medications have been investigated for preventing restenosis, but to date none have been proven to prevent this event. They include the following:

Researchers have tested an antioxidant drug probucol (Lorelco) with some success.
Genetic therapies are under investigation that deliver agents, such as growth factor, that help open remodel the smooth muscles in the arteries.
Calcium channel blockers inhibits thickening in the arteries and are being studied for preventing restenosis. To date, they have had little effect although some, particularly amlodipine, may help prevent repeat procedures.

Experts had hoped the statins, the important cholesterol-lowering agents, might help prevent restenosis. Studies have suggested, however, that they probably have no effect in this setting.

Coating or Materials Used in Stents. Researchers are testing materials and coating for coronary stents that might reduce restenosis. Standard stents are made of stainless steel, but a number of alloys are under investigation.

Drug-coated stents are generating some enthusiasm, particularly with the use of sirolimus, a drug that suppresses factors in the immune system and so may help prevent inflammation and damage.
Stents covered with a membrane made of a material called polytetrafluoroethylene (PTFE) may help prevent restenosis.
Stent coatings that are able to deliver genetic therapies are also being studied.

WHAT OTHER PROCEDURES ARE AVAILABLE FOR CORONARY ARTERY DISEASE?

Atherectomy

Atherectomy is used to remove plaque on the artery walls and clear the narrowed arteries. There are three procedures, directional, rotational, and extractional. With all procedures, a catheter (a thin tube) is inserted into the thigh and threaded up to the blockage. Devices to remove the plaque are inserted through the tube.

With rotational atherectomy, balloon catheter is inserted for determining position. Then a tiny cutter spinning at 2,500 rpm removes plaque fragments from the arterial walls. The tiny pieces are removed through the blood stream.
With extractional atherectomy, a device is used that "shaves" the plaque that has built up on the wall. It is then "vacuumed" out.
With directional atherectomy, the plaques are sliced thinly and then withdrawn.

Complications can be serious, including heart attack, disturbed rhythm, bleeding, and emboli (traveling blood clots). Although they are successful in open arteries, reclosure occurs in up to half of patients. Angioplasty may also be performed to improve the results of these procedures. Atherectomy has been tested to prevent restenosis after angioplasty, but results have been poor.

Myocardial Laser Revascularization

Lasers have been used with both angioplasty and bypass procedures, but the risks have been high and the treatment is expensive. Procedures called myocardial revascularization are being used with some success in relieving severe angina pain in patients who do not respond to other treatments.

Transmyocardial Revascularization. Transmyocardial laser revascularization (TMLR) is a surgical procedure that applies laser energy directly to areas in the heart where blockage has occurred and creates 10 to 50 tiny channels. It has been approved for patients with severe angina who do not respond to other treatments. The procedure itself carries some risks for complications, including some that can be life-threatening. Mortality rates range from 3% to 10%. Less invasive laser techniques and greater experience may improve these results.
Percutaneous Myocardial Revascularization. PMR is a less invasive procedure that uses a holmium YAG laser, which is smaller than the device used in TMLR and does not require open chest surgery and a general anesthetic. Laser energy can be delivered through a fiber-optic tube, which is threaded through an artery in the leg up to the heart. As with TMLR, the laser creates channels in the heart although they penetrate (from the inside out) only halfway into the heart muscle. Although early studies have reported significant relief, this variant has been associated with a high number of post-procedure deaths and a 2000 study failed to find any differences in pain relief after six months accompanied with patients who did not have this procedure.

Both procedures have significantly improved the quality of life and reduced anginal pain. Neither procedure is a cure, however, and they do not to improve survival rates. Many early studies on TMLR have reported that symptom relief does not last beyond a year or so. (Although one US group reported that a significant number of patients still experienced pain relief for as long as nine years after the procedure.) It is still not entirely clear how these procedures actually produce benefits, and some experts suggest that they may have no value beyond the placebo effect. More research is needed.

Enhanced External Counterpulsation (EECP)

A noninvasive technique called enhanced external counterpulsation (EECP) has been used successfully by over a million people in China. The technique uses an air pump that inflates and deflates pressurized cuffs around the legs, causing blood to be pushed into the heart. In different studies, it has relieved angina in over 75% of patients who used it. The benefits persist, and there is some evidence that it produces actual cellular changes that benefit the heart. It even appears to improve depression and anxiety. Those with three diseased vessels, however, do less well, and the procedure is not appropriate for those with heart failure or blood clots in the legs. EECP will not be likely to replace angioplasty or bypass, but it may reduce the need for nitrates.

Other Procedures

Endoscopic Transthoracic Sympathicotomy. A last resort for people with severe untreatable angina is a procedure known as endoscopic transthoracic sympathicotomy. This operation blocks the nerves that cause chest pain and, in one European study, proved to be very beneficial in relieving angina. Because such patients no longer experience any chest pain, however, they may not experience important symptoms of heart attack if they occur.

Ultrasound Thrombolysis. As a potential alternative to angioplasty, researchers have developed an ultrasound thrombolysis device that uses high frequency sound waves to dislodge and dissolve the fatty plaques on the walls of coronary arteries.

WHERE ELSE CAN HELP BE FOUND FOR CORONARY ARTERY DISEASE?

National Heart, Lung, and Blood Institute Information Center, P.O. Box 30105, Bethesda, MD 20824-0105. Call (301-592-8573) or on the Internet (http://www.nhlbi.nih.gov/)

American Heart Association, National Center, 7272 Greenville Ave., Dallas, Texas 75231-4596. Call (1-800-AHA-USA1) or on the Internet (http://www.americanheart.org/)

American College of Cardiology, Heart House, 9111 Old Georgetown Rd., Bethesda, MD 20814-1699. Call (800-253-4636) or (301-897-5400) or on the Internet (http://www.acc.org/)

On the Internet

A very useful web site (http://www.heartinfo.org/).

Aspirin Foundation of American. Call (800-432-3247) or on the internet (http://www.aspirin.org/)