Heart Attack and Acute Coronary Syndrome

Description

Alternative Names

Introduction

The heart is the human body's hardest working organ. Throughout life it continuously pumps blood enriched with oxygen and vital nutrients through a network of arteries to all parts of the body's tissues. In order to perform the arduous task of pumping blood to the rest of the body, the heart muscle itself needs a plentiful supply of oxygen-rich blood, which is provided through a network of coronary arteries. These arteries carry oxygen-rich blood to the heart's muscular walls (the myocardium).

Coronary artery disease is the most common cause of heart attacks, which occurs when blood flow to the myocardium is interrupted.

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

Click the icon to see an image of stable angina.

Stable Angina. Angina is the primary symptom of coronary artery disease and is typically experienced as chest pain. Stable angina is predictable chest pain and can usually be managed with life-style measures and medications, such as low-dose aspirin.

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

Heart Attack. A full blown heart attack occurs when blood flow is blocked and tissue death occurs from loss of oxygen, severely damaging the heart. In such cases, an injury known as an infarct occurs, or in other words, a myocardial infarction, more commonly known as a heart attack.

Click the icon to see an image of an acute myocardial infarction.

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.

Click the icon to see an image of atherosclerosis.

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

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

• Cholesterol is a white, 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.
• In heart disease, free radicals are released in artery linings and oxidize low-density lipoproteins (LDL). The oxidized LDL is the basis for cholesterol build-up on the artery walls.

Click the icon to see an image of arterial plaque build-up.

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 following is one theory about how the inflammatory response contributes to heart disease:

• The injuries to the arteries during oxidation signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. These factors initiate the inflammatory response.
• Macrophages literally "eat" foreign debris, in this case oxidized LDL cholesterol.
• The process converts LDL cholesterol into foamy 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.

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

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

• As this narrowing and hardening process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart.
• Such oxygen deprivation in vital cells is called ischemia. When it affects the coronary arteries, it causes injury to the tissues of the heart.
• Injured inner vessel walls also fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity.

These narrow and inelastic arteries not only slow down blood flow but they also become vulnerable to injury and tears.

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

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 states:

• Stable Angina (which is predictable).
• UnstableAngina (which is 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.

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

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

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.
• 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. [For more detailed information seeWell-Connected Report #3 Coronary Artery Disease and Angina.]

Unstable Angina and Acute Coronary Syndrome

Unstable Angina. Unstable angina is a much more serious situation than stable angina 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.

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

Heart Attack: The Most Serious Outcome of Coronary Artery Disease

Heart attack is the most serious outcome of atherosclerosis. It can occur as a result of one or two effects of atherosclerosis:

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

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

Other Manifestations of Coronary Artery Disease

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

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

Silent Ischemia. Some people with severe coronary artery disease do not experience angina pain, 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. Some studies suggest that people with silent ischemia experience higher complication and mortality rates than those with angina pain. (Angina pain may actually protect the heart by conditioning it before a heart attack.)

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

Symptoms

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

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

Heart Attack Symptoms

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

• Pain is typically 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 be tingling or numb.
• Some people may only have a tingling sensation or a sense of fullness, squeezing, or pressure in the chest.
• In some patients with a history of heart disease, chest pain is mild. Such patients may have experienced unexplained fatigue, depression, and ill health within a month of a heart attack.

Of note: Although chest pain is the classic symptom, it occurs in only about half of patients with a heart attack.

Other Common Symptoms. Other common symptoms of a heart attack include the following:

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

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

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

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

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

Symptoms That Are Less Likely to Indicate a Heart Attack. The following are symptoms that are more likely to be due to causes other than a heart event:

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

The presence of these symptoms, however, does not always rule out a serious heart event.

Ruling Out Other Causes of Symptoms

Chest pain is a very common symptom in the emergency room, but heart problems account for only 10% to a third of all episodes. High on the list of other causes of chest pain are the following:

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

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. It should be noted, however, that only 20% of heart attacks occur in patients with long-standing angina. Therefore, anyone who has heart disease or risk factors for it and experiences heart attack symptoms should contact emergency services.

The patient should chew an aspirin (250 to 500 mg)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.

Prognosis

In 2002, an estimated 650,000 Americans will suffer a first heart attack and 450,000 will have a recurrent episode. Currently, half of the men and 63% of the women who died of heart disease had no warning prior to their fatal attacks. The rate of hospitalization for a first heart attack has not changed significantly over the past few years. (In fact, it has increased in women.) On the positive side, however, the heart attack mortality rate has declined by over 24% between 1988 and 1999 (although mostly in middle-age men). (Because of the aging population, however, the absolute number of attacks fell by only about 6.8%)

Predicting the Severity of a Heart Attack

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

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

Although at this time no tests can reliably predict whether another heart attack will occur, experts estimate that up to 30% of fatal attacks and many follow-up surgeries could be avoided with healthy lifestyle changes and adherence to medical treatments. Two-thirds of patients who have suffered a heart attack, however, do not take the necessary steps to prevent another.

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

• Elderly (particularly those who are thinner).
• Women are more likely to die after a heart attack than men. The risk is highest in younger women (although in the younger population, the risk for having heart attack in the first place and then dying from it is very low). It is still unclear why heart attacks are more severe in this group.
• People with a history of heart disease or risk factors for heart disease.
• People with heart failure.
• People with diabetes.
• People on long-term dialysis.

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

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

Risk for Stroke

A heart attack poses a high risk for stroke, which, according to a major 2002 study, is 2.5% in the first six months and 5% per year thereafter. In the study, patients with a higher risk (about 4%) for stroke within six months of a heart attack were older (over age 75), African American, had a history of stroke, atrial fibrillation, hypertension, diabetes, or peripheral artery disease. Most people who fall into these categories have more than one of these risk factors.

Risk Factors

About 12.6 million Americans currently have heart disease and 1.1 million people are expected to have a serious heart event each 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 rates declined in both men and women as they quit smoking and improved dietary habits. This rate, however, has stabilized in recent years, most likely because of the dramatic increase in obesity in the 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.

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 2002 that four million women had angina compared to 2.4 million men. Younger women with heart disease often do not have the same symptoms as their male counterparts and may be less likely to be diagnosed correctly. They are also more likely than men are to die after a heart attack. Evidence suggests that this is because women tend to be older and sicker than men at the time of a first attack. A 2002 study indicated, however, that with early aggressive treatment women with acute coronary syndrome do as well or better than men with the same condition and treatments.

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

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

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 risk discrimination in obtaining optimal treatments, but women may be at particular risk for unequal treatment. In one study in which female actors portrayed heart patients, African American women were 60% less likely to receive aggressive (and expensive) diagnostic tests than African American men or any Caucasians, even though they presented with similar symptoms.
• While African Americans comprise 13% of the 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.

Cholesterol and Other Lipids

Cholesterol. Cholesterol is a white, powdery substance that is found in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many functions. When cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol, particularly low-density lipoprotein (LDL) cholesterol.

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. 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 troublemakers for the heart. Triglycerides appear to interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. Low HDL is known to be harmful to the heart. The harmful imbalance of high triglycerides with low HDL levels is also associated with obesity (particularly around the abdomen), insulin resistance, and diabetes. Some evidence further suggests that high triglycerides pose other dangers, regardless of cholesterol levels. Triglycerides, for example, may be responsible for blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response--the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries.

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

[For more information, see the Well-Connected Reports #23, Cholesteroland #43, Heart Healthy Diet.]

High Blood Pressure

High blood pressure, or hypertension, has long been a proven cause of coronary artery disease. People in normal health should aim for 139/89 mm Hg or less. Patients with certain health problems should aim lower (e.g., blood pressure in patients with kidney insufficiency, heart failure, or diabetes should be equal to or lower than 130/80 mm Hg).

Obesity and Metabolic Syndrome

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

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

Obesity is highly linked with type 2 diabetes, in any case. And diabetes itself poses a significant risk for high cholesterol levels and heart disease.

[For more information, see the Well-Connected 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. Exercise has a number of effects that benefit the heart and circulation, including improving cholesterol and lipid levels, reducing inflammation in the arteries, assisting weight loss programs, and helping to keep blood vessels flexible and open. Studies continue to show that physical activity and avoiding high-fat foods are the two most successful means of reaching and maintaining heart healthy levels of fitness and weight.

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

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

Important warning note: 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. [SeeWell-ConnectedReport #29, Exercise.]

Diabetes and Insulin Resistance

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

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

Diabetics with heart disease may have a higher risk for silent ischemia, a condition in which people have blocked arteries but do not experience the angina, the chest pain that signals heart disease [For more information, seeWell-Connected Reports #9, Diabetes: Type I or #60, Diabetes: Type II.]

Peripheral Artery Disease

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

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. Although heavy cigarette smokers are at greatest risk, a 2002 study suggested that people who smoke as few as three standard brand cigarettes a day are at higher risk for blood vessel abnormalities that endanger the heart. Regular exposure to passive smoke is now estimated to increase the risk of heart disease in the nonsmoker by between 25% and 91%, causing more than 30,000 deaths each year [For more information, see the Well-Connected Report #41 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.

Stress and Psychologic Factors

Stress. The effects of mental stress on heart disease are controversial. Stress can certainly influence the activity of the heart when it activates the sympathetic nervous system (the automatic part of the nervous system that affects many organs, including the heart). This effect may support the association between acute stress and a higher risk for serious cardiac events, such as heart rhythm abnormalities and heart attacks, in people with heart disease. Nevertheless, not all studies report strong evidence that stress has any effect on the heart, particularly in people without any history of heart disease. [SeeWell-ConnectedReport #31, Stress.]

Depression. Depression increases the severity of heart attack and may even impair a patient's response to medication for heart disease. Although people with heart disease may certainly become depressed, this does not explain entirely the link between the two problems. The data are now suggesting that depression itself may be a true risk factor for heart disease as well as its increased severity. A number of studies have suggested that depression has biologic effects on the heart, including blood clotting and heart rate. A study in 2001, for example, reported an association between depression and a greater risk for death from heart problems even in people without a history of heart disease. A 2002 study reported a higher risk for heart failure in women--although not in men--with depression. The more severe the depression, the more dangerous to the health, although even mild depression, including feelings of hopelessness, experienced over many years, may harm the heart, even in people with no early signs of heart disease. [SeeWell-ConnectedReport #8, Depression.]

Alcohol

Benefits of Moderate Drinking. A number of studies have found heart protection from moderate intake alcohol (defined as one or two glasses a day). The benefits reported have been higher HDL levels, blood clot prevention, and anti-inflammatory properties. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit.

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

Note: Alcohol increases the risk for breast cancer in women. Pregnant women and people who can't drink moderately should not drink at all.

Emerging or Possible Risk Factors for Heart Disease

Homocysteine and Vitamin B Deficiencies. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with a higher risk for heart disease in some (but not all) studies. Such deficiencies produce elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Some studies in 2002 suggest that any risk posed by homocysteine or benefits from folic acid for heart disease are at most modest. One study, however, reported lower failure rates after angioplasty in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of affect its on homocysteine.

C-Reactive Protein. C-reactive protein is a product of the inflammatory process and evidence increasingly supports the idea that high levels strongly predict future heart disease. Some studies suggest, in fact, that measuring this protein may be as useful for determining future risk for heart disease as measuring LDL cholesterol levels. It is not known if the protein plays any causal role or whether it is simply a marker for other factors in the disease process More evidence is needed to determine the benefits of measuring C-reactive protein before it gains acceptance as a routine screening tool.

C. pneumoniae and Other 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 strongest evidence to date supports a possible role from Chlamydia (C.) pneumoniae (a non-bacterial organism that causes mild pneumonia in young adults). C. pneumoniae has been detected in plaques in the arteries of patients with heart disease. In some studies, evidence of previous infection has been associated with a higher risk for heart events.

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

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

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

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

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

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 studies 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.

Diagnosis

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

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

Electrocardiogram (ECG)

An electrocardiogram (ECG or EKG) measures and records the electrical activity of the heart. The waves measured by the ECG correspond to the contraction and relaxation pattern of the different parts of the heart. Specific waves seen on an ECG are named with letters 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 ventricular contractions. (The ventricles are two major pumping chambers in the heart.)
• T and U. These waves follow the ventricular contractions.

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

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.

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

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

• Stable Angina (blood test results or other tests show no serious problems and chest pain resolves). Most patients with angina can go home. (It should be noted that between 25% and 50% of people who suffer from angina or have silent ischemia have normal ECG readings.)
• Acute Coronary Syndrome (ACS). This includes severe and sudden heart conditions that require aggressive treatment but have not developed into a full-blown heart attack. ACS, refers to either unstable angina or NSTEMI (non ST-segment elevation myocardial infarction)--also referred to as non Q-wave myocardial infarction. Unstable angina is potentially serious and chest pain is persistent, but blood tests do not show markers for heart attack. With NSTEMI, the blood tests suggest a developing heart attack, but most likely, injury in the arteries is less serious than with a full-blown heart attack.

Exercise Stress Test

The primary value of exercise stress tests is not to detect coronary artery disease in people without symptoms but to help determine the severity and predict the outcome of an existing heart condition. It is considered for the following people:

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

Basic Procedure. A stress test (exercise tolerance test) monitors the patient's heart rhythms, blood pressure, and clinical status. It can tell how well the heart handles work and if parts of the heart have decreased blood supply. A typical stress test involves the 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, until symptoms of heart trouble occur (e.g., changes in blood pressure, heart rhythm abnormalities, angina, fatigue) or the patient simply wants to stop.
• For patients who cannot exercise, the physician may administer dobutamine or arbutamine, which are agents that simulate the stress of exercise.
• An ECG is used to monitor heart rhythms during a stress test. (An echocardiogram or more advanced imaging technique may also be used to visualize the actions of the heart and blood flow.)

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

[For more information on this test, see the Well-Connected Report #3 Coronary Artery Disease and Angina.]

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:

• To diagnose or determine the severity of unstable angina when less expensive diagnostic approaches are unavailable or unreliable.
• To determine 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 typically used with an exercise stress test to determine blood flow to the heart muscles. It is a reliable measure of severe heart events and may prove to be cost effective in identifying patients at low risk for a heart attack. About a minute before the patient is ready to stop exercising, the physician administers thallium 201 (or more often now, sestamibi), 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. 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.

Advanced Noninvasive Imaging Techniques

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

Click the icon to see an image of a MRI.

Computed Tomography (CT) Scans.Computed tomography (CT) scans used alone or with ECG may be used to detect calcium deposits on the arterial walls, strong indicators of current and future coronary artery disease. In fact, the absence of calcification in the arteries suggests virtually no risk at all for heart disease. (It should be noted that the presence of calcium does not always signify significant narrowing in the arteries.) Advanced CT techniques, such as electron beam computed tomography (EBCT) and helical multislice computed tomography (MSCT) are improving accuracy.

Some experts groups recommend them in selected patients who have an intermediate risk (i.e., a 10% to 20% chance of heart disease within 10 years). In general, the use of these expensive imaging tests are probably not very useful in people at low- or high risk people.

Angiography

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

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

Click the icon to see an image of cardiac catheterization.

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

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

Biologic Markers

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

• Troponins. The proteins cardiac troponin T and I are released when the heart muscle is damaged. Both are proving to be among the best diagnostic indications of heart attacks. They are proving to identify many individuals with ACS, such as older women with serious other conditions, who might otherwise been misdiagnosed.
• Creatine kinase myocardial band (CK-MB). CK-MB has been a standard marker but the MB fraction is not as accurate as troponin levels, since elevated levels can appear in people without heart injury.
• Myoglobin. Myoglobin is a protein found in heart muscles. It is released early in the injured heart and it may be useful in combination with CK-MB and the troponins.
• Other markers are proving to be helpful in identifying heart problems but are not routinely measured at this time except in clinical studies. They include fibrinogen (a protein involved in blood clotting) and C-reactive protein (a product of the inflammatory process). For example, persistently high levels of C-reactive protein in patients with unstable angina may be strong indicators of a future heart attack.

Treatment

Patients with heart disease or those with risk factors should seek emergency medical help immediately if they have any signs or symptoms of an attack. Early treatment is critical for recovery.

When a patient arrives at the hospital with a possible heart attack the patient is given an electrocardiogram within 10 minutes and put on constant monitoring. Blood and other tests are taken to determine the condition.

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

Patients who are diagnosed with acute coronary syndrome (ACS) may be at risk for a full-flown heart attack. ACS refers to either unstable angina or NSTEMI (non ST-segment elevation myocardial infarction). Unstable angina is potentially serious and chest pain is persistent, but blood tests do not show markers for heart attack. With NSTEMI, the blood tests suggest a developing heart attack, but most likely, injury in the arteries is less serious than with a full-blown heart attack.

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

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

Immediate Treatments to Support the Patient

Early supportive treatments are similar for both ACS and heart attack patients.

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

Transfusions. A 2001 study suggested that giving transfusions to elderly heart attack patients with even mild anemia improved short-term survival rates.

Medications for Relieving Symptoms.

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

Anti-Clotting Medications. Appropriate anti-clotting medications are started immediately in all patients.

• Aspirin is given immediately unless the patient had taken aspirin before entering the hospital. It is continued afterward indefinitely.
• Clopidogrel (a more potent anti-platelet agent) is usually added and continued for one to nine months afterward. It is sometimes used in place of aspirin.
• Heparin is generally administered to moderate to high-risk patients. Low-molecular weight heparin (LMWH), such as enoxaparin, is now recommended over standard heparin.
• Glycoprotein IIb/IIIa inhibitors, most often tirofiban, are added for patients undergoing angioplasty. Some studies also suggest that they might be beneficial in some nonsurgical patients with ACS, notably NSTEMI (non ST-segment elevation myocardial infarction).

Opening the Arteries: Thrombolytic Drugs or Emergency Angioplasty (PTCA)

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

The standard medical and surgical solutions for opening arteries are the following.

• Angioplasty, also called percutaneous transluminal coronary angioplasty (PTCA), is the major surgical procedure for opening the arteries.
• Thrombolytics are known as blood-clot-busting drugs and are the standard medications used to open the arteries. They are administered as soon as possible in centers where angioplasty is not available or in patients who are not good candidates for angioplasty.

Some studies suggest that a combination of early administration of a thrombolytic followed by angioplasty may have significant benefits for many patients, but such an approach is not routine.

The best candidates for either thrombolytic therapy or angioplasty are the following:

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

Specific Candidates for Emergency Angioplasty. If it is available, most patients--both men and women--who meet the criteria for either thrombolytic drugs or angioplasty would do better with angioplasty (although only in centers equipped to do this procedure). In fact, in a 2002 study, survival rates at one year were better in women who had had angioplasty than in men. Of concern, however, was another 2002 study reporting that angioplasty rates were 7% lower in women than in men. African Americans--both men and women--were also less likely to be given angioplasty than Caucasian men. These groups are slightly more likely to refuse the procedure than Caucasian men, but this does not explain the wide discrepancy. The reasons for these lower rates require investigation.

Other specific candidates who might be good candidates for angioplasty include the following:

• Elderly patients--even those over 75-- who meet the criteria for both approaches tend to do better with angioplasty than thrombolytic therapy.
• Patients with diabetes who meet the criteria for both approaches.
• Patients under age 75 who go into shock and when angioplasty can be performed within 18 hours of shock. (There is no advantage for patients over 75 who are in shock.)
• There is some evidence to suggest that patients with heart failure may do better with angioplasty than with thrombolytics, but more studies are needed to determine this.

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

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

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

The use of thrombolytics in the following patients should be avoided or used with great caution:

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

Thrombolytics should not be used in the following patients:

• Patients who have experienced any recent major bleeding.
• Patients with depressed ST segments.
• Patients with a history of stroke. (Selected patients whose strokes occurred far in the past may be able to benefit from these drugs, but more research is needed to confirm this.)
• Patients with uncontrolled high blood pressure.

Other Heart Supportive Agents

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

• Beta-blockers reduce the oxygen demand of the heart by slowing the heart rate and lowering arterial pressure. Intravenous administration of beta-blockers (metoprolol or esmolol) within the first few hours of a heart attack can reduce the destruction of heart tissue. Oral agents may be sufficient for some patients with unstable angina.
• Angiotensin converting enzyme (ACE) inhibitors should be given on the first day to all patients, unless there are medical reasons for not taking them.
• Calcium channel blockers may provide relief in patients with unstable angina whose symptoms do not respond to nitrates and beta blockers. They are also useful for patients with Prinzmetal's angina.
• Statins. Statins are important cholesterol lowering agents that are beneficial for heart attack patients and may have heart-protective properties that go beyond lowering cholesterol. Of interest, however, was a 2003 study suggesting that cholesterol levels--whether high or low--had no effect on mortality rates among heart attack survivors over 65. More research is needed.
• Atropine. Atropine may be given for a very low heart rate (bradycardia) or signs of atrioventricular (AV) block, in which electric conduction of nerve impulses to specialized muscles in the heart is slowed or interrupted.

Treatment for Patients in Shock or with Congestive Heart Failure

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

Heart failure. Intravenous furosemide may be administered. Patients may also be given nitrates, and ACE inhibitors, unless they have a severe drop in blood pressure or other conditions that preclude them. Clot-busting drugs or angioplasty may be appropriate and life-saving in many of these patients, although they are less likely to be given these treatments. (A 2003 study suggested that drugs may be more beneficial in this group, but more research is needed to confirm this.)

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

Treatment of Arrhythmias

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

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

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

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

Treating Ventricular Fibrillation.

• Defibrillators. Patients who develop ventricular arrhythmias are given electrical shocks with defibrillators to restore normal rhythms. Some studies suggest that implantable cardioverter-defibrillators may prevent further arrhythmias in heart attack survivors of these events who are at risk for further arrhythmias. At this time, however, their use is investigative in these patients.
• Antiarrhythmic Agents. Antiarrhythmic drugs include lidocaine, procainamide, or amiodarone. Amiodarone or another antiarrhythmic drug may be used afterward to prevent future events.

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

Medications

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

Specific Thrombolytics

The standard thrombolytic drugs used are recombinant tissue plasminogen activators or rt-PAs. They include alteplase (Activase and reteplase (Retavase)). Both are similar in effectiveness, although reteplase is easier to administer. Tenectaplase (TNKase), a newer agent, can be delivered more rapidly than alteplase, and to date, survival rates are similar. Streptokinase (Kabikinase, Streptase) is sometimes used but is somewhat less effective that the others. Other agents include anistreplase (Eminase) and urokinase (Abbokinase)--not available in the U.S.

Thrombolytic Administration

The earlier thrombolytic drugs are administered, the better. The advantages of thrombolytics are highest in the first 90 minutes and are still considerable at three hours. Administering these drugs more than 6 hours after symptoms have started adds little or no benefit. Of interest, some of these agents can now be given by emergency medical technicians (EMTs) before the patient reaches the hospital. Whether this will improve survival compared to angioplasty or other blood-thinning approaches, is not yet clear.

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

Other anti-clotting agents are being tested in combination with thrombolytic agents. For example, studies are reporting modest improvements with the addition of glycoprotein IIb/IIIa receptor antagonists to low-dose thrombolytics.

Complications

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

Surgery

Percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery, known as revascularization procedures, are the standard operations for opening narrowed or blocked arteries.

• Emergency angioplasty is the standard procedure for heart attack patients and more effective than the use of thrombolytic agents for most patients. Unfortunately, not all communities have the facilities for emergency angioplasty. (A 2002 study suggested that in spite of the delay, transporting patients to facilities where angioplasties are available may still be more beneficial than thrombolytics for many individuals.)
• Coronary bypass surgery is typically used as elective surgery for patients with blocked arteries. It may be used after a heart attack if angioplasty or thrombolytics fail or are not appropriate. It is usually not performed for a few days to allow recovery of the heart muscles.

Such procedures are proving to be very important for many patients.

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

Angioplasty (PTCA) 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:

Click the icon to see an image of an angioplasty.

• 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 most often 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. (Stents are being investigated as the initial opening device instead of balloon angioplasty, but benefits are not clear.)
• Once in place, the stent pushes against the wall of the artery to keep it open. Stenting is improving outcome in patients with heart attack who have emergency angioplasty. It also significantly prevents reclosure and reduces heart attack rates in patients with ACS. A 2002 study reported that their safety and effectiveness was sustained for seven to 11 years.

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 best in hospital settings with experienced teams and backup. According to a 2003 study, outcomes are also better if the procedure is done during routine working hours. It is not know if sleep deprivation in the medical professionals or increased clotting factors during the night are responsible for these differences.

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.

Prevention of Restenosis. 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. Of great interest and promise are studies that show no restenosis in patients who have received stents that were coated with the drug sirolimus. [For more information, see the Well-Connected Report #3 Coronary Artery Disease and Angina.]

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

Coronary Artery Bypass Graft Surgery (CABG)

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

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

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

Other Treatments

In addition to thrombolytics, a number of agents are now available for use during a heart attack and for treating acute coronary syndrome. Some of these and other medications are also important for preventing either a first or a second heart attack.

Aspirin and Other 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 with angioplasty and stent placement. They are proving to be helpful for ACS patients with NSTEMI (non ST-segment elevation myocardial infarction) .
• Thienopyrindines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are potent oral platelet inhibitors.

Anticoagulants. Anticoagulants help thin blood and include the following:

• Heparin. Standard, or unfractionated, heparin. Low-molecular weight heparin (LMWH), which include Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep).
• Warfarin (Coumadin).
• Direct thrombin inhibitors. They include argatroban (Novastan), danaproid (Orgaran), and lepirudin (Refludan)

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

• The physician usually gives the patient heparin or aspirin, either alone or in combination with thrombolytic therapy. Aspirin should be given immediately, and heparin is usually started during or at the end of the thrombolytic infusion.
• Other agents, such as glycoprotein IIb/IIIa receptor antagonists, are being tested in combination with thrombolytic agents.

All these drugs pose a risk for bleeding.

Beta-Blockers

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

Administration During a Heart Attack. Intravenous administration of beta-blockers (metoprolol or esmolol) within the first few hours of a heart attack can reduce the destruction of heart tissue. Evidence strongly supports a lower incidence of complications and better survival rates after a heart attack in patients who had been treated with a beta-blocker. In spite of this evidence, beta blockers are greatly underutilized. In one major New York center, for example, 72% of patients who could have benefited from them were not given these important agents after a heart attack.

Prevention After a Heart Attack. Beta-blockers are also important after a heart attack in preventing another heart attack. In fact, among elderly heart attack patients, those who do not use these agents afterward have a much poorer outcome.

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. Dizziness and lightheadedness, especially when getting up from a lying down position.

Other side effects may include cold extremities, asthma, decreased heart function, gastrointestinal problems (e.g., heartburn, gas, diarrhea, or constipation), and sexual dysfunction.

Because they can narrow bronchial airways and constrict blood vessels, patients with asthma, emphysema, and chronic bronchitis should avoid them whenever possible. They should not be used by patients with severe heart failure or severe AV block.

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

In 2002, The National Cholesterol Education Program's Adult Treatment Panel issued its latest recommendations. The results of these guidelines would increase the number of Americans taking LDL-lowering agents from 15 million to 36 million, with significant increases occurring in people under 45 and over 65 years old and among men in all age groups. A number of agents are available for lowering cholesterol and other dangerous fat molecules (lipids). They include the following:

• Statins are now the standard agents for most people who require LDL-lowering therapy. Bile-acid binding resins or niacin may be considered. (Another LDL-lowering agent, probucol, is usually limited to people with genetic disorders that cause severely high cholesterol levels.) If LDL-goals are not achieved, combinations of a statin with a bile-acid resin such ezetimibe (Zetia) or niacin should be considered.
• Fibrates or niacin are beneficial for people who need to lower triglycerides and increase HDL.

[For more detailed information on other cholesterol-lowering agents and cholesterol in general see the Well-Connected Report, Cholesterol, Other Lipids, and Lipoproteins.]

Statins. Statins inhibit the liver enzyme HMG-CoA reductase, which is used in the manufacturing of cholesterol. They are the most effective drugs for the treatment of high cholesterol, and, according to a 2003 major analysis of over 200 studies, they reduce risk for heart events by 60% and stroke by 17%.

Two studies in 2002 and 2003, however, muddied these positive findings. In one, lowering moderately-high LDL cholesterol levels with a statin did not improve survival rates among high-risk patients. Some experts believe that statin treatment was not aggressive enough in this study. In the other 2003 study, however, cholesterol levels--whether high or low--had no effect on mortality rates among heart attack survivors over 65. More research is needed on these findings.

Still, most experts estimate a 25% or more reduction in mortality rates when patients take statins after a heart attack. They may even become important agents for many people at risk for heart disease who have normal cholesterol levels or below. In fact, the benefits of statins may go beyond simply improving cholesterol levels.

Statins include lovastatin (Mevacor), simvastatin (Zocor), and pravastatin (Pravachol). These are the most studied statins and have proven effectiveness and good safety record. Newer synthetic statins including fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor) are proving to be very beneficial.

In many studies the side effects reported by statin users were nearly the same as those taking placebos (inactive agents). Those reported include gastrointestinal discomfort, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. Severe cases of myopathy warrant discontinuation. Patients should tell their physicians about any unusual muscle discomfort or weakness and if their urine becomes brown-colored.

Statins also can effect the liver, particularly at higher doses, so periodic liver function tests should be administered.

Angiotensin Converting Enzyme Inhibitors

Angiotensin converting enzyme (ACE) inhibitors are important agents after a heart attack, particularly in patients at risk for heart failure. Taking an ACE inhibitor at the onset of a heart attack may, in fact, reduce the damage. These agents are commonly used to treat hypertension and are recommended as first-line treatment for people with diabetes and kidney damage, for some heart attack survivors, and for patients with heart failure.

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

Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. Of great concern is research suggesting that aspirin interferes with ACE inhibitors (and other so-called NSAIDs) and increases the risk for heart failure in patients taking ACE inhibitors. An encouraging 2003 analysis, however, reported that ACE inhibitors still significantly reduced risks for adverse heart events, including hospitalizations for heart failure, regardless of whether or not the patients were also taking aspirin.

Magnesium

Magnesium has blood-thinning properties and may help open blood vessels. It is important to correct any magnesium deficiencies in heart attack patients (such as those who were on diuretics). For certain patients who cannot be given thrombolytic therapy, intravenous magnesium has been investigated. The most recent evidence suggests, however, that it offers no significant benefits for patients with heart attack.

Infection-Fighting Agents

Flu Shots. One study reported that influenza vaccinations might protect heart attack patients against another attack during flu season. And a 2002 study reported that flu shots given to patients who had angioplasty were associated with a significantly lower risk for death from heart events.

Antibiotics. Researchers have been investigating antibiotics for treating patients with heart disease and past infection of Chlamydia pneumoniae or H. pylori. Results have been mixed. In one large 2002 study, patients with heart attack or ACS were treated with amoxicillin or azithromycin, two common antibiotics, for a week. A year later they had a 40% lower risk for adverse heart events than those not given antibiotics--regardless of whether they had evidence of infection. Other small studies have also been positive. Some experts believe the protection from of antibiotics may be due to inflammatory effects--rather than anti-bacterial. Of note, some studies have found no protection for the heart from antibiotics.

Rehabilitation

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

Physical Activity and Rehabilitation

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

• Leg exercises may start as early as the first day. The patient usually sits in a chair on the second day, and begins to walk on the second or third day.
• Most patients undergo low-level exercise tolerance tests early in their recovery. One study suggests that exercise testing within three days after a relatively minor attack may allow patients to go home earlier.
• After eight to 12 weeks, many patients, even those with heart failure, benefit from supervised exercise programs. Health professionals should provide the patient with schedules for low-level aerobic home-activity. Strength (resistance) training is also important. (Tai Chi, a Chinese martial art, appears to be very beneficial and safe for people after a heart attack.) It should be noted that the risk for serious heart events during rehabilitation is very low. In one survey, cardiac arrest was 1 per 112,000 patient-hours and nonfatal heart attack rates were 1 per 294,000 patient-hours.

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

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

Emotional Rehabilitation

Major depression affects between 15% and 23% of patients with ACS and heart attacks. Many studies are showing that depression is a major predictor for increased mortality in both women and men. Depressed patients are less likely to comply with their heart medications. Although it is not clear if treating depression has any effect on survival. Psychotherapeutic techniques, especially cognitive behavioral therapies, are very helpful.

Physicians have been reluctant to prescribe antidepressants after ACS or a heart attack, however, because older forms have adverse effects on the heart. Studies on sertraline (Zoloft), one of the selective serotonin reuptake inhibitor (SSRI) antidepressants, however, have not reported harmful effects for heart attack patients. It is not yet clear, if other SSRIs are equally safe and effective.

Resources

• www.nhlbi.nih.gov/nhlbi/nhlbi.htm -- National Heart, Lung, and Blood Institute
• www.acc.org -- American College of Cardiology (800-253-4636)
• www.americanheart.org -- American Heart Association (800-AHA-USA1)
• www.medicalert.org -- Medic Alert (888-633-4298)
• www.americanheart.org -- American Heart Association
• www.heartriskevaluations.com -- Heart risk evaluation
• www.thrombosisconnect.com -- Heart attack treatment