Coronary artery disease (CAD)-obstruction or narrowing of the arteries supplying blood flow to the heart- and its complications remain the most common cause of disability and death in the United States and Western Europe. In the US, CAD claims more lives each year than the next 7 leading causes of death combined. The major complications of CAD are chest pains (angina pectoris), myocardial infarction ("heart attacks"), congestive heart failure, and sudden cardiac death.
Atherosclerosis (hardening of the arteries) very often affects the coronary arteries that supply nourishing blood flow to the heart muscle. The word atherosclerosis is derived from the Greek athero (gruel) and sclerosis (hardening). The lesions or "plaques" within the artery walls consist of localized deposits of fat compounds (lipids) surrounded by cells recruited from the blood stream and scar tissue. Cholesterol is the major lipid found in plaques. Lipids in the artery wall act as irritants. Some plaques are mechanically unstable, and like abscesses, may rupture and expose their contents to the streaming blood. In response to the irritation, white blood cells and platelets are summoned to the scene. White blood cells produce chemicals that cause inflammation just as they would if they were battling an infection. These chemicals promote blood clotting and the formation of scar tissue. Blood clots therefore tend to form at the site of the plaque. Because plaque substances are very potent in causing blood to clot, the ruptured plaques are often covered by clotted blood. As the blood clot grows, it may critically reduce the diameter of the artery so that blood flow is decreased or even stopped. Deprival of blood flow to the cells downstream is known as ischemia (literally "withheld blood"). When ischemia becomes severe enough, the survival of heart muscle cells is endangered and myocardial infarction can result. Even if blood flow is not reduced enough to kill the cells, it may be insufficient to allow the cells to carry on normal activity.
CAD, even when severe, may produce no or few symptoms. In many patients, the first symptom of CAD may represent two catastrophic events - sudden death or a heart attack. In other patients, reduced blood flow or ischemia may cause episodic chest pressure or pain, a symptom signaling the presence of CAD.
CAD is a multifactorial disease where genetic and environmental factors interact in complex ways to cause the disease to progress. The incidence and mortality of CAD increase with age, but the development of CAD is not a simply a result of the aging process. Studies of large populations have identified several characteristics that are associated with increased probability of developing CAD. These "risk factors" include elevated blood cholesterol, high blood pressure, diabetes, obesity, cigarette smoking, and family history of CAD. The sex difference in the incidence and severity of CAD reflects the fact that female hormone (estrogen) has protective effects against CAD and that the male hormone (testosterone) has aggravating effects on CAD progression. The mortality rate for males is 5 times greater than that for females at ages 35-44, but after menopause the mortality rate in females approaches that for age matched males. The risk of cardiac disease in any individual rises substantially when two or more risk factors are present.
Cholesterol and triglycerides are transported in the bloodstream as particles (lipoproteins) in which the lipids are bound to specific proteins. Cholesterol is an essential component of cell membranes and it is the precursor of vital steroid hormones such as cortisone and estrogen. Triglycerides contain fatty acids, a major source of energy for muscles and other organs. Increased dietary fat loads and decreased disposal of lipids due to genetic defects or inactivity can lead to the accumulation of triglyceride- and cholesterol-rich lipoproteins in blood and artery walls. These accumulations are responsible for initiating atherosclerosis and CAD.
It has been estimated that severe genetic defects for handling of lipoproteins occur in at least one out of 500 people in the US. Genetic defects in the handling of lipoproteins become particularly serious when "bad genes" are inherited from both parents. However, many more people in the US are thought to have less severe but still important inherited abnormalities in the handling of lipids. Minor genetic abnormalities of lipoprotein metabolism (dyslipidemia) can be demonstrated in most persons that eat a typical American diet and exhibit elevated blood lipids. Genetic abnormalities of lipid metabolism are often linked with genetic abnormalities producing high blood pressure. As many as 60% of persons with high blood lipids also suffer from high blood pressure. Insulin resistance (sometimes significant enough to cause diabetes) has also been associated with genetic abnormalities of lipid metabolism.
The characterization of abnormal lipid metabolism that may increase atherosclerosis requires blood testing beyond simple measurements of cholesterol levels. However, identification of increased risk can often be made with relatively simple blood testing for cholesterol and triglycerides. There is general agreement that both "bad" (LDL) cholesterol and "good" (HDL) cholesterol should be screened routinely. The extent to which screening should include detailed characterizations of blood lipids has been controversial.
Modern lifestyles in industrialized countries have contributed to increased atherosclerosis. Diets high in fat and low levels of exercise work together to cause fat deposition in the body. In many such individuals, exercise and reduction in fat intake may suffice to reduce blood lipids to acceptable levels. However, for persons unable to change their lifestyle and for those suffering from severe genetic defects in lipoprotein metabolism, medications are necessary to prevent high blood lipids and their consequences.
Hypertension is usually defined as blood pressure greater than 140/90 mmHg. Hypertension accelerates the development of CAD and increases the workload of the heart. The presence of hypertension more than doubles the CAD risk at any given level of cholesterol. As noted elsewhere, hypertension is often found to coexist with other CAD risk factors. Effective drugs exist to lower elevated blood pressure. However, lowering the blood pressure may not by itself halt the atherosclerotic process since other associated abnormalities, in particular dyslipidemia, obesity, and diabetes, so frequently accompany hypertension.
The combination of heightened energy demand and limited energy supply due to CAD has adverse effects on the heart muscle and may represent the major mechanism of chronic heart failure. Beside its effects on the heart, uncontrolled hypertension is also associated with increased risk of stroke, aortic aneurysm formation, and kidney failure.
Diabetics have two times the incidence of CAD as nondiabetics, and CAD is the leading cause of death among adult diabetics. The metabolic interactions between high blood lipids, hypertension, and abnormal insulin function (insulin resistance and hyperinsulinism) are very complex and beyond the scope of this text.
Most diabetics in the US suffer from type II diabetes mellitus, a disorder in which the body continues to produce insulin but in amounts insufficient to control the blood sugar. Insulin resistance-failure of the body to respond normally to insulin-is the factor most responsible for the development of overt diabetes. In response to insulin resistance, the body overproduces insulin. Beside controlling the blood sugar, insulin may act as a growth factor for cells in the blood vessels, causing them to grow inappropriately. High blood glucose levels cause glucose to attach to proteins in the blood (including lipoproteins) in the blood vessels, changing the structure of the molecules and altering the way they function.
Controlling diabetes is an important part of controlling the progression of CAD. Mortality from CAD is elevated in patients with poor diabetes control, and good control of diabetes appears to decrease the CAD mortality of the diabetic patient back to the level of nondiabetic patients. Management of diabetes includes careful attention to diet, regular exercise, and drug therapy. Some drugs (the sulfonylurea compounds) have been suggested to cause increases in the risk of myocardial infarction, but why this may occur is not clear. Control of diabetes also improves the lipid profile of diabetic patients.
The number of overweight and obese people is rising worldwide in industrialized countries. Obesity is on the verge of becoming the leading modifiable risk factor for illness and death in the US. As noted above, obesity is associated with the development of hypertension, diabetes, insulin resistance, and hyperlipidemia.
Control of obesity involves decreasing caloric intake and increasing energy expenditure. Low fat diets alone are seldom successful in controlling obesity since the patient often increases caloric intake from lower fat foods to compensate for the hunger feelings that often persist when fat intake is decreased. Decreasing caloric intake requires decreasing the intake of all foods. Increasing energy expenditure is also very important in the management of obesity. Activities as simple as walking increase caloric expenditure and build muscle mass, which in turn increase energy expenditure further. Exercise can also help suppress appetite.
Control of obesity is a lifelong activity for most people. Eating habits must be watched constantly, and exercise should be continued. Support of family and friends is very important in weight control.
The risk of death from CAD is up to 6 times higher in smokers than in nonsmokers. Smoking acts by adversely altering the lipid profile and by enhancing the inflammatory response to high blood lipids, leading to blood clot formation in the arteries. Smoking also increases levels of stress hormones and increases platelet adhesiveness. These effects combine to increase markedly the likelihood of arrhythmias and heart attacks.
The risk of CAD increases with the number of cigarettes smoked. Filtered cigarettes, which result in delivery of decreased amounts of tar and nicotine, have not proven to be beneficial in decreasing the risk of CAD. Stopping smoking decreases the risk myocardial infarction and of death from CAD up to 50% in the first few years after smoking cessation. The risk of CAD never decreases to that of nonsmokers, however.
Many risk factors can be modified by changes in lifestyle or drug interventions. Correction of risk factors is important even in the absence of any symptoms. Severe complications of CAD including sudden cardiac death occur often without any warning symptoms. Individuals with known risk factors, especially young persons with a family history of premature heart disease, require aggressive risk factor management.
Risk factor interventions include altered lifestyle such a diet (reduced fat and salt) and regular exercise. Drug therapy is recommended when lifestyle interventions are insufficient or unsuccessful. Remarkably effective drug regimes have become available to correct high blood pressure and high cholesterol levels. These include the so-called "statins" (HMGCoA - reductase inhibitors) to lower cholesterol and beta blockers and ACE - inhibitors (angiotensin converting enzyme inhibitors) to lower blood pressure. Aspirin, a drug that suppresses blood clot formation, has been shown to reduce the risk of heart attacks and prolong life expectancy. Estrogen replacement therapy may be effective in reducing post-menopausal CAD progression. In the future, it is hoped that specific genetic defects will be cured by gene therapy.
In persons sustaining an acute heart attack, blood clots that block blood flow can be opened with blood-clot dissolving drugs (thrombolytic agents or "clot busters") or by advancing a balloon catheter and dilating the artery at the site of the blockage. These therapies have markedly reduced deaths from heart attacks but must be used as soon after the onset of the symptoms as possible to be very effective. Drug therapy with beta blockers and ACE inhibitors has also been shown to decrease he damage caused by acute myocardial infarctions.
In persons suffering from chronic symptoms of limited blood flow to the heart, such as chest pains on exertion, narrowed artery segments can often be dilated with balloon catheters. If the blockages occur in critical locations or in several arteries simultaneously, surgeons can often place artery grafts that bypass the aterial narrowing.
In individuals whose first manifestation of CAD is ventricular arrhythmias, treatment with balloon catheters (angioplasty) and coronary bypass surgery may not reduce the risk of sudden arrhythmic death. These patients require specific anti-arrhythmic treatments.