Atherosclerotic Coronary-Artery Disease

Atherosclerosis does not uniformly affect the arterial intima but is localized, involving small foci inside the arteries. It is only when the localized lesions become large enough to interfere with the flow of blood that atherosclerosis produces serious consequences. Coronary arteries are the most vulnerable to lesions restricting blood flow because the heart has the highest rate of using and extracting oxygen from the blood and is very sensitive to its lack. Furthermore, coronary arteries do not have significant interconnections between their branches to offer alternate routes of blood supply when obstruction develops. Atherosclerosis causes a variety of lesions inside coronary arteries; from the standpoint of heart disease,

however, the most important lesion is the atherosclerotic plaque , a small blisterlike protrusion of the intima into the lumen (cavity) of the artery, which can produce stenosis.

The atherosclerotic plaque consists of firm fibrous tissue surrounding a softer center containing fatty substances, cholesterol crystals, and other debris. A plaque in a coronary artery does not significantly interfere with blood flow until the obstruction reaches at least 60 percent of the lumen. The development of a plaque of sufficient size to interfere with blood flow is a slow process, usually taking many years. When the plaque begins to affect blood flow, large collateral channels connecting the branches of the affected artery with those of other coronary arteries may start to develop, thereby supplying the needed blood. The normal interconnections between healthy coronary arteries are tiny branches capable of supplying only minute quantities of blood to the occluded artery in an emergency. However, the gradual progression of coronary stenosis stimulates growth of these collateral interconnections, which often become large enough to take over the entire blood supply from a completely occluded artery. Thus nature may provide a bypass to a stenosed or occluded coronary artery.

The most serious consequences of coronary atherosclerosis are produced by certain complications of this process. These are

rupture of a plaque

hemorrhage into the wall of an artery

formation of a thrombus inside an artery

Each of these complications increases abruptly the degree of stenosis, which usually results in a significant progression of symptoms and other consequences of coronary disease.

In rupture of a plaque (referred to as a "coronary accident"), much as in rupture of an abscess, the fibrous covering splits, permitting its soft contents to spill into the artery. In response, white blood cells and platelets immediately aggregate at the point of rupture to repair the damage. This process not only increases the stenosis but may also stimulate the formation of a thrombus, which could further reduce the lumen of the affected artery or close it off completely. The effect of this kind of accident on the heart depends on how much increase in stenosis has taken place and on whether

compensatory collateral arteries are available. Hemorrhage into the arterial wall (subintimal hemorrhage ) can also suddenly increase the degree of stenosis, although its effects are seldom as dramatic as those of rupture of a plaque. Thrombus formation inside a coronary artery, though a common sequel to plaque rupture, may also occur without it, stimulated by an area of damage in the intima. Coronary thrombosis is the principal cause of myocardial infarction.

The cause of atherosclerosis is not definitely known. Among theories dealing with the initiation of the atherosclerotic process the most widely accepted is the injury hypothesis, which suggests that a localized injury to the intima of a coronary artery is the point of origin of atherosclerotic lesions. It is well recognized that the early stages of atherosclerosis may develop even in adolescents and children. Yellow fatty streaks, the visible precursors of atherosclerotic plaques, are frequently found in arteries of healthy young adults. Local injury to the intima may attract fatty substances, which are then deposited there, initiating a rather complex process leading eventually to large, clinically significant plaques.

Atherosclerotic coronary-artery disease is not distributed evenly around the globe. Its incidence in the developing nations is much lower than in developed countries; in some tribes of Africa it is virtually nonexistent. A major reason for this difference is the amount and type of fatty substances in the diet. Diets rich in foods containing saturated fatty acids and cholesterol, such as prevail in most Western nations, enhance the development of coronary disease.

The principal building block of atherosclerotic plaques is cholesterol—a ubiquitous substance, important in all cell structures, which in combination with proteins is transported in the bloodstream as lipoprotein . Among the various types of lipoproteins two play important roles in the development of coronary atherosclerosis: low-density lipoproteins (LDLs), which transport most of the cholesterol and tend to deposit it in arterial lesions, and high-density lipoproteins (HDLs), which are capable of removing cholesterol from injured arterial walls and transporting it to the liver for use in forming bile.

The relationship between the amount of cholesterol circulating in the blood (serum cholesterol) and coronary-artery disease is well

documented, and the level of serum cholesterol is used as a predictor of coronary disease. That level in the Western population ranges between 150 and 300 mg per 100 milliliters of serum (mg percent). Serum cholesterol is greatly influenced by the amount of saturated fat and cholesterol in the ingested food, although the varying ability of persons to metabolize fatty substances plays an important role as well. The present view is that a desirable level of serum cholesterol in adults is less than 200 mg percent, and a level above 240 mg percent is too high and may require intervention to reduce it. Whereas total serum cholesterol is the widely used risk factor, it is now generally accepted that LDLs ("bad cholesterol") are implicated in atherosclerotic plaque formation, whereas the HDLs ("good cholesterol") inhibit plaque formation. Higher ranges of serum cholesterol may reflect a high-fat diet or inefficient fat metabolism. In one disease, familial hyperlipidemia (it is usually hereditary), grossly abnormal metabolism of fatty substances may raise serum cholesterol as high as 1000 mg percent. There are several varieties of this metabolic disorder, most of which are associated with premature and severe coronary-artery disease.

Triglycerides , another group of chemical substances transported with lipoproteins, are also considered predictors of coronary-artery disease if serum levels are abnormally high, although this relationship is not as clear as that involving LDL cholesterol.

The atherosclerotic process affects men more often than it affects women. It is thought to be stimulated or retarded by the presence or absence of certain risk factors. Inasmuch as the relationship between risk factors and coronary-artery disease is based on statistics rather than direct observation, the importance of these risk factors is not always clear-cut and is the subject of controversy. Risk factors that can be influenced by therapy are of particular importance since their reduction may arrest the progress of atherosclerosis or even cause its regression. Others merely identify subjects at higher-than-average risk of heart attacks.

The three risk factors accepted by most experts as central to address in preventive treatment of atherosclerosis are hypercholesterolemia (high serum cholesterol), smoking, and hypertension (high blood pressure). Risk factors whose role is less established or is questionable include stress, obesity, sedentary habits, diabetes, and the so-called coronary-prone personality. Risk factors that cannot

be altered by treatment include male sex and a family history of heart attacks early in life.

Risk factors for coronary-artery disease should be addressed whenever possible by prophylactic treatment. The most aggressive and widely accepted treatment is aimed at reducing serum cholesterol. It includes two strategies—primary prevention, directed at the entire population of a given area, and secondary prevention, directed at patients who have had heart attacks or have shown other manifestations of the disease.

Primary prevention involves modifying one's diet. Since dietary restrictions may affect quality of life, primary prevention of coronary-artery disease focuses on the least disruptive adjustments in dietary habits. A healthy diet for children and adolescents, if followed by a large segment of that population, could have a significant impact on the future prevalence of coronary-artery disease. Stronger measures, such as drug therapy, are generally indicated only in persons with significant hypercholesterolemia.

Secondary prevention requires a more aggressive approach, including a stricter diet and, if indicated, drug therapy. Two classes of drugs reduce serum cholesterol—those affecting fat metabolism in the body and those interfering with fat absorption in the bowel. The latter drugs may cause gastrointestinal upset but are otherwise well tolerated and are considered safe for long-term, often lifelong, use. Powerful drugs affecting fat metabolism have now been accepted for general use, but not enough time has elapsed to determine whether long-term use of these effective drugs carries any risk to vital organs. They therefore are administered mainly when dietary means fail and the level of serum cholesterol is unusually high.

Complementing these preventive treatments of coronary-artery disease are agents that reduce the risk of thrombus formation. Evidence suggesting that small doses of aspirin may inhibit blood platelets from contributing to thrombus formation has provided a simple and inexpensive means of influencing the process that leads to heart attacks. However, the practical value of aspirin in preventing heart attacks has yet to be clearly established.

Risk modification concerning high blood pressure and smoking is treated as a general health measure rather than as a specific preventive measure in coronary-artery disease. Hypertension requires

treatment irrespective of its role in coronary-artery disease; similarly, the noxious effect of tobacco, the subject of intensive antismoking campaigns, involves other diseases than atherosclerosis. The question whether risk modification can actually produce regression of existing atherosclerotic lesions has not yet been answered, though some studies suggest it can.