(Coronary Heart Disease – Chapter 2)
CAUSES OF CORONARY HEART DISEASE
An unrelenting search has been in progress for more than 50 years attempting to ascertain why and how the coronary arteries are affected by atherosclerosis. The question has never been answered, and the cause of coronary atherosclerosis remains unknown. However, one fundamental fact has emerged: a combination of several factors is undoubtedly involved in the development of CHD; no single mechanism can be held responsible in its own right. According to this concept, all of the following factors (called risk factors) may contribute to the formation and progression of coronary atherosclerosis.
1. Sex and Age
CHD is distinctly more prevalent in men than in women. Indeed, during the child-bearing years women are seemingly protected from CHD unless they have many other risk factors (e.g., hypertension and diabetes). After the menopause, however, the incidence of CHD in females rises rapidly and equals the male rate thereafter. In contrast, symptomatic CHD may occur in men as young as 30 years (or even younger). This sex-age discrepancy suggests that hormonal influences may be important in the disease process.The incidence of CHD increases greatly with age in both sexes. For example, a man in his fifties has four times the risk of a heart attack as a man in his thirties. The fact, however, that young persons may develop CHD makes it clear that coronary atherosclerosis is not simply a disease of aging.
2. Diet, Cholesterol, and Lipoproteins
Several epidemiologic studies have demonstrated that the incidence of premature CHD (i.e., coronary disease occurring before the age of 60) can be correlated with the different dietary patterns of various societies. Specifically, in affluent countries (as the United States), where animal fats constitute a large percentage of the total diet, the frequency of CHD is very high; and in poorer countries, where animal fat intake is much less, the incidence of the disease is low. The gross disparity in the amount of animal fat eaten (e.g., eggs, butter, cream, milk, and fatty meats) in different parts of the world is believed to account for the fact that “normal” serum cholesterol levels in the United States may be 200-240 mg%, whereas in those countries in which CHD is uncommon the comparable levels are only 100-120 mg%. Further evidence in support of the danger of high-fat diets is the reported decrease in the number of deaths from CHD during World War 11 in those countries where animal fats became scarce, followed by a prompt increase in the death rate after the war ended, when the economy improved and fats again became available. From data of this type many researchers have concluded that overeating of animal fats (also called saturated fats) is a prime factor in the etiology of CHD.
More specific information about the danger of high serum cholesterol levels has been obtained from the Framingham Heart Study. In this study more than 5000 men and women in the town of Framingham, Massachusetts, have been examined at regular intervals for more than 25 years to determine which factors contribute to the development of CHD. The results indicate that the risk of a heart attack is at least three times greater in men with serum cholesterol levels of more than 240 mg% than it is in those with levels of less than 200 mg%.
Although serum cholesterol has received the most attention, other serum lipids (e.g., triglycerides) and substances that transport lipids in the blood (lipoproteins) are also recognized as important risk factors for CHD in their own right. It has been shown, for example, that elevated serum triglyceride levels (above 200 mg%) are associated with an increased incidence of CHD even though serum cholesterol levels may be normal or only slightly elevated. In other words, cholesterol and triglyceride levels are not necessarily related and a high concentration of either lipid may indicate an increased risk of CHD. Elevated triglyceride levels, unlike elevated cholesterol levels, are usually induced by the ingestion of carbohydrates (rather than saturated fats) and are commonly associated with diabetes or abnormal glucose tolerance.
Cholesterol and triglycerides, as lipids, are insoluble in plasma and are carried in the blood in combination with a group of proteins, called lipoproteins, that are soluble. Lipoproteins can be separated into three main classes: low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and high-density lipoproteins (HDLs). About two-thirds of the cholesterol in the blood is carried by LDLs while HDLs carry less than one-third. (VLDLs are involved primarily in the transport of triglycerides and carry only small amounts of cholesterol.) Epidemiologic studies have revealed that the higher the concentration of LDH cholesterol, the greater the risk of CHD. On the other hand, there is an inverse association between HDL cholesterol and the incidence of CHD. This means that the higher the percentage of HDL cholesterol (of the total scrim cholesterol), the lower the risk of CHD. In fact this latter relationship appears so definite that HDL cholesterol actually seems to protect against CHD.
* Consequently, prediction of risk of CHD can be enhanced substantially by measuring HDL and LDL cholesterol in conjunction with the total serum cholesterol levels.
High blood pressure is thought to predispose to CHD by accelerating the rate of atherosclerosis and by increasing the oxygen demands of the myocardium. In the Framingham Heart Study it was observed that blood pressures in excess of 160/95 were associated with a fivefold increase in the incidence of CHD compared with normal pressures. Thus from a statistical standpoint hypertension appears to be one of the most serious risk factors.
4. Cigarette Smoking
There is firm statistical evidence to indicate that heavy cigarette smokers have a higher incidence of CHD than nonsmokers. In the Framingham Study, the risk of a heart attack was nearly twice as great in cigarette smokers. However, the risk was associated primarily with middle-aged men and was less impressive in older men and in women. Curiously, cigar and pipe smokers are at no greater risk than nonsmokers, presumably because they do not inhale. The manner in which cigarette smoking affects the coronary arteries is not understood. The suggestion that nicotine may cause sufficient constriction of the arteries to reduce coronary blood flow has not been confirmed. On the other hand, nicotine increases the work of the heart (by increasing the heart rate and blood pressure) and could produce a relative oxygen deficiency. Moreover, cigarette smoking is associated with elevated carbon monoxide levels in the blood, which may also interfere with myocardial oxygenation. Regardless of its mechanism of action, cigarette smoking is generally considered among the most serious risk factors for premature CHD.
A familial pattern of CHD has long been recognized, but the degree of risk is still uncertain (because family histories are unreliable in many instances). However, our own experience suggests that heredity ranks among the highest risk factors, particularly when CHD occurs during the fourth or fifth decade of life. In these latter cases it is commonly found that a man’s father, grandfather, and brothers often developed CHD at about the same age. It has been postulated (but not proven) that the physical structure of the coronary arteries and the rate of atherosclerosis may be genetically determined.
CHD develops more frequently and at all earlier age among diabetic patients than among non-diabetics. Even when diabetes is mild or well controlled the risk of CHD remains substantially greater. These facts along with data indicating that other
metabolic diseases (e.g., gout) are associated with a high incidence of Cl 11) suggest that a biochemical disturbance may be central to the underlying disease process.
7. Sedentary Life
Lack of physical activity has been incriminated as a risk factor in CHD, but the evidence for this belief is still inconclusive. Several studies have revealed, for example, that CHD occurs more frequently in sedentary workers (e.g., postal clerks) than in those whose occupations demand substantial physical activity (e.g., mail carriers); yet many observers have questioned the significance of these findings, noting that there were so many other variables between the two groups that physical inactivity should not be singled out as a risk factor in its own right. Although there is good reason to believe that exercise may benefit the myocardium, it remains to be seen if’ physical activity (or inactivity) affects coronary arteries and influences atherosclerosis.
Insurance company statistics suggest that obesity predisposes to fatal CHD, but (as with physical inactivity) the issue is by no means settled. In fact in the Framingham Study moderate obesity by itself was not associated with an increased incidence of CHD. However, overweight persons are especially prone to hypertension, diabetes, and elevated lipid levels, and it may be that the risk of obesity lies with these secondary effects. In any case obesity is classified as a risk factor even though its mechanism of action is uncertain.
9. Emotional Stress
Epidemiologic studies have consistently shown a markedly higher increase of CHD in industrialized (civilized) countries than in primitive, less-demanding societies. Many believe that this gross disparity is a reflection or a direct result of emotional stress imposed by modern, fast-paced styles of life. For this reason CHD is considered by some to be a disease of “overcivilization.” According to this theory, civilized mail has developed chronic anxiety in attempting to cope with rapidly changing socioeconomic and sociocultural forces, and this tension in some way promotes atherosclerosis. In principle, this is an attractive concept since it has been demonstrated that anxiety is often accompanied by a distinct rise in serum cholesterol, which could favor the development of atherosclerotic plaques. Moreover, stress is known to accelerate Wood coagulation, allowing small clots to form within the coronary arteries. Nevertheless, the relationship between emotional stress and CHD has been difficult to prove, particularly since there are no available methods to actually measure degrees of stress. Some research studies in fact have cast doubt on the importance of stress as a risk factor. For example, one large investigation involving telephone company employees showed that the incidence of CHD was actually less common among high-level executives (who presumably function under great stress) than it was among workers who installed or repaired equipment. Further study will be needed to determine the significance of emotional stress as a risk factor.
10. Behavioral Patterns
Attempts have been made to correlate CHD with certain personality traits and behavioral patterns. The coronary-prone person—called a type A personality—is said to be one who is aggressive, ambitious, highly competitive, and, most of all, possessed with a profound sense of the urgency of time. Those with this type behavioral pattern reportedly have significantly higher cholesterol levels and an increased incidence of CHD than their counterparts (type B personalities), in whom these particular characteristics are not as apparent. This interesting observation requires confirmation, but many now accept type A behavior as a distinct risk factor.
Summary of Risk Factors
It is essential to point out that there is no definite evidence that any of the risk factors just described actually cause CHD. All that can be said is that individuals with multiple risk factors are high-risk candidates for CHD; conversely, the absence of these factors predicts little likelihood of developing the disease. For example, a man with hypertension and a high serum cholesterol level who is a heavy cigarette smoker may have ten times the risk of sustaining a heart attack than a person with none of these factors. In other terms, there is a statistical association between risk factors and CHD but, on the other hand, no proof that these risk factors in themselves are the direct cause of coronary atherosclerosis.