PREVENTIVE

MEDICINE

4,482-490 (1975)

Forum on Cardiovascular Disease Epidemiology Introduction: Opportunities for Primary Prevention of Coronary Artery Disease

NEMAT0. BORHANI Department of Community University of California,

Health, School of Medicine, Davis, California 95616

Although the etiology of coronary artery disease remains unknown, the results of epidemiological studies provide us with enough information about this dreadful malady to consider seriously the opportunities that exist for its primary prevention. In this issue of Preventive Medicine, a series of articles on recent studies on the epidemiology of coronary artery disease and other cardiovascular diseases is presented. All of them were originally presented as part of the program at the recent Scientific Session of the Council of Epidemiology of the American Heart Association.’ The theme of the program as well as the findings of the papers in this Forum focus on the magnitude of the problem that coronary artery disease imposes upon our society and emphasize the need for primary prevention. During the first 75 yr of the 20th century, we have witnessed remarkable achievements in the evolution of public health throughout the world. Our advances in science and technology in public health and environmental sanitation, nutrition, and infectious disease control have enabled us to improve substantially the living conditions of man. Although the application of our scientific achievements has been limited, until recently, to the most industrialized and fully developed nations, the entire world is beginning to harvest the results of these achievements in terms of a significant increase in life expectancy. Table 1 demonstrates the changes in life expectancy that have taken place in the United States since the turn of the century. Although the data presented in Table 1 are for white males, the pattern is almost similar in both sexes. In other words, on the average, the life expectancy of newborn American infants has increased by approximately 20 yr since the turn of the century. Ironically, the observed, and much celebrated, changes in life expectancy are at the same time the best illustration of the magnitude of the problem of coronary artery disease. The observed increase in life expectancy has been, in most part, due to the control of infectious diseases of the early childhood. Thus, as can be seen from Table 1, the distribution of the increase in life expectancy is not uniform among all ages. Indeed, the life expectancy for white males 40 to 60 yr of age has 1 Conference on Cardiovascular Disease Epidemiology, Tampa, Florida, March 1975. 482 Copyright 0 1975 by Academic Press, Inc. All rights of reproduction in my form resewed.

FORUM:

CARDIOVASCULAR

DISEASE

483

EPIDEMIOLOGY

TABLE 1 LIFE EXPECTANCY, 1900-1971, UNITED STATES WHITE MALE Average number of years of lie remaining

Age

1900

1910

1920

1930

1940

1950

1960

1970

1971

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85

48.2 54.4 50.6 46.3 42.2 38.5 34.9 31.3 27.7 24.2 20.8 17.4 14.4 11.5 9.0 6.8 5.1 3.8

50.2 55.4 51.3 46.9 42.7 38.8 34.9 31.1 27.4 23.9 20.4 17.0 14.0 11.3 8.8 6.8 5.1 3.9

56.3 58.3 54.2 49.7 45.6 41.6 37.7 33.7 29.9 26.0 22.2 18.6 15.3 12.2 9.5 7.3 5.5 4.1

59.1 59.4 55.0 50.4 46.0 41.8 37.5 33.3 29.2 25.3 21.5 18.0 14.7 11.8 9.2 7.0 5.3 4.0

62.8 61.7 57.0 52.3 47.8 43.3 38.8 34.4 30.0 25.9 22.0 18.3 15.1 12.1 9.4 7.2 5.4 4.0

66.3 63.8 59.0 54.2 49.5 44.9 40.3 35.7 31.2 26.9 22.9 19.1 15.8 12.8 10.1 7.8 5.9 4.4

67.6 64.6 59.8 54.9 50.2 45.7 41.0 36.3 31.7 27.3 23.2 19.5 16.0 13.0 10.3 8.0 5.9 4.3

68.0 64.6 59.8 54.9 50.3 45.8 41.1 36.5 31.9 27.6 23.4 19.6 16.2 13.1 10.5 8.3 6.5 5.2

68.3 64.8 60.0 55.1 50.5 45.9 41.3 36.6 32.1 27.7 23.5 19.7 16.2 13.2 10.5 8.1 6.3 4.7

changed very little, if any, since 1900. With all our scientific advances in medicine and public health, we have yet to make decisive progress in the control of those diseases that have replaced the infectious disease epidemics of the past. Foremost among the diseases making up the epidemics of today are cardiovascular diseases, especially coronary artery disease. As depicted in Fig. 1, in the United States cardiovascular diseases account for 54.0% of all deaths each year. Coronary artery disease accounts for 34.0% of all deaths. Coronary artery disease kills more Americans each year than any other disease, including cancer and automobile accidents. The toll of death and disability inflicted by coronary artery disease and its sequela is a challenge not only to the members of the health profession, but to the society as a whole. This is a challenge that demands an immediate and coordinated response based on scientific principles, and not merely emotionalism. Coronary artery disease casts a much larger shadow than is recognized by its attendant rates of mortality and morbidity. To the extent that the incidence of this disease increases with age, its very possibility clouds the achievements of growing older. So long as coronary artery disease continues to afflict us, growing older remains a social and economic liability rather than a valued confirmation of human potential. Fortunately, as demonstrated by the data from the Framingham Study (presented in this Forum by Dr. Feinleib and his associates), there are indications of some degree of reduction in major coronary artery disease risk factors, at least in the Framingham population. The results of this study are consistent with some welcome and encouraging suggestions in recently published United States vital statistics that the death rate from coronary artery disease

484

NEMAT

0. BORHANI

FIG. 1. Leading causes of death in the United States (U.S. Vital Statistics Records, 1971).

may be declining. It could be that the observed reduction in coronary artery disease risk factors in Framingham between 1950 and 1972 is, as Dr. Feinleib points out, due to “generally increased health awareness among the public” and/or “the institution of primary prevention measures.” Certainly, these data, coupled with recently published mortality data on coronary artery disease, are encouraging. As encouraging as the data from the Framingham Offspring Study are, the fact that in the same population there has been an increase in the cigarette smoking habit among women is a cause for alarm. Epidemiological studies conducted in the United States and elsewhere have consistently demonstrated a positive association between the cigarette smoking habit and the incidence of coronary artery disease. Yet, there are alarming signs that the habit of cigarette smoking has become quite popular in recent years among women and teenagers, especially girls. Not only is there a body of overwhelming evidence that the cigarette smoking habit increases the risk of coronary artery disease, but there is also evidence that anyone can stop the smoking habit; and when the habit is broken, there is immediate improvement in the individual’s risk of the disease. Exsmokers have a much lower rate of coronary artery disease than the current smokers. Persons who stop their smoking habits may, within a year, have the same risk of coronary artery disease as those who have never smoked. To be sure, in biological phenomena, no single factor operates in isolation. In the case of coronary artery disease, the multifactorial nature of the problem has been demonstrated beyond any doubt. Thus, the habit of cigarette smoking, as pointed out by Dr. Friedman and his associates (presented in their paper on smoking and myocardial infarction), could be operating very logically in conjunction with the individual’s psychological status. Indeed, the data presented by Friedman ef al. in this Forum confirm the possibility that there are subgroups in general populations in whom the cigarette smoking habit alone “is not a predictor of coronary artery disease.” As important as these data are in our under-

FORUM:

CARDIOVASCULAR

DISEASE EPIDEMIOLOGY

485

standing of t.he epidemiology of coronary artery disease, we should never lose sight, however, of. the fact that all scientific conditions that are a prerequisite for launching a massive primary prevention program against cigarette smoking have been met. That is, it has been demonstrated that cigarette smoking is associated with increased risk of coronary artery disease, that the habit can be modified, and that the alteration in the habit will result in reduced risk. Notwithstanding the importance of psychological traits in the epidemiology of coronary artery disease (i.e., the observed difference in the incidence between types A and B behavior), there is now convincing evidence that of all recognized risk factors (other than age and sex), three factors are associated more readily with the incidence of coronary artery disease than others. These are the cigarette smoking habit, elevated serum cholesterol, and elevated blood pressure. These three factors stand out in all epidemiologic studies in their association with excessive risk of premature coronary heart disease. The risk of myocardial infarction, sudden death, and death from other complications of coronary artery disease increases directly with the levels of serum cholesterol and blood pressure and by the number of cigarettes smoked in both men and women. Based on multiple logistics function analysis of the data derived from the prospective epidemiologic studies, the strongest relationship with the increased incidence of coronary artery disease is obtained by combining, in a prediction equation, values of serum cholesterol and blood pressure and the number of cigarettes smoked. We can identify healthy middle-aged men whose probability of future heart attack is increased manyfold by using only these three risk factors, as illustrated in Fig. 2. In addition to their strong association with the incidence of coronary heart disease, these three risk factors are important to recognize

FIG. 2. Probability of developing coronary heart disease in 6 yr by systolic blood pressure, cholesterol, left ventricular hypertrophy by ECG, cigarette smoking, and glucose intolerance (The Framingham Study); 55-yr-old man.

486

NEMAT

0.

BORHANI

because they are relatively easy to identify, and, furthermore, they are amenable to alteration by intervention. With respect to blood pressure, the rate of death from all causes increases proportionally to an increase in the level of blood pressure, even in the range not generally considered extreme by clinical criteria (i.e., diastolic blood pressure of 85 to 94 mm Hg). Seventy-five to eighty percent of the men and women who die each year have some degree of hypertension. Approximately 65% of the mortality in those with elevated blood pressure is from cardiovascular diseases, especially coronary artery disease and stroke. All epidemiological data indicate a regular and marked increase in the incidence of coronary artery disease with the corresponding increment in the level of blood pressure, systolic and diastolic. Further, there is no apparent cutoff point or critical level of blood pressure above which people are at risk of coronary artery disease and below which they are free from it, As pointed out by Sir George Pickering, “arterial blood pressure is a biologic quantity, and its adverse effects are related numerically to it” (4). In considering primary prevention of coronary artery disease, we must, therefore, abandon our old concept of dividing blood pressure distribution into “normal” and “abnormal” levels. We must develop a basic plan of action that maximizes treatment effect of high blood pressure, while minimizing undesirable side effects. Since two papers in this Forum deal with the interesting issue of the role of genetics in the epidemiology of coronary artery disease, it would seem appropriate to discuss briefly the genetic variance in blood pressure. As pointed out by de Faire et al. ( in their paper on the results of the study of the Swedish Twin Registry), it is logical to expect that the genetic mechanism in the incidence of coronary artery disease is perhaps “transmitted through biological factors associated with the incidence of this disease, namely, serum cholesterol and blood pressure.” It is, of course, noteworthy that data presented in this issue, by de Faire and his associates, demonstrate a significantly higher concordance rate for coronary artery disease mortality among the male monozygotic pairs (15.8%) as compared to the male dizygotic pairs (8.0%). The respective figures for female pairs are 11.0% for monozygotics and 7.5% for dizygotics. These findings, as pointed out by the authors themselves, are different from the results of the Danish follow-up study of twins, in which a more pronounced difference in concordance rate between monozygotic and dizygotic pairs was observed for females than for males. It should be noted that both the Swedish and Danish twin registries have made significant contributions to our understanding of the role of genetics in the incidence of coronary artery disease. But we feel it more productive to study the genetic variance of the specific risk factors of coronary artery disease, such as serum cholesterol and blood pressure, than the coronary artery disease. In a recent study of adult white male twins, ascertained through the Twin Registry of the United States National Academy of Science, my colleagues and I made an attempt to determine the genetic variance in blood pressure and serum cholesterol. The design, methodology, and results of this recently completed

FORUM:

CARDIOVASCULAR

DISEASE

EPIDEMIOLOGY

487

multicenter study are published elsewhere (l-3) and need not be repeated here. It is important, however, to emphasize that with respect to blood pressure, we found a highly significant estimate of heritability, both for systolic and diastolic blood pressures. For example our data show that calculated heritability indices were 0.82 and 0.64, respectively, for systolic and diastolic blood pressures. Unfortunately, it is difficult to identify, much less to measure, the influence of environmental factors on blood pressure distribution and sort them out from purely genetic factors. Nevertheless, available evidence from controlled clinical trials indicates that judicious treatment of high blood pressure, not only reduces the level of blood pressure, but alters the pattern of mortality and morbidity associated with it. Results of the Veterans Administration Cooperative Study Group on antihypertensive agents (6, 7) indicate that proper combinations of drug therapy were capable of effecting and sustaining a marked reduction of both systolic and diastolic blood pressure and reducing the rate of nonfatal and fatal complications of high blood pressure. As might be expected, benefits of treatment were more dramatic and immediate for those at the higher levels of blood pressure than for those with moderate or mild elevations of blood pressure. Unfortunately, our present knowledge of the effectiveness of antihypertensive therapy is limited to clinical trials that have been conducted among selected hypertensive individuals with sustained blood pressure elevations, while the risk of mortality and morbidity associated with the levels of blood pressure has been demonstrated by studying, in a prospective manner, the general population subgroups or a representative sample of such population groups. In other words, unlike the case of cigarette smoking, not all the scientific prerequisites for launching a massive community hypertension control program are met at the present time. We do not know, nor do we have at hand scientific evidence, that the efficacy of antihypertensive therapy, reported from clinical trials, can be replicated in community programs. For this reason, the National Heart and Lung Institute’s Collaborative Studies known as the NHLI’s Hypertension Detection and Follow-up Program and the Multiple Risk Factor Intervention Trial, are indeed a welcome opportunity; these studies must be supported to their final conclusions. Otherwise, we may never have scientifically sound answers to the questions that surround the feasibility and effectiveness of community hypertension control programs, or alteration of other risk factors, for the purpose of primary prevention of coronary artery disease. With respect to the role of serum cholesterol in the incidence of coronary artery disease, epidemiological studies in the United States and elsewhere indicate a positive association between the level of serum cholesterol and the incidence of the disease. As depicted in Fig. 2, there is no cutoff point in the level of serum cholesterol above which an individual is at risk and below which he is immune from it. The higher the level of serum cholesterol, the greater the risk. Furthermore, from the point of view of assessing each individual’s coronary artery disease risk profile, it is extremely important to have in mind that apparently insignificant

488

NEMAT

0.

BORHANI

clinical abnormalities, such as slight glucose intolerance, mild elevation of blood pressure, cigarette smoking, or ECG evidence of left ventricular hypertrophy, would increase the risk precipitously at a given level of serum cholesterol. Figure 2 demonstrates coronary artery disease risk profile in a 55year -old man, considering the presence or absence of these factors. Thus, assessment of coronary profile must include checking these so-called “ingredients” of risk in a systematic and objective manner. The purposes of primary prevention programs should be to identify coronary profile in the manner mentioned above and correct (or alter) the multiple-risk factors in an integrated and coordinated manner; obviously, the results of the NHLI’s National Collaborative Program (now in its third year of operation) of the Multiple Risk Factor Intervention Trial (MRFIT) could add substantially to our knowledge and capabilities in this area. It is hoped that one of the greatest contributions of MRFIT would be in the area of methodology of integrated approach to behavioral modification for alteration of coronary artery disease’s multiple risk factors. Notwithstanding the data obtained from prospective epidemiological studies, the role of serum cholesterol and different fractions of plasma lipids in the incidence of coronary artery disease has been (and remains to be ) the subject of controversy. Indeed, there are unanswered questions with regard to the differences in prevalence of coronary artery disease among different populations and the possible predictive value of different lipoprotein fractions in the incidence of coronary artery disease in a given population subgroup. The interesting work of Dr. Tyroler and his associates (as presented in another paper in this Forum) is quite interesting and revealing indeed. These investigators, having observed a difference in the incidence of coronary artery disease between blacks and whites, while controlling for each of the established risk factors, pursued their investigation in Evans County, Georgia, beyond the boundaries of direct observation. And in investigating the lipoprotein patterns in the blacks and white, they found that “significantly higher LDL cholesterol and total triglyceride are present in whites (with high incidence of coronary artery disease); while higher HDL cholesterol was found in blacks (with low incidence of coronary artery disease), in an age, sex, total serum cholesterol matched comparisons.” LDL cholesterol, commonly known as beta lipoprotein, results from the very low density lipoprotein (VLDL) catabolism and includes over one-half of the total serum cholesterol. The HDL cholesterol, or alpha lipoproteins, comprises the smallest lipoproteins. We did not understand, until very recently, the real function of these lipoproteins. The most intriguing aspect of the work reported in this Forum by Tyroler and his associates is the difference in distribution of LDL and HDL cholesterol in blacks and whites. Should the hypothesis that HDL cholesterol exerts an inhibitory effect on atherogenesis prove correct, these findings would assume significance in explaining the observed lower than expected incidence of coronary artery disease among blacks with total serum cholesterol levels similar to that of their white counterparts. Is it possible that the nutritional-metabolic theory in the etiology and pathogenesis of coronary artery disease revolves around the LDL fraction of the serum cholesterol? If the answer to this question is affirma-

FORUM:

CARDIOVASCULAR

DISEASE EPIDEMIOLOGY

489

tive, our efforts towards primary prevention of coronary artery disease should be directed specifically to the modification of LDL cholesterol, not merely the lowering of total serum cholesterol. Obviously, the results of the Evans County Study have important implications in primary prevention of coronary artery disease. The suggestion, made by Tyroler and his colleagues, that there is a need for conducting prospective epidemiological studies to determine the possible role (perhaps a negative one) of HDL cholesterol in the risk of coronary artery disease deserves serious consideration and must be pursued. Also, the suggestion of a possible “genetic mechanism” in the distribution of LDL and HDL cholesterol merits special consideration. Such a hypothesis could explain the lack of concordance in the variance of total serum cholesterol, reported previously by us, between monozygotic and dizygotic twin pairs (l-3). Nevertheless, it is important to remember that from the point of view of primary prevention, it is quite difficult to separate genetic and environmental factors, as is the case with the variance in blood pressure. Thus, although the need for further fundamental research in etiology and pathogenesis of coronary artery disease is obvious, pursuit of such efforts in basic research should not deter us from advocating preventive measures. As suggested by Stamler, the extensive available knowledge concerning the risk factors associated with the incidence of coronary heart disease warrant a “systematic, thoroughgoing sustained nutritional-hygienic intervention to induce favorable living habits, blunt or remove risk factors . . . and thereby prevent the disease” (5). In addition to the articles mentioned above, we are including in this Forum two other papers presented at the Tampa Conference that relate to the general subject of cardiovascular disease. Dr. Abu-Zeid et al. present data for incidence of stroke in Manitoba, Canada, and describe epidemiological features that may help to identify stroke-prone candidates. In another article, Dr. Blackburn and his associates have devised an exercise in coronary risk screening that is now part of the standard second year curriculum for University of Minnesota medical students. Practicing physicians and other members of the health profession have a tremendous responsibility in providing the needed leadership for a major effort to assist the public in the acquisition of essential scientific knowledge regarding the known risk factors associated with the incidence of coronary artery disease and approaches towards its prevention. REFERENCES 1. Borhani, N. O., Feinleib, M., Garrison, R. J., Christian, J. C., and Rosenman, R. H. Genetic variance in blood pressure. The National Heart and Lung Institute twin study. Acta Getter. Med. Gemellol., in press. 2. Christian, J. C., Borhani, N. O., Feinleib, M., Garrison, R. J., and Rosenman, R. H. Genetics of plasma cholesterol and triglycerides. A study of adult male twins. Acta Genet. Med. Gemellol., in press. 3. Feinleib, M., Borhani, N. O., Christian, J. C., Garrison, R. J., and Rosenman, R. H. The National Heart and Lung Institute twin study of cardiovascular disease risk factors. Organization and methodology. Acta Genet. Med. Gemellol., in press. 4. Pickering, G. “High Blood Pressure,” 2nd ed. Grune and Stratton, Inc., New York, 1968. 5. Stamler, J. “Lectures on Preventive Cardiology.” Grune and Stratton, Inc., New York, 1967.

490

NEMAT

0. BORHANI

6. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 to 129 mm Hg. J. Amer. Med. Ass. #)2, 1028-1034 (1967). 7. Veterans Administration Cooperative Study Group on Antihypertensive agents. Effects of treatment on morbidity in hypertension. 11.Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. J. Amer. Med. Ass. 213, 1143-l 152 (1970).

Forum on cardiovascular disease epidemiology. Introduction: opportunities for primary prevention of coronary artery disease.

PREVENTIVE MEDICINE 4,482-490 (1975) Forum on Cardiovascular Disease Epidemiology Introduction: Opportunities for Primary Prevention of Coronary Ar...
810KB Sizes 0 Downloads 0 Views