Drugs 36 (Suppl. 3): 1-4 (1988) 0012-6667/88/0300-000 1/$2.00/0 © ADIS Press Limited All rights reserved .

Risk Factors for Coronary Heart Disease

Selected Recent Epidemiological Advances

Stephen B. Hulley Clinical Epidemiology Program, University of California, San Francisco, California, USA

Summary

Several recent advances in our understanding of the epidemiology and prevention of coronary artery disease are presented. highlighting the current status of the 3 major risk factors: blood cholesterol. blood pressure and cigarette smoking. There is a striking analogy between serum cholesterol and diastolic blood pressure in the pattern of the association with coronary heart disease (CHD). Mortality follow-up of the 361.662 middle-aged men screened for the Multiple Risk Factor Intervention Trial (MRFlT) shows that each ofthese riskfactors identifies a large group of patients (the top 15% ofthe population distribution) who have a 4-fold higher risk ofCHD death than those in the bottom 15%. and that each has a continuously rising gradient of risk for people with intermediary levels. The implication from these findings . and from the clinical trial data. is that public health and clinical policies directed at blood cholesterolshould be made simi/ar to those that have become widespreadfor blood pressure in the past 2 decades; i.e. measuring the level periodically in all adults and intervening to prevent CHD in those at highest risk. The public health campaign to reduce cigarette smoking has been bolstered by new evidence on the hazards of ambient smoke. One example comes from the clinical trial cohort of the MRFlT. in which non-smoking men who were married to smoking wives had nearly twice the all-cause mortality rate of non-smoking men who were married to non-smoking wives. The campaign has caused a striking reduction in the prevalence of smoking over the past 2 decades in the United States and a growing set of ordinances prohibiting smoking in public places. These events are believed to be partly responsiblefor the extraordinary decline in CHD mortality that has been observed in the United States over the past 2 decades and that is likely to occur in many western countries in the 1990s.

1. Epidemiological and Health Policy Analogy between Blood Cholesterol and Blood Pressure It is well known that high blood cholesterol and high blood pressure are both strong, independent risk factors for coronary heart disease (CHD). Yet, until recently, the public awareness and profes-

sional management of these 2 risk factors have been very different. A 1983 survey revealed that 98% of American adults recalled having their blood pressure checked at least once, but that only 35% recalled a blood cholesterol test (Schucker et al. I987a). Another survey revealed that physicians believe less in the efficacy of preventive strategies aimed at blood cholesterol than in similar actions

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Serum 157 187 207 226 253 175 198 216 238 281 cholesterol (mg/dl) Diastolic blood 69 73 77 79 81 84 87 90 94 102 pressure (mm Hg)

Fig. 1. Age-adjusted CHD and total 6-year death rate per 1000 men screened for MRFIT according to serum cholesterol (e--e) or diastolic blood pressure (0-0) percentiles (from Martin et al. 1986, with permission).

directed at blood pressure (Schucker et al. 1987b). Is this double standard for these 2 risk factors rational? In the section below, recent evidence for a striking analogy in the epidemiological characteristics of blood cholesterol and blood pressure is reviewed. Many epidemiological studies - both cohort studies of individuals and international comparisons of populations - have shown that high levels of blood cholesterol and blood pressure are each associated with increased risk of CHD . The risks associated with increased levels of these risk factors have been most precisely revealed in the largest of these studies, a 6-year mortality follow-up of 361,662 men aged 35 to 57 years who were screened for the Multiple Risk Factor Intervention Trial [MRFIT] (fig. 1). The precision is a consequence of the enormous size of this cohort, 70 times larger than the Framingham cohort. The findings indicated that CHD mortality increases progressively in patients with levels of either risk factor that are

above the twentieth percentile, while in those with levels above the eighty-fifth percentile of either risk factor, the relative risk of CHD death is about 4 times that of men in the bottom quartile. The analogy between cholesterol and blood pressure as risk factors is equally striking for CHD and for total mortality . Yet it is important to realise that cholesterol and blood pressure are not appreciably correlated with each other. Thus, each risk factor identifies a separate, large segment of the population that requires intensive treatment. Other reports in this supplement present the evidence from recent clinical trials, which is now at least as strong for blood cholesterol as for blood pressure in showing that treatment of patients with high levels is beneficial (Coronary Drug Project Research Group 1975; Frick et al. 1987; Lipid Research Clinics Program 1984). Also, elsewhere in these proceedings (Hulley, this issue p. 100) and in another report (Hulley & Martin 1986), the similarity between these 2 risk factors in the recent policy guidelines for detection and treatment of patients with high levels has been reviewed.

2. Campaign to Reduce Cigarette Smoking Several recent stud ies have shown that ambient or sidestream smoke is hazardous to the health. One such study is an analysis of the MRFIT cohort that examines CHD incidence and mortality among non-smoking men classified by the smoking status of their wives (table I) [Svendson et al. 1987]. The relative risk of dying is 1.72 when comparing nonsmoking men whose wives smoked with nonsmoking men whose wives did not (p = 0.01), and after adjusting for other risk factors that might have contributed to this association, the relative risk is 1.79 (p < 0.01). Findings of this sort, together with the very large set of evidence on the health hazards of active smoking reviewed in the Surgeon General Report (1983), have contributed to a growing set of ordinances against smoking in public places in the United States. One such measure created by vote of the public in San Francisco in 1984 has required

Risk Factors for CHD

3

Table I. Relative risk estimates, wife who smoked compared with wife who did not smoke , for non-smok ing' men in the Multiple Risk Factor Intervention Trial (1973-82) End-point

Relative risk

Significance

95% Confidence interval

Death from any cause Unadjusted Adjusted b

1.72 1.79

0.01 < 0.01

1.12-2.64 1.17-2.76

Coronary heart disease death Unadjusted Adjusted

1.45 1.59

0.25 0.15

0.77-2.73 0.84-3.02

Fatal or non-fatal coronary heart disease event Unadjusted Adjusted

1.19 1.32

0.29 0.10

0.85-1.65 0.95-1.84

a Includes both persons who have never smoked and ex-smokers who quit before entry into the trial. b Adjusted by Cox proportional hazards regression for age, baseline blood pressure, cholesterol, weight, drinks per week, education and past smoking history.

employers to provide a non-smoking work environment for any employee who requests it. Other examples include the banning of smoking in many public buildings, including restaurants in Beverly Hills (1987) and New York (1988), and the banning of all smoking in airlines travelling within the State of California (1987) and on all Northwest Airlines flights (1988). These social changes have been well received by the public (Martin & Silverman 1986). These extraordinary developments have taken place without important adverse incidents because of a national movement toward the view that smoking is no longer socially acceptable in many circles in the United States. The extent to which smoking has declined over the past 2 decades is shown in table II. These remarkable sociological phenomena are a consequence of the efforts by the Surgeon General and public health workers to disseminate research findings on the health hazards of smoking. It is reasonable to project that the trend toward a non-smoking population will continue in years to come.

3. National Mortality Trends Coronary disease mortality has been declining in the United States for more than 20 years (fig. 2). The magnitude of this decline is about 30% in

Table II. Prevalence (%) of cigarette smoking in the United States in persons aged ~ 20 years

1965 1976 1980 1985

Men

Women

52 42 38

34 32 30 28

33

Source : National Center for Health Statistics .

each major race-sex group. This striking favourable trend is believed to be real, i.e. it is not caused by an artifact in death certification . Although its basis is not known with certainty, it may in part be a reflection of improvements in the treatment of myocardial infarction , with coronary care reducing the case-fatality rate and with l3-blockers and, perhaps, other factors improving long term survival. Risk factor reduction can be extremely effective in this secondary prevention setting and may have played a role (Browner & Hulley in press; Siegel et al. in press). However, part of this decline in CHD mortality is probably due to adoption of primary preventive practices by the population: the decline of the smoking habit that has been noted, improvements

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Fig. 2. Age-adjusted death rates for heart disease according to race and sex, United States 1950-83. Age-adjusted death rates for the black population are shown for 1968-83. Data are shown for all races other than white for 1950-67, but black persons accounted for more than 90% of this population during this period (from the National Center for Health Statistics, Division of Vital Statistics, National Vital Statistics System).

in the detection and treatment of hypertens ion, reductions in blood cholesterol that have resulted from some changes in the dietary habits of the population, and an increased level of physical fitness in the population. These improved risk behaviours should become more prevalent, and coronary death rates should diminish further in the United States. Similar, though smaller, trends are also seen in many other western countries that have high CHD death rates, and these too are likely to grow larger in the next decade (World Health Statistics 1987).

Browner WS, Hulley SB. Implications of hypertens ion trials: effect of risk status on treatment criteria . Hyperte nsion. in press Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. Journal of the American Medical Association 231: 360-381, 1975 Frick MH. Elo O. Haapa K. Heinonen OP. Heinsalm i P. et al. Helsinki Heart Stud y: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidem ia. New England Journal of Med icine 317: 1237-1245. 1987 Hulley SB. Mart in MJ. Health policy for treat ing hyperlipidem ia: analog y with hypertension and prospects for the next decade. American Journal of Cardiology 57: 3H-6H . 1986 Lipid Research Clinics Program . The Lipid Research Clinics Coronary Primary Prevention Trial Results: I. Reduction in the incidence of coronary heart disease. Journal of the American Medical Association 251: 251-264. 1984 Martin MJ. Silverman MF. The San Francisco experience with regulation of smoking in the workplace: the first 12 months. Amer ican Journal of Public Health 76: 585-586, 1986 Martin MJ. Hulley SB. Browner WS. Kuller LH. Wentworth D. Serum cholest erol. blood pressure . and mortal ity: implications from a cohort of 361.662 men. Lancet 2: 933-936. 1986 Schucker B, Bailey K, Heimbach JT. Mattson ME. Willes JT. et al. Change in public perspective on cholesterol and heart disease. Journal of the American Medical Association 258: 35273531, 1987a Schucker B. Wittes JT . Cutler JA. Bailey K. MacKintosh DR. et al. Change in physician perspect ive on cholesterol and heart disease. Journal of the American Medical Association 258: 35213526, 1987b Siegel D. Grad y D. Browner WS, Hulley SB. Risk factor mod ification after myocardial infarction. Annals of Internal Medicine, in press Surgeon General Report . The health consequences of smok ing: card iovascular disease. US DHHS. PHS. 1983 Svendson KH. Kuller LH. Martin MJ. Ockene JK . Effects of passive smok ing in the MR FIT . American Journal of Epidemiology 126: 783-795, 1987 ' World Health Stat istics Annual , p. 8, Gene va. 1987

Author's address : Dr Stephen B. Huller . Clinical Epidemiology Program . University of California. 74 New Montgomery St. San Francisco . CA 94105 (USA).