For the purpose of screening individuals at high risk for coronary heart disease (CHD), serum total cholesterol (TC) of 5.2 mmol/L, has been set as a value dividing "desirable" from intermediate high or elevated levels, and HDL cholesterol (HDL-C) < 0.9 mmol/L has been labeled as abnormally low, implying high CHD risk. It has been conjectured that low HDL-C poses no risk in the absence of elevated LDL cholesterol or TC. To assess the risk of CHD-free men with "isolated low HDL-C," ie, abnormally low HDL-C with desirable TC, we examined the CHD and all-cause mortality of some 8000 Israeli men aged 42 years and older during 1965 through 1986. Men with isolated low HDL-C represented one sixth of the cohort. CHD mortality among these men was 36% higher (age adjusted) than in counterparts with desirable TC, of which > 0.9 mmol/L was contained in the high-density fraction. In men with TC > 5.2 mmol/L, abnormally low HDL-C was associated with a virtually identical CHD mortality risk ratio, 38%. These findings persisted after adjustment for multiple CHD risk factors. The excess CHD risk associated with isolated low HDL-C appeared particularly increased in men with diabetes mellitus, whose death rate was 65% higher than in diabetics with HDL-C > 0.9 mmol/L. A second subgroup result was consistent with equal CHD mortality risk among men in the "desirable" TC range, with or without low HDL-C, if systolic blood pressure was > 160 mm Hg. These are post hoc findings, and hypotheses arising from these observations would require independent examination. Total mortality was not increased in men with isolated low HDL-C compared with men who had HDL-C < 0.9 mmol/L and TC > 5.2 mmol/L at baseline. These results indicate that an increased risk of CHD death is associated with abnormally low HDL-C for cholesterol ranges both below and above 5.2 mmol/L. For the individual, therefore, the risk is multiplied by the same amount regardless of TC. Quitting smoking, increasing physical activity, and decreasing body weight would all contribute to raise HDL-C in individuals of most or all age groups. When examined from a community perspective, the results are consistent with a relatively low population-attributable fraction among CHD-free men. This would tend to support the recommended practice of considering a TC level of 5.2 mmol/L (200 mg/dL) as a threshold for further evaluation in screened individuals without manifest CHD.
Over 10,000 male civil servants and municipal employees in Israel, aged 40 years and above, underwent an extensive clinical, biochemical, anthropometric, sociodemographic and psychosocial evaluation in 1963, 1965 and 1968. Follow-up for mortality was continued through 1986. Over 23 years, a number of previously established risk factors for coronary heart disease (CHD) incidence were found to predict mortality. The long-term follow-up assisted in illustrating temporal patterns. A single casual assessment of blood pressure retained high prediction for long-term mortality. Blood lipids, while significantly associated with both coronary and all-cause mortality, exhibited a small contribution to the latter, when compared to hypertension, cigarette smoking habits and diabetes. Weak associations of long-term coronary mortality with the dietary intake patterns of fatty acids, as reported at baseline, were probably fully mediated by the effect of the diet on serum cholesterol. Religious orthodoxy appeared to provide a degree of immunity, part of which was independent of life-style correlates. A number of now well-established associations in cardiovascular epidemiology were first demonstrated, or amplified, in the study. Patterns of ethnic diversity in the risk factor and prevalence rates of CHD persisted, as viewed from the angle of mortality rates, over nearly a quarter of a decade, highlighting the enigma of a migrant country as a cardiovascular melting pot.
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