American Journal of Epidemiology Vol. 141, No. 9: 822-827
Copyright © 1995 by The Johns Hopkins University School of Hygiene and Public Health
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Role of Smoking in the U-Shaped Relation of Cholesterol to Mortality in Men: The Framingham Study
1Department of Mathematics, Boston University Boston, MA
2Department of Medicine, Section of Preventive Medicine and Epidemiology, Evans Memorial Research Foundation, Boston University School of Medicine Boston, MA
3National Heart, Lung and Blood Institute Bethesda, MD
Reprint requests to Dr. Ralph B. D'Agostino, Department of Mathematics, Boston University, 111 Cummington Street, Boston, MA 02215.
Elevated mortality has been reported at extremes of the serum total cholesterol distribution, with increased coronary mortality reported at high total cholesterol levels and increased cancer and non-cardiovascular/noncancer mortality at low total cholesterol levels. The authors used data collected on 1,959 males aged 35–69 years from the fourth Framingham Study examination to analyze the relations between total serum cholesterol levels and 409 coronary deaths, 325 cancer deaths, and 534 other deaths for a 32-year follow-up. Age- and risk factor-adjusted Cox regressions were computed. Nonlinear (U-shaped) relations were investigated with the use of quadratic regression and with dummy variables using the 160–199 mg/dl group as the comparison group. Subset analyses investigated the relation in smokers and men who drank 
14 alcoholic drinks per week. All analyses were repeated removing those with existing cardiovascular disease and cancer and those who died during the first 5 years of follow-up. A significant U-shaped relation with all-cause mortality was noted, as were an inverse relation to cancer mortality and a monotonic increasing relation with coronary disease mortality. In subset analyses, the association of low serum cholesterol (>160 mg/dl) with cancer mortality was observed in men who smoked cigarettes. Compared with the 160–199 mg/dl group, the relative risk was 3.72 (
= 0.0001, 95% confidence interval 1.91–7.25). Studies of the relation of low total serum cholesterol levels, cigarette smoking, and cancer are needed. Am J Epidemiol 1995; 141:822–7.
epidemiologic methods; cholesterol; smoking
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