Context Based on observational and interventional data for middle-aged cohorts (aged 40-64 years), serum cholesterol level is known to be an established major risk factor for coronary heart disease (CHD). However, findings for younger people are limited, and the value of detecting and treating hypercholesterolemia in younger adults is debated. Objective To evaluate the long-term impact of unfavorable serum cholesterol levels on risk of death from CHD, cardiovascular disease (CVD), and all causes, Design, Setting, and Participants Three prospective studies, from which were selected 3 cohorts of younger men with baseline serum cholesterol level measurements and no history of diabetes mellitus or myocardial infarction. A total of 11 017 men aged 18 through 39 years screened in 1967-1973 for the Chicago Heart Association Detection Project in Industry (CHA); 1266 men aged 25 through 39 years examined in 1959-1963 in the Peoples Cas Company Study (PCI); and 69 205 men aged 35 through 39 years screened in 1973-1975 for the Multiple Risk Factor Intervention Trial (MRFIT). Main Outcome Measures Cause-specific mortality during 25 (CHA), 34 (PCI), and 16 (MRFIT) years of follow-up; mortality risks; and estimated life expectancy in relation to baseline serum cholesterol levels. Results Death due to CHD accounted for 26%, 34%, and 28% of all deaths in the CHA, PC, and MRFIT cohorts, respectively; and CVD death for 34%, 42%, and 39% of deaths in the same cohorts, respectively. Men in all 3 cohorts with unfavorable serum cholesterol levels (200-239 mg/dL [5.17-6.18 mmol/L] and greater than or equal to 240 mg/dl [greater than or equal to 6.21 mmol/L]) had strong gradients of relative mortality risk. For men with serum cholesterol levels of 240 mg/dL or greater (greater than or equal to 6.21 mmol/L) vs favorable levels (<200 mg/dL [<5.17 mmol/L]), CHD mortality risk was 2.15 to 3.63 times greater; CVD disease mortality risk was 2.10 to 2.87 times greater; and all-cause mortality was 1.31 to 1.49 times greater, Hypercholesterolemic men had age-adjusted absolute risk of CHD death of 59 per 1000 men in 25 years (CHA cohort), 90 per 1000 men in 34 years (PCI cohort), and 15 per 1000 men in 16 years (MRFIT cohort). Absolute excess risk was 43.6 per 1000 men (CHA), 81.4 per 1000 men (PCI), and 12.1 per 1000 men (MRFIT). Men with favorable baseline serum cholesterol levels had an estimated greater life expectancy of 3.8 to 8.7 years. Conclusions These results demonstrate a continuous, graded relationship of serum cholesterol level to long-term risk of CHD, CVD, and all-cause mortality, substantial absolute risk and absolute excess risk of CHD and CVD death for younger men with elevated serum cholesterol levels, and longer estimated life expectancy for younger men with favorable serum cholesterol levels.
