A case-control study , nested in a population-based cohort study was used. During a follow-up of 13 years, 166 major coronary events (death from CHD or nonfatal myocardial infarction) occurred in men with evidence of heart disease at baseline and 272 events in men without a history of heart disease. Two controls per case were selected by individual matching. Among men with known heart disease at baseline, the relative risk (95% confidence interval) of CHD events adjusted for age, smoking, hypertension, diabetes mellitus, serum cholesterol level, body mass index, and alcohol consumption was 2.23 (95% confidence interval, 1.03 to 4.85) in the highest serum homocysteine quintile compared with the lowest quintile. Among the men free of heart disease at baseline, the corresponding relative risk was 0.90 (95% confidence interval, 0.51 to 1.60).
A technology assessment report on biochemical markers of cardiovascular disease risk was abstracted in the Health Technology Assessment Database It concludes that relevance of studies of total serum homocysteine (tHcy) as a risk factor for cardiovascular disease is unclear given the decreasing tHcy levels as a result of mandatory folic acid supplementation. It remains unproven whether lowered tHcy levels will result in reduced morbidity and mortality from cardiovascular disease.