Abstract
OBJECTIVE: Prospective assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine (homocysteine) concentration. DESIGN: Nested case-control study. SETTING: Caerphilly and surrounding villages in south Wales, UK. PARTICIPANTS: 2290 men who participated in phase II of the study in 1984. After a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched controls. MAIN OUTCOME MEASURE: Acute myocardial infarction or death from coronary heart disease. RESULTS: The geometric mean serum homocysteine concentration was higher in cases (12.2 micromol/l, 95% confidence interval (CI) 11.8 to 12.6 micromol/l) than in controls (11.8 micromol/l, 95% CI 11.3 to 12.5 micromol/l) (p = 0.09). There was a graded increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first (p = 0.04), which was attenuated when adjusted for confounding variables (p = 0.4). There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI.93 to 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentration with the remaining 80%, the adjusted odds ratio of coronary heart disease was 1.03 (95% CI 0.73 to 1.45) (p = 0.8) and comparing the top 5% with the remaining 95% it was 1.05 (95% CI 0.56 to 1.95) (p = 0.9). CONCLUSIONS: These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalizing the early positive results of observational studies.