Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up

Objective-Prospective assessment of the risk of coronary heart disease asso ciated 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. Af ter a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched contro ls. Main outcome measure-Acute myocardial infarction or death from coronary hea rt disease. Results-The geometric mean serum homocysteine concentration was higher in c ases (12.2 mu mol/l, 95% confidence interval (CI) 11.8 to 12.6 mu mol/l) th an in controls (11.8 mu mol/l, 95% CI 11.3 to 12.5 mu mol/l) (p = 0.09). Th ere was a graded increase in the odds ratio of coronary heart disease acros s quintiles of the homocysteine concentration distribution compared with th e first (p = 0.04), which was attenuated when adjusted for confounding vari ables (p = 0.4). There was a small but non-significant increase in the adju sted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI .93 t o 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentr ation with the remaining 80%, the adjusted odds ratio of coronary heart dis ease 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 homo cysteine concentration is a strong independent risk factor for coronary hea rt disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalising the early positive resul ts of observational studies.