Serum total homocysteine and coronary heart disease: prospective study in middle aged men

Objectives-To examine the prospective relation between total homocysteine a nd major coronary heart disease events. Design-A nested case-control study carried out within the British regional heart study, a prospective investigation of cardiovascular disease in men a ged 40-59 years at entry. Serum total homocysteine concentrations were anal ysed retrospectively and blindly in baseline samples from 386 cases who had a myocardial infarct during 12.8 years of follow up and from 454 controls, frequency matched by age and town. Results-Geometric mean serum total homocysteine was slightly higher in case s (14.2 mu mol/l) than in controls (13.5 mu mol/l), a proportional differen ce of 5.5% (95% confidence interval (CI) -0.02% to 10.8%, p = 0.06). Age ad justed risk of myocardial infarction increased weakly with log total homocy steine concentration; also increase in log total homocysteine (equivalent t o a 47% increase in total homocysteine) was associated with an increase in odds of myocardial infarction of 1.15 (95% CI 1.00 to 1.32; p = 0.05). The relation was particularly marked in the top fifth of the total homocysteine distribution (values >16.5 mu mol/l), which had an odds ratio of 1.77 (95% CI 1.28 to 2.42) compared with lower levels. Adjustment for other risk fac tors had little effect on these findings. Total homocysteine concentrations more than 16.5 mu mol/l accounted for 13% of the attributable risk of myoc ardial infarction in this study population. Serum total homocysteine among control subjects varied between towns and was correlated with town standard ised mortality ratios for coronary heart disease (r = 0.43, p = 0.08). Conclusions-Serum total homocysteine is prospectively related to increased coronary risk and may also be related to geographical variation in coronary risk within Britain. These results strengthen the case for trials of total homocysteine reduction with folate.