A PROSPECTIVE-STUDY OF FOLATE AND VITAMIN-B-6 AND RISK OF MYOCARDIAL-INFARCTION IN US PHYSICIANS

Objective: To assess prospectively the risk of myocardial infarction ( MI) associated with decreased plasma levels of folate and pyridoxal ph osphate (PLP, a form of vitamin B-6) in relation to elevated levels of total homocysteine (tHcy). Design: Nested case-control study using pr ospectively collected blood samples.Setting: Participants in the Physi cians' Health Study. Subjects: 14,916 male physicians, aged 40-84 year s, with no prior MI or stroke provided plasma samples at baseline and were followed for 7.5 years. Samples from 333 men who subsequently dev eloped MI, and their paired controls matched by age and smoking, were analyzed for folate and PLP levels. Measures of Outcome: Acute MI or d eath due to coronary disease. Results: In a model controlling for diab etes, angina, hypertension, Quetelet's index, and total/high-density l ipoprotein cholesterol, men with the lowest 20% of folate levels (<2.0 ng/mL) had a relative risk of 1.4 (95% confidence interval 0.9-2.3) c ompared with those in the top 80%. For the lowest 20% of vitamin B-6 v alues, the relative risk was 1.5 (95% CI: 1.0-2.2). When we included b oth folate and B-6 in a model with cardiovascular risk factors, the re lative risk of MI for low as compared to high levels of folate was 1.3 (95% CI: 0.8-2.1) and for PLP, 1.3 (95% CI: 0.9-2.1). Adding tHcy to this model did not add significant predictive value (chi sq = 2.0, p > 0.05), except in the first half of the follow-up interval when men wi th the top 5% of tHcy values had an almost three-fold increase in risk of MI. Conclusions: Although not statistically significant, these pro spective data are compatible with the hypothesis that low dietary inta ke of folate and/or vitamin B-6 contribute to risk of MI.