PROSPECTIVE-STUDY OF CORONARY HEART-DISEASE INCIDENCE IN RELATION TO FASTING TOTAL HOMOCYSTEINE, RELATED GENETIC POLYMORPHISMS, AND B-VITAMINS - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY

Background-Elevated plasma total homocysteine (tHcy), low B-vitamin in take, and genetic polymorphisms related to tHcy metabolism may play ro les in coronary heart disease (CHD). More prospective studies are need ed. Methods and Results-We used a prospective case-cohort design to de termine whether tHcy-related factors are associated with incidence of CHD over an average of 3.3 years of follow-up in a biracial sample of middle-aged men and women, Age-, race-, and field center-adjusted CHD incidence was associated positively (P<0.05) with tHcy in women but no t men, and CHD was associated negatively (P<0.05) with plasma folate ( women only), plasma pyridoxal 5'-phosphate (both sexes), and vitamin s upplementation (women only). However, after accounting for other risk factors, only plasma pyridoxal 5'-phosphate was associated with CHD in cidence; the relative risk for the highest versus lowest quintile of p yridoxal 5'-phosphate was 0.28 (95% CI=0.1 to 0.7). There was no assoc iation of C-HD with the C677T mutation of the methylenetetrahydrofolat e reductase gene or with 3 mutations of the cystathionine beta-synthas e gene. Conclusions-Our prospective findings add uncertainty to conclu sions derived mostly from cross-sectional studies that tHcy is a major , independent, causative risk factor for CHD. Our findings point more strongly to the possibility that vitamin B-6 offers independent protec tion. Randomized trials, some of which are under way, are needed to be tter clarify the interrelationships of tHcy, B vitamins, and cardiovas cular disease.