Elevated plasma homocyst(e)ine is a risk factor for vascular disease in middle-aged men. Supplementation with folate, and to some extent vitamins B12 and B6, can reduce plasma homocyst(e)ine levels. There is also evidence from in vitro studies that the adverse atherogenic or thrombotic effects of Lp(a) may be greatly enhanced by homocyst(e)ine. The high prevalence of low levels of folate and vitamins B12 and B6 among the elderly in the U.S. has led to the hypothesis that a substantial portion of cardiovascular morbidity and mortality among older persons could be prevented by increasing intake of these nutrients to reduce plasma levels of homocysteine. Little is known, however, regarding the relationship of homocysteine, folate, B vitamins, and Lp(a) to cardiovascular disease among the elderly, among whom CVD represents the leading cause of morbidity and mortality. In this proposed ancillary study to the prospective Cardiovascular Health Study (CHS), the investigators will employ a case-cohort design to test hypotheses that the risk of myocardial infarction and/or stroke is associated with elevated plasma levels of homocysteine, and low plasma levels of folate, vitamins B12 and B6. Further, they will determine whether elevated plasma levels of homocysteine and Lp(a) interact to increase substantially the risk of myocardial infarction and/or stroke above that due to either factor alone. Eligible cases will be all CHS subjects diagnosed with incident fatal or non-fatal acute myocardial infarction, or incident fatal or non-fatal stroke, following the baseline visit (June 1989 through June 1990) through June 1995. The subcohort will consist of subjects selected at random from among all CHS participants. In addition to constituting the comparison group for the events, the sub-cohort will be used to study the relationship between the factors under study and progression of sub- clinical atherosclerosis. For each case and sub-cohort member, an aliquot of fasting plasma drawn at baseline will be analyzed for homocysteine, folate B12, and B6 concentrations. [Values of plasma Lp(a) were determined at baseline.] Results of these assays will be combined with other CHS data to address the hypothesis that the risk of myocardial infarction and/or stroke is associated with elevated plasma levels of homocysteine, and low plasma levels of folate, vitamins B12 and B6.
