Homocysteine and risk of cardiovascular disease among postmenopausal women

Context Individuals with elevated levels of homocysteine tend to have highe r prevalence of cardiovascular disease. However, prospective studies of hom ocysteine are inconsistent and data among women are limited. Objective To determine whether elevated homocysteine levels in healthy post menopausal women predict risk of developing cardiovascular disease. Design Prospective, nested case-control study with a mean 3-year follow-up. Setting The Women's Health Study, an ongoing US primary prevention trial in itiated in 1993. Participants From a total cohort of 28 263 postmenopausal women with no his tory of cardiovascular disease or cancer at baseline, 122 women who subsequ ently experienced cardiovascular events were defined as cases, and 244 age- and smoking status-matched women who remained free of disease during follo w-up were defined as controls. Main Outcome Measures Incidence of death due to cardiovascular disease, non fatal myocardial infarction (MI), stroke, percutaneous transluminal coronar y angioplasty, or coronary artery bypass graft by baseline homocysteine lev el, Results Of the 122 cases, there were 85 events of MI or stroke and 37 coron ary revascularizations. Case subjects had significantly higher baseline hom ocysteine levels than controls (14.1 vs 12.4 mu mol/L; P = .02). Subjects w ith homocysteine levels in the highest quartile had a 2-fold increase in ri sk of any cardiovascular event (relative risk [RR], 2.0; 95% confidence int erval [CI], 1.1-3.8). This effect was largely due to an excess of cases wit h high levels of homocysteine; the RR for those with homocysteine levels at or higher than the 95th percentile (20.7 mu mol/L) was 2.6 (95% CI, 1.1-5. 7), Risk estimates were independent of traditional risk factors and were gr eatest for the end points of MI and stroke (RR for those with baseline homo cysteine levels in the top quartile, 2.2; 95% CI, 1.1-4.6). Self-reported m ultivitamin supplement use at study entry was associated with significantly reduced levels of homocysteine (P<.001). However, the association between increasing quartile of homocysteine level and risk of MI or stroke remained significant in analyses controlling for baseline multivitamin supplement u se (P = .003 for trend), and subgroup analyses limited to women who were (P = .02 for trend) or were not (P = .04 for trend) taking multivitamin suppl ements. Conclusions Among healthy postmenopausal US women, elevated levels of homoc ysteine moderately increased the risk of future cardiovascular disease. Whe ther lowering the homocysteine level reduces risk of cardiovascular events requires testing in randomized controlled trials.