OBJECTIVE: To determine whether an elevated homocysteine level is an independent risk factor for the development of coronary heart disease (CHD) to aid the US Preventive Services Task Force in its evaluation of novel risk factors for incident CHD. METHODS: Studies of homocysteine and CHD were identified by searching MEDLINE (1966 through March 2006). We obtained additional articles by reviewing reference lists from prior reviews, original studies, editorials, and Web sites and by consulting experts. We included prospective cohort studies that measured homocysteine and Framingham risk factors and the incidence of CHD in the general adult population without known CHD. Each study was quality rated using criteria developed by the US Preventive Services Task Force. We conducted a meta-analysis using a random-effects model to determine summary estimates of the risk of major CHD associated with each 5-μmol/L increase in homocysteine level. The systematic review and meta-analysis were conducted between January 25, 2005, and September 17, 2007. RESULTS: We identified 26 articles of good or fair quality. Most studies found elevations of 20% to 50% in CHD risk for each increase of 5 μmol/L in homocysteine level. Meta-analysis yielded a combined risk ratio for coronary events of 1.18 (95% confidence interval, 1.10-1.26) for each increase of 5 μ mol/L in homocysteine level. The association between homocysteine and CHD was similar when analyzed by sex, length of follow-up, outcome, study quality, and study design. CONCLUSION: Each increase of 5 μmol/L in homocysteine level increases the risk of CHD events by approximately 20%, independently of traditional CHD risk factors.
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