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Homocysteine Level and Coronary Heart Disease Incidence: A Systematic Review and Meta-analysis

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 μmol/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.
Mayo Clin Proc. 2008;83(11):1203-1212