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Epidemiologic data and biologic plausibility suggest that homocystein (HCY) may be a risk factor for coronary artery disease (CAD). Plasma HCY and two vitamin cofactors of its metabolism (folate and vitamin B$\sb{12}$) were evaluated for their relationships with early onset CAD in a case-control study of 101 white men aged 50 years or less with angiographically demonstrated CAD and 108 population-based controls.
Plasma folate and vitamin B$\sb{12}$ were significantly inversely correlated with HCY in both cases and controls. Creatinine and protein were significantly positively correlated with HCY both in controls and cases. Daily supplementation of multivitamin B evaluated by a standard food frequency questionnaire was correlated with decreased HCY.
HCY in the highest quintile was associated with a 3.83-fold increased risk of CAD (95 percent confidence interval: 1.67, 8.77) as compared to men in the lowest quintile. When adjusting for standard CAD risk factors (age, HDL and LDL-cholesterol, smoking, hypertension, diabetes and obesity), the odds ratio (OR) for CAD associated with HCY in the highest compared to the lowest quintile was 2.63 (95 percent confidence interval: 0.88, 7.87). When natural logarithm of HCY was used, an inverse interaction was found between HCY and LDL-cholesterol (p $<$ 0.03).
Plasma folate in the lowest quintile (folate $<$ 2.86 ng/ml) was associated with a 2.58 fold increased risk for CAD (95 percent confidence interval: 1.13, 5.86) as compared to the highest quintile (folate $\geq$ 10.87 ng/ml). This effect was apparently mediated through HCY. In univariate analysis, vitamin B$\sb{12}$ was not associated with CAD, but low vitamin B$\sb{12}$ was marginally (p $<$ 0.07) associated with decreased CAD risk after adjusting for standard CAD risk factors and HCY; OR for CAD associated with vitamin B$\sb{12}$ in the lowest as compared to the highest quintile was 0.37 (95 percent confidence interval: 0.13, 1.06).
This study provides further evidence that HCY is an independent risk factor for early onset CAD. Reduction in HCY by increase in folate or multivitamin B supplementation may be effective in reducing the CAD risk.