Homocysteine and risk of coronary artery disease: Folate is the important determinant of plasma homocysteine concentration

Objectives The purposes of this study were to study the effects of folate and vitamins B6 and B12 on plasma homocysteine concentration and to estimate the risks for coronary artery disease (CAD) according to quartiles of plasma homocysteine concentration. Methods The study was designed as a case-reference observational study. Case subjects (CAD group, n = 60) were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery; otherwise, patients were considered for a reference group (n = 60). Risk factors of cardiovascular disease were recorded, including age, sex, blood lipid profile, hypertension, smoking habits, and drinking habits. Plasma homocysteine, folate, pyridoxal 5′-phosphate, and vitamin B12 were measured. Results CAD subjects had significantly higher mean plasma homocysteine concentrations than did the reference subjects (13.9 ± 4.9 versus 9.1 ± 3.3 μmol/L). There were no significant differences between groups with regard to the three B vitamins; however, mean serum folate concentrations for subjects in the highest two quartiles of plasma homocysteine concentration (10.8–13.8 and ≥13.9 μmol/L) were significantly lower than those for subjects in the lowest two quartiles (≤8.0 and 8.1–10.7 μmol/L). Plasma homocysteine was strongly inversely associated with serum folate in the CAD (β= −0.166, P < 0.05), reference (β= −0.178, P < 0.001), and pooled (β = −0.190, P < 0.001) groups. Age, sex, other confounding factors, and B-vitamin–adjusted odds ratios were significantly increased in the highest quartile of homocysteine concentration (odds ration, 5.54; 95% confidence interval, 0.38–81.41). The elevation of 1 ng/mL in serum folate concentration was found to decrease plasma homocysteine by 0.166 μmol/L. Conclusions Serum folate, but not vitamin B6 or B12, was a strong predictor of plasma homocysteine; while all subjects had adequate B-vitamin status. Folate should be considered as a routine supplementation for individuals who have risk factors for CAD, even for individuals with adequate folate status.