HOMOCYSTEINE AND CORONARY-ARTERY DISEASE IN FRENCH-CANADIAN SUBJECTS - RELATION WITH VITAMINS B-12, B-6, PYRIDOXAL-PHOSPHATE, AND FOLATE

We determined plasma levels of homocysteine in 584 healthy subjects (380 men and 204 women) from a major utility company in the province of Quebec, Canada, and in 150 subjects (123 men and 27 women) with angiographically documented coronary artery disease (CAD) (age <60 years). Plasma levels of vitamins B-12, B-6, pyridoxal phosphate (a vitamin B-6 derivative), and folate were also determined. Mean homocysteine revels were higher (p <0.05) in the bottom quartiles for folate, vitamin B-12, and pyridoxal phosphate. A significant correlation was noted between homocysteine levels and folate and vitamin B-12 levels. No significant correlation was found between plasma homocysteine levels and age, lipids and lipoprotein cholesterol, glucose, and the presence of hypertension or cigarette smoking in healthy subjects or in patients with CAD. Control men had higher homocysteine levels than control women (p <0.005). Men and women with CAD had higher levels of homocysteine than controls (11.7 +/- 5.8 vs 9.7 +/- 4.9 nmol/ml [p <0.001] and 12.0 +/- 6.3 vs 7.6 +/- 4.1 nmol/ml, p <0.01, respectively). Women and men with CAD had similar homocysteine levels. The proportion of patients with CAD having homocysteine levels >90th percentile of controls was 18.1% for men and 44.4% for women (both p <0.01). Significantly lower pyridoxal phosphate levels were seen in subjects with CAD, men and women combined (27.7 +/- 29.5 vs 42.1 +/- 38.4 ng/ml, p <0.005). No significant differences were observed for B-12, folate, or total B-6. Multivariate analysis reveals that an elevated homocysteine level is a risk factor for CAD in French Canadian men and women and that reduced levels of pyridoxal phosphate, folate, and vitamin B-12 contribute to elevated plasma homocysteine levels. We conclude that in our subjects of French Canadian descent, plasma levels of homocysteine are influenced by levels of folate, vitamin B-12, and pyridoxal phosphate. In healthy men, mean homocysteine levels are higher than in healthy women. Men and women with CAD had significantly higher homocysteine levels than controls and this elevation is independent of traditional risk factors. Prospective studies are needed to determine the role of homocysteine in CAD. The influence of treatment of elevated homocysteine levels on cardiovascular morbidity and mortality must be assessed.