Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects.

AIMS The contribution of homocysteine and group B vitamins in determining cardiovascular risk is debated. We assessed the predictive value of total homocysteine (tHcy), vitamin B12, folate, and vitamin B6 on the long-term occurrence of coronary and cerebral atherothrombotic events in a nested case-control study. METHODS AND RESULTS Within a cohort of 1021 healthy subjects (490 men and 531 women) recruited in 1987, 66 first-ever coronary and 43 first-ever cerebrovascular events were recorded at a 12-year follow-up (cases, n=109). A total of 109 control subjects (remaining free from events) were matched with cases according to age, sex, smoking, hypertension, dyslipidaemia, and body mass index. Serum samples obtained in 1987 at baseline were used to measure tHcy, folate, and vitamins B12 and B6, as well as C-reactive protein plasma concentrations. We found a significant graded association between tHcy levels and the risk of coronary and cerebrovascular events [odds ratio (OR) for uppermost vs. lowermost quartile=1.34, 95% CI 1.01-1.76)]. Folate and vitamin B12 did not significantly differ between cases and controls, but were negatively (P<0.01) correlated with tHcy. Vitamin B6 did not correlate with tHcy levels, but differed significantly between cases and controls: for subjects in the uppermost quartile vs. the lowermost quartile of vitamin B6, OR=0.69 (95% CI 0.49-0.98). For subjects in the lowermost quartile of vitamin B6 and the uppermost quartile of tHcy, OR=17.50 (95% CI 1.97, 155.59). Cases and controls were not different as to C-reactive protein. CONCLUSION tHcy and plasma vitamin B6 are long-term independent risk factors for coronary and cerebrovascular events.