Background High plasma homocysteine is associated with premature coronary artery disease in men, but the threshold concentration defining this risk and its importance in women and the elderly are unknown. Furthermore, although low B vitamin status increases homocysteine, the link between these vitamins and coronary disease is unclear.

Methods and Results We compared 304 patients with coronary disease with 231 control subjects. Risk factors and concentrations of plasma homocysteine, folate, vitamin B12, and pyridoxal 5′-phosphate were documented. A homocysteine concentration of 14 μmol/L conferred an odds ratio of coronary disease of 4.8 (P<.001), and 5-μmol/L increments across the range of homocysteine conferred an odds ratio of 2.4 (P<.001). Odds ratios of 3.5 in women and of 2.9 in those 65 years or older were seen (P<.05). Homocysteine correlated negatively with all vitamins. Low pyridoxal 5′-phosphate (<20 nmol/L) was seen in 10% of patients but in only 2% of control subjects (P<.01), yielding an odds ratio of coronary disease adjusted for all risk factors, including high homocysteine, of 4.3 (P<.05).

Conclusions Within the range currently considered to be normal, the risk for coronary disease rises with increasing plasma homocysteine regardless of age and sex, with no threshold effect. In addition to a link with homocysteine, low pyridoxal-5′-phosphate confers an independent risk for coronary artery disease.