Abstract 3936: Homocysteine Concentration, 5, 10-Methylenetetrahydrofolate Reductase 677C>T Gene Polymorphism, and Intake of Folate and B-Vitamins in 24,968 Asymptomatic Women
Background: Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease (CVD) in several prospective epidemiological studies. However, recent homocysteine-lowering trials in patients at high risk for CVD failed to show benefit.
Methods: In order to address this apparent paradox, we evaluated homocysteine levels, 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism, and dietary intake of folate/B-vitamins with subsequent CVD events in 24,968 apparently healthy white American women. Plasma homocysteine was measured using an enzymatic assay. MTHFR 677C>T genotype was determined with a multiplex polymerase chain reaction using biotinylated primers.
Results: Homocysteine showed moderately-strong associations with CVD, with unadjusted hazard ratios (95% confidence intervals) comparing top with bottom quintiles for total CVD of 1.92 (1.55–2.37), myocardial infarction 2.32 (1.52–3.54), and ischemic stroke 2.25 (1.45–3.50), all ptrend<0.001, which markedly attenuated after adjusting for traditional risk factors to 1.17 (0.94–1.46), 1.32 (0.85–2.04), and 1.27 (0.80–2.00), ptrend=0.02, 0.06, and 0.32, respectively. Homocysteine was associated with MTHFR genotype (1.4 μmol/L higher for TT vs CC, ptrend<0.001) and inversely with intake of folate, vitamins B2 (riboflavin), B6 (pyridoxine), and B12 (cyanocobolamin), all ptrend<0.001. However, there was no association between MTHFR genotype or folate/B-vitamins with CVD, nor did these modify the association of homocysteine with CVD, myocardial infarction, or stroke.
Conclusions: In this study, the association of homocysteine with CVD was largely attenuated after adjusting for traditional risk factors but was not modified by dietary intake of folate or B-vitamins or MTHFR 677C>T genotype.