Interaction of serum vitamin B and folate with genotypes on risk of ischemic stroke.

Objective: We evaluated the interaction of serum folate and vitamin B with methylenetetrahydrofolate reductase () C677T genotypes on the risk of first ischemic stroke and on the efficacy of folic acid treatment in prevention of first ischemic stroke.

Methods: A total of 20,702 hypertensive adults were randomized to a double-blind treatment of daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. Participants were followed up every 3 months.

Results: Median values of folate and B concentrations at baseline were 8.1 ng/mL and 280.2 pmol/L, respectively. Over a median of 4.5 years, among those not receiving folic acid, participants with baseline serum B or serum folate above the median had a significantly lower risk of first ischemic stroke (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.96), especially in those with 677 CC genotype (wild-type) (HR, 0.49; 95% CI, 0.31-0.78). Folic acid treatment significantly reduced the risk of first ischemic stroke in participants with both folate and B below the median (2.3% in enalapril-folic acid group vs 3.6% in enalapril-only group; HR, 0.62; 95% CI, 0.46-0.86), particularly in 677 CC carriers (1.6% vs 4.9%; HR, 0.24; 95% CI, 0.11-0.55). However, TT homozygotes responded better with both folate and B levels above the median (HR, 0.28; 95% CI, 0.10-0.75).

Conclusions: The risk of first ischemic stroke was significantly higher in hypertensive patients with low levels of both folate and B. Effect of folic acid treatment was greatest in patients with low folate and B with the CC genotype, and with high folate and B with the TT genotype.