Abstract
BACKGROUND: As a risk factor of cardiovascular diseases, homocysteine can be effectively lowered by folate. However, the associations of folate and homocysteine levels with the prognosis of ischemic stroke remained unclear. METHODS AND RESULTS: A total of 3530 patients with ischemic stroke were included. Serum folate and homocysteine levels were measured at admission. The primary outcome was composite of death and major disability (modified Rankin Scale score≥3) at 3 months after stroke onset. Univariate and multivariate logistic regression models were used. The mediation effect of homocysteine was examined. During follow-up, 1056 participants developed the primary outcome. In the univariate model, participants in the highest quartile of folate had a 29% (95% CI, 0.58-0.87) decreased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with the highest quartile of folate was 0.58 (95% CI, 0.46-0.73) for primary outcome. In contrast, participants in the highest quartile of homocysteine had a 52% (95% CI, 1.24-1.98) increased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with highest quartile of homocysteine was 1.57 (95% CI, 1.24-1.98) for primary outcome. In addition, 25.5% of the observed associations between folate and primary outcome was mediated through homocysteine (P=0.012). CONCLUSIONS: High folate levels were associated with low risks of death and major disability among Chinese patients with ischemic stroke, and homocysteine partially mediated the observed potential beneficial role of folate.