Folic acid therapy reduces the risk of mortality associated with heavy proteinuria among hypertensive patients
We aimed to evaluate whether proteinuria and estimated glomerular filtration rate (eGFR) levels can modify the efficacy of folic acid therapy on the risk of all-cause mortality among hypertensive patients in the China Stroke Primary Prevention Trial, a randomized, double-blind, and controlled trial.Methods:
A total of 20 702 hypertensive patients without a history of major cardiovascular diseases were randomly assigned to a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n = 10 348), or 10-mg enalapril alone (n = 10 354). All-cause mortality, a prespecified endpoint of the China Stroke Primary Prevention Trial, was the main outcome in this analysis.Results:
Over a median treatment duration of 4.5 years, in the enalapril alone group, both heavy proteinuria [vs. absent, 10.8 vs. 2.7%; hazard ratio = 3.30; 95% confidence interval (CI): 2.10–5.18] and lower eGFR levels (<60 vs. ≥90 ml/min per 1.73 m2, 13.0 vs. 2.2%; hazard ratio = 1.93; 95% CI: 1.19–3.12) were significantly associated with increased risk of all-cause mortality. Folic acid supplementation significantly reduced the risk of all-cause mortality in patients with heavy proteinuria (6.4% in the enalapril-folic acid vs. 10.8% in the enalapril alone group, hazard ratio = 0.49; 95% CI: 0.26–0.94), but not in those with absent or mild proteinuria (2.8 vs. 2.9%, hazard ratio = 0.99; 95% CI: 0.84–1.17; P for interaction = 0.040). However, eGFR levels did not significantly modify the effect of folic acid supplementation in reducing the risk of all-cause mortality (P for interaction = 0.228).Conclusion:
Among hypertensive patients without a history of major cardiovascular diseases, folic acid therapy could reduce the mortality risk associated with heavy proteinuria.