Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Primary Prevention Trial (CSPPT)

Background: The effect of folic acid supplementation on uric acid (UA) concentrations is still inconclusive. Objective: We aimed to test the efficacy of folic acid therapy in reducing serum UA in hypertensive patients. Design: A total of 15,364 hypertensive patients were randomly assigned to a double-blind daily treatment with a single tablet that contained 10 mg enalapril and 0.8 mg folic acid (n = 7685) or 10 mg enalapril alone (n = 7679). The main outcome was the change in serum UA, which was defined as UA at the exit visit minus that at baseline. Secondary outcomes were as follows: 1) controlled hyperuricemia (UA concentration <357 mu mol/L after treatment) and 2) new-onset hyperuricemia in participants with normal UA concentrations (<357 mu mol/L). Results: After a median of 4.4 y of treatment, the mean +/- SD UA concentration increased by 34.7 +/- 72.5 mu mol/L in the enalaprilalone group and by 30.7 +/- 71.8 mu mol/L in the enalapril-folic acid group, which resulted in a mean group difference of 24.0 mmol/L (95% CI: -6.5, -1.6 mu mol/L; P = 0.001). Furthermore, compared with enalapril alone, enalapril-folic acid treatment showed an increase in controlled hyperuricemia (30.3% compared with 25.6%; OR: 1.31; 95% CI: 1.01, 1.70) and a decrease in new-onset hyperuricemia (15.0% compared with 16.3%; OR: 0.89; 95% CI: 0.79, 0.99). A greater beneficial effect was observed in subjects with hyperuricemia (P-interaction = 0.07) or higher concentrations of total homocysteine (tHcy) (P-interaction = 0.02) at baseline. Furthermore, there was a significant inverse relation (P < 0.001) between the reduction of tHcy and the change in UA concentrations. Conclusions: Enalapril-folic acid therapy, compared with enalapril alone, can significantly reduce the magnitude of the increase of UA concentrations in hypertensive adults.