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 μmol/L after treatment) and 2) new-onset hyperuricemia in participants with normal UA concentrations (<357 μmol/L).

Results

After a median of 4.4 y of treatment, the mean ± SD UA concentration increased by 34.7 ± 72.5 μmol/L in the enalapril-alone group and by 30.7 ± 71.8 μmol/L in the enalapril-folic acid group, which resulted in a mean group difference of -4.0 μmol/L (95% CI: -6.5, -1.6 μmol/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. This trial was registered at clinicaltrials.gov as NCT00794885.