Xianhui Qin1, Youbao Li1, Mingli He2, Genfu Tang3,4, Delu Yin5, Min Liang1, Binyan Wang1, Jing Nie1, Yong Huo6, Xin Xu1, Fan Fan Hou7. 1. National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China. 2. Departments of Neurology and. 3. Institute for Biomedicine and. 4. School of Health Administration, Anhui Medical University, Hefei, China; and. 5. Cardiology, First People's Hospital, Lianyungang, China. 6. Department of Cardiology, Peking University First Hospital, Beijing, China. 7. National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China; ffhouguangzhou@163.com.
Abstract
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.
RCT Entities:
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 hypertensivepatients.Design: A total of 15,364 hypertensivepatients 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.