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) and2) 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.
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.
Xianhui
X
Qin
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.
Youbao
Y
Li
Departments of Neurology and.
Mingli
M
He
Institute for Biomedicine and.|School of Health Administration, Anhui Medical University, Hefei, China; and.
Genfu
G
Tang
Cardiology, First People's Hospital, Lianyungang, China.
Delu
D
Yin
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.
Min
M
Liang
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.
Binyan
B
Wang
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.
Jing
J
Nie
Department of Cardiology, Peking University First Hospital, Beijing, China.
Yong
Y
Huo
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.
Xin
X
Xu
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.
Fan Fan
FF
Hou
D000368:Aged; D002681:China; D019587:Dietary Supplements; D004311:Double-Blind Method; D004338:Drug Combinations; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood*; D033461:Hyperuricemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020521:Stroke; D014527:Uric Acid / Q000097:blood*; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use*
D004338:Drug Combinations; D006710:Homocysteine; D014803:Vitamin B Complex; D014527:Uric Acid; D004656:Enalapril; D005492:Folic Acid
controlled hyperuricemia; folic acid supplementation; new-onset hyperuricemia; total homocysteine; uric acid concentrations