Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients

Xianhui Qin; Jianping Li; J David Spence; Yan Zhang; Youbao Li; Xiaobin Wang; Binyan Wang; Ningling Sun; Fang Chen; Jingxuan Guo; Delu Yin; Liming Sun; Genfu Tang; Mingli He; Jia Fu; Yefeng Cai; Xiuli Shi; Ping Ye; Hong Chen; Shuiping Zhao; Mao Chen; Chuanyu Gao; Xiangqing Kong; Fan Fan Hou; Yining Huang; Yong Huo

doi:10.1161/STROKEAHA.116.014578

Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients

Stroke. 2016 Nov;47(11):2805-2812. doi: 10.1161/STROKEAHA.116.014578. Epub 2016 Oct 11.

Authors

Xianhui Qin¹, Jianping Li¹, J David Spence¹, Yan Zhang¹, Youbao Li¹, Xiaobin Wang¹, Binyan Wang¹, Ningling Sun¹, Fang Chen¹, Jingxuan Guo¹, Delu Yin¹, Liming Sun¹, Genfu Tang¹, Mingli He¹, Jia Fu¹, Yefeng Cai¹, Xiuli Shi¹, Ping Ye¹, Hong Chen¹, Shuiping Zhao¹, Mao Chen¹, Chuanyu Gao¹, Xiangqing Kong¹, Fan Fan Hou¹, Yining Huang², Yong Huo¹

Affiliations

¹ From the Renal Division, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangzhou, China (X.Q., Y.L., B.W., F.F.H.); Department of Cardiology (J.L., Y.Z., Y. Huo) and Department of Neurology (Y. Huang), Peking University First Hospital, Beijing, China; Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, University of Western Ontario, London, Canada (J.D.S.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Cardiology, Peking University People's Hospital, Beijing, China (N.S., H.C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, China (F.C.); Department of Cardiology, Peking University Third Hospital, Beijing, China (J.G.); Department of Cardiology, First People's Hospital, Lianyungang, China (D.Y.); Department of Cardiology, Second People's Hospital, Lianyungang, China (L.S.); Institute for Biomedicine, School of Health Administration (G.T.) and Department of Neurology, First Affiliated Hospital (J.F., X.S.), Anhui Medical University, Hefei, China; Department of Neurology, First People's Hospital, Lianyungang, China (M.H.); Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (Y.C.); Department of Geriatric Cardiology, the General Hospital of the People's Liberation Army, Beijing, China (P.Y.); Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, China (S.Z.); Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China (M.C.); Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China (C.G.); and Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China (X.K.).
² From the Renal Division, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangzhou, China (X.Q., Y.L., B.W., F.F.H.); Department of Cardiology (J.L., Y.Z., Y. Huo) and Department of Neurology (Y. Huang), Peking University First Hospital, Beijing, China; Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, University of Western Ontario, London, Canada (J.D.S.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Cardiology, Peking University People's Hospital, Beijing, China (N.S., H.C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, China (F.C.); Department of Cardiology, Peking University Third Hospital, Beijing, China (J.G.); Department of Cardiology, First People's Hospital, Lianyungang, China (D.Y.); Department of Cardiology, Second People's Hospital, Lianyungang, China (L.S.); Institute for Biomedicine, School of Health Administration (G.T.) and Department of Neurology, First Affiliated Hospital (J.F., X.S.), Anhui Medical University, Hefei, China; Department of Neurology, First People's Hospital, Lianyungang, China (M.H.); Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (Y.C.); Department of Geriatric Cardiology, the General Hospital of the People's Liberation Army, Beijing, China (P.Y.); Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, China (S.Z.); Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China (M.C.); Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China (C.G.); and Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China (X.K.). ynhuang@sina.com huoyong@263.net.cn.

PMID: 27729579
DOI: 10.1161/STROKEAHA.116.014578

Abstract

Background and purpose: We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial.

Methods: A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke.

Results: The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024).

Conclusions: Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Keywords: cholesterol; folic acid; hypercholesterolemia; risk factors; stroke.

Publication types

Randomized Controlled Trial

MeSH terms

Aged
Antihypertensive Agents / administration & dosage
Antihypertensive Agents / pharmacology*
China / epidemiology
Comorbidity
Double-Blind Method
Drug Therapy, Combination
Enalapril / administration & dosage
Enalapril / pharmacology*
Female
Folic Acid / administration & dosage
Folic Acid / pharmacology*
Humans
Hypercholesterolemia / blood*
Hypercholesterolemia / epidemiology
Hypertension / drug therapy*
Hypertension / epidemiology
Male
Middle Aged
Outcome Assessment, Health Care*
Risk
Stroke / epidemiology
Stroke / prevention & control*
Vitamin B Complex / administration & dosage
Vitamin B Complex / pharmacology*

Substances

Antihypertensive Agents
Vitamin B Complex
Enalapril
Folic Acid

Associated data

ClinicalTrials.gov/NCT00794885