Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

Xiping Xu, Yong Huo, Xianhui Qin, Xiaobin Wang, Fan Fan Hou, Binyan Wang, Xiaoshu Cheng, Xiao Huang, Delu Yin, Qiang Dong, Yefeng Cai, Ziyi Zhou, Mingli He, Genfu Tang, Yu Wang, Min Zhao, Yun Song, Lishun Liu, Yan Zhang, Youbao Li, Yaren Yu, Jianping Li

Journal: Stroke 2018;49(1):114-120

PMID: 29273594

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Abstract

BACKGROUND AND PURPOSE

We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial).

METHODS

Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke.

RESULTS

The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant (=0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99).

CONCLUSIONS

Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials.

CLINICAL TRIAL REGISTRATION

URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Address: From the Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University (Z.Z., L.L., Y.S., X.X., X.W.); Institute of Biomedicine, Anhui Medical University, Hefei, China (Z.Z., L.L., G.T., X.X., B.W., X.Q.); Department of Cardiology, Peking University First Hospital, Beijing, China (J.L., Y.Z., Y.H.); State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.Y., Y.L., M.Z., Y.W., X.X., B.W., F.F.H., X.Q.); School of Health Administration, Anhui University, Hefei, China (G.T.); Department of Neurology (M.H.) and Department of Cardiology (D.Y.), First People's Hospital, Lianyungang, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (M.Z., Y.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Q.D.); Department of Cardiovascular Medicine, Second Affiliated Hospital of Nanchang University, China (X.H., X.C.); and Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.).; From the Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University (Z.Z., L.L., Y.S., X.X., X.W.); Institute of Biomedicine, Anhui Medical University, Hefei, China (Z.Z., L.L., G.T., X.X., B.W., X.Q.); Department of Cardiology, Peking University First Hospital, Beijing, China (J.L., Y.Z., Y.H.); State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.Y., Y.L., M.Z., Y.W., X.X., B.W., F.F.H., X.Q.); School of Health Administration, Anhui University, Hefei, China (G.T.); Department of Neurology (M.H.) and Department of Cardiology (D.Y.), First People's Hospital, Lianyungang, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (M.Z., Y.C.); Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China (Q.D.); Department of Cardiovascular Medicine, Second Affiliated Hospital of Nanchang University, China (X.H., X.C.); and Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.). [email protected] [email protected].

DOI: 10.1161/STROKEAHA.117.018273

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MeSH Terms: Aged, Double-Blind Method, Enalapril, Folic Acid, Humans, Hypertension, Male, Middle Aged, Risk Factors, Smoking, Stroke