title: Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention.
abstract: Background:Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown.Objectives:This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations.Design:This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid (n= 10,160) or 10 mg enalapril alone (n= 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables.Results:During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (<5.0 mmol/L), was associated with an increased risk of first stroke (6.0% compared with 2.6%, respectively; HR: 1.9; 95% CI: 1.3, 2.8;P< 0.001). Folic acid treatment reduced the risk of stroke across a wide range of FBG concentrations ≥5.0 mmol/L, but risk reduction was greatest in subjects with FBG concentrations ≥7.0 mmol/L or with diabetes (HR: 0.66; 95% CI: 0.46, 0.97;P< 0.05). There was a significant interactive effect of FBG and folic acid treatment on first stroke (P= 0.01).Conclusions:In Chinese hypertensive adults, an FBG concentration ≥7.0 mmol/L or diabetes is associated with an increased risk of first stroke; this increased risk is reduced by 34% with folic acid treatment. These findings warrant additional investigation. This trial was registered at clinicaltrials.gov as NCT00794885.
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing, China.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing, China.
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Kong
authors.affiliation: National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Xu
authors.affiliation: National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ji
authors.affiliation: National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi, China.
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Health Administration, Anhui Medical University, Hefei, China.
authors.forename: Genfu
authors.initials: G
authors.lastname: Tang
authors.affiliation: National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Qin
authors.affiliation: National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Binyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Cardiology and.
authors.forename: Yundai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.affiliation: Departments of Cardiology and.
authors.forename: Ningling
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Lianyou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.affiliation: Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China; and.
authors.forename: Linong
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing, China; huoyong@263.net.cn lijianpingmedmail@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing, China; huoyong@263.net.cn lijianpingmedmail@126.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002681:China / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood / Q000517:prevention & control*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D006973:Hypertension / Q000150:complications*; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D014803:Vitamin B Complex / Q000097:blood / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D014803:Vitamin B Complex; D005492:Folic Acid
keywords: Chinese; folic acid; hyperglycemia; hypertension; stroke