China Stroke Primary Prevention Trial

Summary

The purpose of this trial is to confirm that enalapril maleate and folic acid tablets is more effective in preventing stroke among the patients with primary hypertension when compared to enalapril maleate.

Timeline

Start

2008-05

Primary completion

2013-08

Completion

2014-06

Publications

• Background Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007 Jun 2;369(9576):1876-1882. doi: 10.1016/S0140-6736(07)60854-X.
• Background Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA. 1997 Jun 11;277(22):1775-81. doi: 10.1001/jama.1997.03540460039030.
• Background Cronin S, Furie KL, Kelly PJ. Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis. Stroke. 2005 Jul;36(7):1581-7. doi: 10.1161/01.STR.0000169946.31639.af. Epub 2005 Jun 9.
• Wang L, Liu Z, Zhang N, Zhang L, Liu X, Fan F, Zhang Y, Li J. Association Between Neutrophil Percentage-to-Albumin Ratio (NPAR) and Risk of Stroke in Patients With Hypertension: A Cohort Study. J Clin Hypertens (Greenwich). 2026 Jan;28(1):e70200. doi: 10.1111/jch.70200.
• Zhang N, Mei J, Fan F, Zhang Y, Zhou Z, Li J. Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model. J Clin Hypertens (Greenwich). 2025 Jan;27(1):e14974. doi: 10.1111/jch.14974.
• Meng Y, Liu L, Chen X, Zhao L, She H, Zhang W, Zhang J, Qin X, Li J, Xu X, Wang B, Hou F, Tang G, Liao R, Huo Y, Li J, Yang L. Associations between brachial-ankle pulse wave velocity and hypertensive retinopathy in treated hypertensive adults: Results from the China Stroke Primary Prevention Trial (CSPPT). J Clin Hypertens (Greenwich). 2024 Jun;26(6):724-734. doi: 10.1111/jch.14820. Epub 2024 Apr 29.
• Li W, Li C, Liu T, Song Y, Chen P, Liu L, Wang B, Qu J. The association of serum choline concentrations with the risk of cancers: a community-based nested case-control study. Sci Rep. 2023 Dec 13;13(1):22144. doi: 10.1038/s41598-023-49610-3.
• Lei W, Liu Z, Su Z, Meng P, Zhou C, Chen X, Hu Z, Xiao A, Zhou M, Huang L, Zhang Y, Qin X, Wang J, Zhu F, Nie J. Hyperhomocysteinemia potentiates megakaryocyte differentiation and thrombopoiesis via GH-PI3K-Akt axis. J Hematol Oncol. 2023 Jul 27;16(1):84. doi: 10.1186/s13045-023-01481-x.
• Li Y, Song Y, Liu L, Wang X, Zhou Z, Zhang N, Wang Z, Chen P, Shi H, Huo Y, Xu X, Li J. Inverse Association Between Baseline Plasma Selenium Concentrations and Risks of Renal Function Decline in Hypertensive Adults. J Nutr. 2023 Jan 14;152(12):2754-2760. doi: 10.1093/jn/nxac211.
• He Q, Zhang N, Liang Q, Wang Z, Chen P, Song Y, Zhou Z, Wei Y, Duan Y, Wang B, Qin P, Qin X, Xu X. Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT). Front Nutr. 2022 Jul 12;9:946277. doi: 10.3389/fnut.2022.946277. eCollection 2022.
• Wei Y, Wang Z, He Q, Siddiqi SM, Zhou Z, Liu L, Song Y, Chen P, Li J, Zhang Y, Mao G, Wang B, Tang G, Qin X, Xu X, Huo Y, Guo H, Zhang H. Inverse Association between Plasma Phylloquinone and Risk of Ischemic Stroke in Chinese Adults with Hypertension and High BMI: A Nested Case-Control Study. J Nutr. 2022 Aug 9;152(8):1927-1935. doi: 10.1093/jn/nxac131.
• Song M, Xu BP, Liang Q, Wei Y, Song Y, Chen P, Zhou Z, Zhang N, He Q, Liu L, Liu T, Zhang K, Hu C, Wang B, Xu X, Shi H. Association of serum choline levels and all-cause mortality risk in adults with hypertension: a nested case-control study. Nutr Metab (Lond). 2021 Dec 20;18(1):108. doi: 10.1186/s12986-021-00637-1.
• Song Y, Li J, Liu L, Xu R, Zhou Z, Xu B, Lin T, Chen P, Li H, Li Y, Liu C, Huang X, Wang B, Zhang Y, Li J, Huo Y, Ren F, Xu X, Zhang H, Qin X. Plasma Vitamin E and the Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study. Front Nutr. 2021 Nov 3;8:734580. doi: 10.3389/fnut.2021.734580. eCollection 2021.
• Wei Y, Xu B, Wang Z, Zhou Z, Liu L, Lin T, Song Y, Li J, Zhang Y, Huo Y, Mao G, Wang B, Tang G, Qin X, Zhang H, Wang X, Guo H, Xu X. Joint Associations between Plasma 25-Hydroxyvitamin D, Glycemic Status, and First Stroke in General Hypertensive Adults: Results from the China Stroke Primary Prevention Trial (CSPPT). J Nutr. 2022 Jan 11;152(1):246-254. doi: 10.1093/jn/nxab339.
• Wang Z, Ma H, Song Y, Lin T, Liu L, Zhou Z, Wei Y, Huang X, Chen P, Liu C, Li Y, Wang B, Li J, Zhang Y, Huo Y, Zhang H, Xu X, Qin X, Guo H. Plasma selenium and the risk of first stroke in adults with hypertension: a secondary analysis of the China Stroke Primary Prevention Trial. Am J Clin Nutr. 2022 Jan 11;115(1):222-231. doi: 10.1093/ajcn/nqab320.
• Zhang Y, Zhou C, Li J, Zhang Y, Xie D, Liang M, Wang B, Song Y, Wang X, Huo Y, Hou FF, Xu X, Qin X. Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults. Cardiovasc Diabetol. 2020 Oct 24;19(1):186. doi: 10.1186/s12933-020-01161-x.
• Xie L, Zhao BX, Luo J, Li Y, Zhu F, Li GF, He M, Wang B, Zhang H, Cai Y, Huo Y, Wang X, Hou FF, Xu X, Qin X, Nie J. A U-shaped association between serum betaine and incident risk of first ischemic stroke in hypertensive patients. Clin Nutr. 2020 Aug;39(8):2517-2524. doi: 10.1016/j.clnu.2019.11.011. Epub 2019 Nov 15.
• Zhang Y, He P, Li Y, Zhang Y, Li J, Liang M, Wang G, Tang G, Song Y, Wang B, Liu C, Liu L, Cui Y, Wang X, Huo Y, Xu X, Qin X. Positive association between baseline brachial-ankle pulse wave velocity and the risk of new-onset diabetes in hypertensive patients. Cardiovasc Diabetol. 2019 Aug 28;18(1):111. doi: 10.1186/s12933-019-0915-0.
• Zhang J, Cao J, Zhang Y, Li H, Zhang H, Huo Y, Li J, Liu X, Wang X, Qin X, Xu X. Baseline Plasma Zinc and Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study. Stroke. 2019 Nov;50(11):3255-3258. doi: 10.1161/STROKEAHA.119.027003. Epub 2019 Aug 26.
• Zhang J, Cao J, Zhang H, Jiang C, Lin T, Zhou Z, Song Y, Li Y, Liu C, Liu L, Wang B, Tang G, Li J, Zhang Y, Cui Y, Huo Y, Yang Y, Ling W, Yang J, Guo H, Wang X, Xu X, Qin X. Plasma copper and the risk of first stroke in hypertensive patients: a nested case-control study. Am J Clin Nutr. 2019 Jul 1;110(1):212-220. doi: 10.1093/ajcn/nqz099.
• Wang J, Guo H, Lin T, Song Y, Zhang H, Wang B, Zhang Y, Li J, Huo Y, Wang X, Qin X, Xu X. A Nested Case-Control Study on Plasma Vitamin E and Risk of Cancer: Evidence of Effect Modification by Selenium. J Acad Nutr Diet. 2019 May;119(5):769-781. doi: 10.1016/j.jand.2018.11.017. Epub 2019 Jan 31.
• Yu Y, Zhang H, Song Y, Lin T, Zhou Z, Guo H, Liu L, Wang B, Liu C, Li J, Zhang Y, Huo Y, Wang C, Wang X, Hou FF, Qin X, Xu X. Plasma retinol and the risk of first stroke in hypertensive adults: a nested case-control study. Am J Clin Nutr. 2019 Feb 1;109(2):449-456. doi: 10.1093/ajcn/nqy320.
• Yang X, Zhang M, Song R, Liu C, Huo Y, Qian G. The modifying effect of the MTHFR genotype on the association between folic acid supplementation and pulse wave velocity: Findings from the CSPPT. Cardiovasc Ther. 2018 Dec;36(6):e12473. doi: 10.1111/1755-5922.12473. Epub 2018 Nov 20.
• Nie J, Xie L, Zhao BX, Li Y, Qiu B, Zhu F, Li GF, He M, Wang Y, Wang B, Liu S, Zhang H, Guo H, Cai Y, Huo Y, Hou FF, Xu X, Qin X. Serum Trimethylamine N-Oxide Concentration Is Positively Associated With First Stroke in Hypertensive Patients. Stroke. 2018 Sep;49(9):2021-2028. doi: 10.1161/STROKEAHA.118.021997.
• Kong X, Huang X, Zhao M, Xu B, Xu R, Song Y, Yu Y, Yang W, Zhang J, Liu L, Zhang Y, Tang G, Wang B, Hou FF, Li P, Cheng X, Zhao S, Wang X, Qin X, Li J, Huo Y. Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke. J Am Coll Cardiol. 2018 May 15;71(19):2136-2146. doi: 10.1016/j.jacc.2018.02.072.
• Huang X, Qin X, Yang W, Liu L, Jiang C, Zhang X, Jiang S, Bao H, Su H, Li P, He M, Song Y, Zhao M, Yin D, Wang Y, Zhang Y, Li J, Yang R, Wu Y, Hong K, Wu Q, Chen Y, Sun N, Li X, Tang G, Wang B, Cai Y, Hou FF, Huo Y, Wang H, Wang X, Cheng X. MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment. Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):679-685. doi: 10.1161/ATVBAHA.117.310211. Epub 2018 Jan 25.
• Zhou Z, Li J, Yu Y, Li Y, Zhang Y, Liu L, Song Y, Zhao M, Wang Y, Tang G, He M, Xu X, Cai Y, Dong Q, Yin D, Huang X, Cheng X, Wang B, Hou FF, Wang X, Qin X, Huo Y. Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men. Stroke. 2018 Jan;49(1):114-120. doi: 10.1161/STROKEAHA.117.018273.
• Huang X, Li Y, Li P, Li J, Bao H, Zhang Y, Wang B, Sun N, Wang J, He M, Yin D, Tang G, Chen Y, Cui Y, Huang Y, Hou FF, Qin X, Huo Y, Cheng X. Association between percent decline in serum total homocysteine and risk of first stroke. Neurology. 2017 Nov 14;89(20):2101-2107. doi: 10.1212/WNL.0000000000004648. Epub 2017 Oct 13.
• Zhang J, Tang G, Xie H, Wang B, He M, Fu J, Shi X, Zhang C, Huo Y, Xu X, Wang K. Higher Adiposity Is Associated With Slower Cognitive Decline in Hypertensive Patients: Secondary Analysis of the China Stroke Primary Prevention Trial. J Am Heart Assoc. 2017 Oct 10;6(10):e005561. doi: 10.1161/JAHA.117.005561.
• Li Y, Liang M, Wang G, Wang B, He M, Tang G, Yin D, Xu X, Huo Y, Cui Y, Hou FF, Qin X. Effects of Folic Acid Therapy on the New-Onset Proteinuria in Chinese Hypertensive Patients: A Post Hoc Analysis of the Renal Substudy of CSPPT (China Stroke Primary Prevention Trial). Hypertension. 2017 Aug;70(2):300-306. doi: 10.1161/HYPERTENSIONAHA.117.09404. Epub 2017 Jun 12.
• Zhao M, Wang X, He M, Qin X, Tang G, Huo Y, Li J, Fu J, Huang X, Cheng X, Wang B, Hou FF, Sun N, Cai Y. Homocysteine and Stroke Risk: Modifying Effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention. Stroke. 2017 May;48(5):1183-1190. doi: 10.1161/STROKEAHA.116.015324. Epub 2017 Mar 30.
• Men X, Sun W, Fan F, Zhao M, Huang X, Wang Y, Liu L, Liu R, Sun W, Peng Q, Qin X, Tang G, Li J, Zhang Y, Cai Y, Hou FF, Wang B, Xu X, Cheng X, Sun N, Huang Y, Huo Y. China Stroke Primary Prevention Trial: Visit-to-Visit Systolic Blood Pressure Variability Is an Independent Predictor of Primary Stroke in Hypertensive Patients. J Am Heart Assoc. 2017 Mar 13;6(3):e004350. doi: 10.1161/JAHA.116.004350.
• Qin X, Li Y, He M, Tang G, Yin D, Liang M, Wang B, Nie J, Huo Y, Xu X, Hou FF. Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Primary Prevention Trial (CSPPT). Am J Clin Nutr. 2017 Apr;105(4):882-889. doi: 10.3945/ajcn.116.143131. Epub 2017 Feb 1.
• Xu RB, Kong X, Xu BP, Song Y, Ji M, Zhao M, Huang X, Li P, Cheng X, Chen F, Zhang Y, Tang G, Qin X, Wang B, Hou FF, Dong Q, Chen Y, Yang T, Sun N, Li X, Zhao L, Ge J, Ji L, Huo Y, Li J. Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention. Am J Clin Nutr. 2017 Mar;105(3):564-570. doi: 10.3945/ajcn.116.145656. Epub 2017 Jan 25.
• Qin X, Li J, Spence JD, Zhang Y, Li Y, Wang X, Wang B, Sun N, Chen F, Guo J, Yin D, Sun L, Tang G, He M, Fu J, Cai Y, Shi X, Ye P, Chen H, Zhao S, Chen M, Gao C, Kong X, Hou FF, Huang Y, Huo Y. 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.
• Xu X, Qin X, Li Y, Sun D, Wang J, Liang M, Wang B, Huo Y, Hou FF; investigators of the Renal Substudy of the China Stroke Primary Prevention Trial (CSPPT). Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease: The Renal Substudy of the China Stroke Primary Prevention Trial. JAMA Intern Med. 2016 Oct 1;176(10):1443-1450. doi: 10.1001/jamainternmed.2016.4687.
• Qin X, Shen L, Zhang R, Li Y, Wang X, Wang B, Jiang X, Jiang H, Lei Y, Hou FF, Gu J, Huo Y. Effect of folic acid supplementation on cancer risk among adults with hypertension in China: A randomized clinical trial. Int J Cancer. 2017 Aug 15;141(4):837-847. doi: 10.1002/ijc.30094. Epub 2017 Jun 5.
• Wei R, Liu LS, Wang LW, Li YB, Zhang T, Liu J, Zuo SW, Jia SH, Song YX, Wu ZY, Duan C, Ge YY, Li HB, Xiong J, Jia X, Wang X, Kong W, Xu XP, Guo W, Huo Y. Association of Resting Heart Rate with Infrarenal Aortic Diameter: A Cross Sectional Study in Chinese Hypertensive Adults. Eur J Vasc Endovasc Surg. 2015 Dec;50(6):714-21. doi: 10.1016/j.ejvs.2015.05.022. Epub 2015 Oct 21.
• Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, Fu J, Cai Y, Shi X, Zhang Y, Cui Y, Sun N, Li X, Cheng X, Wang J, Yang X, Yang T, Xiao C, Zhao G, Dong Q, Zhu D, Wang X, Ge J, Zhao L, Hu D, Liu L, Hou FF; CSPPT Investigators. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015 Apr 7;313(13):1325-35. doi: 10.1001/jama.2015.2274.
• Wang Y, Li X, Qin X, Cai Y, He M, Sun L, Li J, Zhang Y, Tang G, Wang B, Sun N, Xu X, Liu L, Xu X, Huo Y. Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45-75 years. Br J Nutr. 2013 Apr 14;109(7):1284-93. doi: 10.1017/S0007114512003157. Epub 2012 Jul 31.

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