Efficacy of folic acid in stroke primary prevention among patients with H-Type hypertension: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LUO Jinwen ¹ , DUAN Wenhui ² , TAN Yu ² , QU Hua ² ,  SHI Dazhuo ²

1. Beijing University of Chinese Medicine, Beijing 100029, P.R.China;
2. National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing 100091, P.R.China;

Corresponding?author：

SHI Dazhuo, Email: shidazhuo@126.com

Keywords：

Folic acid; H-Type hypertension; Stroke; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.202005174

Video：

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Objectives To systematically review the efficacy of folic acid supplementation in the primary prevention of stroke among patients with H-Type hypertension.Methods PubMed, EMbase, The Cochrane Library, WanFang Data, CNKI, VIP and Sinomed databases were electronically searched to collect randomized controlled trials (RCTs) of folic acid supplementation in the primary prevention of stroke among patients with H-Type hypertension from inception to April, 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software and Stata 12.0 software.Results A total of 12 RCTs involving 18 170 participants were included. The results of meta-analysis showed that H-Type hypertensive patients who received folic acid and antihypertensive had a significant low risk of stroke (RR=0.34, 95%CI 0.21 to 0.55, P<0.000 1) compared with patients who received antihypertensive alone. In the stratified analyses, folic acid >2 mg/d (RR=0.27, 95%CI 0.14 to 0.51, P<0.000 1) and ≤2 mg/d (RR=0.36, 95%CI 0.20 to 0.65, P=0.000 8) both could reduce the risk of stroke. Enalapril folic acid tablets (RR=0.35, 95%CI 0.16 to 0.77, P=0.009) and free combinations of folic acid and antihypertensive drugs (RR=0.29, 95%CI 0.18 to 0.47, P<0.000 01) could lower the incidence of stroke.Conclusions Current evidence shows that the folic acid supplementation significantly reduce the risk of stroke among patients with H-Type hypertension. Enalapril folic acid tablets and free combinations of folic acid with antihypertensive drugs both play an important role in stroke prevention. There is no significant dose-response relationship between dosage of folic acid and prevention of stroke. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.

Citation： LUO Jinwen, DUAN Wenhui, TAN Yu, QU Hua, SHI Dazhuo. Efficacy of folic acid in stroke primary prevention among patients with H-Type hypertension: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2020, 20(10): 1173-1179. doi: 10.7507/1672-2531.202005174 Copy

1.	Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Circulation, 2015, 131(4): e29-322.
2.	Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J, 2015, 14: 6.
3.	Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ, 2002, 325(7374): 1202.
4.	胡大一, 徐希平. 有效控制“H型”高血壓-預防卒中的新思路. 中華內科雜志, 2008, 47(12): 976-977.
5.	Qin X, Huo Y. H-Type hypertension, stroke and diabetes in China: Opportunities for primary prevention. J Diabetes, 2016, 8(1): 38-40.
6.	Towfighi A, Markovic D, Ovbiagele B. Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: a nationwide study. J Neurol Sci, 2010, 298(1-2): 153-157.
7.	Ciaccio M, Bivona G, Bellia C. Therapeutical approach to plasma homocysteine and cardiovascular risk reduction. Ther Clin Risk Manag, 2008, 4(1): 219-224.
8.	Huo Y, Li J, Qin X, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA, 2015, 313(13): 1325-1335.
9.	Wang WW, Wang XS, Zhang ZR, et al. A meta-analysis of folic acid in combination with anti-hypertension a hyperhomocysteinemia. Front Pharmacol, 2017, 8: 585.
10.	Higgins JP, Altman DG, G?tzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ, 2011, 343: d5928.
11.	Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
12.	Yanping Li, Tianyi Huang, Yan Zheng, et al. Folic acid supplementation and the risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAHA, 2016, 5(8): e003768.
13.	Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
14.	李毅, 郭勇, 茍華, 等. 同型半胱氨酸與H型高血壓左室肥厚的相關性及馬來酸依那普利葉酸片的干預效果. 現代生物醫學進展, 2019, 19(18): 3554-3558.
15.	井元輝. 葉酸聯合降壓藥物治療H型高血壓效果. 中國民康醫學, 2019, 31(11): 12-14.
16.	孫慧萍, 張美榮. 馬來酸依那普利葉酸片對H型高血壓患者腦卒中的預防效果. 中國衛生標準管理, 2018, 9(13): 105-107.
17.	趙寶華, 張碩銳, 李長明, 等. 葉酸輔助治療對H型高血壓患者同型半胱氨酸水平及腦卒中發病率的影響. 中國藥業, 2018, 27(5): 39-41.
18.	馮立春. 葉酸聯合降壓藥物治療H型高血壓效果分析. 新鄉醫學院學報, 2018, 35(3): 196-200.
19.	周仕濤. 馬來酸依那普利葉酸片對H型高血壓腦卒中的預防作用. 臨床合理用藥雜志, 2017, 10(28): 80-82.
20.	李哲, 孫凌瑜, 譚琦, 等. 馬來酸依那普利葉酸片對H型高血壓腦卒中的預防性應用價值分析. 中國醫藥科學, 2016, 6(13): 72-75.
21.	田井強, 曾戀. 葉酸對H型高血壓患者Hcy水平及心血管意外發生的影響研究. 當代醫學, 2016, 22(13): 36-37.
22.	翟德林, 李慧. 葉酸干預治療對 H 型高血壓患者血漿同型半胱氨酸血壓水平及主要心腦血管事件的影響. 山西醫藥雜志, 2015, (14): 1672-1674.
23.	謝鋒, 李菁, 楊惠敏, 等. H型高血壓流行病學調查及低劑量葉酸的干預性研究. 中國民族民間醫藥, 2013, 22(12): 54-55.
24.	趙明枝. 葉酸對同型半胱氨酸升高型高血壓的療效觀察. 中國實用神經疾病雜志, 2012, 15(7): 63-64.
25.	Wang Y, Jin Y, Wang Y, et al. The effect of folic acid in patients with cardiovascular disease: a systematic review and meta-analysis. Medicine, 2019, 98(37): e17095.
26.	Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr, 2005, 82(4): 806-812.
27.	郭珊池. 不同劑量葉酸聯合依那普利治療H型高血壓的療效觀察. 長沙: 中南大學, 2014.
28.	石曉輝, 馬小川. 不同劑量葉酸組合依那普利片治療H型高血壓的療效分析. 延安大學學報(醫學科學版), 2013, 11(1): 1-2, 5.
29.	Han L, Wu Q, Wang C, et al. Homocysteine, ischemic stroke, and coronary heart disease in hypertensive patients: a population-based, prospective cohort study. Stroke, 2015, 46(7): 1777-1786.
30.	Lee M, Hong KS, Chang SC, et al. Efficacy of homocysteine-lowering therapy with folic acid in stroke prevention: a meta-analysis. Stroke, 2010, 41(6): 1205-1212.
31.	Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet, 2007, 369(9576): 1876-1882.
32.	孫寧玲, 秦獻輝, 李建平, 等. 依那普利葉酸片固定復方與依那普利和葉酸自由聯合在H型高血壓人群中降低同型半胱氨酸的療效比較. 中國新藥雜志, 2009, 18(17): 1635-1640.

1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Circulation, 2015, 131(4): e29-322.
2. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J, 2015, 14: 6.
3. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ, 2002, 325(7374): 1202.
4. 胡大一, 徐希平. 有效控制“H型”高血壓-預防卒中的新思路. 中華內科雜志, 2008, 47(12): 976-977.
5. Qin X, Huo Y. H-Type hypertension, stroke and diabetes in China: Opportunities for primary prevention. J Diabetes, 2016, 8(1): 38-40.
6. Towfighi A, Markovic D, Ovbiagele B. Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: a nationwide study. J Neurol Sci, 2010, 298(1-2): 153-157.
7. Ciaccio M, Bivona G, Bellia C. Therapeutical approach to plasma homocysteine and cardiovascular risk reduction. Ther Clin Risk Manag, 2008, 4(1): 219-224.
8. Huo Y, Li J, Qin X, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA, 2015, 313(13): 1325-1335.
9. Wang WW, Wang XS, Zhang ZR, et al. A meta-analysis of folic acid in combination with anti-hypertension a hyperhomocysteinemia. Front Pharmacol, 2017, 8: 585.
10. Higgins JP, Altman DG, G?tzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ, 2011, 343: d5928.
11. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
12. Yanping Li, Tianyi Huang, Yan Zheng, et al. Folic acid supplementation and the risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAHA, 2016, 5(8): e003768.
13. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109): 629-634.
14. 李毅, 郭勇, 茍華, 等. 同型半胱氨酸與H型高血壓左室肥厚的相關性及馬來酸依那普利葉酸片的干預效果. 現代生物醫學進展, 2019, 19(18): 3554-3558.
15. 井元輝. 葉酸聯合降壓藥物治療H型高血壓效果. 中國民康醫學, 2019, 31(11): 12-14.
16. 孫慧萍, 張美榮. 馬來酸依那普利葉酸片對H型高血壓患者腦卒中的預防效果. 中國衛生標準管理, 2018, 9(13): 105-107.
17. 趙寶華, 張碩銳, 李長明, 等. 葉酸輔助治療對H型高血壓患者同型半胱氨酸水平及腦卒中發病率的影響. 中國藥業, 2018, 27(5): 39-41.
18. 馮立春. 葉酸聯合降壓藥物治療H型高血壓效果分析. 新鄉醫學院學報, 2018, 35(3): 196-200.
19. 周仕濤. 馬來酸依那普利葉酸片對H型高血壓腦卒中的預防作用. 臨床合理用藥雜志, 2017, 10(28): 80-82.
20. 李哲, 孫凌瑜, 譚琦, 等. 馬來酸依那普利葉酸片對H型高血壓腦卒中的預防性應用價值分析. 中國醫藥科學, 2016, 6(13): 72-75.
21. 田井強, 曾戀. 葉酸對H型高血壓患者Hcy水平及心血管意外發生的影響研究. 當代醫學, 2016, 22(13): 36-37.
22. 翟德林, 李慧. 葉酸干預治療對 H 型高血壓患者血漿同型半胱氨酸血壓水平及主要心腦血管事件的影響. 山西醫藥雜志, 2015, (14): 1672-1674.
23. 謝鋒, 李菁, 楊惠敏, 等. H型高血壓流行病學調查及低劑量葉酸的干預性研究. 中國民族民間醫藥, 2013, 22(12): 54-55.
24. 趙明枝. 葉酸對同型半胱氨酸升高型高血壓的療效觀察. 中國實用神經疾病雜志, 2012, 15(7): 63-64.
25. Wang Y, Jin Y, Wang Y, et al. The effect of folic acid in patients with cardiovascular disease: a systematic review and meta-analysis. Medicine, 2019, 98(37): e17095.
26. Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr, 2005, 82(4): 806-812.
27. 郭珊池. 不同劑量葉酸聯合依那普利治療H型高血壓的療效觀察. 長沙: 中南大學, 2014.
28. 石曉輝, 馬小川. 不同劑量葉酸組合依那普利片治療H型高血壓的療效分析. 延安大學學報(醫學科學版), 2013, 11(1): 1-2, 5.
29. Han L, Wu Q, Wang C, et al. Homocysteine, ischemic stroke, and coronary heart disease in hypertensive patients: a population-based, prospective cohort study. Stroke, 2015, 46(7): 1777-1786.
30. Lee M, Hong KS, Chang SC, et al. Efficacy of homocysteine-lowering therapy with folic acid in stroke prevention: a meta-analysis. Stroke, 2010, 41(6): 1205-1212.
31. Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet, 2007, 369(9576): 1876-1882.
32. 孫寧玲, 秦獻輝, 李建平, 等. 依那普利葉酸片固定復方與依那普利和葉酸自由聯合在H型高血壓人群中降低同型半胱氨酸的療效比較. 中國新藥雜志, 2009, 18(17): 1635-1640.

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Efficacy of folic acid in stroke primary prevention among patients with H-Type hypertension: a meta-analysis

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