B族维生素干预血浆同型半胱氨酸水平防治心脑血管疾病作用的Meta分析_《中国循证医学杂志》

作者：

张琛 ^1,2 ,  朱惠莲 ¹

1. 中山大学公共卫生学院营养学系（广州 510080）；2. 广州医学院图书馆（广州 510182）;

关键词：

B 族维生素同型半胱氨酸心脑血管疾病 Meta 分析

DOI：

10.7507/1672-2531.20090013

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的　评价通过补充B 族维生素降低血浆同型半胱氨酸（Hcy）水平对心脑血管疾病的防治作用。
方法　以“homocysteine”、“cardiovascular disease”、“cerebrovascular disease”、“B vitamins”、“randomized controlledtrial”等为检索词，检索PubMed、Ovid、Springer 等电子数据库；并同时运用手工检索和文献追溯手段，收集国外1998 ～ 2008 年6 月公开发表的关于补充B 族维生素干预血浆同型半胱氨酸水平的随机对照试验。两名评价者独立依据纳入和排除标准筛选文献，提取资料并进行方法学质量评估。统计学分析采用RevMan 4.2 软件。
结果　共纳入16 个随机对照试验（共27 043 例）。Meta 分析结果表明，干预组与对照组之间心血管事件（CVE）、冠心病（CHD）、脑卒中和总病死率的差异均无统计学意义，其RR（95%CI）分别为0.98（0.94，1.03）、0.99（0.92，1.07）、0.90（0.80，1.02）、0.98（0.92，1.05）。剔除评分较低的研究后做敏感性分析，结果不变。
结论　 ① 目前的研究尚未能证实同型半胱氨酸和心脑血管疾病之间存在因果关系，尚需大量大规模的前瞻性随机对照试验来验证。② 目前还没有足够证据说明补充B 族维生素会减少心血管事件发生的危险，故不推荐把补充B 族维生素作为心脑血管疾病的二级预防措施。

引用本文： 张琛,朱惠莲. B族维生素干预血浆同型半胱氨酸水平防治心脑血管疾病作用的Meta分析. 中国循证医学杂志, 2009, 09(1): 55-62. doi: 10.7507/1672-2531.20090013 复制

1.	孔灵芝, 胡盛寿. 中国心血管病报告. 北京: 中国大百科全书出版社. 2008, 4.
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3.	The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke. JAMA, 2002, 16: 2015-2022.
4.	Sackett DL, Clarke M, Oxman AD, et al. Cochrane Reviewers, Handbook 4.2,In Review Manager.Versions 4.2.Oxford, England: The cochrane collaboration, 2002, 13-36.
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6.	Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteinelowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention:the Swiss Heart Study: a randomized controlled trial. JAMA, 2002, 288: 973-979.
7.	Righetti M, Ferrario GM, Milani S, et al. Effects of folic acid treatment on homocysteine levels and vascular disease in hemodialysis patients. Med Sci Monit, 2003, 9: P119-P124.
8.	Lange H, Suryapranata H, De Luca G, et al. Folate therapy and instent restenosis after coronary stenting. N Engl J Med, 2004, 350: 2673-2681.
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10.	Wrone EM, Hornberger JM, Zehnder JL, et al. Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease. J Am Soc Nephrol, 2004, 15: 420-426.
11.	Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, et al. Secondary prevention with folic acid: results of the Goes extension study. Heart, 2005, 91: 1213-1214.
12.	Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med, 2006, 354: 1578-1588.
13.	Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med, 2006, 354: 1567-1577.
14.	Righetti M, Serbelloni P, Johansson I, et al. Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients. Blood Purif, 2006, 24: 379-386.
15.	Zoungas S, McGrath BP, Branley P, et al. Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial. J Am Coll Cardiol, 2006, 47: 1108-1116.
16.	Haijer M, Willems HP, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism:a randomized, placebo-controlled, doubleblind trial. Blood, 2007, 109: 139-144.
17.	Jamison RL, Hartigan P, Kaufman JS, et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA, 2007, 298(10): 1163-1170.
18.	Ebbing Marta. the European Society of Cardiology Congress 2007.
19.	Albert CM, Cook NR, Gaziano JM, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA, 2008, 299(17): 2027-2036.
20.	Mann JF, Sheridan P, McQueen MJ, et al. Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease- -results of the renal Hope-2 study. Nephrol Dial Transplant, 2008, 23(2): 645-653.
21.	Wald NJ. Folic acid and the prevention of neural-tube defects. N Engl J Med, 2004, 350: 101-103．.
22.	Bor MV, Refsum H, Bisp MR, et al. Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment:a randomized placebocontrolled study. Clin Chem, 2003, 49: 155-161.
23.	Matsubara K, Mori M, Matsuura Y, et al. Pyridoxal 5-phosphate and pyridoxal inhibit angiogenesis in serum-free rat aortic ring assay. Int J Mol Med, 2001, 8: 505-508.
24.	Ulrich CM, Potter JD. Folate and cancer--timing is everything. JAMA, 2007, 297(21): 2408-2409.
25.	Moat SJ, Doshi SN, Lang D, et al. Treatment of coronary heart disease with folic acid: Is there a future? Am J Physiol Heart Circ Physiol, 2004, 287: H1-H7.
26.	Kothekar MA. Homocysteine in cardiovascular disease: A culprit or an innocent bystander? Indian J Med Sci, 2007, 61(6): 361-371.
27.	Bostom AG, Carpenter MA, Kusek Jw, et al. Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation(FAVORIT) trial. Am Heart J, 2006, 152: 448.e1-7.
28.	SEARCH Study Collaborative Group. Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12064 myocardial infarction survivors. Am Heart J, 2007, 154: 815-823.
29.	VITATOPS Trial Study Group. VITATOPS, the vitamins to prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke. Int J Stroke, 2007, 2(2): 144-150.

1. 孔灵芝, 胡盛寿. 中国心血管病报告. 北京: 中国大百科全书出版社. 2008, 4.
2. Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA, 1995, 274: 1049-1057.
3. The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke. JAMA, 2002, 16: 2015-2022.
4. Sackett DL, Clarke M, Oxman AD, et al. Cochrane Reviewers, Handbook 4.2,In Review Manager.Versions 4.2.Oxford, England: The cochrane collaboration, 2002, 13-36.
5. Baker F, Picton D, Blackwood S, et al. Blinded comparison of folic acid and placebo in patients with ischemic heart disease: an outcome trial [abstract]. Circulation, 2002, 106(suppl 2): 741S.
6. Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteinelowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention:the Swiss Heart Study: a randomized controlled trial. JAMA, 2002, 288: 973-979.
7. Righetti M, Ferrario GM, Milani S, et al. Effects of folic acid treatment on homocysteine levels and vascular disease in hemodialysis patients. Med Sci Monit, 2003, 9: P119-P124.
8. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and instent restenosis after coronary stenting. N Engl J Med, 2004, 350: 2673-2681.
9. Toole JF, Mal inow MR, Chambles s LE, e t al . Lower ing homocysteine in patients with ischemic stroke to prevent recurrent stroke,myocardial infarction,and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA, 2004, 291: 565-575.
10. Wrone EM, Hornberger JM, Zehnder JL, et al. Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease. J Am Soc Nephrol, 2004, 15: 420-426.
11. Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, et al. Secondary prevention with folic acid: results of the Goes extension study. Heart, 2005, 91: 1213-1214.
12. Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med, 2006, 354: 1578-1588.
13. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med, 2006, 354: 1567-1577.
14. Righetti M, Serbelloni P, Johansson I, et al. Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients. Blood Purif, 2006, 24: 379-386.
15. Zoungas S, McGrath BP, Branley P, et al. Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial. J Am Coll Cardiol, 2006, 47: 1108-1116.
16. Haijer M, Willems HP, Blom HJ, et al. Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism:a randomized, placebo-controlled, doubleblind trial. Blood, 2007, 109: 139-144.
17. Jamison RL, Hartigan P, Kaufman JS, et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA, 2007, 298(10): 1163-1170.
18. Ebbing Marta. the European Society of Cardiology Congress 2007.
19. Albert CM, Cook NR, Gaziano JM, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA, 2008, 299(17): 2027-2036.
20. Mann JF, Sheridan P, McQueen MJ, et al. Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease- -results of the renal Hope-2 study. Nephrol Dial Transplant, 2008, 23(2): 645-653.
21. Wald NJ. Folic acid and the prevention of neural-tube defects. N Engl J Med, 2004, 350: 101-103．.
22. Bor MV, Refsum H, Bisp MR, et al. Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment:a randomized placebocontrolled study. Clin Chem, 2003, 49: 155-161.
23. Matsubara K, Mori M, Matsuura Y, et al. Pyridoxal 5-phosphate and pyridoxal inhibit angiogenesis in serum-free rat aortic ring assay. Int J Mol Med, 2001, 8: 505-508.
24. Ulrich CM, Potter JD. Folate and cancer--timing is everything. JAMA, 2007, 297(21): 2408-2409.
25. Moat SJ, Doshi SN, Lang D, et al. Treatment of coronary heart disease with folic acid: Is there a future? Am J Physiol Heart Circ Physiol, 2004, 287: H1-H7.
26. Kothekar MA. Homocysteine in cardiovascular disease: A culprit or an innocent bystander? Indian J Med Sci, 2007, 61(6): 361-371.
27. Bostom AG, Carpenter MA, Kusek Jw, et al. Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation(FAVORIT) trial. Am Heart J, 2006, 152: 448.e1-7.
28. SEARCH Study Collaborative Group. Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12064 myocardial infarction survivors. Am Heart J, 2007, 154: 815-823.
29. VITATOPS Trial Study Group. VITATOPS, the vitamins to prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke. Int J Stroke, 2007, 2(2): 144-150.

《中国循证医学杂志》

B族维生素干预血浆同型半胱氨酸水平防治心脑血管疾病作用的Meta分析

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《中国循证医学杂志》

B族维生素干预血浆同型半胱氨酸水平防治心脑血管疾病作用的Meta分析

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