联用叶酸、维生素B6和维生素B12降低同型半胱氨酸水平影响心血管疾病风险的荟萃分析

Meta-analysis of clinical trials of folic acid, vitamin B12 and B6 supplementation on plasma homocysteine level and risk of cardiovascular disease

目的 通过荟萃分析评价联合应用叶酸、维生素B6和维生素B12降低同型半胱氨酸水平是否会影响心血管疾病的发生风险.方法 通过检索Embase、Pubmed、Ovid、Biosis、中国知网期刊数据库（CNKI）、万方、维普中文科技期刊数据库（VIP）、中国生物医学文献数据库（CBM）,获得1994年2月至2014年2月发表的有关叶酸、维生素B6和维生素B12联合应用影响心血管疾病发生风险的随机对照试验（分为维生素组与安慰剂组）.由2位研究者按照纳入和排除标准独立选择文献、提取资料和评价质量,采用Review Manager 5.2软件进行荟萃分析.采用漏斗图及Egger检验评价发表偏倚.结果 共纳入12篇文献和34 481例研究对象.纳入研究的发表偏倚较小（漏斗图示研究处于漏斗图顶部,分布均匀,左右对称;Egger检验P＞0.10）,异质性较低（卡方检验,I2＜50％）.各项研究维生素组与安慰剂组的基础同型半胱氨酸水平差异均无统计学意义（P均＞0.05）,随访期间维生素组同型半胱氨酸水平均低于安慰剂组（P均＜0.05）.荟萃分析显示,维生素组与安慰剂组之间的心血管事件、冠心病、心肌梗死和心因性死亡发生率差异均无统计学意义,其RR（95％ CI）分别为0.98（0.93 ～ 1.03）、0.97（0.87 ～1.07）、1.00（0.92 ～ 1.08）和0.92（0.82 ～ 1.03）.结论 叶酸、维生素B6和维生素B12联合应用可以降低心血管病或高危患者的同型半胱氨酸水平,但是不能降低心血管疾病的发生风险,不推荐联合使用叶酸、维生素B6和维生素B12作为心血管疾病的二级预防措施.

Objective To evaluate the effects of folic acid,vitamin B6 and B12 supplementation on plasma homocysteine level and risk of cardiovascular disease.Methods The databases,including Embase,Pubmed,Ovid,Biosis,China National Knowledge Infra-structure（CNKI）,Wanfang Data,VIP Database for Chinese Technical Periodical （VIP）,Chinese Biomedical Literature Database （CMB）,were searched to identify random control trials between February 1994 to February 2014 on the effect of folic acid,vitamin B6 and B12 supplementation on plasma homocysteine level and risk of cardiovascular disease.The screening,data extraction and quality assessment were conducted in accordance with the inclusion and exclusion criteria by two reviewers independently.The software Review Manager 5.2 was used.Funnel plots and Egger＆#39;s regression test were applied to evaluate the publication bias.Results Data from 12 studies including 34 481 patients were analyzed using a fixed-effects model.Funnel plot and Egger＆#39;s test（P 〉 0.10） confirmed the absence of publication bias.No statistically significant heterogeneity was detected on testing after excluding the sources of heterogeneity （chi-square test,I2 〈 50%）.Baseline homocysteine levels were similar between the placebo and folic acid,vitamin B6 and B12 groups （all P 〉 0.05）.Mean homocysteine levels were significantly lower with folic acid,vitamin B6 and B12 therapy compared with placebo during follow-up （all P 〈 0.05）.The pooled relative risks with 95% confidence intervals of outcomes for patients treated with folic acid,vitamin B6 and B12 supplementation compared with placebo were 0.98 （0.93-1.03） for cardiovascular event,0.97 （0.87-1.07） for coronary artery disease,1.00 （0.92-1.08） for myocardial infarction and 0.92（0.82-1.03） for cardiovascular death.Conclusions Folic aicd combined with vitamin B6 and B12 treatment significantly reduced plasma homocysteine level,but did not affect the risk of cardiovascular disease.Thus,folic acid combined with vitamin B6 and B12 should not be recommended as secondary prevention of cardiovascular diseases.