叶酸、维生素B12和B6联合使用对心脑血管病发生风险影响随机对照试验的Meta分析

Meta-analysis on effect of combined supplementation of folic acid, vitamin B12 and B6 on risk of cardio-cerebrovascular diseases in randomized control trials

目的 评价联合补充叶酸、维生素B12和B6对心脑血管疾病发生风险的影响。方法 检索1980-2014年有关补充叶酸、维生素B12和B6与心脑血管疾病发生关系的随机对照试验文献，筛选符合条件的研究。研究指标包括心脑血管疾病事件、心肌梗死及中风，效应指标为反映发生风险的相对危险度（RR）及其95%CI。运用Meta分析方法进行效应综合，并做亚组分析和敏感性分析。采用Jadad评分对文献质量进行评价。结果 共纳入11项随机对照试验研究，包含26 395名研究对象。有8项研究综合显示3种B族维生素联合使用对心脑血管疾病事件的发生无显著影响（RR=1.00，95%CI：0.94～1.07）；9项研究综合显示3种B族维生素联合使用对心肌梗死的发生无显著影响（RR=1.03，95%CI：0.94～1.13）。9项研究综合显示3种B族维生素联合使用可使中风的发生风险降低14%（RR=0.86，95%CI：0.78～0.95）。维生素B合剂组与对照组同型半胱氨酸水平比较，联合服用叶酸、维生素B12和B6能使同型半胱氨酸水平降低2.53 μmol/L（95%CI：-3.93～-1.12）；亚组分析显示，随访时间、维生素剂量、疾病史均对心脑血管疾病事件的研究结论无显著影响；而中风的亚组分析显示，随着随访时间延长，补充B族维生素能降低中风的发生风险，叶酸和维生素B12在小剂量下预防中风的作用更为显著，而维生素B6随着剂量的增加效果显著，有心脑血管病史者联合补充B族维生素降低中风风险的效果较好。结论 联合补充叶酸、维生素B12和B6对心脑血管疾病事件、心肌梗死的发生无显著影响，但可以降低中风发生的风险和同型半胱氨酸的水平。

Objective To evaluate the effect of the combined supplementation of folic acid, vitamin B12 and B6 on the risk of cardio-cerebrovascular diseases. Methods The literatures of randomized control trials about the relationship between the combined supplementation of folic acid, vitamin B12 and B6 and risk of cardio-cerebrovascular diseases from 1980 to 2014 were retrieved, and the eligible studies were screened for a Meta-analysis. The study indicators were the incidences of cardiovascular disease events, myocardial infarction and stroke. The cffect indicators were relative risk （RR） and 95% confidence interval （CI）. Jadad score was used for the quality evaluation of the trials used in the study. Results The literatures of 11 randomized control trials, involving 26 395 patients, were used in the Meta-analysis. The combined supplementation of B vitamins had no effect on the incidence of cardiovascular disease events （RR=1.00, 95%CI：0.94-1.07） based on 8 studies. The combined supplementation of B vitamins had no effect on the incidence of myocardial infarction （RR=1.03, 95%CI：0.94-1.13） based on 9 studies. The combined supplementation of B vitamins could reduce the incidence of stroke by 14% （RR=0.86, 95%CI：0.78-0.95） based on 9 studies. Compared with the control group, Taking folic acid combined with vitamin B12 and B6 could reduce the level of homocysteine by 2.53 μmol/L （95%CI：-3.93-1.12）. Subgroup analysis indicated that the follow-up time, the dosage of folic acid and vitamin B12 and B6, the history of diseases had no confounding effect on the incidence of cardio-cerebrovascular disease events. But the subgroup analysis for stroke showed that with the extension of follow-up time, the supplementation of B vitamins could reduce the risk of stroke. The effect of folic acid and B12 in small dosage seemed more significant in the prevention of stroke, while the preventive effect of B6 increased with increasing dosage. The preventive effect of combined supplementation of B vitamins was more significant for the patients with a history of cardio-cerebrovascular diseases. Conclusion Taking folic acid combined with vitamin B6 and B12 might have no significant effect on the incidences of cardio-cerebrovascular disease events and myocardial infarction, but could lower the risk of stroke and the level of homocysteine.