降低同型半胱氨酸预防心血管事件的试验：大型随机试验的设计与效能综述

Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials.

出版信息

Am Heart J. 2006 Feb;151(2):282-7. doi: 10.1016/j.ahj.2005.04.025.

DOI:10.1016/j.ahj.2005.04.025

Abstract

BACKGROUND

Dietary supplementation with folic acid and vitamin B12 lowers blood homocysteine concentrations by about 25% to 30% in populations without routine folic acid fortification of food and by about 10% to 15% in populations with such fortification. In observational studies, 25% lower homocysteine has been associated with about 10% less coronary heart disease (CHD) and about 20% less stroke.

METHODS

We reviewed the design and statistical power of 12 randomized trials assessing the effects of lowering homocysteine with B-vitamin supplements on risk of cardiovascular disease.

RESULTS

Seven of these trials are being conducted in populations without fortification (5 involving participants with prior CHD and 2 with prior stroke) and 5 in populations with fortification (2 with prior CHD, 2 with renal disease, and 1 with prior stroke). These trials may not involve sufficient number of vascular events or last long enough to have a good chance on their own to detect reliably plausible effects of homocysteine lowering on cardiovascular risk. But, taken together, these 12 trials involve about 52,000 participants: 32,000 with prior vascular disease in unfortified populations and 14,000 with vascular disease and 6000 with renal disease in fortified populations. Hence, a combined analysis of these trials should have adequate power to determine whether lowering homocysteine reduces the risk of cardiovascular events within just a few years.

CONCLUSION

The strength of association of homocysteine with risk of cardiovascular disease may be weaker than had previously been believed. Extending the duration of treatment in these trials would allow any effects associated with prolonged differences in homocysteine concentrations to emerge. Establishing a prospective meta-analysis of the ongoing trials of homocysteine lowering should ensure that reliable information emerges about the effects of such interventions on cardiovascular disease outcomes.

摘要

背景

在未对食品进行常规叶酸强化的人群中，通过饮食补充叶酸和维生素B12可使血液同型半胱氨酸浓度降低约25%至30%，而在进行了此类强化的人群中，可降低约10%至15%。在观察性研究中，同型半胱氨酸降低25%与冠心病（CHD）风险降低约10%以及中风风险降低约20%相关。

方法

我们回顾了12项随机试验的设计和统计效能，这些试验评估了使用B族维生素补充剂降低同型半胱氨酸对心血管疾病风险的影响。

结果

其中7项试验在未进行强化的人群中开展（5项涉及既往有冠心病的参与者，2项涉及既往有中风的参与者），5项在进行了强化的人群中开展（2项涉及既往有冠心病的参与者，2项涉及肾病患者，1项涉及既往有中风的参与者）。这些试验可能未纳入足够数量的血管事件，或持续时间不够长，以至于无法仅凭自身就有很大机会可靠地检测出降低同型半胱氨酸对心血管风险的合理影响。但是，这12项试验总共涉及约52,000名参与者：未强化人群中有32,000名既往有血管疾病，强化人群中有14,000名有血管疾病以及6000名有肾病。因此，对这些试验进行综合分析应具有足够的效能，能够在短短几年内确定降低同型半胱氨酸是否会降低心血管事件风险。