Hodis Howard N, Mack Wendy J, Dustin Laurie, Mahrer Peter R, Azen Stanley P, Detrano Robert, Selhub Jacob, Alaupovic Petar, Liu Chao-ran, Liu Ci-hua, Hwang Juliana, Wilcox Alison G, Selzer Robert H
Atherosclerosis Research Unit, Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, Calif. 90033, USA.
Stroke. 2009 Mar;40(3):730-6. doi: 10.1161/STROKEAHA.108.526798. Epub 2008 Dec 31.
Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression.
In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 micromol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B(12)+50 mg vitamin B(6)) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome).
Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (P=0.31). However, among subjects with baseline tHcy >or=9.1 micromol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (P=0.02); among subjects with a baseline tHcy <9.1 micromol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups.
High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin "replete" individuals at low risk for cardiovascular disease with a fasting tHcy >or=9.1 micromol/L.
尽管血浆总同型半胱氨酸（tHcy）水平与心血管疾病相关，但同型半胱氨酸是动脉粥样硬化性血管疾病的病因还是标志物仍不明确。我们确定补充B族维生素降低tHcy水平是否能减少亚临床动脉粥样硬化进展。
在这项双盲临床试验中，将506名年龄在40至89岁、初始tHcy>8.5微摩尔/升且无糖尿病和心血管疾病的参与者随机分为高剂量B族维生素补充组（5毫克叶酸+0.4毫克维生素B12+50毫克维生素B6）或匹配的安慰剂组，为期3.1年。使用高分辨率B型超声测量颈动脉内膜中层厚度（主要结局），并使用多排螺旋CT测量主动脉和冠状动脉钙化（次要结局），评估3个血管床的亚临床动脉粥样硬化进展情况。
尽管补充B族维生素组的总体颈动脉内膜中层厚度进展率低于安慰剂组，但未发现组间有统计学显著差异（P=0.31）。然而，在基线tHcy≥9.1微摩尔/升的受试者中，随机分配到B族维生素补充组的受试者与安慰剂组相比，颈动脉内膜中层厚度进展的平均速率有统计学显著降低（P=0.02）；在基线tHcy<9.1微摩尔/升的受试者中，没有显著的治疗效果（治疗交互作用的概率值=0.02）。补充B族维生素对主动脉或冠状动脉钙化的总体进展或亚组内进展均无影响。
在空腹tHcy≥9.1微摩尔/升、心血管疾病风险低且营养良好的健康B族维生素“充足”个体中，高剂量补充B族维生素可显著降低早期亚临床动脉粥样硬化（颈动脉内膜中层厚度）的进展。
