Homocysteine metabolism and risk of myocardial infarction: Relation with vitamins B-6, B-12, and folate
Homocysteine metabolism and risk of myocardial infarction: Relation with vitamins B-6, B-12, and folate
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DOI：
10.1093/oxfordjournals.aje.a008828
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发表时间：
1996-05-01
影响因子：
5
通讯作者：
Willett, WC
中科院分区：
文献类型：
--
作者：
Verhoef, P;Stampfer, MJ;Willett, WC
血浆同型半胱氨酸水平升高是血管疾病的独立危险因素。在一项病例对照研究中，作者研究了空腹血浆同型半胱氨酸和维生素（同型半胱氨酸代谢的重要辅助因子）与心肌梗死风险的关系。这些病例是1982年和1983年登记的130名波士顿地区首次心肌梗死住院患者和118名年龄小于76岁的对照人群。维生素B-6、B-12和叶酸的膳食摄入量通过食物频率问卷进行估计。校正性别和年龄后，作者发现病例组血浆同型半胱氨酸水平的几何平均值比对照组高11%（p = 0.006）。没有明显过量的病例水平极高。血浆同型半胱氨酸每增加9 μ mol/L（约1个标准差），经年龄和性别校正的比值比为1.35（95%置信区间1.05-1.75; p趋势= 0.007）。在进一步控制其他几个风险因素后，比值比没有受到影响，但置信区间更宽，趋势的p值不太显著。膳食和血浆中维生素B-6和叶酸水平在病例组低于对照组，这些维生素与心肌梗死风险呈负相关，独立于其他潜在风险因素。维生素B-12与心肌梗死无明显相关性，尽管在病例中甲基丙二酸水平显著升高。通过比较病例组和对照组中几种同型半胱氨酸代谢物的平均水平，作者发现同型半胱氨酸再甲基化受损（依赖于叶酸和维生素B-12，而不是维生素B-6依赖的转硫作用）是病例中同型半胱氨酸水平升高的主要原因。因此，血浆叶酸和（在较小程度上）血浆维生素B-12（但不是血浆维生素B-6）与血浆同型半胱氨酸呈负相关，即使浓度处于正常值的高端。这些数据进一步证明血浆同型半胱氨酸是心肌梗死的独立危险因素。在这一人群中，叶酸是血浆同型半胱氨酸最重要的决定因素，即使在这种维生素明显充足的营养状况下也是如此。
Elevated plasma homocyst(e)ine levels are an independent risk factor for vascular disease. In a case-control study, the authors studied the associations of fasting plasma homocyst(e)ine and vitamins, which are important cofactors in homocysteine metabolism, with the risk of myocardial infarction. The cases were 130 Boston area patients hospitalized with a first myocardial infarction and 118 population controls, less than 76 years of age, enrolled in 1982 and 1983. Dietary intakes of vitamins B-6, B-12, and folate were estimated from a food frequency questionnaire. After adjusting for sex and age, the authors found that the geometric mean plasma homocyst(e)ine level was 11% higher in cases compared with controls (p = 0.006). There was no clear excess of cases with extremely elevated levels. The age- and sex-adjusted odds ratio for each 9-mu mol/liter (approximately 1 standard deviation) increase in plasma homocyst(e)ine was 1.35 (95% confidence interval 1.05-1.75; p trend = 0.007). After further control for several other risk factors, the odds ratio was not affected, but the confidence interval was wider and the p value for trend was less significant. Dietary and plasma levels of vitamin B-6 and folate were lower in cases than in controls, and these vitamins were inversely associated with the risk of myocardial infarction, independently of other potential risk factors. Vitamin B-12 showed no clear association with myocardial infarction, although methylmalonic acid levels were significantly higher in cases. Comparing the mean levels of several homocysteine metabolites among cases and controls, the authors found that impairment of remethylation of homocyst(e)ine (dependent on folate and vitamin B-12 rather than on vitamin B-6-dependent transsulfuration) was the predominant cause of high homocyst(e)ine levels in cases. Accordingly, plasma folate and, to a lesser extent, plasma vitamin B-12, but not plasma vitamin B-6, correlated inversely with plasma homocyst(e)ine, even for concentrations at the high end of normal values. These data provide further evidence that plasma homomocyst(e)ine is an independent risk factor for myocardial infarction. In this population, folate was the most important determinant of plasma homocyst(e)ine, even in subjects with apparently adequate nutritional status of this vitamin.