Wald N J, Watt H C, Law M R, Weir D G, McPartlin J, Scott J M
Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, England.
Arch Intern Med. 1998 Apr 27;158(8):862-7. doi: 10.1001/archinte.158.8.862.
Results from prospective studies of serum homocysteine levels and ischemic heart disease (IHD) are inconclusive. We carried out a further prospective study to help clarify the position.
In the British United Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years, we measured homocysteine levels in stored serum samples and analyzed data from 229 men without a history of IHD at study entry who subsequently died of IHD and 1126 age-matched control subjects (nested case-control design).
Serum homocysteine levels were significantly higher in men who died of IHD than in men who did not (mean, 13.1 vs 11.8 micromol/L; P<.001). The risk of IHD among men in the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times after adjusting for other risk factors) the risk among men in the lowest quartile (95% confidence interval [CI], 1.8-4.7). There was a continuous dose-response relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L increase in the serum homocysteine level. After adjustment for apolipoprotein B levels and blood pressure, this estimate was 33% (95% CI, 22%-59%). In a meta-analysis of the retrospective studies of homocysteine level and myocardial infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%) increase in risk for a 5-micromol/L increase in the homocysteine level, possibly because the participants were younger; the relationship between serum homocysteine level and IHD seems to be stronger in younger persons than in older persons.
Our positive results help resolve the uncertainty that resulted from previous prospective studies. The epidemiological, genetic, and animal evidence together indicate that the association between serum homocysteine level and IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be expected to reduce mortality from IHD.
血清同型半胱氨酸水平与缺血性心脏病（IHD）前瞻性研究的结果尚无定论。我们开展了一项进一步的前瞻性研究以助阐明这一情况。
在英国联合 Provident 协会（BUPA）针对 21520 名年龄在 35 至 64 岁男性的前瞻性研究中，我们测量了储存血清样本中的同型半胱氨酸水平，并分析了 229 名在研究开始时无 IHD 病史且随后死于 IHD 的男性以及 1126 名年龄匹配的对照受试者的数据（巢式病例对照设计）。
死于 IHD 的男性血清同型半胱氨酸水平显著高于未死于 IHD 的男性（均值分别为 13.1 与 11.8 μmol/L；P<0.001）。血清同型半胱氨酸水平处于最高四分位数的男性发生 IHD 的风险是最低四分位数男性的 3.7 倍（调整其他风险因素后为 2.9 倍）（95%置信区间[CI]，1.8 - 4.7）。存在连续的剂量反应关系，血清同型半胱氨酸水平每升高 5 μmol/L，风险增加 41%（95%CI，20% - 65%）。调整载脂蛋白 B 水平和血压后，这一估计值为 33%（95%CI，22% - 59%）。在同型半胱氨酸水平与心肌梗死回顾性研究的荟萃分析中，年龄调整后的关联更强：同型半胱氨酸水平每升高 5 μmol/L，风险增加 84%（95%CI，52% - 123%），这可能是因为参与者更年轻；血清同型半胱氨酸水平与 IHD 之间的关系在年轻人中似乎比在老年人中更强。
我们的阳性结果有助于解决先前前瞻性研究导致的不确定性。流行病学、遗传学和动物证据共同表明血清同型半胱氨酸水平与 IHD 之间的关联可能是因果关系。因此，普遍增加叶酸（可降低血清同型半胱氨酸水平）的摄入量有望降低 IHD 的死亡率。
