Boushey C J, Beresford S A, Omenn G S, Motulsky A G
Northwest Prevention Effectiveness Center, University of Washington, Seattle 98195-7236, USA.
JAMA. 1995 Oct 4;274(13):1049-57. doi: 10.1001/jama.1995.03530130055028.
To determine the risk of elevated total homocysteine (tHcy) levels for arteriosclerotic vascular disease, estimate the reduction of tHcy by folic acid, and calculate the potential reduction of coronary artery disease (CAD) mortality by increasing folic acid intake.
MEDLINE search for meta-analysis of 27 studies relating homocysteine to arteriosclerotic vascular disease and 11 studies of folic acid effects on tHcy levels.
Studies dealing with CAD, cerebrovascular disease, and peripheral arterial vascular disease were selected. Three prospective and six population-based case-control studies were considered of high quality. Five cross-sectional and 13 other case-control studies were also included. Causality of tHcy's role in the pathogenesis of vascular disease was inferred because of consistency across studies by different investigators using different methods in different populations.
Elevations in tHcy were considered an independent graded risk factor for arteriosclerotic vascular diseases. The odds ratio (OR) for CAD of a 5-mumol/L tHcy increment is 1.6 (95% confidence interval [CI], 1.4 to 1.7) for men and 1.8 (95% CI, 1.3 to 1.9) for women. A total of 10% of the population's CAD risk appears attributable to tHcy. The OR for cerebrovascular disease (5-mumol/L tHcy increment) is 1.5 (95% CI, 1.3 to 1.9). Peripheral arterial disease also showed a strong association. Increased folic acid intake (approximately 200 micrograms/d) reduces tHcy levels by approximately 4 mumol/L. Assuming that lower tHcy levels decrease CAD mortality, we calculated the effect of (1) increased dietary folate, (2) supplementation by tablets, and (3) grain fortification. Under different assumptions, 13,500 to 50,000 CAD deaths annually could be avoided; fortification of food had the largest impact.
A 5-mumol/L tHcy increment elevates CAD risk by as much as cholesterol increases of 0.5 mmol/L (20 mg/dL). Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease. Clinical trials are urgently needed. Concerns about masking cobalamin deficiency by folic acid could be lessened by adding 1 mg of cobalamin to folic acid supplements.
确定总同型半胱氨酸（tHcy）水平升高与动脉硬化性血管疾病的风险，评估叶酸降低tHcy的效果，并计算通过增加叶酸摄入量可能降低的冠状动脉疾病（CAD）死亡率。
通过MEDLINE检索，对27项有关同型半胱氨酸与动脉硬化性血管疾病的研究以及11项叶酸对tHcy水平影响的研究进行荟萃分析。
选取了涉及CAD、脑血管疾病和外周动脉血管疾病的研究。三项前瞻性研究和六项基于人群的病例对照研究被认为质量较高。还纳入了五项横断面研究和13项其他病例对照研究。由于不同研究者在不同人群中使用不同方法进行的研究结果具有一致性，因此推断tHcy在血管疾病发病机制中的作用具有因果关系。
tHcy升高被认为是动脉硬化性血管疾病的一个独立的分级风险因素。tHcy每增加5 μmol/L，男性患CAD的比值比（OR）为1.6（95%置信区间[CI]，1.4至1.7），女性为1.8（95% CI，1.3至1.9）。人群中约10%的CAD风险似乎归因于tHcy。脑血管疾病（tHcy增加5 μmol/L）的OR为1.5（95% CI，1.3至1.9）。外周动脉疾病也显示出很强的相关性。增加叶酸摄入量（约200微克/天）可使tHcy水平降低约4 μmol/L。假设较低的tHcy水平可降低CAD死亡率，我们计算了（1）增加膳食叶酸、（2）片剂补充和（3）谷物强化的效果。在不同假设下，每年可避免13,500至50,000例CAD死亡；食品强化的影响最大。
tHcy每增加5 μmol/L，CAD风险升高的幅度与胆固醇增加0.5 mmol/L（20 mg/dL）相当。通过降低tHcy水平增加叶酸摄入量有望预防动脉硬化性血管疾病。迫切需要进行临床试验。通过在叶酸补充剂中添加1毫克钴胺素，可减少对叶酸掩盖钴胺素缺乏的担忧。
