Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
N Engl J Med. 2010 Nov 18;363(21):2015-26. doi: 10.1056/NEJMoa1003603. Epub 2010 Aug 28.
Results from prospective cohort studies and randomized, controlled trials have provided evidence of a protective effect of n-3 fatty acids against cardiovascular diseases. We examined the effect of the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and of the plant-derived alpha-linolenic acid (ALA) on the rate of cardiovascular events among patients who have had a myocardial infarction.
In a multicenter, double-blind, placebo-controlled trial, we randomly assigned 4837 patients, 60 through 80 years of age (78% men), who had had a myocardial infarction and were receiving state-of-the-art antihypertensive, antithrombotic, and lipid-modifying therapy to receive for 40 months one of four trial margarines: a margarine supplemented with a combination of EPA and DHA (with a targeted additional daily intake of 400 mg of EPA-DHA), a margarine supplemented with ALA (with a targeted additional daily intake of 2 g of ALA), a margarine supplemented with EPA-DHA and ALA, or a placebo margarine. The primary end point was the rate of major cardiovascular events, which comprised fatal and nonfatal cardiovascular events and cardiac interventions. Data were analyzed according to the intention-to-treat principle, with the use of Cox proportional-hazards models.
The patients consumed, on average, 18.8 g of margarine per day, which resulted in additional intakes of 226 mg of EPA combined with 150 mg of DHA, 1.9 g of ALA, or both, in the active-treatment groups. During the follow-up period, a major cardiovascular event occurred in 671 patients (13.9%). Neither EPA-DHA nor ALA reduced this primary end point (hazard ratio with EPA-DHA, 1.01; 95% confidence interval [CI], 0.87 to 1.17; P=0.93; hazard ratio with ALA, 0.91; 95% CI, 0.78 to 1.05; P=0.20). In the prespecified subgroup of women, ALA, as compared with placebo and EPA-DHA alone, was associated with a reduction in the rate of major cardiovascular events that approached significance (hazard ratio, 0.73; 95% CI, 0.51 to 1.03; P=0.07). The rate of adverse events did not differ significantly among the study groups.
Low-dose supplementation with EPA-DHA or ALA did not significantly reduce the rate of major cardiovascular events among patients who had had a myocardial infarction and who were receiving state-of-the-art antihypertensive, antithrombotic, and lipid-modifying therapy. (Funded by the Netherlands Heart Foundation and others; ClinicalTrials.gov number, NCT00127452.).
前瞻性队列研究和随机对照试验的结果提供了 n-3 脂肪酸对心血管疾病具有保护作用的证据。我们研究了海洋 n-3 脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）以及植物衍生的α-亚麻酸（ALA）对心肌梗死后患者心血管事件发生率的影响。
在一项多中心、双盲、安慰剂对照试验中，我们随机分配了 4837 名年龄在 60 至 80 岁之间（78%为男性）、曾患心肌梗死并接受最先进的降压、抗血栓和调脂治疗的患者，接受 40 个月的四种试验人造黄油中的一种：一种添加 EPA 和 DHA 的人造黄油（目标额外每日摄入 400 毫克 EPA-DHA），一种添加 ALA 的人造黄油（目标额外每日摄入 2 克 ALA），一种添加 EPA-DHA 和 ALA 的人造黄油，或安慰剂人造黄油。主要终点是主要心血管事件的发生率，包括致命和非致命心血管事件和心脏介入。数据根据意向治疗原则进行分析，并使用 Cox 比例风险模型。
患者平均每天食用 18.8 克人造黄油，这导致在活性治疗组中额外摄入 226 毫克 EPA 与 150 毫克 DHA、1.9 克 ALA 或两者的混合物。在随访期间，671 名患者（13.9%）发生主要心血管事件。EPA-DHA 或 ALA 均未降低这一主要终点（EPA-DHA 的风险比为 1.01；95%置信区间 [CI]，0.87 至 1.17；P=0.93；ALA 的风险比为 0.91；95%CI，0.78 至 1.05；P=0.20）。在预先指定的女性亚组中，ALA 与安慰剂和 EPA-DHA 单独相比，主要心血管事件的发生率降低接近显著水平（风险比，0.73；95%CI，0.51 至 1.03；P=0.07）。研究组之间的不良事件发生率无显著差异。
低剂量补充 EPA-DHA 或 ALA 并未显著降低接受最先进降压、抗血栓和调脂治疗的心肌梗死后患者的主要心血管事件发生率。（由荷兰心脏基金会等资助；ClinicalTrials.gov 编号，NCT00127452）。
