Patients with well-controlled LDL (low-density lipoprotein) levels still have residual cardiovascular risk associated with elevated triglycerides. Epidemiological studies have shown that elevated fasting triglyceride levels associate independently with incident cardiovascular events, and abundant recent human genetic data support the causality of TGRLs (triglyceride-rich lipoproteins) in atherothrombosis. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower blood triglyceride concentrations but likely exert additional atheroprotective properties at higher doses. Omega-3 fatty acids modulate T-cell differentiation and give rise to various prostaglandins and specialized proresolving lipid mediators that promote resolution of tissue injury and inflammation. The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) with an EPA-only formulation lowered a composite of cardiovascular events by 25% in patients with established cardiovascular disease or diabetes mellitus and other cardiovascular risk factors. This clinical benefit likely arises from multiple molecular mechanisms discussed in this review. Indeed, human plaques readily incorporate EPA, which may render them less likely to trigger clinical events. EPA and DHA differ in their effects on membrane structure, rates of lipid oxidation, inflammatory biomarkers, and endothelial function as well as tissue distributions. Trials that have evaluated DHA-containing high-dose omega-3 fatty acids have thus far not shown the benefits of EPA alone demonstrated in REDUCE-IT. This review will consider the mechanistic evidence that helps to understand the potential mechanisms of benefit of EPA.

中文翻译：

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Omega-3脂肪酸二十碳五烯酸的心血管保护新兴机制。

LDL（低密度脂蛋白）水平得到良好控制的患者仍然存在与甘油三酸酯升高相关的残留心血管风险。流行病学研究表明，空腹甘油三酯水平升高与心血管事件无关，并且最近的大量人类遗传数据支持TGRLs（富含甘油三酸酯的脂蛋白）在动脉粥样硬化中的因果关系。诸如二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）之类的Omega-3脂肪酸可降低血液中甘油三酸酯的浓度，但在高剂量时可能具有附加的抗动脉粥样硬化特性。Omega-3脂肪酸可调节T细胞分化，并产生各种前列腺素和专门的可分解脂质的介质，从而促进组织损伤和炎症的消退。仅采用EPA制剂的REDUCE-IT（通过艾考索芬乙基干预试验减少心血管事件）可将已确诊患有心血管疾病或糖尿病和其他心血管危险因素的患者的心血管事件复合降低25％。该临床益处可能来自本综述中讨论的多种分子机制。确实，人斑易于掺入EPA，这可能使它们不太可能触发临床事件。EPA和DHA对膜结构，脂质氧化速率，炎性生物标志物和内皮功能以及组织分布的影响不同。迄今为止，评估含DHA的高剂量omega-3脂肪酸的试验尚未显示出REDUCE-IT中单独使用EPA的益处。