Current Atherosclerosis Reports ( IF 5.7 ) Pub Date : 2022-12-29 , DOI: 10.1007/s11883-022-01075-x Samuel C R Sherratt 1, 2 , Peter Libby 3 , Matthew J Budoff 4 , Deepak L Bhatt 5 , R Preston Mason 2, 3
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Purpose of Review
The omega-3 fatty acids (n3-FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have recently undergone testing for their ability to reduce residual cardiovascular (CV) risk among statin-treated subjects. The outcome trials have yielded highly inconsistent results, perhaps attributable to variations in dosage, formulation, and composition. In particular, CV trials using icosapent ethyl (IPE), a highly purified ethyl ester of EPA, reproducibly reduced CV events and progression of atherosclerosis compared with mixed EPA/DHA treatments. This review summarizes the mechanistic evidence for differences among n3-FAs on the development and manifestations of atherothrombotic disease.
Recent Findings
Large randomized clinical trials with n3-FAs have produced discordant outcomes despite similar patient profiles, doses, and triglyceride (TG)-lowering effects. A large, randomized trial with IPE, a prescription EPA only formulation, showed robust reduction in CV events in statin treated patients in a manner proportional to achieved blood EPA concentrations. Multiple trials using mixed EPA/DHA formulations have not shown such benefits, despite similar TG lowering. These inconsistencies have inspired investigations into mechanistic differences among n3-FAs, as EPA and DHA have distinct membrane interactions, metabolic products, effects on cholesterol efflux, antioxidant properties, and tissue distribution. EPA maintains normal membrane cholesterol distribution, enhances endothelial function, and in combination with statins improves features implicated in plaque stability and reduces lipid content of plaques.
Summary
Insights into reductions in residual CV risk have emerged from clinical trials using different formulations of n3-FAs. Among high-risk patients on contemporary care, mixed n3-FA formulations showed no reduction in CV events. The distinct benefits of IPE in multiple trials may arise from pleiotropic actions that correlate with on-treatment EPA levels beyond TG-lowering. These effects include altered platelet function, inflammation, cholesterol distribution, and endothelial dysfunction. Elucidating such mechanisms of vascular protection for EPA may lead to new interventions for atherosclerosis, a disease that continues to expand worldwide.
中文翻译：
Omega-3 脂肪酸在心血管疾病中的作用：争论仍在继续
审查目的
omega-3 脂肪酸 (n3-FAs)、二十碳五烯酸 (EPA) 和二十二碳六烯酸 (DHA) 最近在接受他汀类药物治疗的受试者中进行了降低残余心血管 (CV) 风险的能力测试。结果试验产生了高度不一致的结果，这可能归因于剂量、配方和成分的变化。特别是，与混合 EPA/DHA 治疗相比，使用高度纯化的 EPA 乙酯二十碳五烯乙酯 (IPE) 的 CV 试验可重复地减少 CV 事件和动脉粥样硬化的进展。本综述总结了 n3-FA 在动脉粥样硬化血栓形成疾病的发展和表现方面存在差异的机制证据。
最近的发现
尽管患者情况、剂量和甘油三酯 (TG) 降低效果相似，但使用 n3-FA 的大型随机临床试验产生了不一致的结果。一项使用 IPE（一种仅使用 EPA 的处方制剂）进行的大型随机试验表明，他汀类药物治疗患者的 CV 事件以与达到的血液 EPA 浓度成正比的方式显着降低。使用混合 EPA/DHA 配方的多项试验并未显示出此类益处，尽管 TG 降低程度相似。这些不一致激发了对 n3-FA 之间机制差异的研究，因为 EPA 和 DHA 具有不同的膜相互作用、代谢产物、对胆固醇流出的影响、抗氧化特性和组织分布。EPA维持正常的膜胆固醇分布，增强内皮功能，
概括
使用不同 n3-FA 配方的临床试验已经出现了对降低残余 CV 风险的见解。在接受现代护理的高危患者中，混合 n3-FA 制剂未显示 CV 事件减少。IPE 在多项试验中的独特优势可能来自多效性作用，这些作用与除 TG 降低之外的治疗 EPA 水平相关。这些影响包括改变血小板功能、炎症、胆固醇分布和内皮功能障碍。阐明 EPA 的这种血管保护机制可能会导致针对动脉粥样硬化的新干预措施，动脉粥样硬化是一种在全球范围内持续蔓延的疾病。
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