Department of Medicine, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York, USA.
Curr Opin Endocrinol Diabetes Obes. 2021 Apr 1;28(2):85-89. doi: 10.1097/MED.0000000000000619.
The role of triglyceride-rich lipoproteins (TRLs) in the development of atherosclerotic cardiovascular disease (ASCVD) is at the forefront of current research and treatment development programs. Despite extreme lowering of LDL-cholesterol there remains a high risk of cardiovascular disease and mortality. Recent large epidemiological, genomic wide association studies and Mendelian randomization studies have identified novel mechanisms and targets regulating TRL. This review will focus on recent and ongoing clinical trials that aim to reduce cardiovascular risk by decreasing plasma levels of TRL.
Ongoing efforts of basic and clinical scientist have described novel TRL regulating mechanism. The concentration on lifestyle changes is key to prevention and treatment guidelines. There is continue evidence that supports previous guidelines using fibrates alone and in combination with niacin to reduce TRLs, in special cases. The recent results from the REDUCE-IT study support the use of eicosapentaenoic acid (EPA) for risk reduction and ASCVD, but recently presented data from the Long-Term Outcome Study to Assess Statin Residual Risk Reduction With Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia and Omega-3 Fatty Acids in Elderly Patients With Acute Myocardial Infarction studies do not support the use of combination EPA/docosahexaenoic acid. The latter highlights the need for further studies into the pathways regulating ASCVD risk reduction after EPA administration. The identification of novel targets, such as apolipoprotein C3 and angiopoietin-like protein-3, are driving the development of novel treatments, and is the focus of this review.
The current management of elevated triglyceride levels and the effect on cardiovascular outcomes is an emerging area of research. New data from fish oil studies suggest differences in EPA vs. EPA/docosahexaenoic acid cardio protection outcomes. The preliminary data from ongoing clinical trials of novel triglyceride-lowering therapeutics are promising. These programs will ultimately provide foundations for future triglyceride-lowering guidelines.
富含甘油三酯的脂蛋白（TRLs）在动脉粥样硬化性心血管疾病（ASCVD）的发展中的作用是当前研究和治疗开发计划的前沿。尽管 LDL 胆固醇的水平已经极低，但心血管疾病和死亡率的风险仍然很高。最近的大型流行病学、全基因组关联研究和孟德尔随机化研究已经确定了调节 TRL 的新机制和靶点。本综述将重点介绍旨在通过降低 TRL 血浆水平来降低心血管风险的正在进行的临床试验。
基础和临床科学家的持续努力描述了新的 TRL 调节机制。对生活方式改变的关注是预防和治疗指南的关键。有持续的证据支持以前的指南，即单独使用贝特类药物和烟酸联合使用来降低 TRL，在特殊情况下。最近 REDUCE-IT 研究的结果支持使用二十碳五烯酸（EPA）来降低风险和 ASCVD，但最近提出的数据来自长期结果研究，以评估他汀类药物残留风险降低与 Epanova 在高心血管风险伴高甘油三酯血症患者中的应用以及老年急性心肌梗死患者中的 ω-3 脂肪酸，不支持联合使用 EPA/二十二碳六烯酸。后者强调需要进一步研究 EPA 给药后调节 ASCVD 风险降低的途径。新靶点的鉴定，如载脂蛋白 C3 和血管生成素样蛋白 3，正在推动新疗法的发展，这是本综述的重点。
目前对升高的甘油三酯水平的管理及其对心血管结局的影响是一个新兴的研究领域。来自鱼油研究的新数据表明，EPA 与 EPA/二十二碳六烯酸在心脏保护方面的结果存在差异。正在进行的新型降低甘油三酯治疗药物的临床试验的初步数据很有希望。这些项目最终将为未来的降低甘油三酯指南提供基础。
