Gabani Mohanad, Shapiro Michael D, Toth Peter P
Division of Cardiology, Wake Forest Baptist Health Winston-Salem, North Carolina, US.
CGH Medical Center Sterling, Illinois, US.
Eur Cardiol. 2023 Sep 28;18:e56. doi: 10.15420/ecr.2023.16. eCollection 2023.
Atherosclerotic cardiovascular disease (ASCVD) is the world's leading cause of death. ASCVD has multiple mediators that therapeutic interventions target, such as dyslipidaemia, hypertension, diabetes and heightened systemic inflammatory tone, among others. LDL cholesterol is one of the most well-studied and established mediators targeted for primary and secondary prevention of ASCVD. However, despite the strength of evidence supporting LDL cholesterol reduction by multiple management strategies, ASCVD events can still recur, even in patients whose LDL cholesterol has been very aggressively reduced. Hypertriglyceridaemia and elevated levels of triglyceride-rich lipoproteins (TRLs) may be key contributors to ASCVD residual risk. Several observational and genetic epidemiological studies have highlighted the causal role of triglycerides within the TRLs and/or their remnant cholesterol in the development and progression of ASCVD. TRLs consist of intestinally derived chylomicrons and hepatically synthesised very LDL. Lifestyle modification has been considered the first line intervention for managing hypertriglyceridaemia. Multiple novel targeted therapies are in development, and have shown efficacy in the preclinical and clinical phases of study in managing hypertriglyceridaemia and elevated TRLs. This comprehensive review provides an overview of the biology, pathogenicity, epidemiology, and genetics of triglycerides and TRLs, and how they impact the risk for ASCVD. In addition, we provide a summary of currently available and novel emerging triglyceride-lowering therapies in development.
动脉粥样硬化性心血管疾病（ASCVD）是全球首要死因。ASCVD有多种治疗干预所针对的介质，如血脂异常、高血压、糖尿病以及全身炎症反应增强等。低密度脂蛋白胆固醇（LDL胆固醇）是针对ASCVD一级和二级预防研究最多且最确定的介质之一。然而，尽管有证据支持通过多种管理策略降低LDL胆固醇，但即使是LDL胆固醇已大幅降低的患者，ASCVD事件仍可能复发。高甘油三酯血症和富含甘油三酯的脂蛋白（TRL）水平升高可能是ASCVD残余风险的关键因素。多项观察性和遗传流行病学研究强调了TRL中的甘油三酯和/或其残粒胆固醇在ASCVD发生和发展中的因果作用。TRL由肠道来源的乳糜微粒和肝脏合成的极低密度脂蛋白组成。生活方式改变被认为是治疗高甘油三酯血症的一线干预措施。多种新型靶向治疗方法正在研发中，并且在治疗高甘油三酯血症和升高的TRL的临床前和临床研究阶段已显示出疗效。这篇综述全面概述了甘油三酯和TRL的生物学、致病性、流行病学和遗传学，以及它们如何影响ASCVD风险。此外，我们总结了目前可用的以及正在研发的新型降甘油三酯疗法。
