Bubb Kristen J, Nelson Adam J, Nicholls Stephen J
Biomedicine Discovery Institute, Clayto, VIC, Australia.
Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Clayton, VIC, Australia.
Expert Rev Cardiovasc Ther. 2022 Mar;20(3):185-191. doi: 10.1080/14779072.2022.2058489. Epub 2022 Mar 28.
Dyslipidemia therapeutics have primarily focused on lowering levels of low-density lipoprotein cholesterol. However, many patients continue to experience cardiovascular events, despite effective lowering of LDL-C. This has prompted efforts to target additional risk factors to achieve more effective prevention of cardiovascular disease. Emerging evidence suggests that triglyceride rich lipoproteins play a causal role in atherosclerosis, highlighting the potential for specific therapeutic lowering.
(1) Evidence to support the causal role of triglyceride rich lipoproteins in atherosclerotic cardiovascular disease. (2) Use of existing lipid modifying therapies to target triglyceride rich lipoproteins. (3) Development of novel therapeutic agents that target triglyceride rich lipoproteins and their potential impact on cardiovascular risk.
EXPERT OPINION/COMMENTARY: Evidence from preclinical, observational and genetic studies highlight the role of triglyceride rich lipoproteins in the causal pathway of atherosclerotic cardiovascular disease. A number of existing agents have the potential to reduce residual cardiovascular risk associated with hypertriglyceridemia. However, emerging agents have the potential to substantially and preferentially lower triglyceride levels beyond contemporary therapeutics. How they will modulate cardiovascular risk will ultimately be determined by large clinical outcomes trials. They do provide the opportunity to substantially influence the way we target dyslipidemia in the prevention of cardiovascular disease.
血脂异常治疗主要集中在降低低密度脂蛋白胆固醇水平。然而，尽管低密度脂蛋白胆固醇得到有效降低，许多患者仍会发生心血管事件。这促使人们努力针对其他危险因素，以更有效地预防心血管疾病。新出现的证据表明，富含甘油三酯的脂蛋白在动脉粥样硬化中起因果作用，凸显了特异性治疗性降低的潜力。
（1）支持富含甘油三酯的脂蛋白在动脉粥样硬化性心血管疾病中起因果作用的证据。（2）使用现有的脂质调节疗法针对富含甘油三酯的脂蛋白。（3）开发针对富含甘油三酯的脂蛋白的新型治疗药物及其对心血管风险的潜在影响。
专家意见/评论：临床前、观察性和遗传学研究的证据凸显了富含甘油三酯的脂蛋白在动脉粥样硬化性心血管疾病因果途径中的作用。一些现有药物有可能降低与高甘油三酯血症相关的残余心血管风险。然而，新出现的药物有可能比当代疗法更显著且优先地降低甘油三酯水平。它们如何调节心血管风险最终将由大型临床结局试验来确定。它们确实提供了一个机会，可极大地影响我们在预防心血管疾病中针对血脂异常的方式。
