Department of Medical Biotechnology and Nanotechnology, Mashhad University of Medical Sciences, Mashhad, Iran.
Cardiometabolic Service, Department of Cardiology, Royal Perth Hospital, School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
Curr Med Chem. 2021;28(29):6066-6081. doi: 10.2174/0929867328666210208182326.
The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non- ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.
众所周知，血浆中高密度脂蛋白胆固醇（HDL-C）浓度降低与动脉粥样硬化性心血管疾病（ASCVD）风险增加呈负相关。然而，ASCVD 患者的血浆 HDL-C 浓度变化很大。在临床结局试验中，增加 HDL-C 浓度的药物治疗与 ASCVD 事件的减少无关。高密度脂蛋白胆固醇与 ASCVD 之间的因果关系也受到孟德尔随机化研究和与血浆 HDL-C 浓度相关的遗传变异的全基因组关联研究的质疑。几项流行病学研究中观察到的血浆 HDL-C 浓度与死亡率之间的 U 形关联表明，低和非常高的血浆 HDL-C 浓度都与 ASCVD 和非 ASCVD 死亡率的病因有关。这些数据并不完全支持 HDL-C 与 ASCVD 风险之间存在因果关系。因此，关于 HDL 与 ASCVD 之间关联的假设已从关注血浆浓度转移到功能概念，特别是细胞胆固醇流出和 HDL 全颗粒转运。在这篇综述中，我们专注于这些新概念，并提供了一个理解和测试 HDL 在 ASCVD 中作用的新框架。
