Department of Internal Medicine, Emory University School of Medicine, USA.
Division of Cardiology, Emory University School of Medicine, USA.
Eur J Prev Cardiol. 2021 Apr 10;28(2):166–173. doi: 10.1177/2047487319848214. Epub 2019 May 13.
The measurement of high-density lipoprotein cholesterol is highly utilized by clinicians to help predict cardiovascular risk, but this measure is not causally associated with atherosclerotic cardiovascular disease events. The use of Mendelian randomization studies has led to a change in investigative attention from the high-density lipoprotein cholesterol concentration to its physiological functions. High-density lipoprotein plays key roles in important pathways related to the development of atherosclerotic disease including reverse cholesterol transport, oxidation and inflammation, and endothelial function as well as in other physiological systems including immune system modulation, cellular apoptosis, and endothelial progenitor cell homeostasis. The identification of dysfunctional high-density lipoprotein may better predict future cardiovascular events compared to numerical high-density lipoprotein cholesterol and aid in enhanced clinical risk stratification. The emergence of discrete physiological measurements of high-density lipoprotein, such as cholesterol efflux capacity and the high-density lipoprotein inflammatory index, may provide an opportunity for clinical application in the future. However, the validity of these measurements and their commercial availability remain barriers to a realistic transition to clinical medicine.
高密度脂蛋白胆固醇的测量被临床医生广泛用于帮助预测心血管风险，但该指标与动脉粥样硬化性心血管疾病事件并无因果关系。孟德尔随机研究的应用使得研究重点从高密度脂蛋白胆固醇浓度转移到其生理功能上。高密度脂蛋白在与动脉粥样硬化疾病发展相关的重要途径中发挥关键作用，包括胆固醇逆转运、氧化和炎症以及内皮功能，同时也在包括免疫系统调节、细胞凋亡和内皮祖细胞动态平衡在内的其他生理系统中发挥作用。与单纯的高密度脂蛋白胆固醇数值相比，功能失调的高密度脂蛋白的识别可能更好地预测未来的心血管事件，并有助于加强临床危险分层。高密度脂蛋白的离散生理测量的出现，如胆固醇流出能力和高密度脂蛋白炎症指数，可能为未来的临床应用提供机会。然而，这些测量的有效性及其商业可用性仍然是向临床医学实际转化的障碍。
