Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Clin Chim Acta. 2025 Jan 15;565:119982. doi: 10.1016/j.cca.2024.119982. Epub 2024 Oct 2.
High plasma lipoprotein(a) (Lp(a)) levels increase the cardiovascular risk in populations with atherosclerotic cardiovascular disease (ASCVD). Apolipoprotein (a) [apo(a)], a unique protein component of Lp(a), plays an important role in the pathogenesis of atherosclerosis. Statins, the primary medication in managing ASCVD, lower low-density lipoprotein cholesterol (LDL-C) but concurrently elevate plasma Lp(a) levels, contributing to an increased residual cardiovascular risk. In turn, proprotein convertase subtilisin/kexin-type 9 (PCSK9) inhibitors, a novel class of LDL-C lowering drugs, effectively reduce plasma Lp(a) levels, which is believed to decrease residual cardiovascular risk. However, the mechanism by which PCSK9 inhibitors reduce Lp(a) levels remains unknown. In addition, there are some clinical limitations of PCSK9 inhibitors. Here, we systematically review the past, present, and prospects of studies pertaining to Lp(a), PCSK9 inhibitors, and ASCVD.
血浆脂蛋白(a)（Lp(a)）水平升高会增加动脉粥样硬化性心血管疾病（ASCVD）患者的心血管风险。载脂蛋白(a)（apo(a)）是 Lp(a）的独特蛋白成分，在动脉粥样硬化的发病机制中发挥重要作用。他汀类药物是治疗 ASCVD 的主要药物，可降低低密度脂蛋白胆固醇（LDL-C），但同时会升高血浆 Lp(a）水平，导致残余心血管风险增加。相反，前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂是一种新型 LDL-C 降低药物，可有效降低血浆 Lp(a）水平，据信可降低残余心血管风险。然而，PCSK9 抑制剂降低 Lp(a）水平的机制尚不清楚。此外，PCSK9 抑制剂还存在一些临床局限性。本文系统综述了 Lp(a）、PCSK9 抑制剂和 ASCVD 的过去、现在和未来的研究。
