Lipoprotein(a) in atherosclerotic cardiovascular disease and proprotein convertase subtilisin/kexin-type 9 inhibitors

Clin Chim Acta. 2025 Jan 15:565:119982. doi: 10.1016/j.cca.2024.119982. Epub 2024 Oct 2.

Abstract

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.

Keywords: Atherosclerotic cardiovascular disease; Lipid-lowering drugs; Lipoprotein(a); Proprotein convertase subtilisin/kexin-type 9 inhibitors.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / metabolism
  • Cardiovascular Diseases / drug therapy
  • Humans
  • Lipoprotein(a)* / blood
  • PCSK9 Inhibitors*
  • Proprotein Convertase 9 / metabolism

Substances

  • Lipoprotein(a)
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9