Lipoprotein(a) in atherosclerosis: from pathophysiology to clinical relevance and treatment options

Ann Med. 2020 Aug;52(5):162-177. doi: 10.1080/07853890.2020.1775287. Epub 2020 Jun 8.

Abstract

Lipoprotein(a) (Lp(a)) was discovered more than 50 years ago, and a decade later, it was recognized as a risk factor for coronary artery disease. However, it has gained importance only in the past 10 years, with emergence of drugs that can effectively decrease its levels. Lp(a) is a low-density lipoprotein (LDL) with an added apolipoprotein(a) attached to the apolipoprotein B component via a disulphide bond. Circulating levels of Lp(a) are mainly genetically determined. Lp(a) has many functions, which include proatherosclerotic, prothrombotic and pro-inflammatory roles. Here, we review recent data on the role of Lp(a) in the atherosclerotic process, and treatment options for patients with cardiovascular diseases. Currently 'Proprotein convertase subtilisin/kexin type 9' (PCSK9) inhibitors that act through non-specific reduction of Lp(a) are the only drugs that have shown effectiveness in clinical trials, to provide reductions in cardiovascular morbidity and mortality. The effects of PCSK9 inhibitors are not purely through Lp(a) reduction, but also through LDL cholesterol reduction. Finally, we discuss new drugs on the horizon, and gene-based therapies that affect transcription and translation of apolipoprotein(a) mRNA. Clinical trials in patients with high Lp(a) and low LDL cholesterol might tell us whether Lp(a) lowering per se decreases cardiovascular morbidity and mortality.KEY MESSAGESLipoprotein(a) is an important risk factor in patients with cardiovascular diseases.Lipoprotein(a) has many functions, which include proatherosclerotic, prothrombotic and pro-inflammatory roles.Treatment options to lower lipoprotein(a) levels are currently scarce, but new drugs are on the horizon.

Keywords: Lipoprotein(a); atherosclerosis; pathophysiology; treatment.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents / therapeutic use
  • Atherosclerosis / blood
  • Atherosclerosis / physiopathology*
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / drug effects
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lipoprotein(a) / blood*
  • Lipoprotein(a) / drug effects
  • PCSK9 Inhibitors*
  • Proprotein Convertase 9 / pharmacology
  • Risk Assessment

Substances

  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoprotein(a)
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9