Lipoprotein(a) as an Old and New Causal Risk Factor of Atherosclerotic Cardiovascular Disease

J Atheroscler Thromb. 2019 Jul 1;26(7):583-591. doi: 10.5551/jat.RV17034. Epub 2019 Apr 30.

Abstract

Lipoprotein(a) [Lp(a)], discovered in 1963, has been associated with atherosclerotic cardiovascular disease (ASCVD) independent of other traditional risk factors, including LDL cholesterol. Lp(a) is an apolipoprotein B (apoB)-containing lipoprotein, which contains an LDL-like particle. Unlike LDL, which is a primary therapeutic target to decrease ASCVD, current guidelines recommend measuring Lp(a) for risk assessments because there is no clear evidence demonstrating the clinical benefit of decreasing Lp(a) using classical drugs such as niacin. However, recent Mendelian randomization studies indicate that Lp(a) causally correlates with ASCVD. In addition, novel drugs, including PCSK9 inhibitors, as well as antisense oligonucleotide for apo(a), have exhibited efficacy in decreasing Lp(a) substantially, invigorating a discussion whether Lp(a) could be a novel therapeutic target for further ASCVD risk reduction. This review aims to provide current understanding, and future perspectives, of Lp(a), which is currently considered a mere biomarker but may emerge as a novel therapeutic target in future clinical settings.

Keywords: Aortic valve stenosis; Atherosclerotic cardiovascular disease; LDL; Lipoprotein(a).

Publication types

  • Review

MeSH terms

  • Apolipoproteins B / blood
  • Apolipoproteins B / chemistry
  • Atherosclerosis / blood*
  • Atherosclerosis / drug therapy
  • Biomarkers / blood
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lipoprotein(a) / blood*
  • Lipoprotein(a) / chemistry
  • Niacin / therapeutic use
  • Oligonucleotides, Antisense / therapeutic use
  • Proprotein Convertase 9 / antagonists & inhibitors
  • Risk Assessment
  • Risk Factors
  • Serine Proteinase Inhibitors

Substances

  • Apolipoproteins B
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoprotein(a)
  • Oligonucleotides, Antisense
  • Serine Proteinase Inhibitors
  • Niacin
  • PCSK9 protein, human
  • Proprotein Convertase 9