Lipoprotein(a): the revenant

Eur Heart J. 2017 May 21;38(20):1553-1560. doi: 10.1093/eurheartj/ehx033.


In the mid-1990s, the days of lipoprotein(a) [Lp(a)] were numbered and many people would not have placed a bet on this lipid particle making it to the next century. However, genetic studies brought Lp(a) back to the front-stage after a Mendelian randomization approach used for the first time provided strong support for a causal role of high Lp(a) concentrations in cardiovascular disease and later also for aortic valve stenosis. This encouraged the use of therapeutic interventions to lower Lp(a) as well numerous drug developments, although these approaches mainly targeted LDL cholesterol, while the Lp(a)-lowering effect was only a 'side-effect'. Several drug developments did show a potent Lp(a)-lowering effect but did not make it to endpoint studies, mainly for safety reasons. Currently, three therapeutic approaches are either already in place or look highly promising: (i) lipid apheresis (specific or unspecific for Lp(a)) markedly decreases Lp(a) concentrations as well as cardiovascular endpoints; (ii) PCSK9 inhibitors which, besides lowering LDL cholesterol also decrease Lp(a) by roughly 30%; and (iii) antisense therapy targeting apolipoprotein(a) which has shown to specifically lower Lp(a) concentrations by up to 90% in phase 1 and 2 trials without influencing other lipids. Until the results of phase 3 outcome studies are available for antisense therapy, we will have to exercise patience, but with optimism since never before have we had the tools we have now to prove Koch's extrapolated postulate that lowering high Lp(a) concentrations might be protective against cardiovascular disease.

Keywords: Cardiovascular prevention; Lipids; Pharmacological therapies; Risk factors.

Publication types

  • Review

MeSH terms

  • Aortic Valve Stenosis / etiology
  • Blood Component Removal / methods
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / drug effects
  • Evidence-Based Medicine
  • Humans
  • Hypercholesterolemia / prevention & control
  • Hyperlipidemias / prevention & control
  • Hypolipidemic Agents / therapeutic use
  • Lipoprotein(a) / drug effects*
  • Lipoprotein(a) / metabolism
  • Lipoprotein(a) / physiology
  • Oligonucleotides, Antisense / therapeutic use
  • PCSK9 Inhibitors
  • Practice Guidelines as Topic
  • Risk Factors
  • Vascular Calcification / etiology


  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Lipoprotein(a)
  • Oligonucleotides, Antisense
  • PCSK9 Inhibitors
  • PCSK9 protein, human