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A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies

Sotirios Tsimikas1

  • 1Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California San Diego, La Jolla, California.

Journal of the American College of Cardiology
|February 11, 2017
PubMed

Insights

Elevated lipoprotein(a) (Lp[a]) is a significant risk factor for cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS). Emerging therapies show promise in lowering Lp[a] levels, potentially reducing residual cardiovascular risk.

Area of Science:

  • Cardiology
  • Genetics
  • Pharmacology

Background:

  • Elevated lipoprotein(a) (Lp[a]) is a substantial contributor to cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS).
  • Lp[a] is recognized as an independent, genetic, and likely causal risk factor across diverse patient populations and treatments.
  • Statins may paradoxically increase Lp(a) levels, potentially explaining residual cardiovascular risk.

Purpose of the Study:

  • To review the current understanding of Lp(a) in relation to CVD and CAVS.
  • To discuss existing controversies surrounding Lp(a) as a risk factor.
  • To summarize emerging therapies aimed at reducing plasma Lp(a) levels.

Main Methods:

  • Review of genetic, epidemiological, translational, and pathophysiological studies.
  • Analysis of clinical trial data and patient observations.
  • Evaluation of emerging pharmacological and RNA-targeted therapies.

Main Results:

  • Isoform-independent assays and extensive research confirm Lp(a) as a causal risk factor for CVD and CAVS.
  • Current therapies like PCSK9 inhibitors and mipomersen achieve modest Lp(a) reduction (20-30%).
  • Novel RNA-targeted therapies demonstrate significant Lp(a) reduction (>80%).

Conclusions:

  • The "Lp(a) hypothesis" can now be rigorously tested in clinical trials due to advancements in Lp(a) lowering therapies.
  • Reducing plasma Lp(a) levels is a promising strategy for mitigating CVD and CAVS risk.
  • Further research and clinical trials are essential to validate the efficacy of novel Lp(a)-lowering treatments.

Keywords:
aortic stenosiscardiovascular diseasegenome-wide association studiestherapy

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