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Lipoprotein(a) and cardiovascular and valvular diseases: A genetic epidemiological perspective

Benoit J Arsenault1, Pia R Kamstrup2

  • 1Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada.

Atherosclerosis
|May 23, 2022
PubMed

Insights

High Lipoprotein(a) (Lp[a]) levels significantly increase residual cardiovascular disease risk, impacting lifespan and healthspan. Understanding Lp(a) is crucial for managing heart attack and stroke risk in high-risk patients.

Area of Science:

  • Cardiovascular Medicine and Genetics
  • Lipid Metabolism and Atherosclerosis
  • Genetics of Lifespan and Healthspan

Background:

  • Cardiovascular disease (CVD) rates have declined, yet residual risk persists in high-risk patients despite advanced treatments.
  • Lipoprotein(a) (Lp[a]) has emerged as a key contributor to this residual cardiovascular risk over the last 10-15 years.
  • Elevated Lp(a) levels affect up to 1 billion people globally, placing them in a high-risk category for cardiovascular events.

Purpose of the Study:

  • To review evidence linking Lipoprotein(a) (Lp[a]) to cardiovascular diseases (CVD), valvular heart disease, lifespan, and healthspan.
  • To identify clinically relevant Lp(a) threshold values and modulating risk factors for CVD.
  • To outline key research questions for optimizing CVD risk reduction in individuals with high Lp(a).

Main Methods:

  • Comprehensive review of large-scale genetic association studies.
  • Analysis of prospective studies investigating Lp(a) associations.
  • Examination of Lp(a) links to coronary artery disease, calcific aortic valve stenosis, and other cardiovascular and non-cardiovascular conditions.

Main Results:

  • Lipoprotein(a) (Lp[a]) is causally associated with coronary artery disease (CAD), calcific aortic valve stenosis (CAVS), peripheral arterial disease (PAD), and ischemic stroke (IS).
  • High Lp(a) levels are a significant genetic determinant of human lifespan and healthspan.
  • Specific Lp(a) thresholds are identified as potentially clinically relevant for assessing cardiovascular risk.

Conclusions:

  • Lipoprotein(a) (Lp[a]) represents a critical, genetically determined risk factor for atherosclerotic and valvular heart diseases.
  • Managing high Lp(a) is essential for reducing residual cardiovascular risk and improving patient outcomes.
  • Further research is needed to establish optimal strategies for risk reduction in individuals with elevated Lp(a) levels.

Keywords:
Calcific aortic valve stenosisCoronary artery diseaseHeart failureIschemic strokeLipoprotein(a)Peripheral arterial disease

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