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Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice

  • Evidence-Based Medicine (L. Roever, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

A considerable body of data from genetic and epidemiological studies strongly support a causal relationship between high lipoprotein(a) [Lp(a)] levels, and the development of atherosclerosis and cardiovascular disease. This relationship is continuous, unrelated to Lp(a) threshold, and independent of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. Unfortunately, the mechanism(s) through which Lp(a) promotes atherosclerosis are not clarified yet. Suggested hypotheses include: an increased Lp(a)-associated cholesterol entrapment in the arterial intima followed by inflammatory cell recruitment, abnormal upload of proinflammatory oxidized phospholipids, impaired fibrinolysis by inhibition of plasminogen activation, and enhanced coagulation, through inhibition of the tissue factor pathway inhibitor. This review is aimed at summarizing the available evidence on the topic.

Recent Findings

There are two clinical forms, isolated hyperlipidemia(a) [HyperLp(a)] with acceptable LDL-C levels (< 70 mg/dL), and combined elevation of Lp(a) and LDL-C in plasma. To date, no drugs that selectively decrease Lp(a) are available. Some novel lipid-lowering drugs can lower Lp(a) levels, but to a limited extent, as their main effect is aimed at decreasing LDL-C levels. Significant Lp(a) lowering effects were obtained with nicotinic acid at high doses. However, adverse effects apart, nicotinic acid is no longer prescribed and available in Europe for clinical use, after European Agency of Medicines (EMA) ban.

Summary

The only effective therapeutic option for now is Lipoprotein Apheresis (LA), albeit with some limitations. Lastly, it is to be acknowledged that the body of evidence confirming that reducing plasma isolated elevation of Lp(a) brings cardiovascular benefit is still insufficient. However, the growing bulk of clinical, genetic, mechanistic, and epidemiological available evidence strongly suggests that Lp(a) is likely to be the smoking gun.

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Authors and Affiliations

  1. Clinical Division of Endocrinology and Metabolism - Department of Medicine III - Medical University of Vienna, Universitätsring 1, 1010, Wien, Austria

    Thomas M. Stulnig

  2. Department of Molecular Medicine, Lipid Clinic and Atherosclerosis Prevention Centre –“Sapienza” University of Rome, Extracorporeal Therapeutic Techniques Unit, Regional Centre for Rare Diseases, Immunohematology and Transfusion Medicine, “Umberto I” Hospital, Rome, Italy

    Claudia Morozzi & Claudia Stefanutti

  3. Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Wien, Austria

    Roman Reindl-Schwaighofer

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Correspondence to Claudia Stefanutti.

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Glossary

Kringle

protein structure characterized by an amino acid chain wrapped in fashion to remember a Danish pastry called “Kringle.” This conformation is maintained from three intra-catenary disulfide bridges present in fixed positions of the sequence primary amino acid.

SNP

Single-nucleotide polymorphism.

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Stulnig, T.M., Morozzi, C., Reindl-Schwaighofer, R. et al. Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice. Curr Atheroscler Rep 21, 37 (2019). https://doi.org/10.1007/s11883-019-0803-9

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