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Lp(a): Addressing a Target for Cardiovascular Disease Prevention

  • Lipid Abnormalities and Cardiovascular Prevention (G De Backer, Section Editor)
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Abstract

Purpose of Review

To review the current recommendations for lipoprotein(a) (Lp(a)) screening, the evidence behind the thresholds for increased cardiovascular disease (CVD) risk, and the available data supporting Lp(a) lowering.

Recent Findings

Lp(a) is almost entirely genetically determined and has an independent causal association with CVD. Measurement of Lp(a) is challenging given the structural heterogeneity of apolipoprotein a (apo(a)), for which isoform-insensitive immunoassays should be used. Current guidelines do not recommend treatment to lower Lp(a) but rather focus on intensified preventive measures including low-density lipoprotein cholesterol (LDL-C) lowering in patients with high Lp(a). Evidence suggests that levels higher than 50 mg/dL (125 nmol/L) identify significantly increased CVD risk. Mendelian randomization studies suggest that in order to have a clinically significant reduction in coronary heart disease, Lp(a) levels should be reduced by at least 60–70 mg/dL to attain a significant benefit. Ongoing studies of targeted therapy with antisense oligonucleotides (ASO) have shown promising reductions in Lp(a) up to 80%, but a cardiovascular outcomes trial is needed.

Summary

There is unquestionably an increased risk for CVD in patients with elevated Lp(a); however, measurement assay issues and the lack of Lp(a)-targeted therapies with proven outcome reduction limit the clinical utility of this important risk factor. Available evidence suggesting specific thresholds for clinically significant CVD risk are based on European or Caucasian populations, not accounting for important racial differences. Novel Lp(a)-targeted emerging therapies may need to account for an expected reduction of at least 60–70 mg/dL to achieve a clinically significant benefit.

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  1. Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8830, USA

    Nestor Vasquez & Parag H. Joshi

  2. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Parag H. Joshi

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Nestor Vasquez declares that he has no conflict of interest. Parag H. Joshi reports grant support from the AHA, Novo Nordisk, GlaxoSmithKline, Sanofi/Regeneron, AstraZeneca, and Pfizer; and personal fees from Regeneron and Bayer; and equity interest in the Global Genomics Group.

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Vasquez, N., Joshi, P.H. Lp(a): Addressing a Target for Cardiovascular Disease Prevention. Curr Cardiol Rep 21, 102 (2019). https://doi.org/10.1007/s11886-019-1182-0

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