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Review
. 2022 Nov;24(11):831-838.
doi: 10.1007/s11883-022-01060-4. Epub 2022 Sep 6.

Lp(a): a New Pathway to Target?

Nick S Nurmohamed  1   2 , Jordan M Kraaijenhof  1 , Erik S G Stroes  3
Affiliations
Review

Lp(a): a New Pathway to Target?

Nick S Nurmohamed et al. Curr Atheroscler Rep. 2022 Nov.

Abstract

Purpose of review: Over the past decades, genetic and observational evidence has positioned lipoprotein(a) as novel important and independent risk factor for cardiovascular disease (ASCVD) and aortic valve stenosis.

Recent findings: As Lp(a) levels are determined genetically, lifestyle interventions have no effect on Lp(a)-mediated ASCVD risk. While traditional low-density lipoprotein cholesterol (LDL-C) can now be effectively lowered in the vast majority of patients, current lipid lowering therapies have no clinically relevant Lp(a) lowering effect. There are multiple Lp(a)-directed therapies in clinical development targeting LPA mRNA that have shown to lower Lp(a) plasma levels for up to 90%: pelacarsen, olpasiran, and SLN360. Pelacarsen is currently investigated in a phase 3 cardiovascular outcome trial expected to finish in 2024, while olpasiran is about to proceed to phase 3 and SLN360's phase 1 outcomes were recently published. If proven efficacious, Lp(a) will soon become the next pathway to target in ASCVD risk management.

Keywords: ASCVD; AVS; Lipoprotein(a).

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Conflict of interest statement

NN is co-founder of Lipid Tools. ESGS reports advisory board/lecturing fees paid to the institution of ESGS by Amgen, Novartis, Sanofi, Regeneron, Esperion, and IONIS. JMK has nothing to disclose.

Figures

Fig. 1
Fig. 1
Lp(a): a new pathway to target. Overview figure illustrating the hazard ratios (HR) for myocardial infarction (MI) and aortic valve (AoV) disease associated with lipoprotein(a) (Lp[a]) levels above the 95th percentile as well as Lp(a)-directed therapeutics in clinical development. ASCVD, atherosclerotic cardiovascular disease; AVS, aortic valve stenosis; ASO, antisense oligonucleotide; siRNA, small interfering RNA. Created with BioRender.com
See this image and copyright information in PMC

References

    1. Berg K, Dahlén G, Frick MH. Lp(a) lipoprotein and pre-β1-lipoprotein in patients with coronary heart disease. Clin Genet John Wiley & Sons, Ltd. 1974;6:230–5. - PubMed
    1. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69:692–711. doi: 10.1016/j.jacc.2016.11.042. - DOI - PubMed
    1. Mehta A, Vasquez N, Ayers CR, Patel J, Hooda A, Khera A, et al. Independent association of lipoprotein(a) and coronary artery calcification with atherosclerotic cardiovascular risk. J Am Coll Cardiol Am College Cardiol Foundation. 2022;79:757–68. doi: 10.1016/j.jacc.2021.11.058. - DOI - PMC - PubMed
    1. Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, et al. 2018 Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol. 2018;3:619–27. doi: 10.1001/jamacardio.2018.1470. - DOI - PMC - PubMed
    1. Tipping RW, Ford CE, Simpson LM, Walldius G, Jungner I, Folsom AR, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA - J Am Med Assoc. 2009;302:412–423. doi: 10.1001/jama.2009.1063. - DOI - PMC - PubMed