The Present and Future
State-of-the-Art Review
NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis

https://doi.org/10.1016/j.jacc.2017.11.014Get rights and content
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Abstract

Pathophysiological, epidemiological, and genetic studies provide strong evidence that lipoprotein(a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). Specific therapies to address Lp(a)-mediated CVD and CAVD are in clinical development. Due to knowledge gaps, the National Heart, Lung, and Blood Institute organized a working group that identified challenges in fully understanding the role of Lp(a) in CVD/CAVD. These included the lack of research funding, inadequate experimental models, lack of globally standardized Lp(a) assays, and inadequate understanding of the mechanisms underlying current drug therapies on Lp(a) levels. Specific recommendations were provided to facilitate basic, mechanistic, preclinical, and clinical research on Lp(a); foster collaborative research and resource sharing; leverage expertise of different groups and centers with complementary skills; and use existing National Heart, Lung, and Blood Institute resources. Concerted efforts to understand Lp(a) pathophysiology, together with diagnostic and therapeutic advances, are required to reduce Lp(a)-mediated risk of CVD and CAVD.

Key Words

aortic stenosis
cardiovascular disease
lipoprotein(a)
metabolism
pathophysiology
therapy

Abbreviations and Acronyms

apo
apolipoprotein
CAVD
calcific aortic valve disease
CD36
cluster of differentiation 36 receptor
ICD-10
International Classification of Diseases-10th Revision
Lp(a)
lipoprotein(a)
LRP1
low-density lipoprotein receptor–related protein 1
OxPL
oxidized phospholipids
PCSK9
proprotein convertase subtilisin kexin type 9
SNP
single-nucleotide polymorphism
SR-BI
scavenger receptor B-I

Cited by (0)

The contents of this paper are solely the responsibility of the authors and do not necessarily reflect the official views of the National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health (NIH), or the U.S. government. Dr. Tsimikas has received research support from the Fondation Leducq and NIH grants R01-HL119828, R01-HL078610, R01 HL106579, R01 HL128550, R01 HL136098, P01 HL136275 and R35 HL135737; currently has a dual appointment at the University of California San Diego and Ionis Pharmaceuticals; and is a coinventor and receives royalties from patents owned by the University of California San Diego on oxidation-specific antibodies. Dr. Fazio has served as an advisor/consultant for Merck, Kowa, Amarin, Amgen, Akcea, and Pfizer; and has received research support from NIH NHLBI grant R01132985. Dr. Ferdinand has served as a consultant for Amgen, Sanofi, Novartis, Quantum Genomics, and Boehringer Ingelheim. Dr. Ginsberg is supported by NIH 1R35HL135833; has received research support from Merck, Sanofi/Regeneron, Amgen, Ionis Pharmaceuticals, and Pfizer Cardiovascular Research; and has served as a consultant for Amgen, Ionis, and Sanofi/Regeneron. Dr. Koschinsky has served as a consultant for Ionis Pharmaceuticals, Sanofi, and Eli Lilly; and has received research support from the Canadian Institutes of Health Research (MOP# 126076), the Heart and Stroke Foundation of Ontario (G-13-0003091), the Natural Sciences and Engineering Research Council (RGPIN/5006-2015), the Pfizer ASPIRE Cardiovascular Grant, Ionis Pharmaceuticals, Regeneron Pharmaceuticals, Eli Lilly, and Pfizer. Dr. Marcovina has served as an advisor/consultant to Denka Seiken, MedTest, and Amgen. Dr. Moriarty has served as an advisor/consultant to Amgen, Regeneron, Sanofi, RegenXBio, Duke Clinical Research, Alexion, Esperion, Eliaz Therapeutics, and Ionis; has served on the speakers bureau for Amgen, Sanofi, and Regeneron; and has received research support from Regeneron, Sanofi, Amgen, Ionis, Catabasis, Pfizer, Novartis, Kaneka, Stage 2 Innovations, Zydus Discovery, Gemphire, Kowa, Akcea, FH Foundation, and Genzyme. Dr. Rader has served as a consultant for Novartis. Dr. Reyes-Soffer has served as an advisor/consultant for Merck; and has received research support from Merck, Sanofi/Regeneron, Ionis Pharmaceuticals, Pfizer Cardiovascular Research, and NIH grants UL1TR001873 and KL2TR001874. Dr. Santos has served as an advisor/consultant to Amgen, AstraZeneca, Biolab, Boehringer Ingelheim, Genzyme, Merck, Novo Nordisk, Pfizer, Eli Lilly, Kowa, Unilever, Sanofi/Regeneron, Torrent, and Procaps; has received research honoraria from Pfizer, Akcea, Amgen, and Sanofi; and has received speaker honoraria from Amgen, Biolab, Sanofi/Regeneron, and Merck. Dr. Thanassoulis has served as an advisor/consultant to Servier Canada, Amgen, and Ionis; has served on the speakers bureau of Servier Canada, Regeneron, and Sanofi; and has received research support from Ionis, Servier Canada, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and NIH grant R01 HL128550. Dr. Witztum has served as a consultant to Ionis Pharmaceuticals; is supported by NIH grants P01 HL088093, R01 HL119828, R35 HL135737, and P01 HL1136275; and is coinventor and receives royalties from patents owned by the University of California San Diego on oxidation-specific antibodies. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Except for the first author and National Heart, Lung, and Blood Institute (NHLBI) coauthors, the remaining coauthors are listed alphabetically.

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© 2018 by the American College of Cardiology Foundation. Published by Elsevier.