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Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes

Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes


Title: Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes
Author: Gudbjartsson, Daniel   orcid.org/0000-0002-5222-9857
Thorgeirsson, Gudmundur   orcid.org/0000-0002-7146-1395
Sulem, Patrick   orcid.org/0000-0001-7123-6123
Helgadottir, Anna   orcid.org/0000-0002-1806-2467
Gylfason, Arnaldur
Sæmundsdóttir, Jóna
Björnsson, Eyþór
Norðdahl, Guðmundur L.
Jónasdóttir, Áslaug
Jónasdóttir, Aðalbjörg
... 22 more authors Show all authors
Date: 2019-12-17
Language: English
Scope: 2982-2994
University/Institute: Háskóli Íslands (HÍ)
University of Iceland (UI)
Reykjavik University (RU)
Háskólinn í Reykjavík (HR)
School: School of Engineering and Natural Sciences (UI)
Verkfræði- og náttúruvísindasvið (HÍ)
Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
School of Science and Engineering (RU)
Tækni- og verkfræðideild (HR)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Journal of the American College of Cardiology;74(24)
ISSN: 0735-1097
DOI: 10.1016/j.jacc.2019.10.019
Subject: Coronary artery disease; Genetics; Lp(a); Mendelian randomization; Type 2 diabetes; Kransæðasjúkdómar; Erfðafræði; Blóðrásarsjúkdómar; Gen; Sykursýki
URI: https://hdl.handle.net/20.500.11815/1499

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Citation:

Gudbjartsson, Daniel F, Thorgeirsson, Gudmundur, Sulem, Patrick, Helgadottir, Anna, Gylfason, Arnaldur, Saemundsdottir, Jona, . . . Stefansson, Kari. (2020). Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes., Gudbjartsson DF, Thorgeirsson G, Sulem P, et al. Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes. J Am Coll Cardiol. 2019;74(24):2982–2994. doi:10.1016/j.jacc.2019.10.019.

Abstract:

Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of Lp(a) have been associated with type 2 diabetes (T2D). Objectives: This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) [apo(a)] size, and whether the relationship between Lp(a) and T2D risk is causal. Methods: This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D. Results: Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D. Conclusions: Molar concentration is the attribute of Lp(a) that affects risk of cardiovascular diseases. Low Lp(a) concentration (bottom 10%) increases T2D risk. Pharmacologic reduction of Lp(a) concentration in the 20% of individuals with the greatest concentration down to the population median is predicted to decrease CAD risk without increasing T2D risk.

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This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/)

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