Genetic Risk of Coronary Artery Disease, Features of Atherosclerosis, and Coronary Plaque Burden

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Genetic Risk of Coronary Artery Disease, Features of Atherosclerosis, and Coronary Plaque Burden. / Christiansen, Morten Krogh; Nissen, Louise; Winther, Simon; Møller, Peter Loof; Frost, Lars; Johansen, Jane Kirk; Jensen, Henrik Kjærulf; Guðbjartsson, Daníel; Holm, Hilma; Stefánsson, Kári; Bøtker, Hans Erik; Bøttcher, Morten; Nyegaard, Mette.

I: Journal of the American Heart Association, Bind 9, Nr. 3, e014795, 2020.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{98db57ac21ba450db4fd33002048dd24,
title = "Genetic Risk of Coronary Artery Disease, Features of Atherosclerosis, and Coronary Plaque Burden",
abstract = "Background Polygenic risk scores (PRSs) based on risk variants from genome-wide association studies predict coronary artery disease (CAD) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18-segment model and characterized by stenosis severity and composition (soft [0%-19% calcified], mixed-soft [20%-49% calcified], mixed-calcified [50%-79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS, coronary artery calcium score increased by 78% (P=4.1e-26) and segment stenosis score increased by 16% (P=2.4e-29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [OR]: 1.78, P=5.6e-16), calcified (OR: 1.69, P=6.5e-17), mixed-calcified (OR: 1.67, P=7.3e-9), mixed-soft (OR: 1.45, P=1.6e-6), and soft plaques (OR: 1.49, P=2.5e-6), and a higher prevalence of plaque in each coronary vessel (all P<1.0e-4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all P>0.05). Conclusions Our results suggest that polygenic risk based on large genome-wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.",
keywords = "atherosclerosis, coronary artery disease, coronary computed tomography angiography, plaque",
author = "Christiansen, {Morten Krogh} and Louise Nissen and Simon Winther and M{\o}ller, {Peter Loof} and Lars Frost and Johansen, {Jane Kirk} and Jensen, {Henrik Kj{\ae}rulf} and Dan{\'i}el Gu{\dh}bjartsson and Hilma Holm and K{\'a}ri Stef{\'a}nsson and B{\o}tker, {Hans Erik} and Morten B{\o}ttcher and Mette Nyegaard",
year = "2020",
doi = "10.1161/JAHA.119.014795",
language = "English",
volume = "9",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell Publishing, Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Genetic Risk of Coronary Artery Disease, Features of Atherosclerosis, and Coronary Plaque Burden

AU - Christiansen, Morten Krogh

AU - Nissen, Louise

AU - Winther, Simon

AU - Møller, Peter Loof

AU - Frost, Lars

AU - Johansen, Jane Kirk

AU - Jensen, Henrik Kjærulf

AU - Guðbjartsson, Daníel

AU - Holm, Hilma

AU - Stefánsson, Kári

AU - Bøtker, Hans Erik

AU - Bøttcher, Morten

AU - Nyegaard, Mette

PY - 2020

Y1 - 2020

N2 - Background Polygenic risk scores (PRSs) based on risk variants from genome-wide association studies predict coronary artery disease (CAD) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18-segment model and characterized by stenosis severity and composition (soft [0%-19% calcified], mixed-soft [20%-49% calcified], mixed-calcified [50%-79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS, coronary artery calcium score increased by 78% (P=4.1e-26) and segment stenosis score increased by 16% (P=2.4e-29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [OR]: 1.78, P=5.6e-16), calcified (OR: 1.69, P=6.5e-17), mixed-calcified (OR: 1.67, P=7.3e-9), mixed-soft (OR: 1.45, P=1.6e-6), and soft plaques (OR: 1.49, P=2.5e-6), and a higher prevalence of plaque in each coronary vessel (all P<1.0e-4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all P>0.05). Conclusions Our results suggest that polygenic risk based on large genome-wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.

AB - Background Polygenic risk scores (PRSs) based on risk variants from genome-wide association studies predict coronary artery disease (CAD) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18-segment model and characterized by stenosis severity and composition (soft [0%-19% calcified], mixed-soft [20%-49% calcified], mixed-calcified [50%-79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS, coronary artery calcium score increased by 78% (P=4.1e-26) and segment stenosis score increased by 16% (P=2.4e-29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [OR]: 1.78, P=5.6e-16), calcified (OR: 1.69, P=6.5e-17), mixed-calcified (OR: 1.67, P=7.3e-9), mixed-soft (OR: 1.45, P=1.6e-6), and soft plaques (OR: 1.49, P=2.5e-6), and a higher prevalence of plaque in each coronary vessel (all P<1.0e-4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all P>0.05). Conclusions Our results suggest that polygenic risk based on large genome-wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.

KW - atherosclerosis

KW - coronary artery disease

KW - coronary computed tomography angiography

KW - plaque

UR - http://www.scopus.com/inward/record.url?scp=85078332202&partnerID=8YFLogxK

U2 - 10.1161/JAHA.119.014795

DO - 10.1161/JAHA.119.014795

M3 - Journal article

C2 - 31983321

VL - 9

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 3

M1 - e014795

ER -