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A genetic risk score is associated with increased coronary plaque burden but not specific plaque features: a coronary computed tomography study

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A genetic risk score is associated with increased coronary plaque burden but not specific plaque features: a coronary computed tomography study. / Christiansen, Morten Krogh; Nissen, Louise; Winther, Simon; Frost, Lars; Johansen, Jane Kirk; Jensen, Henrik Kjærulf; Bøtker, Hans Erik; Böttcher, Morten; Nyegaard, Mette.

2019. Abstract fra European Society of Cardiology Congress 2019, Paris, Frankrig.

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

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Christiansen, Morten Krogh o.a.. A genetic risk score is associated with increased coronary plaque burden but not specific plaque features: a coronary computed tomography study. European Society of Cardiology Congress 2019, 31 aug. 2019, Paris, Frankrig, Konferenceabstrakt til konference, 2019.

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@conference{3bf1e88d492b4a81838c1b4b6e2c04eb,
title = "A genetic risk score is associated with increased coronary plaque burden but not specific plaque features: a coronary computed tomography study",
abstract = "Background Genetic risk scores (GRSs) based on risk variants identified from genome-wide association studies (GWASs) predict coronary artery disease (CAD) risk. However, it is unknown whether the GRS is associated with coronary plaque burden or specific high-risk plaque features responsible for the clinical disease onset. Purpose To investigate if a GRS is associated with coronary plaque burden and specific plaque characteristics, in patients with suspected stable CAD referred for coronary computed tomography angiography (CTA). Methods We consecutively included and genotyped 1645 patients undergoing coronary CTA. Using LDPred, a previously validated GRS was calculated as the weighted sum of the number of CAD risk variants identified from the CARDIoGRAMplusC4D GWAS meta-analysis. Plaques were evaluated using an 18-segment model and characterized by stenosis severity (0%, 1-49%, 50-69%, 70-100%) and composition (calcified (>80% calcified), mixed-calcified (50-80% calcified), mixed-soft (20-50% calcified), or soft (<20% calcified)). The segment stenosis score and the coronary artery calcium score (CACS) were used as measures of plaque burden. Multivariate regression models were used to assess the effect per standard deviation (SD) of the GRS with adjustment for age, sex, hypertension, hypercholesterolemia, BMI, chest pain symptoms, and active smoking. Results For each SD increase in the GRS, the segment stenosis score increased with 49% (p=8.6e-27) and CACS increased with 110% (p=2.3e-24). The GRS was associated with a higher risk of plaque stenosis >50% (OR: 1.74, p=3.2e-15), calcified (OR: 1.65, p=3.0e-16), mixed-calcified (OR: 1.64, p=1.5e-8), mixed-soft (OR: 1.44, p=1.6e-6), and soft plaques (OR: 1.40, p=3.0e-6), and all coronary vessels were more often affected with plaques (all p-values <1.0e-4). When analyzing the plaque characteristics (3007 plaques in 849 patients), the GRS was associated with stenosis severity (OR per severity category: 1.15 (p=0.005), but not with extent of calcification, proximal location, or presence in any of the major coronary vessels (all p-values >0.05). Conclusion The GRS was strongly associated with the extent and severity of CAD at coronary CTA, but not any specific plaque characteristics per se. The results may suggest that polygenic risk based on large CAD-GWAS increases CAD risk through increased coronary plaque burden rather than specific plaque features.",
author = "Christiansen, {Morten Krogh} and Louise Nissen and Simon Winther and Lars Frost and Johansen, {Jane Kirk} and Jensen, {Henrik Kj{\ae}rulf} and B{\o}tker, {Hans Erik} and Morten B{\"o}ttcher and Mette Nyegaard",
year = "2019",
month = aug,
day = "31",
language = "Dansk",
note = "European Society of Cardiology Congress 2019, ESC Congress 2019 ; Conference date: 31-08-2019 Through 04-09-2019",
url = "https://www.escardio.org/Congresses-&-Events/ESC-Congress/About-the-congress",

}

RIS

TY - ABST

T1 - A genetic risk score is associated with increased coronary plaque burden but not specific plaque features: a coronary computed tomography study

AU - Christiansen, Morten Krogh

AU - Nissen, Louise

AU - Winther, Simon

AU - Frost, Lars

AU - Johansen, Jane Kirk

AU - Jensen, Henrik Kjærulf

AU - Bøtker, Hans Erik

AU - Böttcher, Morten

AU - Nyegaard, Mette

PY - 2019/8/31

Y1 - 2019/8/31

N2 - Background Genetic risk scores (GRSs) based on risk variants identified from genome-wide association studies (GWASs) predict coronary artery disease (CAD) risk. However, it is unknown whether the GRS is associated with coronary plaque burden or specific high-risk plaque features responsible for the clinical disease onset. Purpose To investigate if a GRS is associated with coronary plaque burden and specific plaque characteristics, in patients with suspected stable CAD referred for coronary computed tomography angiography (CTA). Methods We consecutively included and genotyped 1645 patients undergoing coronary CTA. Using LDPred, a previously validated GRS was calculated as the weighted sum of the number of CAD risk variants identified from the CARDIoGRAMplusC4D GWAS meta-analysis. Plaques were evaluated using an 18-segment model and characterized by stenosis severity (0%, 1-49%, 50-69%, 70-100%) and composition (calcified (>80% calcified), mixed-calcified (50-80% calcified), mixed-soft (20-50% calcified), or soft (<20% calcified)). The segment stenosis score and the coronary artery calcium score (CACS) were used as measures of plaque burden. Multivariate regression models were used to assess the effect per standard deviation (SD) of the GRS with adjustment for age, sex, hypertension, hypercholesterolemia, BMI, chest pain symptoms, and active smoking. Results For each SD increase in the GRS, the segment stenosis score increased with 49% (p=8.6e-27) and CACS increased with 110% (p=2.3e-24). The GRS was associated with a higher risk of plaque stenosis >50% (OR: 1.74, p=3.2e-15), calcified (OR: 1.65, p=3.0e-16), mixed-calcified (OR: 1.64, p=1.5e-8), mixed-soft (OR: 1.44, p=1.6e-6), and soft plaques (OR: 1.40, p=3.0e-6), and all coronary vessels were more often affected with plaques (all p-values <1.0e-4). When analyzing the plaque characteristics (3007 plaques in 849 patients), the GRS was associated with stenosis severity (OR per severity category: 1.15 (p=0.005), but not with extent of calcification, proximal location, or presence in any of the major coronary vessels (all p-values >0.05). Conclusion The GRS was strongly associated with the extent and severity of CAD at coronary CTA, but not any specific plaque characteristics per se. The results may suggest that polygenic risk based on large CAD-GWAS increases CAD risk through increased coronary plaque burden rather than specific plaque features.

AB - Background Genetic risk scores (GRSs) based on risk variants identified from genome-wide association studies (GWASs) predict coronary artery disease (CAD) risk. However, it is unknown whether the GRS is associated with coronary plaque burden or specific high-risk plaque features responsible for the clinical disease onset. Purpose To investigate if a GRS is associated with coronary plaque burden and specific plaque characteristics, in patients with suspected stable CAD referred for coronary computed tomography angiography (CTA). Methods We consecutively included and genotyped 1645 patients undergoing coronary CTA. Using LDPred, a previously validated GRS was calculated as the weighted sum of the number of CAD risk variants identified from the CARDIoGRAMplusC4D GWAS meta-analysis. Plaques were evaluated using an 18-segment model and characterized by stenosis severity (0%, 1-49%, 50-69%, 70-100%) and composition (calcified (>80% calcified), mixed-calcified (50-80% calcified), mixed-soft (20-50% calcified), or soft (<20% calcified)). The segment stenosis score and the coronary artery calcium score (CACS) were used as measures of plaque burden. Multivariate regression models were used to assess the effect per standard deviation (SD) of the GRS with adjustment for age, sex, hypertension, hypercholesterolemia, BMI, chest pain symptoms, and active smoking. Results For each SD increase in the GRS, the segment stenosis score increased with 49% (p=8.6e-27) and CACS increased with 110% (p=2.3e-24). The GRS was associated with a higher risk of plaque stenosis >50% (OR: 1.74, p=3.2e-15), calcified (OR: 1.65, p=3.0e-16), mixed-calcified (OR: 1.64, p=1.5e-8), mixed-soft (OR: 1.44, p=1.6e-6), and soft plaques (OR: 1.40, p=3.0e-6), and all coronary vessels were more often affected with plaques (all p-values <1.0e-4). When analyzing the plaque characteristics (3007 plaques in 849 patients), the GRS was associated with stenosis severity (OR per severity category: 1.15 (p=0.005), but not with extent of calcification, proximal location, or presence in any of the major coronary vessels (all p-values >0.05). Conclusion The GRS was strongly associated with the extent and severity of CAD at coronary CTA, but not any specific plaque characteristics per se. The results may suggest that polygenic risk based on large CAD-GWAS increases CAD risk through increased coronary plaque burden rather than specific plaque features.

M3 - Konferenceabstrakt til konference

T2 - European Society of Cardiology Congress 2019

Y2 - 31 August 2019 through 4 September 2019

ER -