Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Feb 2020)

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

  • Morten Krogh Christiansen,
  • Louise Nissen,
  • Simon Winther,
  • Peter Loof Møller,
  • Lars Frost,
  • Jane Kirk Johansen,
  • Henrik Kjærulf Jensen,
  • Daníel Guðbjartsson,
  • Hilma Holm,
  • Kári Stefánsson,
  • Hans Erik Bøtker,
  • Morten Bøttcher,
  • Mette Nyegaard

DOI
https://doi.org/10.1161/JAHA.119.014795
Journal volume & issue
Vol. 9, no. 3

Abstract

Read online

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 P0.05). 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