Polygenic Risk Is Associated With Long-Term Coronary Plaque Progression and High-Risk Plaque

JACC Cardiovasc Imaging. 2024 Dec;17(12):1445-1459. doi: 10.1016/j.jcmg.2024.06.015. Epub 2024 Aug 14.

Abstract

Background: The longitudinal relation between coronary artery disease (CAD) polygenic risk score (PRS) and long-term plaque progression and high-risk plaque (HRP) features is unknown.

Objectives: The goal of this study was to investigate the impact of CAD PRS on long-term coronary plaque progression and HRP.

Methods: Patients underwent CAD PRS measurement and prospective serial coronary computed tomography angiography (CTA) imaging. Coronary CTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography imaging). The relationship between CAD PRS and change in percent atheroma volume (PAV), percent noncalcified plaque progression, and HRP prevalence was investigated in linear mixed-effect models adjusted for baseline plaque volume and conventional risk factors.

Results: A total of 288 subjects (mean age 58 ± 7 years; 60% male) were included in this study with a median scan interval of 10.2 years. At baseline, patients with a high CAD PRS had a more than 5-fold higher PAV than those with a low CAD PRS (10.4% vs 1.9%; P < 0.001). Per 10 years of follow-up, a 1 SD increase in CAD PRS was associated with a 0.69% increase in PAV progression in the multivariable adjusted model. CAD PRS provided additional discriminatory benefit for above-median noncalcified plaque progression during follow-up when added to a model with conventional risk factors (AUC: 0.73 vs 0.69; P = 0.039). Patients with high CAD PRS had an OR of 2.85 (95% CI: 1.14-7.14; P = 0.026) and 6.16 (95% CI: 2.55-14.91; P < 0.001) for having HRP at baseline and follow-up compared with those with low CAD PRS.

Conclusions: Polygenic risk is strongly associated with future long-term plaque progression and HRP in patients suspected of having CAD.

Keywords: atherosclerosis; atherosclerosis imaging; atherosclerotic cardiovascular disease; coronary CT angiography; coronary artery disease; polygenic risk score; quantitative computed tomography.

MeSH terms

  • Aged
  • Algorithms
  • Artificial Intelligence
  • Computed Tomography Angiography*
  • Coronary Angiography*
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / genetics
  • Coronary Vessels / diagnostic imaging
  • Disease Progression*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Multifactorial Inheritance*
  • Phenotype
  • Plaque, Atherosclerotic*
  • Predictive Value of Tests*
  • Prevalence
  • Prognosis
  • Prospective Studies
  • Radiographic Image Interpretation, Computer-Assisted
  • Risk Assessment
  • Risk Factors
  • Time Factors