Polygenic Risk is Associated with Long-Term Coronary Plaque Progression and High-Risk Plaque

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.