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Published on: January 15, 2022
Polygenic Risk Is Associated With Long-Term Coronary Plaque Progression and High-Risk Plaque
Nick S Nurmohamed1, Injeong Shim2, Emilie L Gaillard3
1Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Division of Cardiology, The George Washington University School of Medicine, Washington, DC, USA.
Insights
High coronary artery disease polygenic risk score (PRS) is linked to increased long-term plaque buildup and high-risk plaque features. This finding highlights PRS as a significant predictor for future cardiovascular events.
Area of Science:
- Cardiovascular disease research
- Genetics and personalized medicine
- Medical imaging analysis
Background:
- The relationship between coronary artery disease (CAD) polygenic risk score (PRS) and long-term plaque progression, including high-risk plaque (HRP) features, remains largely uncharacterized.
- Understanding this association is crucial for refining risk stratification and guiding preventative strategies in individuals at risk for CAD.
Purpose of the Study:
- To investigate the impact of CAD PRS on the progression of coronary artery plaque over the long term.
- To assess the association between CAD PRS and the development of high-risk plaque (HRP) features.
Main Methods:
- Prospective study involving patients undergoing CAD PRS measurement and serial coronary computed tomography angiography (CTA) imaging over a median of 10.2 years.
- Utilized an artificial intelligence-based algorithm for quantitative analysis of coronary CTA scans to assess plaque volume and characteristics.
- Employed linear mixed-effect models to analyze the relationship between CAD PRS, percent atheroma volume (PAV) progression, noncalcified plaque progression, and HRP prevalence, adjusting for conventional risk factors.
Main Results:
- Patients with high CAD PRS exhibited significantly higher baseline PAV (10.4% vs 1.9%) and a greater association with PAV progression (0.69% increase per 10 years per 1 SD increase in CAD PRS).
- CAD PRS demonstrated added value in discriminating above-median noncalcified plaque progression compared to conventional risk factors alone (AUC 0.73 vs 0.69).
- High CAD PRS was strongly associated with the presence of HRP at both baseline (OR 2.85) and follow-up (OR 6.16).
Conclusions:
- Polygenic risk significantly influences long-term coronary plaque progression and the development of high-risk plaque features in patients suspected of having CAD.
- CAD PRS serves as a valuable independent predictor of future cardiovascular plaque burden and adverse plaque morphology.
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.
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