Key result
Higher CAD polygenic risk is associated with increased CAD-RADS severity and greater plaque burden.
Why the study?
The association between the polygenic risk score for coronary artery disease (PRS-CAD) and imaging-derived disease severity in low-to-intermediate risk populations remained incompletely characterized.
Does the polygenic risk score for coronary artery disease correlate with CAD-RADS 2.0 disease severity and quantitative plaque features on CCTA in patients with suspected CAD?
Observational (n=951)
Does the polygenic risk score for coronary artery disease correlate with CAD-RADS 2.0 disease severity and quantitative plaque features on CCTA in patients with suspected CAD?
In individuals at low-to-intermediate clinical risk undergoing CCTA, polygenic risk score is modestly but significantly associated with CAD-RADS 2.0 severity and quantitative non-calcified and total plaque burden.
Background The association between the polygenic risk score for coronary artery disease (PRS-CAD) and imaging-derived disease severity in low-to-intermediate risk populations remains incompletely characterized. Integrating genetic risk with advanced coronary imaging may refine cardiovascular risk stratification beyond traditional factors. Objectives This study aimed to evaluate the relationship between PRS-CAD and coronary artery disease severity assessed by the CAD-RADS 2.0 classification and advanced plaque features derived from coronary computed tomography angiography (CCTA). Methods A total of 951 patients undergoing CCTA for suspected CAD were analyzed. PRS-CAD was calculated from genotyped blood samples, while plaque characteristics were quantified using an artificial intelligence–based software. CAD severity was graded according to the CAD-RADS 2.0 system. Correlations between PRS-CAD and quantitative plaque parameters were assessed using Spearman’s rank analysis. Results PRS-CAD was significantly associated with CAD-RADS categories (p = 0.012), indicating a genetic contribution to coronary disease severity. Moreover, PRS-CAD correlated positively with quantitative markers of atherosclerotic burden, including percent area stenosis (ρ ≈ 0.10, p < 0.005), non-calcified plaque volume (ρ ≈ 0.06, p = 0.03), percent atheroma volume (ρ ≈ 0.08, p = 0.007), and total plaque volume (ρ ≈ 0.06, p = 0.035). No significant association was observed with calcified plaque volume (ρ ≈ 0.05, p = 0.07), while a weak inverse correlation was found with plaque length (ρ ≈ −0.10, p = 0.0005). Among conventional risk factors, hypertension, diabetes, dyslipidemia, waist circumference, high-sensitivity C-reactive protein, and uric acid were also positively associated with CAD-RADS severity (all p < 0.001). Conclusions In a large cohort of individuals at low-to-intermediate clinical risk, PRS-CAD was modestly but significantly associated with coronary atherosclerosis severity and plaque composition as determined by CCTA. These findings support the incremental role of genetic profiling in conjunction with imaging-based assessment for improving the stratification and management of patients at risk for coronary artery disease.
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Mushtaq et al. (2026) conducted an observational in Suspected coronary artery disease (low-to-intermediate clinical risk) (n=951). Polygenic risk score for coronary artery disease (PRS-CAD) was evaluated on Coronary artery disease severity assessed by the CAD-RADS 2.0 classification and quantitative CCTA plaque features (p=0.012). Polygenic risk score for CAD was significantly associated with CAD-RADS 2.0 severity (p=0.012) and correlated with percent area stenosis (ρ≈0.10, p<0.005) and total plaque volume (ρ≈0.06, p=0.035).
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