American journal of preventive cardiology · 2026
Use of a polygenic risk score to enhance early detection of coronary atherosclerosis.
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Petranović Milena, Lai Yi-Pin, Huck Daniel, Shiyovich Arthur, Besser Stephanie A, Blair Camila V, Berman Adam N, Singh Avinainder, Weber Brittany, Fahed Akl C, Miao Joanne, Hainer Jon, Kamanu Frederick K, Melloni Giorgio E M, Cardoso Rhanderson, Hedgire Sandeep, Ghoshhajra Brian, Carli Marcelo Di, Sabatine Marc S, Gupta Rajat M, Ruff Christian T, Blankstein Ron, Marston Nicholas A
Аннотация
BACKGROUND: Coronary CT angiography (CCTA) enables early noninvasive detection of coronary atherosclerosis, but its use in younger adults is limited by low pretest probability. Coronary artery disease polygenic risk score (CAD-PRS) may help identify individuals with increased likelihood of coronary plaque.
METHODS: We conducted a retrospective cohort study of patients without prior coronary artery disease who underwent CCTA between 2004 and 2021 and were genotyped through the Mass General Brigham Biobank (n = 1991), with follow-up through 2024. CAD-PRS was analyzed continuously and by risk categories (high [top decile], intermediate, low [bottom decile]). Plaque was classified as absent (CAD-RADS 0), non-obstructive (CAD-RADS 1-2), or obstructive (CAD-RADS 3-5). Extensive plaque was defined as ≥3-vessel involvement. Relative risk regression evaluated associations with plaque stratified by age. Kaplan-Meier and Cox proportional hazards models evaluated associations with adverse cardiovascular outcomes.
RESULTS: Plaque was present in 65.6% of participants, extensive plaque in 32.2%, and obstructive disease in 24.6%. Compared with the low-PRS group, high CAD-PRS was associated with greater risk of any plaque (RR 1.68, 95% CI 1.48-1.92), extensive plaque (RR 2.62, 95% CI 1.94-3.54), and obstructive disease (RR 2.82, 95% CI 1.87-4.27) (all P < .001). Associations were strongest among younger individuals (PRS-age interaction P = .017). CAD-PRS improved discrimination beyond age, sex, and traditional risk factors (C-statistic 0.832 [95% CI, 0.814-0.851] vs 0.803 [0.782-0.823]). High CAD-PRS was independently associated with increased cardiovascular events (aHR 2.76, 95% CI 1.55-4.92, P < .001).
CONCLUSIONS: High CAD-PRS was independently associated with greater presence, extent, and severity of CAD on CCTA. The impact of genetic risk was strongest in younger adults-a group for whom identifying early atherosclerotic plaque may have the greatest impact.
METHODS: We conducted a retrospective cohort study of patients without prior coronary artery disease who underwent CCTA between 2004 and 2021 and were genotyped through the Mass General Brigham Biobank (n = 1991), with follow-up through 2024. CAD-PRS was analyzed continuously and by risk categories (high [top decile], intermediate, low [bottom decile]). Plaque was classified as absent (CAD-RADS 0), non-obstructive (CAD-RADS 1-2), or obstructive (CAD-RADS 3-5). Extensive plaque was defined as ≥3-vessel involvement. Relative risk regression evaluated associations with plaque stratified by age. Kaplan-Meier and Cox proportional hazards models evaluated associations with adverse cardiovascular outcomes.
RESULTS: Plaque was present in 65.6% of participants, extensive plaque in 32.2%, and obstructive disease in 24.6%. Compared with the low-PRS group, high CAD-PRS was associated with greater risk of any plaque (RR 1.68, 95% CI 1.48-1.92), extensive plaque (RR 2.62, 95% CI 1.94-3.54), and obstructive disease (RR 2.82, 95% CI 1.87-4.27) (all P < .001). Associations were strongest among younger individuals (PRS-age interaction P = .017). CAD-PRS improved discrimination beyond age, sex, and traditional risk factors (C-statistic 0.832 [95% CI, 0.814-0.851] vs 0.803 [0.782-0.823]). High CAD-PRS was independently associated with increased cardiovascular events (aHR 2.76, 95% CI 1.55-4.92, P < .001).
CONCLUSIONS: High CAD-PRS was independently associated with greater presence, extent, and severity of CAD on CCTA. The impact of genetic risk was strongest in younger adults-a group for whom identifying early atherosclerotic plaque may have the greatest impact.