Addition of CAD polygenic risk score to coronary artery calcium score enhances prediction of MACE

Figures

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  Figure 1. Forest plot of hazard ratios for MACE prediction across models. Forest plot showing hazard ratios (HR) and 95% confidence intervals for major adverse cardiovascular events (MACE) prediction across different risk models in the Sanford Health discovery cohort. Models are presented in order of increasing complexity: 1) CAC score alone (per 100 Agatston units); 2) CAC+age+sex; 3) CAC+clinical risk factors (age, sex, hypertension, diabetes, smoking, LDL-C); 4) PRS alone (per 1-SD increase); 5) CAC+PRS; 6) CAC+PRS+clinical risk factors; Hazard ratios are displayed with 95% confidence intervals (horizontal lines) and point estimates (squares sized proportional to precision). The vertical dashed line indicates HR = 1.0 (no effect). C-indices for each model are displayed on the right. The combined CAC+PRS+clinical risk factors model demonstrates the highest discriminatory performance (C-index=0.779).

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  Figure 2. Sensitivity and specificity for MACE prediction using different testing modalities. Receiver operating characteristic (ROC) curves comparing the predictive performance of PRS alone, CACS alone, and the combined PRS+CACS model for major adverse cardiovascular events (MACE). The diagonal dashed line represents the line of no discrimination (AUC=0.50). The PRS model is represented by black curve, the CACS model by blue curve, and the PRS+CACS model by green curve respectively.

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  Figure 3. Kaplan–Meier Curves showing event-free survival for different combinations of CACS and PRS risk categories. Kaplan–Meier survival curves depicting time-to-MACE events stratified by combined risk categories of CACS and PRS. Patients were classified into four groups based on high (>85th percentile) or low (≤85th percentile) CACS and PRS values: (1) Low PRS+Low CACS (green line), (2) Low PRS+High CACS (blue line), (3) High PRS+Low CACS (orange line), and (4) High PRS+High CACS (red line). The x-axis represents follow-up time in years, and the y-axis represents the cumulative probability of remaining event-free (survival probability). Log-rank test was used to compare survival distributions across groups.