Comparative prognostic value of coronary artery calcium, plaque burden, and obstructive disease on coronary CT angiography

Background and Aims Coronary artery calcium (CAC) scoring is an established marker of cardiovascular risk. In patients undergoing coronary computed tomography angiography (CCTA) for chest pain, the relative prognostic importance of total plaque burden and obstructive coronary artery disease (CAD) remains uncertain. We compared the long-term prognostic performance of CAC, plaque extent quantified by segment involvement score (SIS), and obstructive CAD, and evaluated their incremental value beyond clinical risk factors. Methods We included 12,439 consecutive patients undergoing CAC scoring and CCTA between 2013 and 2022. Median (IQR) age at inclusion was 58 (49-61), 6116 (49.2%) were women and 2187 (17.6%) had obstructive CAF. Major adverse cardiovascular events (MACE), defined as fatal or non-fatal myocardial infarction and stroke, were obtained through national registry linkage. Multivariable Cox regression assessed independent associations. Discrimination was evaluated using time-dependent area under the curve (AUC) analyses. Incremental prognostic value was assessed using changes in AUC and continuous net reclassification improvement (NRI). Results Among 11,610 complete-case patients (606 events), high plaque burden (SIS >= 4) was independently associated with MACE (HR 1.58, 95% CI 1.26–1.99, p<0.001). Obstructive CAD was also independently associated with events (HR 1.45, 95% CI 1.21–1.74, p<0.001). Addition of obstructive CAD to clinical variables modestly improved discrimination (ΔAUC 0.008, p=0.027). CAC provided incremental prognostic information beyond clinical risk factors and showed a moderate incremental value beyond obstructive disease. However, obstructive CAD did not improve discrimination beyond plaque burden (ΔAUC 0.001, p=0.511), whereas plaque burden significantly improved discrimination beyond obstructive disease (ΔAUC 0.009, p=0.037). Continuous NRI demonstrated significant reclassification improvement when plaque burden was added to clinical plus obstructive models (NRI 0.254, 95% CI 0.154–0.354, p<0.001), primarily driven by improved nonevent classification. Conclusion In patients undergoing CCTA for chest pain, CAC, obstructive CAD, and plaque burden each provide independent prognostic information. However, overall plaque extent appears to offer the greatest incremental value beyond clinical risk factors and stenosis severity, suggesting that total atherosclerotic burden may better capture long-term risk than obstructive disease alone.