Importance Despite the increasing use of coronary computed tomographic angiography (CCTA) in patients with known or suspected coronary artery disease (CAD), comparatively little is known about its predictive value for adverse events or clinical applicability of volumetric plaque analysis. Objective To assess the incremental prognostic value of quantitative CAD measures in symptomatic outpatients without known CAD. Design, Setting, and Participants This post hoc analysis involved a prospective randomized clinical trial conducted across 193 clinical sites in North America. Participants were symptomatic outpatients without known CAD who were randomized to receive CCTA. The trial was conducted from July 27, 2010, to October 31, 2014, and the data analyzed for this report from January 2021 to July 2024. Exposures Core laboratory-based quantitative plaque measures, including total plaque volume (TPV), calcified (CPV) and noncalcified (NCPV) plaque volume, low-attenuation plaque volume (LAPV), total plaque burden (TPB), and noncalcified plaque burden (NCPB), normalized with vessel volume. Main Outcomes and Measures The primary outcome was major adverse cardiovascular events MACE (composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina). Optimal predictive cut points for plaque measures were identified using Euclidean distance methods and tested in multivariable Cox regression models. Results Among 4267 patients, the mean (SD) age was 60.4 (8.2) years; 2199 patients (51.5%) were female and 2068 (48.5%) were male. The median (IQR) TPV was 39.8 mm 3 (0-167) mm 3 . Patients with TPV at the median or higher were older (mean SD age, 62.1 8.4 vs 58.7 7.5 years for those with lower than median TPV), more likely to be male (1286/2133 60.3% vs 782/2134 36.6%, respectively), and had higher median (IQR) atherosclerotic cardiovascular disease risk scores (14.4 8.8-24.0 vs 7.9 4.5-13.4, respectively). TPB showed similar demographic associations. Both TPB and NCPB independently predicted MACE after adjusting for clinical risk factors, statin use, and qualitative CCTA findings (TPB: adjusted HR aHR, 1.18; 95% CI, 1.05-1.34; P = .006; NCPB: aHR, 1.20; 95% CI, 1.05-1.37; P = .007). Optimal cutoffs of TPV 87 mm 3 or greater, TPB 35% or greater, and NCPB 20% or greater were each associated with nearly a 2-fold increase in MACE risk (TPV: aHR, 2.07; 95% CI, 1.24-3.49; TPB: aHR, 1.96; 95% CI, 1.21-3.17; and NCPB: aHR, 1.77; 95% CI, 1.12-2.82). Conclusions and Relevance In symptomatic patients without known CAD, coronary plaque volumes and burdens are low but are related to CAD risk factors and independently predictive of MACE. The clinical utility of quantitative CCTA-based cardiovascular risk estimation in early CAD requires prospective evaluation. Trial Registration ClinicalTrials.gov Identifier: NCT01174550
Karády et al. (2026) studied this question.