The presence and volume of plaque in patients with coronary artery disease (CAD) is associated with traditional cardiovascular risk factors and major adverse cardiovascular events (MACE), a new substudy of the PROMISE trial shows. These results were reported by Júlia Karády, MD, PhD, MPH, of Massachusetts General Hospital, Boston, and colleagues from Hungary, Germany and the U.S., in a manuscript published online Wednesday in JAMA Cardiology. Coronary computed tomographic angiography (CCTA) is often used to help with the management of known or suspected CAD, but data is lacking when it comes to the impact of plaque volume and presence on adverse events and clinical outcomes. This prospective, post hoc analysis utilized data from a randomized clinical trial that took place across 193 clinical centers in North America. PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) evaluated 10,003 outpatients without known CAD. Patients were randomized 1:1 to receive CCTA or functional testing. Patients were randomized between July 27, 2010, and October 31, 2024. Data were analyzed between January 2021 and July 2024 for this present substudy, and only patients who received CCTA were included (patients who underwent functional testing were excluded). Quantitative plaque measures included total plaque volume (TPV), calcified and noncalcified plaque volume (CPV and NCPV), low-attenuation plaque volume (LAPV), total plaque burden (TPB) and noncalcified plaque burden (NCPB). These were normalized with vessel volume. A composite of death, nonfatal myocardial infarction (MI) or hospitalization made up the MACE for the primary endpoint in this substudy. A total of 4,267 patients were analyzed (mean age=60.4 years, 51.5% female). Patients who measured at the median TPV (39.8 mm3) or higher were older, on average (mean age=62.1 years), than those with lower-than-median TPV (mean age=58.7 years). Patients with had median-or-higher TPV were also more likely to be male (60.3%) and had higher median atherosclerotic cardiovascular disease risk scores (14.9) compared with those who had below-median TPV levels (36.6% male; 7.9 risk scores). Outcomes for TPB were similar to TPV. TPB and NCPB independently predicted MACE when investigators adjusted for clinical risk factors, patients’ use of statins and qualitative CCTA outcomes (TPB: adjusted hazard ratio [aHR]=1.18; 95% confidence interval [CI]=1.05-1.34; p=0.006) (NCPB: aHR=1.20; 95% CI=1.05-1.37; p=0.007). Patients were also at double the risk of MACE if they had rates above the optimal cutoff for TPV (87 mm3 or more), TPB (35% or more) and NCPB (20% or more). The authors noted several limitations of this subanalysis: plaque analysis is time- and resource-intensive and may not be applicable across clinical settings, plaque quantification is vendor-specific and lacks standardized parameters, these findings may not be generalizable to high-risk cohorts or patients outside North America, the follow-up period (median=25 months) may not show the full picture of long-term effects, regression models did not include glomerular filtration rates and the exploratory nature of the analysis. Across the board, the presence and volume of coronary plaque predict MACE and are associated with CAD risk factors in patients who are symptomatic without known CAD. Source: Karády J, Mayrhofer T, Brendel JM, et al. Prognostic value of plaque volume in patients with first diagnosis of coronary artery disease: A substudy of the PROMISE randomized clinical trial. JAMA Cardiol. 2026 February 11 (Article in Press). Image Credit: Dragana Gordic – stock.adobe.com