The study, led by Dr. Júlia Karády and colleagues from the Cardiovascular Imaging Research Center at Massachusetts General Hospital, Boston, examined 4,267 symptomatic outpatients across 193 North American sites. Participants underwent CCTA as part of the trial between 2010 and 2014, and plaque quantification analyses were conducted from 2021 to 2024.
Researchers focused on core laboratory–assessed plaque metrics, including total plaque volume (TPV), total and noncalcified plaque burden (TPB and NCPB), calcified and noncalcified plaque volumes, and low-attenuation plaque volume, all normalized to vessel size. The primary endpoint was MACE, defined as death, nonfatal myocardial infarction, or hospitalization for unstable angina.
The key findings were as follows:
- Higher coronary plaque measures were associated with an increased risk of major adverse cardiovascular events (MACE), independent of clinical risk factors, statin use, significant stenosis, CAC scores, and high-risk plaque features.
- Patients with total plaque volume (TPV) ≥87 mm³, total plaque burden (TPB) ≥35%, or noncalcified plaque burden (NCPB) ≥20% had nearly double the risk of MACE compared to those below these thresholds.
- Continuous measures of TPB and NCPB independently predicted adverse cardiovascular outcomes after adjusting for traditional risk factors.
- Patients with higher TPV and plaque burden were generally older, more likely to be male, and had higher atherosclerotic cardiovascular risk scores.
- The median TPV across the cohort was 39.8 mm³, indicating that even relatively low plaque volumes had clinical significance when quantified.
The study highlights the potential of quantitative CCTA analysis to enhance risk stratification beyond conventional metrics, such as CAC scores and the presence of obstructive lesions. By providing more granular insight into the total and noncalcified plaque burden, clinicians may be able to identify high-risk patients earlier and tailor preventive strategies accordingly.
However, the authors caution that these results are exploratory. The parent PROMISE trial did not demonstrate improved outcomes from an initial CCTA-based strategy versus functional testing, and plaque quantification remains resource-intensive and vendor-specific. Limitations include the predominantly North American outpatient population, a relatively short follow-up period (median 25 months), and the lack of standardized plaque measurement protocols.
Despite these challenges, the findings suggest that quantitative assessment of coronary plaque holds promise for improving early detection of cardiovascular risk in symptomatic patients without known CAD. The authors advocate for further prospective studies to evaluate the clinical utility of CCTA-based plaque quantification in routine practice.
Reference:
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. Published online February 11, 2026. doi:10.1001/jamacardio.2025.5520
Disclaimer: This website is primarily for healthcare professionals. The content here does not replace medical advice and should not be used as medical, diagnostic, endorsement, treatment, or prescription advice. Medical science evolves rapidly, and we strive to keep our information current. If you find any discrepancies, please contact us at corrections@medicaldialogues.in. Read our Correction Policy here. Nothing here should be used as a substitute for medical advice, diagnosis, or treatment. We do not endorse any healthcare advice that contradicts a physician's guidance. Use of this site is subject to our Terms of Use, Privacy Policy, and Advertisement Policy. For more details, read our Full Disclaimer here.
NOTE: Join us in combating medical misinformation. If you encounter a questionable health, medical, or medical education claim, email us at factcheck@medicaldialogues.in for evaluation.