New research suggests that certain thresholds for quantitative assessments of total plaque burden (TPB), total plaque volume (TPV) and non-calcified plaque burden (NCPB) — derived from coronary computed tomography angiography (CCTA) — are indicative of significantly higher risks for major adverse cardiovascular events (MACE) in people with no known history of coronary artery disease (CAD).
For the sub-study from the PROMISE randomized clinical trial, recently published in JAMA Cardiology, researchers assessed the prognostic impact of TPB, TPV and NCPB in 4,267 symptomatic patients with an unknown history of CAD. The median TPV of the cohort was 39.8 mm3, according to the study.
After a multivariable analysis, the study authors found that patients with a TPB > 87 mm3 had more than double the risk for developing MACE. Patients with a TPB > 35 percent had nearly double the risk for MACE and those with NCPB > 20 percent had a 77 percent higher risk for MACE, according to the researchers.
Factoring in statin use, qualitative CCTA findings and clinical risk factors, the study authors noted that high TPB and high NCPB were independently prognostic for MACE with 18 percent and 20 percent higher adjusted risks, respectively, for MACE.
“Our data suggest that among people with a first evaluation for CAD, TPB and NCPB may be predictive of MACE after adjustment for cardiovascular risk factors, statin use, and established qualitative CCTA findings, such as (coronary artery calcium) score, obstructive stenosis 50% or more, and (high-risk plaque) features,” noted lead study author Julia Karady, M.D., Ph.D., MPH, who is affiliated with the Cardiovascular Imaging Research Center and the Radiology Department at Massachusetts General Hospital in Boston, and colleagues.
Three Key Takeaways
• Quantitative plaque thresholds on CCTA stratify MACE risk. In symptomatic patients without known CAD from the PROMISE trial (published in JAMA Cardiology), a total plaque burden (TPB) > 87 mm³ more than doubled MACE risk, TPB > 35 percent nearly doubled risk, and non-calcified plaque burden (NCPB) > 20% was associated with a 77 percent higher risk.
• Independent prognostic value beyond traditional markers. Even after adjustment for clinical risk factors, statin use, and qualitative CCTA findings (including CAC score, ≥ 50% stenosis, and high-risk plaque features), elevated TPB and NCPB remained independently associated with higher MACE risk (18 percent and 20 percent higher adjusted risk, respectively).
• Potential implications for preventive strategy but more validation is needed. Quantitative plaque assessment may enhance risk stratification in patients undergoing first evaluation for suspected CAD, particularly in lower-risk populations. However, lack of standardized measurement parameters and limited generalizability warrant further study before routine guideline integration.
While momentum appears to be building in the literature for the prognostic value of plaque quantification assessment along with potential FDA recognition of NCBV as a prognostic biomarker, the study authors emphasized the need for more CCTA studies in lower-risk populations.
“… They are arguably the group in whom additional prognostic data and more aggressive treatment may be most beneficial. … Despite data from PROMISE, CONFIRM, and other studies showing that even non-obstructive plaque increases the likelihood of events, guidelines rarely offer recommendations for intensifying preventive strategies based on the findings of non-obstructive CAD,” pointed out Karady and colleagues.
(Editor’s note: For related content, see “Where Do Things Stand with AI-Powered Plaque Quantification for CCTA Exams?: An Interview with Ron Blankstein, MD,” “Can AI Assessment of Non-Calcified Plaque Volume Enhance CT Assessment of MACE Risk Beyond CAC Scoring?” and “Emerging CCTA Research Shows Prognostic Value of AI Quantification of Plaque Burden for Assessing Cardiovascular Risks.”)
In regard to study limitations, the authors acknowledged a lack of standardized parameters for the measurement of quantitative plaque burden and noted the omission of estimated glomerular filtration rate in the regression models for the study. The researchers also cautioned that the study findings, drawn from an outpatient North American population having initial evaluation for suspected CAD, may not be applicable to high-risk cohorts, people with a history of CAD and asymptomatic individuals.
