Diagnostic value of total coronary plaque burden for predicting obstructive coronary artery disease: sex-specific thresholds from the COPRODUCTION Registry

Background Growing evidence indicates that total coronary plaque burden is a stronger long-term predictor of major adverse cardiovascular events than stenosis severity or ischemia detection. Coronary computed tomography angiography (CCTA) enables comprehensive quantification of coronary plaque volume. The relationship between plaque burden and degree of stenosis remains to be characterised. Purpose This study aimed to define CCTA-derived thresholds of total coronary plaque burden that predict or reliably exclude obstructive coronary artery disease (CAD) in an ESC guideline-based cohort. Methods This analysis of the COPRODUCTION registry included patients who underwent clinically indicated CCTA (Dual-Source-CT-Scanner SOMATOM Force) at a German outpatient center between July 2017 and June 2020. Quantitative plaque analysis of all coronary arteries was performed using validated semi-automated software (syngo.via Frontier CT Coronary Plaque Analysis, version 5.0.2). Obstructive CAD was defined as ≥50% luminal diameter reduction in any coronary segment. Results This analysis included 5,412 patients (60.8% male; mean age 63 ± 11.5 years). Coronary plaques were present in 3,629 patients (67.1%). Total coronary plaque burden demonstrated excellent discrimination for obstructive CAD (AUC 0.90). The optimal overall cut-off derived from the Youden index was 51.85 mm³ (sensitivity 0.88; specificity 0.77). In sex-specific analyses, diagnostic performance remained high, with distinct thresholds: 68.45 mm³ in males (AUC 0.89; sensitivity 0.89; specificity 0.74) and 21.18 mm³ in females (AUC 0.92; sensitivity 0.93; specificity 0.77). Vessel-specific analyses revealed the highest plaque volume threshold in the left anterior descending artery (34.45 mm³), followed by the left circumflex artery (11.25 mm³) and the right coronary artery (7.25 mm³), indicating vessel-dependent plaque burden requirements for ≥50% luminal stenosis. The minimum plaque volumes associated with at least one significant stenosis were 22.0 mm³ in males and 12.4 mm³ in females, both yielding a false-negative rate <5%. Patients below these thresholds rarely exhibited obstructive disease. Conclusions Total coronary plaque burden demonstrated excellent diagnostic performance for detecting obstructive CAD, with robust accuracy and distinct sex-specific thresholds. Importantly, vessel-specific analyses revealed substantial variability in plaque volumes associated with ≥50% luminal stenosis, with the highest threshold observed in the left anterior descending artery, indicating relevant anatomical differences in plaque-stenosis relationships. Notably, significant coronary stenoses may already occur at relatively low levels of total plaque burden. These findings emphasize the importance of quantitative and sex-specific plaque assessment to improve CCTA-based individualized clinical decision-making.