Prognostic Value of Plaque Burden Beyond Stenosis Severity in Patients with Stable Chest Pain Undergoing Coronary CT Angiography

Abstract

Introduction: Coronary computed tomography angiography (CCTA) is a noninvasive test for suspected coronary artery disease (CAD), but the prognostic value of integrating plaque burden into CAD-RADS 2.0 has not been fully evaluated. We aimed to assess whether the high-risk CAD-RADS 2.0 category, which combines stenosis severity and segment involvement score (SIS), provides prognostic information beyond stenosis severity in patients with stable chest pain. Methods: We retrospectively included 563 consecutive patients with stable chest pain who underwent CCTA between 2017 and 2022. CAD-RADS 1.0 categories and CAD-RADS 2.0 plaque burden grades were assigned by experienced radiologists. High-risk CAD-RADS 2.0 was defined as CAD-RADS ≥ 3 or any CAD-RADS with P-SIS ≥ 3. The primary endpoint was major adverse cardiovascular events (MACEs). Given the limited number of events, multivariable analysis was restricted to clinically justified parsimonious Cox proportional hazards models. A model including age, sex, and significant stenosis was compared with a model including age, sex, and the high-risk CAD-RADS 2.0 category. A formally nested extended model additionally included severe-to-extensive plaque burden. Results: Over a median follow-up of 51.2 months, 41 patients (7.3%) experienced MACEs. Among patients with non-obstructive CAD (CAD-RADS 1–2), 29 of 477 (6.1%) experienced MACEs, and 85.4% of these events occurred in patients with severe or extensive plaque burden (P3–P4). After adjustment for age and sex, significant stenosis was not associated with MACEs, whereas the high-risk CAD-RADS 2.0 category was independently associated with MACEs (HR 2.88, 95% CI 1.07–7.75; p = 0.036). Addition of plaque burden to a model including age, sex, and significant stenosis increased the Harrell C-index from 0.760 to 0.772 and significantly improved model fit (likelihood-ratio χ2 = 5.41; p = 0.020). In the extended model, plaque burden remained independently associated with MACEs (HR 2.81, 95% CI 1.10–7.19; p = 0.031). Conclusions: In patients with stable chest pain undergoing CCTA, the high-risk CAD-RADS 2.0 category was independently associated with MACEs. Formal incremental analyses demonstrated that plaque burden provided prognostic information beyond age, sex, and significant stenosis. These findings support the prognostic relevance of integrating plaque burden into CCTA-based risk classification but require confirmation in larger prospective and externally validated cohorts.