Spatial extent of pericoronary adipose tissue inflammation combined with coronary plaque burden improves risk stratification in chronic coronary artery disease

Background Pericoronary adipose tissue (PCAT) inflammation on coronary CT angiography (CCTA) is associated with adverse outcomes, yet the prognostic value of its spatial extent and its interaction with structural plaque vulnerability markers such as low-attenuation plaque (LAP) remain insufficiently defined in chronic coronary artery disease (CAD). Purpose To assess the prognostic impact of multivessel PCAT inflammation and to determine whether integrating inflammation extent with LAP burden improves risk stratification for cardiovascular events in chronic CAD. Methods This retrospective observational study included 839 patients with chronic CAD undergoing CCTA. PCAT inflammation was defined as vessel-specific PCAT FAI in the highest quartile for each major coronary artery; inflammatory extent was categorized by the number of inflamed vessels (0, 1, or ≥2). High LAP burden was defined as LAP >4%. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), and unstable angina requiring coronary revascularization. The secondary endpoint comprised cardiovascular and non-cardiovascular death, non-fatal MI, unstable angina requiring coronary revascularization, and any coronary revascularization. Cox regression with time-dependent PCI was performed. Discrimination was assessed using area under the curve (AUC). Results Over a median follow-up of 3.8 years, 29 primary and 74 secondary events occurred. Event rates increased stepwise with higher inflammatory vessel count (Figure), and were also significantly higher in patients with LAP >4%. In multivariable Cox models, multivessel PCAT inflammation independently predicted the primary endpoint (HR 2.76, 95% CI 1.33–5.74; p=0.007). The combined phenotype (multivessel PCAT inflammation and LAP >4%) identified the highest-risk group (HR 7.94, 95% CI 2.45–25.8; p<0.01). Predictive performance was modest for multivessel PCAT inflammation (AUC 0.614) and LAP >4% (AUC 0.598), but their combination significantly improved discrimination for both the primary (p=0.038) and secondary endpoints (p=0.038). Conclusions Diffuse pericoronary inflammation and high LAP burden represent complementary biological and structural markers of coronary vulnerability on CCTA. Their integration refines risk stratification beyond anatomical assessment and may identify patients with heightened residual inflammatory risk who could benefit from intensified preventive strategies.