Pericoronary adipose tissue inflammation mediates the atherogenic effects of lipids on multivessel coronary artery disease: a CCTA-based radiomics analysis.

Objective: The atherogenic index of plasma (AIP) is a robust predictor of cardiovascular risk. However, its mechanism of action in the severity of coronary artery disease (CAD) remains unknown. We investigated whether pericoronary adipose tissue inflammation [assessed using the fat attenuation index (FAI)] mediates the association between AIP and CAD in middle-aged and older adults. Methods: A total of 450 patients who underwent coronary computed tomography angiography at Yan'an University Affiliated Hospital (2022-2024) were enrolled in this study. Coronary atherosclerotic disease (CAD) severity was defined as multivessel CAD (MVCAD; ≥50% stenosis in ≥2 arteries). The fat attenuation index (FAI) was measured around the right coronary artery (RCA-FAI) using a standardized radiomics protocol. Logistic regression and mediation analyses (PROCESS macro, 1,000 bootstrap samples) were used to quantify these associations. Results: The atherogenic index of plasma (AIP) independently predicted MVCAD (OR = 2.35, 95% CI: 1.96-5.10, P < 0.01). The RCA-FAI showed a dose-dependent CAD risk (OR = 1.33 per one-unit increase, P < 0.01), with a 33% higher risk per FAI increment. Mediation analysis revealed that the RCA-FAI explained 27.9% of the AIP-MVCAD association (P < 0.05). Stratification by glucose metabolism status confirmed the consistent role of the RCA-FAI across subgroups, whereas the AIP-CAD association was significant only in normoglycemic individuals. Conclusion: This is the first study to demonstrate that coronary arterial inflammation (RCA-FAI) partially mediates the atherogenic effects of AIP on MVCAD, suggesting a dual pathway of lipid-driven inflammation and metabolic dysregulation. Our findings highlight RCA-FAI as a promising imaging biomarker for CAD risk stratification, irrespective of glucose metabolism status.