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.