Chronic Inflammation in Patients with Chronic Coronary Syndrome Who Have Been Taking Lipid-Lowering Drugs as a Residual Risk Factor – a Bidirectional Synergistic Correlation with Epicardial Adipose Tissue

Runze Zhu,1– 3 Wenxian Wang,1– 3 Yan Gao,2,3 Bowen Li,1– 3 Wanting Wang,1– 3 Jie Liu,2– 4 Liang Wu,2– 4 Shifeng Yang,2,3 Ximing Wang1– 3 1School of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Ministry of Education, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Jinan, Shandong, People’s Republic of China; 4School of Medical Imaging, Binzhou Medical University, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Ximing Wang, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324, Jing 5 Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 15168886672, Email [email protected]: Patients with coronary heart disease on long-term lipid-lowering agents typically maintain relatively low lipid levels. However, an elevated systemic inflammatory state represents another major risk factor for poor prognosis in these individuals. This study aims to investigate the relationship between systemic inflammation and adverse outcomes in patients with chronic coronary syndrome(CCS), as well as its synergistic interaction with epicardial adipose tissue (EAT).Methods: This is a double-center retrospective cohort study. From March 2017 to September 2023, We retrospectively included 278 patients with CCS from two medical institutions in China, all of whom had been receiving long-term statin therapy. Participants underwent cardiovascular magnetic resonance (CMR) imaging and blood testing. Systemic inflammatory response index (SIRI) were derived, and CMR parameters, including EAT volume, were measured. Cox regression analysis was used to evaluate the association between each variable and major adverse cardiovascular events (MACEs). Mediation analysis was applied to assess the interrelationships among systemic inflammatory markers, indexed EAT volume, and CMR parameters.Results: Both the SIRI and indexed EAT volume were independently associated with MACEs. Combining SIRI and indexed EAT volume significantly improved the predictive capacity for MACEs. EAT volume partially mediated the relationship between SIRI and MACEs, and similarly, SIRI partially mediated the association between EAT volume and MACEs. Additionally, we observed analogous interrelationships among SIRI, indexed EAT volume, and extracellular volume (ECV).Conclusion: In patients with CCS on long-term statin therapy, elevated SIRI and increased EAT volume represent more important risk factors than lipid levels. SIRI and EAT volume interact with each other and collectively contribute to a poor prognosis in these patients. Keywords: chronic inflammation, chronic coronary syndrome, epicardial adipose tissue, systemic inflammatory response index, cardiovascular magnetic resonance