Epicardial adipose tissue thickness is associated with circulating biomarkers in individuals without known cardiac disease across a broad adiposity spectrum.

Epicardial adipose tissue (EAT) is closely linked to obesity-related cardiac dysfunction, yet the biological changes underlying EAT expansion before overt heart disease remain poorly understood. Circulating biomarkers may provide insight into early mechanisms connecting excess adiposity, EAT, and cardiac remodeling. We investigated the association between serially measured circulating proteins and EAT thickness in adults without known cardiac disease across a wide range of adiposity. Participants aged 35-65 years were enrolled from two prospective multicenter cohorts, including individuals with severe obesity undergoing bariatric surgery and with normal BMI. Blood samples were collected from all participants at baseline and from those who underwent bariatric surgery also one-year post-surgery, to measure 92 proteins using the OLINK-CV-III panel. Linear mixed models were used to assess associations between biomarkers and EAT thickness, with correction for multiple testing. Eighteen biomarkers were significantly associated with EAT thickness, reflecting pathways related to inflammation, extracellular matrix remodeling, and metabolic regulation. Strongest associations with EAT were observed for fatty-acid-binding-protein 4, tumor-necrosis-factor-receptor 2, and chemokine-ligand 16. Thirteen of these biomarkers were also associated with global longitudinal strain, a marker of subclinical cardiac dysfunction, suggesting that EAT may function both as a marker and mediator of early cardiometabolic and cardiac dysfunction.