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Objective Cardiovascular diseases are a leading cause of morbidity and mortality in SLE. In this target population, epicardial adipose tissue (EAT) volume is increased, but its determinants and roles are poorly understood. This study aimed to assess the circulating metabolomic and lipidomic signatures associated with EAT in SLE.Methods A comprehensive analysis of the circulating metabolome and lipidome was conducted in a monocentric and retrospective cohort of patients with SLE followed at the French Referral Center (Pitié-Salpêtrière Hospital) who underwent a cardiac CT scan. Coronary artery calcium (CAC) scores and EAT volumes were collected. An increased indexed EAT (EATi) volume was defined by an EAT volume >68 mL/m 2 as previously described.Results A total of 179 SLE patients were included (mean age, 43±14 years; 100% female). Mean EATi volume was 63±37 mL/m 2 and was increased (>68 mL/m2) in 61 patients (34.1%). Increased EATi volume was significantly associated with age, body mass index, triglyceride levels, CAC score, prior atherosclerotic cardiovascular disease and 47 metabolites/lipid species. A stepwise linear regression identified five key metabolites and lipid species independently associated with EATi volume. A lipidomic and metabolic signature yielded a good area under the curve for EATi volume status prediction (0.80; 95% CI 0.73 to 0.87).Conclusions EAT volume is increased and associated with a distinct serum lipidomic and metabolomic signature in SLE.