Abstract / Summary
Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in heart failure and chronic kidney disease, but their vascular effects in atrial fibrillation remain incompletely characterized. We assessed whether SGLT2 inhibitor use is associated with endothelial and oxidative biomarker profiles and whether empagliflozin and dapagliflozin differ in this respect. Methods In this single-center cross-sectional study with prospective recruitment, 287 patients with non-valvular atrial fibrillation receiving long-term oral anticoagulation were included. Six biomarkers were assigned a priori to endothelial, oxidative and integrative domains. Patients receiving an SGLT2 inhibitor (n = 168) were compared with those not receiving one (n = 119), and empagliflozin (n = 98) with dapagliflozin (n = 70). Associations were assessed using multiple regression adjusted for age, sex, eGFR, type 2 diabetes, chronic heart failure, left ventricular ejection fraction, left atrial dimension and coronary artery disease, with Holm correction across the six panel markers. Results In crude analyses, SGLT2 inhibitor use was associated with higher sVCAM-1 and sE-selectin and lower angiopoietin-2 and GDF-15 concentrations, while 8-OHdG and advanced oxidation protein products did not differ. After multivariable adjustment, only sVCAM-1 remained associated with SGLT2 inhibitor use (+ 12.8%; 95% CI + 3.6 to + 22.9; p = 0.006; Holm-adjusted p = 0.036). Differences in NT-proBNP and high-sensitivity troponin T observed in crude analyses disappeared after adjustment. Empagliflozin and dapagliflozin did not differ across any of the eight analytes measured; the comparison had 80% power to detect a difference of approximately 0.44 standard deviations. Conclusions In patients with non-valvular atrial fibrillation, endothelial but not oxidative biomarker profiles differed according to SGLT2 inhibitor exposure, although only sVCAM-1 remained independently associated after adjustment. Empagliflozin and dapagliflozin were not statistically distinguishable within the resolution of this study. These cross-sectional findings do not establish causality and support prospective evaluation of sVCAM-1 as a marker of endothelial heterogeneity.