Cardio-kidney-metabolic complexity in patients with atrial fibrillation: an analysis from the prospective GLORIA-AF registry phase III

Background: Cardio-Kidney-Metabolic (CKM) syndrome results from the complex interaction of cardiovascular, renal and metabolic comorbidities. Data on the epidemiology and clinical impact of the CKM syndrome in patients with atrial fibrillation (AF) are limited. We evaluated CKM domains and their impact in a real-world cohort of patients with AF. Methods: From the prospective global GLORIA-AF Registry phase III study, we defined CKM domains according to cardiovascular, renal and metabolic comorbidities or conditions in patients with AF and CHA2DS2-VASc score ≥ 1. We analysed the association of the number and groups of CKM domains with use of oral anticoagulant (OAC) and the risk of major outcomes via multiple-adjusted regression analyses. Our primary outcome was a composite of all-cause death and major adverse cardiovascular events. Results: 16,070 patients (age 70.1 ± 10.4 years, 45.2% females) were included; 1931 (12.0%) presented with all 3 CKM domains, with substantial geographical variation in the distribution of CKM domains. OAC use increased with the number of CKM domains (Odds Ratio [OR] and 95% Confidence Intervals [CI]: 1.40 [1.14-1.72] and 1.38 [1.07-1.78] for 2 vs. 0 and 3 vs. 0 CKM domains, respectively). Over a 3-year follow-up, the incidence of the primary composite outcome increased with the number of CKM domains, with highest hazard observed in patients with 3 domains (Hazard Ratio [HR] and 95%CI: 1.69 [1.20-2.37]). Among groups of CKM domains, those characterized by the kidney domain showed the highest association with the risk of clinical outcomes. Conclusions: In patients with AF, CKM domains are commonly found, and their prevalence is heterogeneous across geographical regions. CKM syndrome influences OAC use and had detrimental prognostic effects, with an increasing risk of all-cause death and MACE as the burden of CKM domains increased.