Impact of Differences in Kidney Function Estimation by Creatinine compared to Cystatin C on Clinical Outcomes in Patients with Atrial Fibrillation

Abstract Background and Aims Differences between cystatin C-based and creatinine-based glomerular filtration rate estimations (eGFRdiff) have been associated with adverse outcomes. We aimed to investigate the prevalence of eGFRdiff and its association with clinical outcomes and brain lesions in patients with AF. Methods We analyzed 3,804 patients with AF enrolled in two prospective, multicenter cohort studies. The eGFRdiff was calculated by “cystatin C-based eGFR - creatinine-based eGFR”. Patients were stratified into three groups: eGFRdiff >10, -10 to 10, and <-10 mL/min/1.73 m2. Associations with high-sensitivity troponin T (hs-TnT), NT-proBNP, major adverse cardiovascular events (stroke/systemic embolism, myocardial infarction and cardiovascular death), first heart failure (HF) hospitalization, and MRI-detected brain lesions were assessed. Results Mean age was 71 years, 28% were female, and 49% had paroxysmal AF. An eGFRdiff of >10, -10 to 10 and <-10 ml/min/1.73 m2 was present in 17.7%, 71.7%, and 10.6% of the patients, respectively. Incidence rates per 100 patient-years increased across these groups for MACE (1.7, 3.9, 6.8) and HF-hospitalization (1.2, 3.5, 6.1). Similarly, the prevalence of MRI-detected brain infarcts (28%, 39%, 42%) and moderate-to-severe white matter hyperintensities (38%, 55%, 63%) increased with greater eGFRdiff. Levels of hs-TnT and NT-proBNP were inversely correlated with eGFRdiff. In multivariable-adjusted linear models, lower eGFRdiff was associated with MACE (p = 0.006) and HF-hospitalization (p = 0.015). Conclusion A substantial proportion of patients with AF exhibit clinically relevant eGFRdiff. More negative eGFR difference was associated with elevated cardiac biomarkers, greater burden of ischemic brain lesions, and increased risk of cardiovascular events and HF hospitalization.