Association of estimated glomerular filtration rate slope with mortality and cardiovascular events in Japanese patients with atrial fibrillation: the Fushimi AF Registry

Background A steeper decline in estimated glomerular filtration rate (eGFR) slope has been reported to be associated with increased mortality and cardiovascular events in patients with chronic kidney disease, diabetes mellitus, and heart failure. However, data on the relationship between eGFR slope and mortality or cardiovascular events in patients with atrial fibrillation (AF) remain limited. Purpose To investigate the association between eGFR slope and mortality and cardiovascular events in patients with AF. Method The Fushimi AF Registry is a community-based prospective survey of AF patients in Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. In the entire cohort, patients with baseline eGFR data and at least three eGFR measurements during annual follow-up over 5 years were included. We divided the 592 eligible patients into a rapid decliner group (eGFR slope < −3 ml/min/1.73m2/year) and a slow decliner group (eGFR slope ≥ −3 ml/min/1.73m2/year). We calculated eGFR slope for each patient using linear regression of serial eGFR measurements. Result The rapid decliner group included more women, had a higher prevalence of prior heart failure, used fewer mineralocorticoid receptor antagonists, and used more loop diuretics. Prevalences of hypertension, diabetes, and chronic kidney disease were comparable between the two groups, whereas baseline eGFR was higher in the rapid decliner group. During the median follow-up of 2,194 days, the mortality was significantly higher in rapid decliner group than slow decliner group (2.91% vs. 1.58% per person-year, log rank p=0.01). The incidence rate of a composite endpoint of cardiovascular death, myocardial infarction and stroke was comparable between the two groups (2.39% vs. 1.97% per person-year, log rank p=0.56). The incidence rate of hospitalization for heart failure was significantly higher in rapid decliner group than slow decliner group (5.19% vs. 2.59% per person-year, log rank p=0.001). In multivariate Cox regression analyses, a rapid decline in eGFR (steeper negative eGFR slope) was independently associated with increased risks of all cause death (adjusted hazard ratio 2.68; 95% confidence interval 1.20-5.97, p=0.016) and heart failure hospitalization (adjusted hazard ratio 2.27; 95% confidence interval 1.24-4.16, p=0.008). Conclusion In patients with AF, a rapid decline in eGFR is a strong and independent predictor of mortality and heart failure hospitalization, but not of atherosclerotic cardiovascular events. Monitoring longitudinal eGFR slope may help identify vulnerable patients and guide closer surveillance and therapeutic optimization.