Abstract
BACKGROUND: Kidney dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF). It poses therapeutic challenges and is associated with worse clinical outcomes. Obesity is increasingly recognized as a key factor in HFpEF pathogenesis, yet its impact on kidney function remains unclear. METHODS: We conducted a retrospective analysis using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Obesity was examined using body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR). The primary outcome was a decline in estimated glomerular filtration rate (eGFR) by >30% from baseline. Single eGFR decline was defined as meeting this threshold with one qualifying follow-up eGFR; persistent eGFR decline was defined by meeting it on two consecutive qualifying eGFR values. Univariable and multivariable Cox proportional hazards regression models were performed, modeling each exposure as a continuous variable and as quartiles. RESULTS: A total of 1765 patients were included (mean age 72±10 years, median eGFR of 60.8 [IQR 47.8, 76.1] ml/min/1.73m (2) ) with a median follow up of 3.3 years. There were 690 (39.1%) patients who met the definition of single eGFR>30% decline, and 459 (26%) patients who met the definition of persistent eGFR>30% decline. Compared to the lowest quartile, there was a significantly higher risk of >30% eGFR decline in the highest quartile of BMI (HR=1.26 [95% CI 1.00, 1.60]), WC (HR=1.35 [1.06, 1.71]) and WHtR (HR=1.27 [1.00, 1.61]), with similar trends in continuous analyses. All associations were attenuated and no longer met statistical significance when using the outcome of persistent kidney function decline. CONCLUSIONS: Obesity is independently associated with declines in kidney function in patients with HFpEF. Associations were similar but attenuated and no longer met statistical significance for persistent declines in kidney function, suggesting that perhaps obesity is a risk factor for fluctuations in eGFR in HFpEF.