Association of Obesity with Kidney Function Outcomes in Heart Failure with Preserved Ejection Fraction

Background: Reduced kidney function is highly prevalent among patients with heart failure with preserved ejection fraction (HFpEF), leading to worse outcomes. While obesity plays a key role in HFpEF pathophysiology, its impact on kidney function remains unclear. Methods: Using data from the Treatment of Preserved Cardiac Function Heart Failure with Aldosterone Antagonist trial, we examined obesity using body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) with a primary outcome of >30% decline in estimated glomerular filtration rate (eGFR). Meeting the >30% eGFR decline endpoint was defined by a single qualifying value and then persistent decline required two consecutive values. Multivariate Cox proportional hazards models were used to evaluate associations, adjusting for demographic and comorbid conditions including age, sex, diabetes, hypertension, baseline eGFR and randomization arm. Results: Among 1765 patients (mean age 72±10 years, median eGFR 60.8 [IQR 47.8, 76.1] ml/min/1.73m 2 ), 687 (39.%) experienced a >30% eGFR decline, and 261 (15%) had a persistent >30% decline over a median 3.3-year follow up. Higher BMI (HR 1.10 [1.01, 1.20], WC (HR 1.10 [1.00, 1.20]) and WHtR (HR 1.13 [1.04, 1.23]) were associated with >30% eGFR decline after multivariable adjustment. Associations between measures of obesity and persistent kidney function decline were not significant. Conclusions: Obesity is associated with declines in kidney function among patients with HFpEF, independent of traditional risk factors such as diabetes and hypertension.