Abstract Body (Do not enter title and authors here): Background
Obesity is considered one of the key drivers of the cardiovascular-kidney-metabolic syndrome. Obesity is highly prevalent among patients with heart failure with preserved ejection fraction (HFpEF) but there are few studies evaluating its relation with kidney function decline in this population.

Hypothesis
We hypothesized that among patients with HFpEF, obesity measured by body mass index (BMI) and waist circumference (WC), is associated with increased risk of worse kidney outcomes.

Methods
We performed a retrospective analysis using data from the TOPCAT (Spironolactone for Heart Failure with Preserved Ejection Fraction) trial, which was a multicenter, randomized trial assessing the effect of spironolactone vs placebo in patients with HFpEF. Our exposures of interest included BMI ≥30 kg/m² and WC ≥102cm in men and ≥88cm in women. The association between obesity with eGFR decline by >40%, a validated surrogate endpoint for kidney failure, was examined using multivariable Cox proportional hazards models. Covariates included age, sex, comorbidities, baseline eGFR, and treatment group.

Results
Among 3445 subjects over a mean follow up of 3.3 years, mean baseline eGFR was 67 ml/min/1.73m2; 1902 (55%) had BMI ≥30 kg/m2 and 2284 (72%) had high WC. After multivariable adjustment, subjects with high BMI had an increased risk (HR 1.39 CI 1.14-1.70) of >40% eGFR decline. Similarly, those with high WC had a higher risk of >40% eGFR decline (HR 1.54 CI 1.19-2.01) (Figure 1, Table 1). There was no significant interaction by randomization to spironolactone. After adjusting for covariates, no significant interaction by sex was found in the BMI group. In the WC group, while interaction was significant (p=0.02), this effect was not observed when assessing WC as a continuous variable.

Conclusion
Obesity, whether assessed by BMI or WC, is associated with higher risk of eGFR decline in patients with HFpEF. Further investigation stratifying men and women is needed.