Abstract

Introduction: N-terminal pro B type natriuretic peptide (NT-proBNP) is associated with increased cardiovascular events in heart failure with preserved ejection fraction (HFpEF). Adiposity is inversely correlated with NT-proBNP. It remains unclear whether obese HFpEF patients exhibit disproportionate outcomes with lower NT-proBNP. Hypothesis: We aimed to study the relationship between NT-proBNP and BMI in the Johns Hopkins University (JHU) HFpEF cohort to identify patient characteristics with increased NT-proBNP in obese HFpEF patients, adjusting for the inverse relation between NT-proBNP and BMI. Methods: We identified 338 individuals from June 2013 to November 2022. Univariate linear regression was performed between NT-proBNP and BMI. The cohort was split based on the median BMI and studentized residuals from NT-proBNP-BMI relationship (low BMI high BNP [Group 1] high BMI high BNP [Group 2] low BMI low BNP [Group 3] high BMI low BNP [Group 4]). Kruskal-Wallis test or Chi-square test was used to compare groups. Results: The median BMI of the cohort was 37kg/m 2 , and with every 1kg/m 2 increase in the BMI, the cut-off for elevated NT-proBNP reduced by 4 pg/ml. High BMI HFpEF patients were younger, predominantly female, and on diuretics (p<0.05 for all), independent of their NT-proBNP levels. Group 4 patients performed better on the 6-minute walk test (240±136 m), had better renal function (eGFR: 68.7±27.3), and less left ventricular (LV) hypertrophy and only mild diastolic dysfunction on echocardiography. Surprisingly, Group 2 resembled Group 1 despite having 70% reduced median NT-proBNP (1898[1047,4409] vs 574[207,1322], p<0.0001). Both “high BNP” groups exhibited lower event free survival for all -cause mortality(p=0.0001) and HF-hospitalization(p<0.05). Conclusions: NT-proBNP is predictive of clinical outcomes in HFpEF even in the presence of obesity. BMI adjusted NT-proBNP may be useful in the diagnosis and prognosis of HFpEF.

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