Body Mass Index, Natriuretic Peptides, and Risk of Adverse Outcomes in Patients With Heart Failure and Preserved Ejection Fraction: Analysis From the TOPCAT Trial

BACKGROUND: The prognostic interrelationship between natriuretic peptide (NP) levels and body mass index (BMI) among patients with chronic stable heart failure with preserved ejection fraction is not well characterized. METHODS AND RESULTS: Participants from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial enrolled in the Americas meeting inclusion by the NP stratum were stratified into 4 data‐derived categories by BMI and standardized NP‐z score. Adjusted Cox‐proportional models determined the independent association of BMI, NP‐z score, and BMI/NP categories with composite primary end point, heart failure hospitalization, and all‐cause mortality. The study population included 997 participants. There was a U‐shaped relationship between BMI and NP with elevated NP levels noted at extremes of BMI distribution. There was also a U‐shaped relationship between BMI and risk of adverse clinical outcomes with the lowest risk among patients approximating a BMI of 25 kg/m(2). In contrast, higher NP levels were linearly associated with higher risk of adverse clinical outcomes. For BMI/NP‐based categories, participants in the high BMI/high NP group had greater prevalence of cardiac structural and functional abnormalities and the highest risk of adverse clinical outcomes (hazard ratio for primary end point; 95% confidence interval: 2.29 [1.36–3.84] Reference: low BMI/low NP). CONCLUSIONS: There is a U‐shaped association between BMI and NP levels among patients with chronic heart failure with preserved ejection fraction. Higher NP levels are independently associated with a higher risk of mortality across both high and low BMI strata. Among obese patients with heart failure with preserved ejection fraction, elevated NP levels identify a higher risk phenotype with a significantly increased incidence of both mortality and heart failure hospitalization.