Natriuretic Peptide Cut Points for Heart Failure Classification in Individuals With and Without Obesity

BACKGROUND: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines introduced elevated natriuretic peptide (NP) levels as a criterion for defining stage B heart failure (HF), or pre-HF, to identify individuals at greatest risk for future HF. Given the known NP deficiency in obesity, we aimed to assess whether a single NP cut point would disproportionately up-classify individuals with versus without obesity to stage B HF. METHODS: Participants free of HF from 5 community-based cohorts were included. We examined the reclassification of individuals to stage B HF using the 2022 versus 2013 guidelines, stratified by obesity class. Cox proportional hazards models were used to assess the association of NPs with incident HF across obesity classes. RESULTS: Among 32 735 participants, 35% had normal weight, 40% were overweight, 17% had obesity class 1, and 8% had obesity class 2/3. When applying the 2022 versus 2013 criteria, the proportion of individuals up-classified to stage B HF using the NP criterion was 62% among those with normal weight, 51% for those overweight, 47% for individuals with obesity class 1, and 42% for individuals with obesity class 2/3. Over a median follow-up of 13 years, 3077 HF events occurred. Both higher NP and body mass index were associated with greater HF risk, as expected ( P <0.0001 for both). Importantly, body mass index modified the association of NP with HF risk, such that higher NP concentration was associated with greater HF risk among individuals with lower body mass index. The optimal NT-proBNP (N-terminal pro-B-type natriuretic peptide) cut point to predict future HF risk was lower among individuals with obesity (80 pg/mL; 95% CI, 53–121) compared with normal-weight individuals (109 pg/mL; 95% CI, 80–157). CONCLUSIONS: The application of a single NP cut point resulted in fewer individuals with obesity being up-classified to stage B HF compared with normal-weight individuals. Adjusting NP cut points for individuals with obesity may improve the accuracy of HF risk stratification.