Natriuretic peptides are key biomarkers used to risk-stratify patients with heart failure (HF), but current guideline thresholds do not typically account for body mass index (BMI).¹ A new pooled analysis suggests that these fixed thresholds may underestimate risk in patients with HF and higher BMI, questioning the one-size-fits-all approach.²

This study was a participant-level pooled analysis of four global, randomised outcomes trials: I-PRESERVE, TOPCAT, PARAGON-HF, and DELIVER. The analysis included 14,750 adults with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). The cohort had a mean age of 72 years, 50% were female, and the mean BMI was 30 kg/m². The median N-terminal pro–B-type natriuretic peptide (NT-proBNP) level was 836 pg/mL.²

The primary endpoint was the composite of cardiovascular (CV) death or HF hospitalisation. Secondary endpoints included CV death and all-cause death. The association between NT-proBNP and these clinical outcomes was evaluated according to BMI.²

Researchers found that a higher baseline BMI was significantly and nonlinearly associated with lower NT-proBNP levels. Over a median follow-up of 2.8 years, each doubling of baseline NT-proBNP was associated with a 40% higher adjusted rate of CV death or HF hospitalisation (HR: 1.40; 95% CI: 1.36–1.43; p<0.001). However, this association was incrementally blunted with higher baseline BMI (p for interaction = 0.008).²

For the same absolute risk of the primary endpoint (5 events per 100 person-years), NT-proBNP levels in participants without atrial fibrillation were nearly three-fold lower among those with a BMI ≥35 kg/m² (158 pg/mL) compared to those with a BMI <35 kg/m² (450 pg/mL).²

Furthermore, at a contemporary NT-proBNP-based trial eligibility threshold, the absolute risk of CV death or HF hospitalisation ranged from 3.5 per 100 person-years among individuals with a BMI <30 kg/m² to 7.3 per 100 person-years among those with a BMI ≥40 kg/m².²

The analysis concluded that current NT-proBNP thresholds substantially underestimate the absolute risk of adverse HF outcomes among persons with higher BMI. These data question the utility of single fixed thresholds for risk stratification. The findings suggest that implementing lower, BMI-specific NT-proBNP cutoffs may more appropriately identify risk in patients with HFmrEF/HFpEF and obesity.²

References

1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. https://doi.org/10.1016/j.jacc.2021.12.012

2. Ostrominski JW, Neuen BL, Claggett BL, et al. Natriuretic Peptides, Body Mass Index, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JACC. 2025;86(20):1823-1839. https://doi.org/10.1016/j.jacc.2025.08.028

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