Related Experiment Video
Updated: Sep 9, 2025
Cutoff Value of Phase Angle by Bioelectrical Impedance Analysis at Admission as a Prognostic Factor in Patients with Acute Heart Failure
Published on: June 10, 2025
Natriuretic Peptides, Body Mass Index, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved
John W Ostrominski1, Brendon L Neuen2, Brian L Claggett3
1Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Higher body mass index (BMI) is linked to lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in heart failure (HF) patients. Current NT-proBNP thresholds may underestimate risk in individuals with higher BMI.
Area of Science:
- Cardiology
- Biomarker Research
- Obesity Medicine
Background:
- Natriuretic peptides are key heart failure (HF) biomarkers for risk stratification and clinical trial eligibility.
- Current HF guidelines and trial criteria often do not incorporate adiposity measures like body mass index (BMI).
Purpose of the Study:
- To investigate the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and clinical outcomes in HF with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).
- To stratify this association based on body mass index (BMI) categories.
Main Methods:
- A pooled analysis of 4 global, randomized, controlled HF trials.
- Evaluated NT-proBNP association with cardiovascular death or HF hospitalization, cardiovascular death, HF hospitalization, and all-cause death.
- Stratified analyses by BMI as a continuous and categorical variable.
Main Results:
- Higher baseline BMI was non-linearly associated with lower NT-proBNP levels in 14,750 participants.
- Increased NT-proBNP independently predicted adverse cardiovascular outcomes, but this association was blunted in higher BMI groups.
- For a similar absolute risk, NT-proBNP levels were significantly lower in individuals with BMI ≥35 kg/m² compared to those with BMI <35 kg/m².
Conclusions:
- Standard NT-proBNP thresholds may underestimate the absolute risk of adverse HF outcomes in patients with higher BMI.
- Fixed NT-proBNP cutoffs may not be optimal for risk stratification across all BMI ranges.
- Lower NT-proBNP thresholds may be necessary for accurate risk assessment in higher BMI populations.
Background:
Natriuretic peptides are the primary biomarkers recommended in heart failure (HF) guidelines to risk stratify patients in clinical practice and serve as key eligibility criteria in contemporary clinical trials. However, threshold levels typically do not account for measures of adiposity, such as body mass index (BMI).
Objective:
The purpose of this study was to evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) with clinical outcomes in individuals with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), stratified according to BMI.
Methods:
In this participant-level pooled analysis of 4 global, randomized, outcomes trials including adults with HFmrEF/HFpEF, the association between NT-proBNP and clinical outcomes (cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death) was evaluated according to BMI as a continuous and categorical variable.
Results:
Among 14,750 participants (mean age, 72 ± 9 years; 50% female; mean BMI, 30 ± 6 kg/m2; median NT-proBNP, 836 pg/mL), 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 covariate-adjusted rate of cardiovascular death or HF hospitalization (HR: 1.40; 95% CI: 1.36-1.43; P < 0.001); however, this association appeared incrementally blunted with higher baseline BMI (Pinteraction = 0.008). For the same absolute risk of cardiovascular death or HF hospitalization (5 events per 100 person-years), NT-proBNP levels in participants without atrial fibrillation were nearly 3-fold lower among those with BMI ≥35 kg/m2 (158 pg/mL) vs <35 kg/m2 (450 pg/mL). At a contemporary NT-proBNP-based trial eligibility threshold, absolute risk of cardiovascular death or HF hospitalization ranged from 3.5 per 100 person-years among persons with BMI <30 kg/m2 to 7.3 per 100 person-years among those with BMI ≥40 kg/m2.
Conclusions:
In this analysis, current NT-proBNP thresholds substantially underestimated the absolute risk of adverse HF outcomes among persons with higher BMI. These data question single fixed thresholds and instead suggest that lower NT-proBNP cutoffs may more appropriately risk stratify patients with higher BMI. (Irbesartan in Heart Failure and Preserved Ejection Fraction [I-PRESERVE], NCT00095238; Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT], NCT00094302; Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin Receptor Blocker Global Outcomes in HF with Preserved Ejection Fraction [PARAGON-HF], NCT01920711; Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER], NCT03619213).
Related Concept Videos
01:29Heart Failure II: Pathophysiology
01:30Heart Failure V: Medical Management
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:30Heart Failure VII: Nursing Interventions
01:22Heart Failure Drugs: Diuretics
01:28Mitral Regurgitation IV: Nursing Management