BMI significantly lowers NT-proBNP levels, meaning standard biomarker cutoffs may underdiagnose heart failure in obese patients.
40%Higher rate of cardiovascular death or HF hospitalization per doubling of NT-proBNP
What the researchers found
For the same absolute risk level, NT-proBNP levels in obese patients with HFpEF were significantly lower than in lean patients, suggesting BMI-adjusted thresholds are needed.
Why it matters
Heart failure diagnosis and clinical trial enrollment rely heavily on natriuretic peptide levels. If obesity suppresses these levels, many obese patients may be underdiagnosed or excluded from trials.
The numbers in context
- 14,750 participants pooled from 4 trials; mean age 72, 50% female, mean BMI 30
- Each doubling of NT-proBNP linked to 40% higher event rate (HR 1.40, 95% CI 1.36-1.43)
- Same-risk NT-proBNP: 158 pg/mL at BMI 35+ vs 450 pg/mL at BMI <25 (about 3x lower)
- Absolute risk at trial threshold: 3.5 per 100 person-years (BMI <25) vs 7.3 per 100 person-years (BMI 40+)
- Median follow-up: 2.8 years
How the study worked
Participant-level pooled analysis of 4 global randomized outcomes trials of adults with HFmrEF/HFpEF, with median follow-up of 2.8 years.
Who was studied
N=14,750 adults with HFmrEF/HFpEF from 4 global randomized trials. Mean age 72, 50% female, mean BMI 30. Median follow-up 2.8 years.
What this study cannot tell us
Post-hoc pooled analysis; BMI is an imperfect measure of adiposity. Results may not apply to HF with reduced ejection fraction.
How to read the evidence
Large pooled participant-level analysis from 4 randomized controlled trials. High-quality evidence for the association but BMI-adjusted cutoffs need prospective validation.
When this study was published
Published in 2025 with data from major HFpEF/HFmrEF trials.
The bigger picture
As obesity-related heart failure becomes more common, adjusting diagnostic biomarker thresholds for body weight could improve detection and ensure appropriate treatment.
Questions still open
- What BMI-specific NT-proBNP cutoffs would optimize heart failure diagnosis?
- Could other biomarkers better capture heart failure risk in obese patients?
- Should clinical trials adopt BMI-stratified enrollment criteria?
Common questions
Why are NT-proBNP levels lower in obese patients?
Does this mean obese patients are being missed for heart failure?
Read the original research
Natriuretic Peptides, Body Mass Index, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction.
Journal of the American College of Cardiology, 86(20), 1823-1839
Citation
Ostrominski, John W; Neuen, Brendon L; Claggett, Brian L; Anand, Inder S; Desai, Akshay S; Jhund, Pardeep S; Lam, Carolyn S P; Pfeffer, Marc A; Pitt, Bertram; Zannad, Faiez; Zile, Michael R; Packer, Milton; Docherty, Kieran F; McMurray, John J V; Solomon, Scott D; Vaduganathan, Muthiah. (2025). Natriuretic Peptides, Body Mass Index, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction.. Journal of the American College of Cardiology, 86(20), 1823-1839. https://doi.org/10.1016/j.jacc.2025.08.028