N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation. 2016 Feb 16;133(7):631-8. doi: 10.1161/CIRCULATIONAHA.115.017298. Epub 2016 Jan 8.


Background: Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories.

Methods and results: We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990-1992) with BMI ≥18.5 kg/m(2). We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r=-0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m(2); improvement in C statistic, 0.032; 95% confidence interval, 0.011-0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was <5% among normal-weight individuals but >10% among the severely obese.

Conclusions: Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population.

Keywords: epidemiology; heart failure; natriuretic peptides; obesity; risk assessment.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / blood*
  • Atherosclerosis / diagnosis
  • Atherosclerosis / epidemiology
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Heart Failure / blood*
  • Heart Failure / diagnosis
  • Heart Failure / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Obesity / blood*
  • Obesity / diagnosis
  • Obesity / epidemiology
  • Peptide Fragments / blood*
  • Prospective Studies
  • Residence Characteristics*
  • Risk Factors


  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain