Obesity Paradox and the Effect of NT-proBNP on All-Cause and Cause-Specific Mortality

Clin Cardiol. 2024 Nov;47(11):e70044. doi: 10.1002/clc.70044.

Abstract

Background: In heart failure patients, obesity is associated with better outcomes as compared to normal weight, a phenomenon called the obesity paradox.

Objective: To examine if obesity modifies the relationship between NT-proBNP and all-cause and cause-specific mortality in adults without coronary artery disease or heart failure history.

Methods: We used the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and linked it with mortality through December 31, 2019. Participants > 18 years were categorized into normal weight (BMI ≤ 25 kg/m2), overweight (BMI > 25-29.9 kg/m2) and obese (BMI > 29.9 kg/m2). NT-proBNP levels were categorized as low (< 126 pg/mL) or high (≥ 126 pg/mL). Using Cox proportional hazard models, we examined effect modification by obesity using interaction, without and with adjusting for potential confounders.

Results: Of the 12 621 participants, 2794 (22%) died during 202 859 person-years follow-up. In adjusted models, normal-weight participants with high NT-proBNP had 2 times higher all-cause mortality risk than those with low NT-proBNP (HR = 2.05; 95%CI = 1.74, 2.41; p < 0.001); however, this mortality risk was 27% lower in obese participants (HR interaction = 0.73; 95%CI = 0.59, 0.92; p = 0.008). Similarly, in normal-weight participants, the difference in other-cause mortality risk between high and low NT-proBNP participants was significant in adjusted models (HR = 2.27; 95%CI = 1.81, 2.85; p < 0.001) and obese participants had 48% lower other-cause mortality risk between those with high and low NT-proBNP (interaction HR = 0.52; 95%CI = 0.36, 0.77; p = 0.001). Conversely, obesity did not modify the relationship between NT-proBNP and cardiovascular or cancer mortality.

Conclusions: In patients free of heart failure or coronary artery disease, obesity may be protective against mortality associated with high NT-proBNP.

Keywords: NT‐proBNP; healthy population; mortality; obesity paradox.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers* / blood
  • Body Mass Index
  • Cause of Death* / trends
  • Female
  • Follow-Up Studies
  • Heart Failure / blood
  • Heart Failure / mortality
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain* / blood
  • Nutrition Surveys*
  • Obesity Paradox
  • Obesity* / blood
  • Obesity* / complications
  • Obesity* / mortality
  • Peptide Fragments* / blood
  • Prognosis
  • Retrospective Studies
  • Risk Assessment / methods
  • Risk Factors
  • Survival Rate / trends
  • United States / epidemiology

Substances

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