Plasma natriuretic peptide levels and the risk of cardiovascular events and death

N Engl J Med. 2004 Feb 12;350(7):655-63. doi: 10.1056/NEJMoa031994.


Background: The natriuretic peptides are counterregulatory hormones involved in volume homeostasis and cardiovascular remodeling. The prognostic significance of plasma natriuretic peptide levels in apparently asymptomatic persons has not been established.

Methods: We prospectively studied 3346 persons without heart failure. Using proportional-hazards regression, we examined the relations of plasma B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide to the risk of death from any cause, a first major cardiovascular event, heart failure, atrial fibrillation, stroke or transient ischemic attack, and coronary heart disease.

Results: During a mean follow-up of 5.2 years, 119 participants died and 79 had a first cardiovascular event. After adjustment for cardiovascular risk factors, each increment of 1 SD in log B-type natriuretic peptide levels was associated with a 27 percent increase in the risk of death (P=0.009), a 28 percent increase in the risk of a first cardiovascular event (P=0.03), a 77 percent increase in the risk of heart failure (P<0.001), a 66 percent increase in the risk of atrial fibrillation (P<0.001), and a 53 percent increase in the risk of stroke or transient ischemic attack (P=0.002). Peptide levels were not significantly associated with the risk of coronary heart disease events. B-type natriuretic peptide values above the 80th percentile (20.0 pg per milliliter for men and 23.3 pg per milliliter for women) were associated with multivariable-adjusted hazard ratios of 1.62 for death (P=0.02), 1.76 for a first major cardiovascular event (P=0.03), 1.91 for atrial fibrillation (P=0.02), 1.99 for stroke or transient ischemic attack (P=0.02), and 3.07 for heart failure (P=0.002). Similar results were obtained for N-terminal pro-atrial natriuretic peptide.

Conclusions: In this community-based sample, plasma natriuretic peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors. Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Atrial Natriuretic Factor / blood*
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Female
  • Heart Failure / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Mortality*
  • Multivariate Analysis
  • Natriuretic Peptide, Brain / blood*
  • Natriuretic Peptides / blood*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Protein Precursors / blood*
  • Risk


  • Biomarkers
  • N-terminal proatrial natriuretic peptide
  • Natriuretic Peptides
  • Protein Precursors
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor