Prognostic value of established and novel biomarkers in patients with shortness of breath attending an emergency department

Clin Biochem. 2010 Jun;43(9):714-9. doi: 10.1016/j.clinbiochem.2010.02.002. Epub 2010 Feb 11.


Objectives: Acute dyspnea is a common cause for emergency department visits. The aim of this study was to evaluate the prognostic value of established and novel biomarkers in patients with acute dyspnea.

Design and methods: We measured 10 biomarkers [B-type natriuretic peptide (BNP), midregional pro-A-type natriuretic peptide (MR-proANP), midregional-proadrenomedullin (MR-proADM), copeptin, C-terminal endothelin-1 precursor fragment (CT-proET-1), soluble ST2 (sST2), chromogranin A (CgA), adiponectin, proguanylin, and prouroguanylin] in 251 consecutive patients with acute dyspnea presenting to the emergency department of a tertiary care hospital. Outcome measure was all-cause mortality at 1 year.

Results: At baseline decedents (n=62) had significantly higher median plasma concentrations of all 10 biomarkers than survivors (n=189). Applying univariate Cox proportional-hazard regression analyses, all biomarkers were significant outcome predictors displaying risk ratios (RR) from 1.4 to 2.4 (per 1 SD increase in log transformed values). In multivariate Cox proportional-hazard regression analysis, however, only MR-proANP (RR 1.6; 95% CI, 1.1-2.2; p=0.008), sST2 (RR 1.7; 95% CI, 1.3-2.3; p<0.001), and CgA (RR 1.5; 95% CI, 1.2-1.9, p<0.001) were independently associated with 1-year mortality. We provide a possible explanation for the complementary prognostic value of those three biomarkers in our cohort, where coincidence of heart failure and inflammatory pulmonary disease was common and also related to worse outcome.

Conclusions: Our evaluation of biomarkers in patients with acute dyspnea suggests that MR-proANP, sST2, and CgA are strong, independent and complementary outcome predictors. MR-proANP is considered a specific marker of cardiac stretch, sST2 might reflect both inflammation and cardiac stretch, and CgA obviously indicates neuroendocrine activation in various diseases.

MeSH terms

  • Acute Disease
  • Adrenomedullin / blood
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Chromogranin A / blood
  • Dyspnea / complications
  • Dyspnea / diagnosis*
  • Dyspnea / mortality
  • Emergency Service, Hospital*
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Male
  • Middle Aged
  • Prognosis
  • Protein Precursors / blood
  • Receptors, Cell Surface / blood
  • Risk Factors
  • Survival Rate


  • Biomarkers
  • Chromogranin A
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Protein Precursors
  • Receptors, Cell Surface
  • proadrenomedullin
  • Adrenomedullin