A multicenter comparison of established and emerging cardiac biomarkers for the diagnostic evaluation of chest pain in the emergency department

Am Heart J. 2011 Aug;162(2):276-282.e1. doi: 10.1016/j.ahj.2011.05.022.


Background: The aim of this study is to assess the role of novel biomarkers for the diagnostic evaluation of acute coronary syndrome (ACS).

Methods: Among 318 patients presenting to an emergency department with acute chest discomfort, we evaluated the diagnostic value of 5 candidate biomarkers (amino terminal pro-B-type natriuretic peptide [NT-proBNP], ischemia modified albumin, heart fatty acid binding protein, high-sensitivity troponin I [hsTnI], and unbound free fatty acids [FFAu]) for detecting ACS, comparing their results with that of conventional troponin T (cTnT).

Results: Sixty-two subjects (19.5%) had ACS. The sensitivity and negative predictive values of NT-proBNP (73%, 90%) and hsTnI (57%, 89%) were higher than that of cTnT (22%, 84%). Unbound free fatty acids had the highest overall combination of sensitivity (75%), specificity (72%), and negative predictive values (92%) of all the markers examined. A significant increase in the C-statistic for cTnT resulted from the addition of results for NT-proBNP (change 0.09, P = .001), hsTnI (change 0.13, P < .001), and FFAu (change 0.15, P < .001). In integrated discrimination improvement and net reclassification improvement analyses, NT-proBNP, hsTnI, and FFAu added significant diagnostic information to cTnT; when changing the diagnostic criterion standard for ACS to hsTnI, FFAu still added significant reclassification for both events and nonevents. In serial sampling (n = 180), FFAu added important reclassification information to hsTnI.

Conclusion: Among emergency department patients with symptoms suggestive of ACS, neither ischemia modified albumin nor heart fatty acid binding protein detected or excluded ACS, whereas NT-proBNP, hsTnI, or FFAu added diagnostic information to cTnT. In the context of hsTnI results, FFAu measurement significantly reclassified both false negatives and false positives at baseline and in serial samples.

Trial registration: ClinicalTrials.gov NCT00355992.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / diagnosis*
  • Albumins / metabolism
  • Biomarkers / blood*
  • Chest Pain / blood
  • Chest Pain / diagnosis*
  • Chest Pain / etiology
  • Diagnosis, Differential
  • Emergency Service, Hospital*
  • Fatty Acid-Binding Proteins / blood
  • Fatty Acids, Nonesterified / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Predictive Value of Tests
  • Prognosis
  • Protein Precursors
  • Reproducibility of Results
  • Troponin T / blood


  • Albumins
  • Biomarkers
  • Fatty Acid-Binding Proteins
  • Fatty Acids, Nonesterified
  • Peptide Fragments
  • Protein Precursors
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain

Associated data

  • ClinicalTrials.gov/NCT00355992