Comparison of Cardiac and Non-Cardiac Biomarkers for Risk Stratification in Elderly Patients with Non-Massive Pulmonary Embolism

PLoS One. 2016 May 24;11(5):e0155973. doi: 10.1371/journal.pone.0155973. eCollection 2016.


Biomarkers unrelated to myocardial necrosis, such as cystatin C, copeptin, and mid-regional pro-adrenomedullin (MR-proADM), showed promise for cardiovascular risk prediction. Knowing whether they are comparable to cardiac biomarkers such as high-sensitive cardiac-troponin T (hs-cTnT) or N-terminal pro-Brain natriuretic peptide (NT-proBNP) in elderly patients with acute non-massive pulmonary embolism (NMPE) remains elusive. This study aims at comparing the prognostic accuracy of cardiac and non-cardiac biomarkers in patients with NMPE aged ≥65 years over time. In the context of the SWITCO65+ cohort, we evaluated 227 elderly patients with an available blood sample taken within one day from diagnosis. The primary study endpoint was defined as PE-related mortality and the secondary endpoint as PE-related complications. The biomarkers' predictive ability at 1, 3, 12 and 24 months was determined using C-statistics and Cox regression. For both study endpoints, C-statistics (95% confidence interval) were stable over time for all biomarkers, with the highest value for hs-cTnT, ranging between 0.84 (0.68-1.00) and 0.80 (0.70-0.90) for the primary endpoint, and between 0.74 (0.63-0.86) and 0.65 (0.57-0.73) for the secondary endpoint. For both study endpoints, cardiac biomarkers were found to be independently associated with risk, NT-proBNP displaying a negative predictive value of 100%. Among non-cardiac biomarkers, only copeptin and MR-proADM were independent predictors of PE-related mortality but they were not independent predictors of PE-related complications, and displayed lower negative predictive values. In elderly NMPE patients, cardiac biomarkers appear to be valuable prognostic to identify very low-risk individuals.

Trial registration: NCT00973596.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / blood*
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Female
  • Glycopeptides / blood*
  • Humans
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Prognosis
  • Protein Precursors / blood*
  • Pulmonary Embolism / diagnosis*
  • Pulmonary Embolism / metabolism
  • Survival Analysis
  • Troponin T / blood*


  • Biomarkers
  • Glycopeptides
  • Peptide Fragments
  • Protein Precursors
  • Troponin T
  • copeptins
  • mid-regional pro-adrenomedullin, human
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Adrenomedullin

Associated data


Grant support

This cohort study was supported by the Swiss National Science Foundation (Grant no. 33CSO-122659/139470: Reagents costs were partly supported by Roche (Switzerland), and Thermo Scientific (BRAHMS AG, Hennigsdorf/Berlin, Germany) which were not involved in data analyses or results interpretation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.