An exploratory panel of biomarkers for risk prediction in pulmonary hypertension: emerging role of CT-proET-1

J Heart Lung Transplant. 2013 Dec;32(12):1214-21. doi: 10.1016/j.healun.2013.06.020. Epub 2013 Aug 2.


Background: Pulmonary arterial hypertension (PAH) is a rare, deadly condition. Although risk stratification is extremely important for assessment of prognosis and to guide therapy, there is lack of evidence concerning the role of novel biomarkers. In a pivotal study, we sought to comparatively investigate the predictive power of several new biomarkers in PAH.

Methods: Patients with prevalent PAH were enrolled in the study protocol, which included clinical, functional and echocardiographic assessment. Blood samples were collected at baseline for determination of NT-proBNP, CT-proET-1, MR-proANP, MR-proADM, copeptin and troponin I. Patients were clinically followed-up up to 12 months for first occurrence of hospital admission due to PAH-related clinical worsening, heart/lung transplantation or all-cause mortality.

Results: Among the 28 included patients the pre-specified end-point occurred in 8 (29% event rate). There were higher baseline levels of CT-proET-1, copeptin, MR-proANP, NT-proBNP and troponin I in patients who reached the composite end-point. They also had larger right atria. In multivariate Cox regression, CT-proET-1 was the only biomarker associated with increased hazard of reaching the primary composite end-point (hazard ratio per tertile increase = 10.1; 95% CI 2.0 to 50.6).

Conclusions: CT-proET-1 provided prognostic information independent of other biomarkers. Importantly, we have provided the first evidence that CT-proET-1 may be superior to commonly used biomarkers.

Keywords: biomarkers; copeptin; endothelin-1; natriuretic peptides; prognosis; pulmonary hypertension; troponin.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Atrial Natriuretic Factor / blood*
  • Biomarkers / blood
  • Cohort Studies
  • Echocardiography
  • Endothelin-1 / blood*
  • Familial Primary Pulmonary Hypertension
  • Female
  • Follow-Up Studies
  • Glycopeptides / blood*
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / epidemiology*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Regression Analysis
  • Risk Factors
  • Troponin I / blood*


  • Biomarkers
  • C-terminal proendothelin-1
  • Endothelin-1
  • Glycopeptides
  • Peptide Fragments
  • Troponin I
  • copeptins
  • midregional pro-atrial natriuretic peptide, human
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor