title: MR-proADM Predicts Exercise Capacity and Survival Superior to Other Biomarkers in PH.
abstract: OBJECTIVE
  Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH).
  
  
  METHODS
  125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated.
  
  
  RESULTS
  MR-proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %.
  
  
  CONCLUSIONS
  Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.
authors.affiliation: Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany. martin.kolditz@uniklinikum-dresden.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Kolditz
authors.affiliation: Department of Pneumology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Seyfarth
authors.affiliation: Department of Internal Medicine V, Saarland University Medical Center, Homburg, Saarland, Germany.
authors.forename: Heinrike
authors.initials: H
authors.lastname: Wilkens
authors.affiliation: Department of Internal Medicine B, Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Ewert
authors.affiliation: Department of Internal Medicine B, Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Bollmann
authors.affiliation: BRAHMS GmbH (Thermo Fisher Scientific), Hennigsdorf, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Dinter
authors.affiliation: BRAHMS GmbH (Thermo Fisher Scientific), Hennigsdorf, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hertel
authors.affiliation: Department of Pneumology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Klose
authors.affiliation: Department of Internal Medicine/Cardiology, DRK Kliniken Berlin Köpenick, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Opitz
authors.affiliation: Center for Pulmonary Hypertension at Thoraxclinic Heidelberg, Heidelberg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Grünig
authors.affiliation: Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Höffken
authors.affiliation: Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Halank
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002908:Chronic Disease; D019332:Endothelin-1 / Q000097:blood*; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005858:Germany; D006020:Glycopeptides / Q000097:blood*; D006325:Heart Atria; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D011655:Pulmonary Embolism / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure; D014655:Vascular Resistance
chemical_list: D015415:Biomarkers; C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D006020:Glycopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C048197:copeptins; C574167:mid-regional pro-adrenomedullin, human; C552580:midregional pro-atrial natriuretic peptide, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor
keywords: Biomarker; Exercise capacity; Prognosis; Pulmonary hypertension