title: Circulating levels of copeptin predict outcome in patients with pulmonary arterial hypertension.
abstract: OBJECTIVE
  To determine the levels of circulating copeptin in patients with pulmonary arterial hypertension (PAH), and to evaluate its relation with disease severity, outcome and response to treatment.
  
  
  BACKGROUND
  Vasopressin is a key regulator of body fluid homeostasis. The co-secreted protein copeptin serves as surrogate for plasma vasopressin levels and increases in acute and chronic left ventricular dysfunction. Copeptin has not been studied in PAH.
  
  
  METHODS
  Serum copeptin levels were evaluated in a retrospective cohort of 92 treatment-naïve patients with PAH, 39 patients with normal right ventricular hemodynamics (diseased controls) and 14 apparently healthy individuals (healthy controls). In a second prospective cohort of 15 patients with PAH, serial changes of copeptin levels after initiation of PAH treatment were measured. Copeptin levels were compared with clinical, biochemical and hemodynamic parameters as well as response to treatment and clinical outcome.
  
  
  RESULTS
  Circulating copeptin levels were elevated in PAH patients compared to diseased controls (20.1 pmol/l vs. 5.1 pmol/l; p = 0.001). Baseline levels of copeptin correlated with NYHA functional class (r = 0.46; p = 0.01), 6 minute walking distance (r = -0.26; p = 0.04), NT-proBNP (r = 0.49, p = 0.01), creatinine (r = 0.39, p = 0.01) and estimated glomerular filtration rate (r = -0.32, p = 0.01). Copeptin levels did not correlate with hemodynamics but decreased after initiation of PAH therapy (p = 0.001). Elevated copeptin levels were associated with shorter survival (p < 0.001) and independent predictors of mortality in a multiple Cox regression analysis (HR1.4; 95% confidence interval 1.1-2.0; p = 0.02).
  
  
  CONCLUSIONS
  Patients with PAH had elevated copeptin levels. High circulating levels of copeptin were independent predictors of poor outcome, which makes copeptin a potentially useful biomarker in PAH.
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School, 30623 Hannover, Germany. nickel.nils@mh-hannover.de.
authors.forename: Nils P
authors.initials: NP
authors.lastname: Nickel
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Heiko
authors.initials: H
authors.lastname: Golpon
authors.forename: Karen M
authors.initials: KM
authors.lastname: Olsson
authors.forename: Korbinian
authors.initials: K
authors.lastname: Brand
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; D010446:Peptide Fragments; C048197:copeptins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain