title: Endothelin-1/endothelin-3 ratio: a potential prognostic factor of pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a rare condition characterized by elevated pulmonary artery pressure leading to right-heart failure and death. Endothelin (ET)-1 has been shown to play a significant pathogenic role in PAH. ET-3 has not yet been investigated in PAH.
  
  
  METHODS
  ET-1 and ET-3 plasma concentrations were measured in 33 PAH patients prior to any specific PAH therapy and in 9 control subjects. In PAH patients, hemodynamic parameters measured by right-heart catheterization, 6-min walk distance (6MWD), New York Heart Association (NYHA) functional class, and time until lung transplantation or death were recorded.
  
  
  RESULTS
  In patients with PAH, levels of ET-1 were increased while those of ET-3 were decreased, as compared to control subjects (p < 0.005 for both comparisons). ET-1/ET-3 ratio varied little in control subjects, while it increased threefold in PAH patients (p < 0.0001). ET-1 correlated positively with right atrial pressure (RAP), indexed total pulmonary resistance, and negatively with cardiac index and venous saturation of oxygen (Svo(2)). ET-3 correlated positively with 6MWD. ET-1/ET-3 ratio correlated positively with RAP, negatively with Svo(2) and 6MWD, and was also associated with NYHA functional class. ET-1/ET-3 ratio was associated with prognosis in this sample of PAH patients treated with specific therapies.
  
  
  CONCLUSIONS
  PAH is characterized by elevated ET-1 and ET-1/ET-3 ratio and decreased ET-3 plasma concentrations. All of them correlate with hemodynamic and clinical markers of disease severity. ET-1/ET-3 ratio might be a novel prognostic factor in PAH. These preliminary data should be validated in a large prospective multicenter cohort of PAH patients.
authors.affiliation: Centre des Maladies Vasculaires Pulmonaires, UPRES EA 2705, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud. 157 rue de la Porte de Trivaux, 92140 Clamart, France.
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Rogerio
authors.initials: R
authors.lastname: Souza
authors.forename: Christoph
authors.initials: C
authors.lastname: Binkert
authors.forename: Walter
authors.initials: W
authors.lastname: Fischli
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Martine
authors.initials: M
authors.lastname: Clozel
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood*; D019334:Endothelin-3 / Q000097:blood*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D019334:Endothelin-3