title: Independent association of urinary F2-isoprostanes with survival in pulmonary arterial hypertension.
abstract: OBJECTIVE
  Within the past decade, biochemical markers have emerged as attractive tools to assess pulmonary arterial hypertension (PAH) prognosis, being noninvasive and easily repeatable.The objective of this study was to determine whether biomarkers measured at initial diagnostic right-sided heart catheterization predict 3-year all-cause mortality for incident cases of PAH independently of clinical and hemodynamic parameters.
  
  
  METHODS
  Patients with incident PAH were enrolled between December 2003 and April 2006 in six centers from the French Network on Pulmonary Hypertension and followed for 3 years.Venous blood samples were taken during right-sided heart catheterization, and analyses were centralized.
  
  
  RESULTS
  Among 110 enrolled patients, 11 underwent lung or heart/lung transplantation, and 27 died during follow-up. The Kaplan-Meier estimates of survival were 91%, 78%, and 75% at 1, 2, and 3 years, respectively. Plasma big endothelin-1 (hazard ratio [HR] per 1-SD increase, 1.48; 95% CI,1.14-1.92), serum troponin T . 0.01 mg/L (HR, 2.35; 95% CI, 1.05-5.29), and urinary F 2 -isoprostanes(15-F2t -isoprostane) (HR per 1-SD increase, 1.76; 95% CI, 1.31-2.36) were associated with increased unadjusted hazard of death. In multivariate analysis adjusting for patient characteristics, the level of urinary F 2 -isoprostanes was the only biomarker that remained independently associated with increased hazard of death (HR per 1-SD increase, 1.82; 95% CI, 1.28-2.60).
  
  
  CONCLUSIONS
  This study shows that levels of urinary F 2 -isoprostane, a biomarker of lipid peroxidation,quantified at initial diagnostic right-sided heart catheterization are independently associated with mortality in a cohort of patients with incident PAH.
authors.affiliation: Clinical Pharmacology Department, French Institut National pour la santé et la Recherche Médicale (INSERM) CIC3, Grenoble, France; INSERM U1042, Grenoble, France. Electronic address: Jean-Luc.Cracowski@ujf-grenoble.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Cracowski
authors.affiliation: Physiology Department, University Hospital, Besançon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Degano
authors.affiliation: Pulmonology Department, University Hospital, Nancy, France.
authors.forename: François
authors.initials: F
authors.lastname: Chabot
authors.affiliation: Quality of Care Unit, Grenoble, France; Techniques de l'Ingénierie Médicale et de la Complexité unité mixte de recherche 5525 Centre national de la recherche scientifique, University Joseph Fourier, Grenoble, France.
authors.forename: José
authors.initials: J
authors.lastname: Labarère
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.affiliation: Department of Integrated Biology, Grenoble, France; INSERM U1042, Grenoble, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Monneret
authors.affiliation: Department of Medical Sciences and Biotechnology, Unit of Vascular Medicine, Sapienza University of Rome, Latina, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Iuliano
authors.affiliation: Intensive Care Unit, University Hospital, Grenoble, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Schwebel
authors.affiliation: Pulmonology Department, University Hospital, Strasbourg, France.
authors.forename: Ari
authors.initials: A
authors.lastname: Chaouat
authors.affiliation: Pulmonology Department, University Hospital, Marseille, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Reynaud-Gaubert
authors.affiliation: Department of Integrated Biology, Grenoble, France; INSERM U1042, Grenoble, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Faure
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Experimental and Clinical Pharmacology and Toxicology, Erlangen-Nürnberg University, Erlangen, Germany.
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.affiliation: Department of Integrated Biology, Grenoble, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Renversez
authors.affiliation: Clinical Pharmacology Department, French Institut National pour la santé et la Recherche Médicale (INSERM) CIC3, Grenoble, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Cracowski
authors.affiliation: Centre de Référence de l'Hypertension Pulmonaire Sévère' Pulmonology and Respiratory Intensive Care Department, Antoine Béclère Hospital, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U999, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; University Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Centre de Référence de l'Hypertension Pulmonaire Sévère' Pulmonology and Respiratory Intensive Care Department, Antoine Béclère Hospital, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U999, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; University Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: Azzedine
authors.initials: A
authors.lastname: Yaïci
authors.affiliation: Centre de Référence de l'Hypertension Pulmonaire Sévère' Pulmonology and Respiratory Intensive Care Department, Antoine Béclère Hospital, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U999, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; University Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: Centre de Référence de l'Hypertension Pulmonaire Sévère' Pulmonology and Respiratory Intensive Care Department, Antoine Béclère Hospital, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U999, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; University Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D015415:Biomarkers / Q000652:urine*; D002423:Cause of Death / Q000639:trends; D004797:Enzyme-Linked Immunosorbent Assay; D028441:F2-Isoprostanes / Q000652:urine*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000401:mortality*; D053208:Kaplan-Meier Estimate; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes