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Original Research: Pulmonary Vascular Disease |

Independent Association of Urinary F2-Isoprostanes With Survival in Pulmonary Arterial HypertensionUrinary F2-Isoprostanes and Survival

Jean-Luc Cracowski, MD, PhD; Bruno Degano, MD, PhD; François Chabot, MD; José Labarère, MD, PhD; Edzard Schwedhelm, PhD; Denis Monneret, PhD; Luigi Iuliano, MD, PhD; Carole Schwebel, MD; Ari Chaouat, MD, PhD; Martine Reynaud-Gaubert, MD, PhD; Patrice Faure, MD, PhD; Renke Maas, MD; Jean-Charles Renversez, MD, PhD; Claire Cracowski, MD; Olivier Sitbon, MD, PhD; Azzedine Yaïci, MD; Gerald Simonneau, MD; Marc Humbert, MD, PhD
Author and Funding Information

From the Clinical Pharmacology Department, French Institut National pour la santé et la Recherche Médicale (INSERM) CIC3 (Drs J.-L. Cracowski and C. Cracowski), Quality of Care Unit (Dr Labarère), Department of Integrated Biology (Drs Monneret, Faure, and Renversez), and Intensive Care Unit (Dr Schwebel), University Hospital, Grenoble, France; INSERM U1042 (Drs J.-L. Cracowski, Monneret, and Faure) and Techniques de l’Ingénierie Médicale et de la Complexité unité mixte de recherche 5525 Centre national de la recherche scientifique (Dr Labarère), University Joseph Fourier, Grenoble, France; Physiology Department (Dr Degano), University Hospital, Besançon, France; Pulmonology Department (Dr Chabot), University Hospital, Nancy, France; Department of Clinical Pharmacology and Toxicology (Drs Schwedhelm and Maas), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Medical Sciences and Biotechnology (Dr Iuliano), Unit of Vascular Medicine, Sapienza University of Rome, Latina, Italy; Pulmonology Department (Dr Chaouat), University Hospital, Strasbourg, France; Pulmonology Department (Dr Reynaud-Gaubert), University Hospital, Marseille, France; Institute for Experimental and Clinical Pharmacology and Toxicology (Dr Maas), Erlangen-Nürnberg University, Erlangen, Germany; Centre de Référence de l’Hypertension Pulmonaire Sévère’ Pulmonology and Respiratory Intensive Care Department (Drs Sitbon, Yaïci, Simonneau, and Humbert), Antoine Béclère Hospital, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U999 (Drs Sitbon, Yaïci, Simonneau, and Humbert), Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; and University Paris-Sud (Drs Sitbon, Yaïci, Simonneau, and Humbert), Kremlin-Bicêtre, France.

Correspondence to: Jean-Luc Cracowski, MD, PhD, Unité de Pharmacologie Clinique, INSERM CIC3, Grenoble University Hospital, BP 217, 38043 Grenoble Cedex 09, France; e-mail: Jean-Luc.Cracowski@ujf-grenoble.fr


For editorial comment see page 816

Funding/Support: The study was supported by the French Health Ministry, the French Institut National pour la santé et la Recherche Médicale (INSERM), and by unrestricted research grants from AGIRàdom, Pneumologie Developpement, and Pfizer, Inc.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(4):869-876. doi:10.1378/chest.11-1267
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Objectives:  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 F2-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 F2-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 F2-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.

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