Jean-Luc Cracowski1, Bruno Degano2, François Chabot3, José Labarère4, Edzard Schwedhelm5, Denis Monneret6, Luigi Iuliano7, Carole Schwebel8, Ari Chaouat9, Martine Reynaud-Gaubert10, Patrice Faure6, Renke Maas11, Jean-Charles Renversez12, Claire Cracowski13, Olivier Sitbon14, Azzedine Yaïci14, Gerald Simonneau14, Marc Humbert14. 1. 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. 2. Physiology Department, University Hospital, Besançon, France. 3. Pulmonology Department, University Hospital, Nancy, France. 4. 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. 5. Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6. Department of Integrated Biology, Grenoble, France; INSERM U1042, Grenoble, France. 7. Department of Medical Sciences and Biotechnology, Unit of Vascular Medicine, Sapienza University of Rome, Latina, Italy. 8. Intensive Care Unit, University Hospital, Grenoble, France. 9. Pulmonology Department, University Hospital, Strasbourg, France. 10. Pulmonology Department, University Hospital, Marseille, France. 11. 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. 12. Department of Integrated Biology, Grenoble, France. 13. Clinical Pharmacology Department, French Institut National pour la santé et la Recherche Médicale (INSERM) CIC3, Grenoble, France. 14. 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.
Abstract
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 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.
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 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: Joshua P Fessel; Charles R Flynn; Linda J Robinson; Niki L Penner; Santhi Gladson; Christie J Kang; David H Wasserman; Anna R Hemnes; James D West Journal: Am J Respir Cell Mol Biol Date: 2013-11 Impact factor: 6.914
Authors: Kelley L Colvin; Melanie J Dufva; Ryan P Delaney; D Dunbar Ivy; Kurt R Stenmark; Michael E Yeager Journal: Front Pediatr Date: 2014-02-03 Impact factor: 3.418