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

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 PAR independently of clinical and hemodynamic parameters. Methods: Patients with incident PAR 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-F-2t- 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 PAR. CHEST 2012; 142(4):869-876