Urinary F2-isoprostanes, a biomarker of lipid peroxidation, independently correlate with survival in a multicenter prospective cohort of incident pulmonary arterial hypertension

Rationale:Within the last decade biochemical markers have emerged as attractive tools to assess pulmonary arterial hypertension prognosis, being non-invasive and easily repeatable.ObjectivesTo determine whether biomarkers measured at initial diagnostic right heart catheterization predict 3-year all-cause mortality for incident cases of pulmonary arterial hypertension, independently of clinical and hemodynamic parameters.MethodsIncident cases of pulmonary arterial hypertension were enrolled between December 2003 and April 2006 in 6 centers from the French Network on Pulmonary Hypertension and followed during 3 years. Venous blood samples were taken during right heart catheterization and analyses were centralized.ResultsAmong 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 standard deviation [SD] increase, 1.48, 95% confidence interval [CI], 1.14 to 1.92), serum troponin T >0.01 mg/L (HR, 2.35, 95%CI, 1.05 to 5.29) and urinary F(2)-isoprostanes (15-F(2t)-isoprostane) (HR per 1 SD increase, 1.76, 95%CI, 1.31 to 2.36) were associated with increased unadjusted hazard of death. In multivariate analysis adjusting for patients' characteristics, urinary F(2)-isoprostanes were the only biomarker that remained independently associated with increased hazard of death (HR, 1.82 per 1 SD increase, 95%CI, 1.28 to 2.60).ConclusionThis study shows that urinary F(2)-isoprostane levels, biomarkers of lipid peroxidation, quantified at initial diagnostic right heart catheterization are independently associated with mortality in a cohort of patients with incident pulmonary arterial hypertension.