Abstract 9958: The Cardiovascular Risk Factor 8-iso-Prostaglandin F2alpha Independently Predicts Mortality in Pulmonary Artery Hypertension
Background. F2-isoprostanes, among them 8-iso-Prostaglandin F2alpha (8-iso-PGF2α), have emerged as cardiovascular risk factors, activating the thromboxane A2 receptor (TP) and mediating vasoconstriction, impaired angiogenesis, altered platelet activity, and smooth muscle cell proliferation. Pulmonary artery hypertension (PAH) is a rare progressive disease with a 3-year mortality rate of 30-50 %. To date, new therapeutic options in PAH are sparse.
Methods. We therefore investigated the prognostic value of 8-iso-PGF2α in a cohort of 110 newly diagnosed, treatment naïve, PAH patients. Eligible patients from 6 centers of the French Network on Pulmonary Hypertension were screened and patients were followed for 3 years. Urinary 8-iso-PGF2α determined by gas chromatography-mass spectrometry (GC-MS), along with other clinical and biochemical characteristics was evaluated at the time of diagnosis, i.e. right heart catheterisation.
Results. Among 110 enrolled patients, 11 underwent heart and/or lung transplantation and 27 died during follow-up. Plasma big endothelin-1 (hazard ration [HR] per 1 standard deviation [SD] increase, 1.48, 95 % confidence interval [CI] 1.14 - 1.92), serum troponin T >0.01 mg/L (HR: 2.35, CI: 1.05 - 5.3], and urinary 8-iso-PGF2α (HR: 1.76, CI: 1.31 - 2.36) were associated with unadjusted risk. In multivariate Cox proportional hazard models, adjusting for variables with p<0.1, only 8-iso-PGF2α was independently associated with mortality (HR:1.82, CI:1.28 - 2.60).
Conclusions. The endogenous TP agonist 8-iso-PGF2α independently predicts mortality in newly diagnosed PAH patients. Pharmacological inhibition of the TP in these selected patients may be a new valuable option additive to standard treatment.
- © 2011 by American Heart Association, Inc.