Abstract 12889: Myeloperoxidase Predicts Prognosis and Exercise Capacity in Patients With Pulmonary Arterial Hypertension
Background: Myeloperoxidase (MPO), a heme protein abundantly expressed by polymorphonuclear neutrophils (PMN) depletes vascular nitric oxide (NO) bioavailability and has been identified as powerful prognostic indicator for heart failure and coronary artery disease. Given the critical role of vascular NO bioavailability and leukocyte activation, respectively in pulmonary arterial hypertension (PHT) we tested the diagnostic and prognostic information obtained from circulating MPO in patients diagnosed for PHT of non-myocardial origin.
Methods: We included 61 patients with PHT class I/IV (mean age: 52±13 years, 64% females) and 74 controls to determine plasma MPO levels, NT-pro BNP and high sensitive C-reactive protein (hsCRP), forearm flow-mediated dilation (FMD) and 6-minute walking test distance. The patients were followed over a median of 65 weeks.
Results: In comparison to controls median MPO levels were significantly elevated in patients with PHT (431 [interquartile range (IR): 301–605] vs 495 [IR: 360–792] pmol/l, p<0.05). During follow up PHT patients within the lowest tertile of plasma MPO levels (χ2: 4.2, p<0.05), had a significantly lower mortality as compared to PHT patients in the other two tertiles, which was also observable for NT-pro BNP (χ2: 4.2, p<0.05) and hsCRP levels (χ2: 4.7, p<0.05). Furthermore, patients within the lowest tertile of MPO levels exhibited a significantly improved exercise capacity as measured by the 6-minute walking test distance at baseline and during follow-up (BL: 409 vs. 324m; p<0.05, 3mo: 427 vs. 331m; p<0.05, 6mo: 464 vs. 333m; p<0.01, 9mo: 437 vs. 339m; p<0.05, 12mo: 435 vs. 375m; ns). No association of FMD with outcome was observed in this cohort of patients.
Conclusions: The current data reveal that MPO plasma levels are elevated in patients with PHT and indicate MPO to be prognostic in these patients. Given the significance of endothelial NO bioavailability in the pulmonary circulation, activation of PMN and release of MPO may emerge as as critical confounder in the pathogenesis of PHT.
- © 2010 by American Heart Association, Inc.