Myeloperoxidase, osteopontin and asymmetrical dimethylarginine as biomarkers of pulmonary hypertension severity

Abstract

Background: The aim of the study was to assess the possible relationship between novel biomarkers and basic determinants of PH severity. Methods: We examined 62 pts with PH (mean age 43.2±15.4 yrs, 19 M): 37 with idiopathic pulmonary arterial hypertension, 7 with scleroderma, 7 with corrected congenital heart disease, 11 with inoperable chronic thromboembolic pulmonary hypertension (iCTEPH) and 12 healthy controls (35.4±11.7 yrs, 5M). Plasma osteopontin (OPN), plasma myeloperoxidase (MPO), serum Asymmetrical Dimethylarginine (ADMA) by ELISA and serum NT pro-BNP (Elecsys) levels were determined. ECHO, 6MWT, right heart catheterization and cardiac MRI were performed. Results: Plasma OPN, ADMA and MPO levels in patients with PH were elevated in comparison with healthy control subjects. Plasma MPO levels predict significantly increase in pulmonary vascular resistance index (PVRI) (beta= 0.512, F=16.0, p<0.001). In contrast, serum ADMA and plasma OPN levels predict decreased 6-min walking distance (beta = -0.31,F=4.83. p=0.03 and beta = -0.41, F=7.5, p<0.001, respectively). OPN (r=0.131, p<0.05), MPO (r=0.131, p<0.05); and ADMA (r=0.457, p<0.001) levels were associated with such prognostic marker as NT-proBNP. Increased plasma OPN levels were correlated with RV end-diastolic diameter by ECHO (r=0.28, p<0.05) and RV size according to MRI data (r=0.35, p<0.05). High OPN level also was associated with low pulmonary artery distensibility index (r= -0.467, p<0.05). View this table: Biomarkers and clinical characteristics Conclusions: MPO levels mainly predict hemodynamic disorders, whereas OPN levels reflect degree of pulmonary vascular remodeling. ADMA and OPN levels both predict exercise intolerance. We assume that markers of endothelial dysfunction, oxidative stress and inflammation could be used for assessment of PH severity.