Hetman O. Optimization of the diagnosis and treatment of pulmonary hypertension in patients with chronic obstructive pulmonary disease and coronary heart disease based on the assessment of osteopontin, interleukin-2, -4.

The dissertation is devoted to increase of the effectiveness of diagnosis of pulmonary hypertension in case of combination of COPD and CHD based on determination of the influence of various links of the system of pro- and anti-inflammatory cytokines and the possibility of its correction with the help of the pleiotropic effects of statins. The data obtained confirmed an increase in the activity of osteopontin and interleukin-2 in patients with a combination of COPD and CHD; they are associated with the level of pressure in the pulmonary artery against the background of structural and functional changes in the heart. Increase of the level of osteopontin in the blood serum for more than 38,25 ng /ml should be considered as an early marker and independent predictor of pulmonary hypertension (PH) in patients with COPD and concomitant CHD. It was revealed that in patients with COPD and coronary heart disease with the development of PH, a cytokine-mediated mechanism of inflammation predominates that is induced by likely increase in the level of interleukin-2 and the protein of the extracellular matrix - osteopontin: they reliably correlate with a decrease of the parameters of RVFAC and TAPSE, right ventricular ejection fraction (RVEF) compared with the group of patients with COPD and CHD without PH, reflect the degree of remodeling of the right heart against the background of the formation of pulmonary hypertension. It has been proven that in patients with COPD and CHD, compensatory anti-inflammatory mechanisms are exhausted against the background of a high level of systemic inflammation. It has been proven that the number of exacerbations of COPD in comorbid patients with pulmonary hypertension is for 14% higher than the number of exacerbations in patients with COPD and CHD with normal pulmonary artery pressure. Lipid metabolism disorder is more apparent in the group with the presence of increased pulmonary artery pressure, what is associated in its turn with decrease of respiratory function and the development of chronic hypoxia. The use of atorvastatin at a dose of more than 60.2 mg / day in patients with COPD and concomitant coronary heart disease with PH during the period of 6 months is justified, along with the achievement of the target lipid level, what resulted in a significant decrease in the number of exacerbations of COPD and a decrease of osteopontin level by 31.4% , and IL-2 2.7 times in the absence of significant changes of IL-4. In patients without signs of lesser circuit hypertension in the course of the treatment with atorvastatin, only a trend to a decrease in osteopontin and IL-2 levels was observed.