The dynamics of endothelial dysfunction markers among patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease under the influence of treatment

Abstract

The objective of the research - to determine the dynamics of endothelial dysfunction markers among patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease under the influence of treatment.Material and methods. The results of the study are based on data from a comprehensive survey of 170 patients with chronic obstructive pulmonary disease (COPD) aged from 40 to 65 years, 123 of which had pulmonary hypertension and 47 ones had no pulmonary hypertension. Also 31 almost healthy people were examined on an outpatient basis. Patients with pulmonary hypertension on a background of COPD were divided into two subgroups of observations depending on the treatment. The first subgroup was used as the background therapy and the second subgroup - background therapy with the roflumilast. Markers of endothelial function were determined during screening and after 12 months of follow-up.Results. The median level of endothelin-1 in the group of patients with pulmonary hypertension on the background of COPD was 3.17 [2.19 ; 4.14] fmol/ ml and was significantly higher, both against the value of 1.78 [1.25 ; 2.18] fmol/ml in the group of COPD patients without pulmonary hypertension (p < 0.05), and 10.2 times higher than versus the level of 0.31 [0.19 ; 0.36] fmol/ml in the group of healthy individuals (p<0.05). The amount of nitrogen oxide metabolites (NO2+NO3) was significantly lower (by 15.8 %) in the group of patients with pulmonary hypertension on the background of COPD versus the value of 22.00 [21.00 ; 23,00] mmol/l in the group of COPD patients without pulmonary hypertension, and is 37 % lower than in the group of healthy individuals, where the level of this indicator was 26,00 [25,00 ; 28,00] mmol/l (p<0.05). Then a correlation analysis was performed. Significant relationships were determined between the following indicators: duration of COPD and NO3 level (R = -0.29, p = 0.001); duration of COPD and NO2+ NO3 level (R - 0.26, p = 0.003); mean pulmonary artery pressure and endothelial-1 level (R = +0.70, p = 0.001); mean pulmonary artery pressure and NO2 level (R = -0.59, p = 0.001); mean pulmonary artery pressure and NO2+ NO3 (R = -0.50, p = 0.001). The level of endothelin-1 and nitrogen oxide metabolites in the blood plasma of patients was comparable between the first and second subgroups of observation during screening (p > 0.05). After 12 months, there was a statistically significant decrease of Δ1% = -57.53 % endothelin-1 to 1.87 [1.44; 2.36] fmol/ml in the first subgroup and Δ2% = -82.34 % to 1.62 [1.37; 1.92] fmol/ml in the second subgroup. After 12 months of therapy in both subgroups, the level of total nitrogen oxide metabolites in blood plasma significantly increased Δ1% = 10.00 % to 21.00 [18.00 ; 23.00] mmol/l in the basic therapy subgroup, and Δ2% = 19.05 % to 24.00 [22.00; 26.00] mmol/l in the roflumilast subgroup, (p < 0.05). A statistically significant difference in endothelin-1 levels and the amount of nitrogen oxide metabolites between subgroups was determined after 12 months of treatment.Conclusions. Among patients with COPD, endothelial dysfunction occurs, characterized by an increase in the concentration of endothelin-1 and a decrease in nitrogen oxide metabolites in the blood plasma. An increase in the level of endothelin-1 in blood plasma has a direct correlation with the value of the mean pulmonary artery pressure. Background therapy among patients with pulmonary hypertension on the background of COPD improves the state of endothelial function, with increased nitrogen oxide metabolites in the blood plasma. When added to background therapy, roflumilast significantly reduced the concentration of endothelin-1 in blood plasma.