Objective — to investigate clinical outcomes and dynamics of brain natriuretic peptide, blood levels of fibrosis and inflammation biomarkers, echocardiographic parameters against the background of non-invasive respiratory therapy in patients with atrial fibrillation (AF) and obstructive sleep apnea (OSA). Design and methods. The study included 239 patients with obstructive sleep apnea verified by night respiratory monitoring. All examined patients underwent anthropometric measurements, transthoracic echocardiography, and determined concentrations of fibrosis and inflammation biomarkers, and N-terminal precursor of brain natriuretic peptide. Patients with atrial fibrillation and moderate-to-severe OSA were included in the prospective branch of the study, 21 patients regularly used non-invasive respiratory therapy (PAP-therapy), 80 patients did not receive regular respiratory support. After 1 year of follow-up, echocardiographic parameters, blood biomarker levels, and clinical outcomes were re-evaluated. Results. AF was more common in patients with moderate-to-severe OSA than in those with mild sleep- disordered breathing (p = 0,009 and p = 0,004, respectively). Blood concentrations of brain natriuretic peptide, fibrosis biomarkers (galectin-3, GDF-15, CTGF) and inflammation (interleukin-6) decreased after 12 months of PAP-therapy (p < 0,0001), while they did not change in patients who did not use PAP-therapy regularly. Echocardiographic parameters characterizing atrial remodeling (size, volume, and volume indices of both atria), as well as pulmonary artery size and pulmonary artery pressure decreased with the use of noninvasive respiratory therapy (p < 0,05). The use of PAP-therapy reduced the risk of recurrent AF by 54,4 % (OR = 0,46, 95 % CI 0,25–0,84, p < 0,01), the clinical composite endpoint by 31,6 % (OR = 0,68, 95 % CI 0,50–0,93, p < 0,01), and the prognostic composite endpoint by 76,9 % (OR = 0,23, 95 % CI 0,06–0,89, p = 0,007). Conclusion. The regular use of PAP-therapy as part of a complex treatment in patients with moderate-tosevere OSA and AF reduces the risk of arrhythmia recurrence, arterial hypertension without achieving target blood pressure, clinical and prognostic combined endpoints, and is accompanied by a decrease in blood concentrations of proinflammatory and profibrogenic markers and atrial dilation, and a decrease in pulmonary artery pressure.

Background. Ischemic stroke (IS) in patients with type 2 diabetes mellitus (DM 2) is characterized by a more severe course and worse functional outcomes compared to individuals without diabetes, which increases the number of patients disabled by the end of hospitalization. Predicting the outcome of stroke upon admission to hospital can help optimize treatment, diagnostic and rehabilitation measures and improve the quality of treatment. The use of laboratory biomarkers (LBM) in predicting the outcome of IS is a promising area of modern medicine. Objective. To create a prognostic model for the outcome of non-lacunar ischemic stroke (NlIS) in patients with DM 2 based on the LBM study. Design and methods. We studied the serum concentrations of 78 LBM in 55 patients with DM 2 admitted to the hospital due to the development of NlI S. Machine learning (ML) was used to search for a relationship between LBM levels at the time of patient admission to hospital and outcomes of the acute period of stroke. Results. We established the threshold concentrations of interleukin (IL)-13 (3,605 pg/mL), IL-6 (1,47 pg/mL), apolipoprotein CII (1516000000,0 ng/mL), soluble IL-4 receptor (581,912 pg/mL) and syndecan 4 (26,785 ng/mL) that determine the functional outcome of IS, as well as the threshold values of the alpha subunit of the soluble IL-2 receptor (480,802 pg/mL), IL-21 (1,024 pg/mL), protein 15 containing a disintegrin and metalloproteinase domain (3076,733 ng/mL), soluble vascular endothelial growth factor receptor 2 (16,300,003 pg/mL) that determine the neurological outcome of IS in patients with DM 2. Models for predicting the functional and neurological outcome of IS in patients with DM 2 are proposed. Conclusion. LBM research can be a useful auxiliary tool for predicting the outcomes of NlIS in patients with DM 2, which provides opportunities for implementing a personalized approach to the management of these patients and improving the quality of their treatment.

Background. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by severe vascular wall remodeling, impaired angiogenesis, and aseptic inflammation of the pulmonary artery branches. All these changes lead to right ventricular heart failure, which is the cause of death in patients with PAH. Vascular damage and right ventricular failure are considered the main cause of respiratory dysfunction in pulmonary hypertension. However, changes in the respiratory tract remain largely unnoticed. The aim of this study was to investigate changes in gene expression in the lung tissue of rats with PAH induced by monocrotaline administration. Materials and methods. Wistar male rats (n = 12) were used in the experiment. To simulate PAH, animals were subcutaneously injected with a monocrotaline solution (Sigma-A ldrich, USA) at a dosage of 60 mg/kg. Six weeks after administration of monocrotaline, studies were performed: right ventricular catheterization (RV), histological examination of bronchi and pulmonary arteries, genetic analysis. Results. Totally 298 differentially expressed genes (DEGs) were detected, including 107 with increased and 191 with decreased gene expression. The most pronounced dysregulation of biological processes in the cluster with increased DEG expression was associated with phagocytosis, regulation of the immune response, and cellular response to lipoproteins. In the decreased DEG expression cluster, processes associated with cilia, their movement, and assembly were predominantly represented, indicating a connection with the ciliated epithelium of the bronchi. To confirm this, a histological study of the bronchi was performed. The obtained results demonstrate significant changes in the morphology of bronchi with a diameter from 100 to 1000 μm: a significant increase in the bronchial wall thickness index (PAH — 46,0 [38,8; 54,1] %, healthy animals (Intact) — 29,7 [24,8; 36,0] %, p ˂ 0,001), the height of bronchial epithelium (PAH — 12,5 [11,0; 14,6] μm, Intact — 8,0 [7,2; 9,6] μm, p ˂ 0,001), as well as the number of epithelial cells per 50 μm of the analyzed bronchial wall (PAH — 11,5 [10,7; 13,2], Intact — 8,2 [7,7; 9,0], p ˂ 0,001). Conclusions. Thus, transcriptional profiling indicated remodeling processes not only of the pulmonary vessels, but also of the lower respiratory tract, which was confirmed by histological examination.

Objective — the main objective of the study is to test the hypothesis that achieving lower recommended target levels (LRT) of blood pressure (BP) in elderly and senile patients with arterial hypertension (HTN) will be no less safe than achieving higher recommended target levels (HRT) of BP in elderly and senile patients with HTN, which will be assessed using home BP measurement data and a remote monitoring system for the effectiveness and safety of antihypertensive therapy. Design and methods. The study is expected to include 60 patients aged 65 years and older, who will be randomly assigned to the LRT or HRT BP group with the achievement of recommended target levels of SBP (according to home BP measurement data) of less than 125 or less than 135 mmHg. The effectiveness of the intervention will be assessed by the following indicators: the frequency of episodes of arterial hypotension (SBP less than 100 mmHg) with or without clinical manifestations; frequency of fainting or pre-syncope; frequency of falls in general and traumatic falls; assessment using the AHT tolerability scale (scale developed by Duarte-Silva D. et al., 2014); assessment of quality of life using the disease- specific Quality of Life Questionnaire on Hypertension scale; duration of the period during which SBP will be in the therapeutic range as a percentage of the total observation period. In addition, it is supposed to assess the indicators of frailty and indicators of cognitive functions. The analysis of the obtained data will be performed using the Win Ratio method in a hierarchical order. Expected results. The study will provide data on the possibilities of remote monitoring with the selection of AHT in individuals aged 65 years and older in order to achieve target BP levels, as well as information on the tolerability of AHT when it is selected in order to achieve lower recommended BP levels in such patients.

Objective. To measure the maternal serum cell free fetal DNA (CFFDNA) and establish the relationship between preeclampsia (PE) and maternal serum (CFFDNA) levels. Design and methods. A nested case-control study was carried out on 30 (PE) subjects and 30 matched controls aged 18–40 years old who were submitted at the Ain-S hams University maternity hospital. All subjects had a single viable fetus beyond 20-week gestational age. Upon enrollment, blood samples were collected, and the CFFDNA was subsequently measured in subjects and controls. Results. The CFFDNA level differed significantly between the analyzed groups, showing higher levels in PE diagnosed individuals than in controls. Additionally, the maternal serum CFFDNA level, utilizing an area under the curve of 0,979, predicted PE. Conclusion. Maternal serum cell free DNA can be utilized for PE prediction. The mean levels of CFFDNA correlate with developing maternal complications in PE.

Background. Individuals with hypertension tend to have higher liver function test (LFT) levels and an increased risk of hypertension when abnormal LFT levels are present. The dysfunction of the liver is identified as a significant contributor to the development of hypertension. Objective. The article specifically focuses on review of various LFT markers such as albumin, alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), serum bilirubin, lactate dehydrogenase, prothrombin time (PT) and their role in hypertension. Results. The increase in albumin concentration from approximately 40 to 50 g/l within the physiological range correlated with a rise in systolic blood pressure ranging from 5 to 11 mmHg in males and from 6 to 17 mmHg in females. Also, there is a negative correlation between serum ALP and indices of artery anatomy and function in hypertensive African men. Moreover, an inverse correlation between elevated ALT levels and hypertension in Chinese adults, suggesting that elevated ALT may precede the onset of hypertension. The overall prevalence of elevated ALT and AST among freshmen was 6,8 % and 2,3 %, respectively, suggesting a strong correlation between ALT levels and hypertension in both males and females. Another study indicated that higher GGT levels were associated with an increased risk of hypertension. In men with pre-hypertension, but not in normotensive individuals, serum bilirubin levels negatively correlated with arterial stiffness. No significant relationship between arterial stiffness and bilirubin levels was observed in women. An increase in serum LDH level is linked to the severity of pregnancy-induced hypertension and complications for both mother and fetus. Systolic blood pressure and diastolic blood pressure showed a positive correlation with activated partial thromboplastin time (APPT) in hypertensive patients. These findings suggest that PT and APTT measurements could be used as indicators to assess hemostatic abnormalities in individuals with hypertension and guide antihypertensive medication. The exact mechanisms by which the liver function panel influences hypertension were not reported.