STUDY OF CLINICAL AND PATHOGENETIC EFFECTS OF ANTI-VIRAL DRUG BASED ON FAVIPIRAVIR IN COMORBID PATIENTS WITH COVID-19 AT THE OUTPATIENT STAGE OF TREATMENT

In many ways, arterial hypertension and obesity determine the likelihood of a severe course and lethal outcomes in COVID-19. This fact justifies the expediency of an early use of drugs with a direct antiviral action, the analysis of their efficacy not only in the acute, but also in the postcovid period.The aim of the research was to analyze the outpatient cards and case histories of the COVID-19 patients to study the effect of the early (up to the 5th day after the onset of the first symptoms of the disease) use of the drug based on favipiravir, on the frequency of patients’ hospitalizations with arterial hypertension and obesity, as well as to determine the cytokine status characteristics of this patient category in the postcovid period.Materials and methods. “An open prospective comparative study of the “Areplivir®” (favipiravir) efficacy in the debut of COVID-19 in comorbid patients” was carried out in the Republic of Mordovia (the analysis of the hospitalizations frequency and blood levels of M-CSF, EPO in 218 patients, in terms of the use of the antiviral preparation).Results. According to the results of the analysis, it was found out that, despite the presence of comorbid conditions that increase the risk of developing a severe course of COVID-19, i.e. obesity and essential arterial hypertension, in the group of patients taking favipiravir, the need for hospitalization was twice as low (p < 0.05), in relation to the comparison group. The analysis of the cytokine status revealed that in the postcovid period, in the group that took the drug based on favipiravir at the outpatient stage, the average level of M-CSF was significantly lower (p> 0.05), and EPO was higher (p> 0.05) than in the patients from the group “without antiviral drugs at the outpatient stage”. Indirectly, according to the previously obtained data, that acts as a potential marker for reducing the risk of long-term cardiovascular complications of COVID-19.Conclusion. This study showed that an early prescription of favipiravir contributes to a decrease in the rate of COVID-19 patients’ hospitalization even against the background of concomitant hypertension and obesity, due to a decrease in the likelihood of moderate and severe courses of the disease, and also leads to an earlier objective and subjective recovery. The results demonstrated a high potential benefit of an early favipiravir use in the novel coronavirus infection and in the prevention of postcovid complications.

The severity of essential hypertension in terms of blood pressure values does not depend on NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphisms in the West-Ukrainian population

Objective: to evaluate the association of essential arterial hypertension (EAH) and its severity with genes polymorphism of NOS3 (rs2070744) and GNB3 (rs5443) in West-Ukrainian population. Materials and methods. One-hundred EAH patients (48 – healthy control) participated in the cohort case-control study. Blood pressure (BP), Creatinine, glucose, lipids panel were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFX96™Real-Time PCR). Risk assessed by Relative Risk, Odds Ratio and 95% Confidential intervals. Results. A mutation of the NOS3 gene (786T>C, rs2070744) and the GNB3 gene (825C>T, rs5443) in the homozygous state in the West-Ukrainian population suffers from EAH occurs with a frequency of 16.67% and 8.33%, with no differences with the control subjects (p>0.05). In both groups dominate the T-allele of the NOS3 gene and the C-allele of the GNB3 gene: in patients by 12.5% ​​(c2=4.50; p=0.034) and 41.66% (c2=50.0; p<0.001), in the control – by 25.0% (c2=12.0; p<0.001) and 40.0% (c2=33.33; p<0.001), respectively. The results of the binary logistic regression analysis did not confirm the prediction of the EAH appearance by polymorphic variants of the NOS3 (rs2070744) and GNB3 (rs5443) genes. However, the TT genotype of the GNB3 gene (rs5443) increases unreliably the EAH risk almost twice as likely [OR=2.0; OR 95%CI:0.40-10.82; p>0.05]. Epidemiological analysis did not confirm the association of the NOS3 gene with the EAH severity. But T-allele of the GNB3 gene increases the probability of high normal BP almost 5 times [OR=4.86; OR 95%CI:0.99-24.75; p=0.042]. Conclusions: NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphisms are not associated with blood pressure values and EAH severity as well.

PREVALENCE OF ESSENTIAL ARTERIAL HYPERTENSION IN CHILDREN AND ADOLESCENTS OF DAGESTAN AND THE CONTENT OF Mg, K, Ca, Zn, Pb IN SOILS AND NATURAL WATERS OF THE TERRITORY

The aim of the study is to determine the role of geochemical factors (the content of Mg, K, Ca, Zn, Pb in soils and natural waters of the plain zone of Dagestan) in the prevalence of essential arterial hypertension (EAH) among the population of children. Materials and methods of research: an observational cross-sectional (one-step) study of the prevalence of EAH in the child population was carried out. The prevalence rates of EAH among children in the plain zone of the Republic of Dagestan are calculated for 100,000 children 0–17 years old, without taking into account gender differences. The content of elements (Mg, K, Ca, Zn, Pb) in the environment (soil, natural waters) was determined by atomic absorption spectroscopy. Results: one-way analysis of variance (One-Way ANOVA) of indicators of the content of metals (Mg, K, Ca, Zn, Pb) in the regions and objects (soils, natural waters) of the study revealed a statistically significant difference in the data (for soils: F=81,06772, p<0,0002; for natural waters: F=58,86451, p<0,00001). The dependence of children's EAH on the content of chemical elements in the objects of the biosphere of Dagestan was determined, which was expressed in an increase in the number of patients with EAH when Pb content exceeded (r=+ 0,576, r=+ 0,759) and with the decrease of Mg (r=–0,668, r=–0,173), K (r=–0,440, r=–0,636), Ca (r=–0,693, r=–0,533), Zn (r=–0,051, r=–0,827) in soils and natural waters. Conclusion: when assessing the pathogenesis of EAH in the population of children, the content of Mg, K, Ca, Zn, Pb in soil and water should be taken into account, since these microelements, entering the body with water and food, affect the elemental status of child's body.

Effect of device-guided paced breathing of biofeedback on blood pressure, stress and anxiety levels in hypertensives

The present study aimed to evaluate the influence of cardiac coherence through Biofeedback Therapy (BT) with paced breathing on blood pressure, stress and anxiety levels in individuals with essential arterial hypertension. The participants underwent 8 sessions of paced breathing guided by biofeedback visual therapy for 20 minutes, in which they were evaluated through clinical assessment, Hamilton Anxiety Rating Scale, Perceived Stress Scale and cardiovascular variables. Comparisons of means were performed using the paired and unpaired Student's t-test. Statistically significant correlations were considered when p ≤ 0.05 with a 95% confidence interval. The effect size (Cohen's d) and common language effect size were calculated to assess the effect of such therapy. Sixteen patients with mean age of 57.3 ± 14 years old participated in this study. Comparisons between mean initial and final systolic blood pressure levels (SBP) in women (p = 0.007; Cohen's d = 0.50), pre- and post-training heart rate (p = 0.02; Cohen's d = 0.60) and anxiety levels (p = 0.01; Cohen's d = 1.04) were significant. Comparisons between pre- and post-training SBP (p = 0.006; Cohen's d = 0.81) and pre- and post-training anxiety levels (p = 0.04; Cohen's d = 0.32) were significant among males. In conclusion, paced breathing training with biofeedback therapy can be promising to reduce anxiety levels in individuals with essential arterial hypertension.

Asymptomatic Hyperuricemia and Functional State of the Kidneys in Patients with Essential Arterial Hypertension and Concomitant Diabetes Mellitus Type 2

Introduction: The manuscript analyzes the frequency of asymptomatic hyperuricemia in association with disturbance of glucose and lipid metabolism, inflammatory process, and kidney changes in patients with essential arterial hypertension (EAH) and concomitant diabetes mellitus type 2 (DM2). Aim: To determine the frequency of asymptomatic hyperuricemia in patients with EAH and concomitant DM2 and their effects on the main indicators of comorbid pathology. Materials and methods: 120 patients (51 males and 69 females), aged 45-69 years with average age being (58.2±5.7) years, were studied: 25 patients with treatment-compensated EAH, 1-2 degree, II stage (Group I); 25 patients with subcompensated DM2 (Group II) and 70 patients with treatment-compensated EAH, 1-2 degree, II stage and concomitant subcompensated DM2 (Group III). Control group consisted of 20 practically healthy volunteers - 8 (40.0%) males and 12 (60.0%) females, aged (54.7±4.9) years. Groups were randomized according to age, sex, BMI, duration of EAH and DM2. Results and discussion: Asymptomatic hyperuricemia were observed in 36.0% of group І patients, in 24.0% of group II patients and in 46.7% of group ІІІ patients. Relevant correlations were found between uric acid level in the blood and such indicators as/for systolic blood pressure (SBP), glycated hemoglobin (HbA1C), dyslipidemia, inflammatory process, and kidney damage. Conclusion: Asymptomatic hyperuricemia has a negative effect on the main indicators of comorbid pathology - in this case, EAH and concomitant DM2.

Distribution of Polymorphic Marker of Genes of the Renin-angiotensin System RAS (AGT, AGTR1, АСЕ), ITGB3, PPARG) in Pa-tients With Essential Arterial Hypertension Depending on the Nature of the Nocturnal De-crease of BP

A clinical-genetic study using ABPM (24-hour BP monitoring) and Holter’s ECG methods in 49 pa-tients with essential arterial hypertension (group 1: 17 patients without sufficient nocturnal BP de-crease СI≤10%, and group 2: 32 patients with suf-ficient nocturnal BP decrease СI≥10%,) was per-formed for comparative analysis of the genotype frequencies of ACE, AGT, AGTR1, ITGB3, and PPARG. The study was conducted in order to clari-fy the pathogenetic mechanisms of the implementa-tion of different dynamics of nocturnal blood pres-sure in patients with hypertension without metabol-ic syndrome. It was found that in group 1, protec-tive genotype II of the ACE gene was more com-mon (p ≤ 0.025) than in the population data. A sig-nificant increase (p ≤ 0.025) in the frequency of the CC genotype of the AGTR1 gene responsible for the formation of insulin resistance compared to the population data was combined with a significant increase in the frequency of autonomic dysfunction in patients of group 1 - 83.4% vs. 64.5% group 2 respectively. The results obtained indicate the pos-sible pathogenetic links between genetically deter-mined insulin resistance and autonomic nervous system dysfunction and allows us to determine therapeutic approaches for correcting the noctur-nal blood pressure profile.

Salt and Sugar: Two Enemies of Healthy Blood Pressure in Children

The prevalence of essential arterial hypertension in children and adolescents has grown considerably in the last few decades, making this disease a major clinical problem in the pediatric age. The pathogenesis of arterial hypertension is multifactorial, with one of the components being represented by incorrect eating habits. In particular, excessive salt and sugar intake can contribute to the onset of hypertension in children, particularly in subjects with excess weight. Babies have an innate predisposition for sweet taste, while that for salty taste manifests after a few weeks. The recent modification of dietary styles and the current very wide availability of salt and sugar has led to an exponential increase in the consumption of these two nutrients. The dietary intake of salt and sugar in children is in fact much higher than that recommended by health agencies. The purpose of this review is to explore the mechanisms via which an excessive dietary intake of salt and sugar can contribute to the onset of arterial hypertension in children and to show the most important clinical studies that demonstrate the association between these two nutrients and arterial hypertension in pediatric age. Correct eating habits are essential for the prevention and nondrug treatment of essential hypertension in children and adolescents.

Effects of Uric Acid Lowering Therapy in Patients With Essential Arterial Hypertension

Background Asymptomatic hyperuricemia (AHU) is defined as elevated serum uric acid (UA) concentration without symptoms. This study aimed to determine the effects of AHU treatment with allopurinol on selected hypertension mediated organ damage (HMOD) indices in patients with uncomplicated essential arterial hypertension (AH). MethodsPatients aged 30-70 years with AHU and essential hypertension grade 1-2 with adequate blood pressure (BP) control, without previous urate lowering therapy (ULT) were divided into two groups: a) receiving allopurinol (ULT group) and b) age-and sex matched patients without ULT (control group). Both groups received UA-lowering diet. BP (office, 24 hour and central), echocardiographic parameters, pulse-wave velocity, carotid intima-media thickness (IMT) and lab tests (high-sensitivity C-reactive protein (hs-CRP) were measured at baseline and at 6 months follow-up.ResultsOut of 100 participants 87 completed the study (44 ULT patients and 43 controls). At 6 months follow-up, there was a significantly greater reduction in serum UA concentration in the ULT group than in the control group (464±68.8 µmol/l vs 314±55.6 µmol/l, p<0.0001). Patients receiving allopurinol had significant reductions in office systolic (137±11.8 mmHg vs 134±9.3 mmHg; p=0.025) and diastolic BP (83±9.9 mmHg vs 79±8.7 mmHg, p=0.017), central systolic BP (56±8.9 mmHg vs 51±12.9 mmHg, p=0.046), pulse pressure (43±10.4 mmHg vs 39±11.2 mmHg, p=0.017), IMT (0.773±0.121 mm vs 0.752±0.13 mm, p=0.044), left atrium volume index (40±13.5 ml/m2 vs 38±12.3 ml/m2, p=0.044), and hs-CRP level (3.36±2.73 mg/l vs 2.74±1.91 mg/l, p=0.028) compared to controls. The decrease in UA concentration was significantly related to the reduction in IMT (R=0.37, p<0.001), central SBP (R=0.26, p=0.015) and hs-CRP concentration (R=0.30, p=0.004). Multivariate regression analysis revealed the independent relationship between reduction in IMT and UA lowering (R=0.3234, R2=0.0722, p<0.026).ConclusionsIn patients with AH and asymptomatic hyperuricemia treatment with allopurinol leads to further improvement in BP control and reduction in HMOD intensity, in particular IMT. The decrease in hs-CRP concentration associated with ULT may have a beneficial effect on patient long-term prognosis.

INTEGRATIVE MORPHOMETRIC CHARACTERISTIC OF ENDOTHELIAL DYSFUNCTION IN THE CASES OF CHILDREN WITH ESSENTIAL ARTERIAL HYPERTENSION

The aim: To optimize the treatment of children with Essential Arterial Hypertension (EAH) in assotiation with Endotelial Dysfunction (ED) by studying the clinical and morphofunctional characteristics of the cardiovascular system disorders and correction of endothelial dysfunction with the using of essential phospholipids. Materials and methods: The study group consisted of 80 children and 30 – a control group. The next stage included the division of 80 children into 2 subgroups. Patients in the first subgroup received basic treatment (angiotensin-converting enzyme inhibitor of the third generation), the second – optimized treatment (basic treatment was with addition of certified drug lecithin). Doses were determined according to the instructions and age for 2 months. In the study were used: ECG, Echocardiography, Ultrasonography, Morphofunctional studies of the endothelium. Results: There is a dynamic decreasing in the level of left ventricular myocardial mass index (LV MMI), reduction of end-diastolic volume (EDV) and increase in the absolute values of shock volume (SV), ejection fraction( EF) under the influence of optimized treatment due to the inclusion of lecithin in the treatment of children with EAH with ED. The Ve/Va ratio had a tendency to increase. Vasoconstriction of vessels after the reactive hyperemia test was significantly reduced, but the degree of vasodilation varied depending on the method of therapy. The intima-media thickness (IMT) decreased in 1.12 times in the cases of children with an optimized treatment, accompanied by a decreasing of DEC by 2-times. Levels of the aortic stiffness index had a tendency of decreasing (from 0.88 ± 0.02 to 0.71 ± 0.01 and to 0.63 ± 0.01, respectively, by groups and in comparison with the control group – 0.55 ± 0 , 01), which reflects the improvement of hemodynamic parameters. The dynamic parameters obtained in the cases of patients with EAH in association with ED, taking into account the impact of the optimized treatment had positive correction on the total risk of cardiovascular complications, changes in the profile of LV diastolic filling, dysfunction of arterial endothelium. Conclusions: The inclusion of essential phospholipids in the treatment of children with EAH and ED helps to optimize the profile of LV diastolic filling and exclude vascular endothelial dysfunction and indicate a positive effect of optimized treatment on the overall risk of cardiovascular complications.