The angiotensin-converting enzyme (ACE) is constitutively expressed on the surface of endothelial, epithelial and immune system cells (macrophages, dendritic cells). The lungs are believed to be the main source of circulating ACE. However, other organs such as the small intestine, kidneys, heart, brain, epididymis, and prostate have also been found to express ACE at levels comparable to those in the lungs. ACE expression is regulated not only passively by the number of endothelial cells, but also by endothelial function. In general, the biochemical environment is the driving force behind the enzymatic activity of ACE, influencing cells capable of expressing ACE and regulatory proteins. The discovery of tissue ACE has changed our understanding of the pathophysiology of many diseases. In particular, it turned out that renal versus circulating ACE is more important in the development of arterial hypertension, diabetic nephropathy, acute and chronic kidney disease.

New coronavirus disease (COVID-19) caused by SARS-CoV-2 is associated with a high mortality rate and is a major public health problem worldwide. In publications from the early months of the COVID-19 pandemic, the authors reported that hypertension (HTN) is associated with higher susceptibility to SARS-CoV-2 infection, severe disease, and increased mortality associated with COVID-19. The risk of more severe clinical manifestations of COVID-19 is higher in men and increases dramatically with age. However, according to the results of multivariate analyses with the inclusion of data on age, risk factors (RF) of cardiovascular diseases (CVD), diabetes mellitus, the independent role of HTN in the development and outcome of COVID-19 was not confirmed, while age turned out to be the most significant factor. The authors made the conclusion that HTN may not play an independent role in SARS-CoV-2 infection and the course of COVID-19, and the formation of adverse outcomes is influenced by old age. However, age-related changes include accumulated chronic diseases, their RF, target organ damage etc. Morphofunctional changes caused by a long course of HTN, the development of associated clinical conditions can increase the susceptibility of the cardiovascular system to the damaging effects of SARS-CoV-2, as well as contribute to the formation of adverse outcomes of COVID-19. In addition, diabetes mellitus, obesity, and other metabolic disorders associated with HTN negatively contribute to the course of COVID-19 and the risk of mortality. A more severe course of COVID-19 in HTN patients, especially the elderly, may be facilitated by the mechanisms of cellular and immune inflammation common in these diseases. The endothelial monolayer plays an important role. Endothelial injury and endothelial dysfunction in HTN and endothelitis in COVID-19 may reinforce each other, increasing the likelihood of cardiovascular events in patients with COVID-19. An important pathogenetic mechanism of HTN — the renin-angiotensin- aldosterone system (RAAS) activation — plays a significant role in the genesis of COVID-19. Angiotensin-converting enzyme 2 (ACE) is a key receptor for SARS-CoV-2 entry into human cells, providing a link between COVID-19 and RAAS. In this regard, it was expected that ACE inhibitors and angiotensin II receptor blockers (ARB), which modulate the RAAS, may increase the risk of SARS-CoV-2 infection and worsen outcomes in COVID-19. However, in further experimental and clinical studies, these assumptions were not confirmed. Moreover, currently international experts strongly recommend that ACE inhibitors or ARB be continued in HTN patients with COVID-19, as they protect against cardiovascular complications and improve prognosis. Observations have shown that COVID-19 significantly increases the likelihood of developing HTN, acute coronary syndrome, cardiac arrhythmias, right ventricular dysfunction, myocardial fibrosis, heart failure, and also increases the risk of death from CVD. Further clinical and long-term prospective studies are needed to evaluate the role of past COVID-19 as a RF for CVD and mortality.

Objective. The aim of the study was to evaluate the level of expression of the NOS2, NOS3, SONE genes in peripheral blood leukocytes (PBL) of patients with hypertension (HTN) and to study the relationship between the level of transcripts of these genes and the content of nitric oxide metabolites and markers of endothelial dysfunction.

Design and methods. The study included healthy people (25 people) and patients with HTN (stages I–II) before prescribing antihypertensive drugs (15 people) and taking cardioselective β-adrenergic receptor blockers for more than a year (metoprolol (25 mg per day) or bisoprolol (5–10 mg per day)) (20 people). The level of gene transcripts was assessed by real-time polymerase chain reaction (PCR). The level of nitric oxide metabolites was determined by the colorimetric method using the Griess reagent. The content of asymmetric dimethylarginine (ADMA), soluble forms of vascular cell adhesion molecule (sVCAM), and intercellular adhesion molecule (sICAM) in blood plasma was determined by ELISA. The content of malondialdehyde (MDA) in blood plasma was determined spectrophotometrically by color reaction with thiobarbituric acid. Statistical processing of the results was carried out using the Statgraphics Centurion XVI software package (version 16.1.11).

Results. The level of nitric oxide metabolites in the blood plasma of HTN patients without antihypertensive therapy was 2,1 times higher than in healthy individuals (p = 0,001) and 1,7 times higher than in patients with HTN taking metoprolol or bisoprolol (p = 0,002). The relative content of mRNA of the NOS3 gene in PBL of individuals included in the study did not differ (p > 0,05). The level of NOS2 gene transcripts in PBL of HTN patients before the prescription of antihypertensive drugs exceeded that in healthy individuals (p = 0,0009) and in HTN patients taking metoprolol or bisoprolol (p = 0,0002). The number of SONE transcripts in the PBL of HTN patients was higher than in people with normal blood pressure (p < 0,00001 when comparing patients before the prescription of antihypertensive therapy and individuals from the control group; p = 0,04 when comparing patients with HTN taking antihypertensive drugs and normotensive subjects). The content of MDA, ADMA, sVCAM was higher in the plasma of HTN patients without antihypertensive therapy compared with people from the control group (p = 0,005, 0,003, 0,039, respectively) and patients taking metoprolol or bisoprolol (p = 0,0006, 0,019, 0,016, respectively). The content of nitric oxide metabolites positively correlated with NOS2, SONE, VCAM1 mRNA level in PBL, the content of MDA and ADMA in blood plasma (p < 0,05). A positive correlation was found between the concentration of MDA and ADMA in plasma (p = 0,03).

Conclusions. An increase in the level of nitric oxide metabolites in HTN is associated with an increase in the transcriptional activity of the NOS2 gene, a disturbance of the redox balance of the body, and the development of endothelial dysfunction. The SONE gene is probably involved in the modulation of nitric oxide levels in HTN not only as an antisense transcript that destabilizes the mRNA of the NOS3 gene in vascular endothelial cells, but also indirectly, namely, through the regulation of homeostasis of immune system cells through autophagy.

Background. Ischemic stroke is one of the leading causes of death in patients with type 2 diabetes mellitus (DM). According to the results of clinical and experimental studies, the ability of glucagon-like peptide-1 receptor agonists (GLP-1RA) to reduce the risk and severity of stroke in DM has been proven; data on the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) effect are scarce. There has been no direct comparative study of the GLP-1RA and SGLT-2i neuroprotective effect.

Objective. To evaluate and to compare the effect of GLP-1RA of varying duration of action and SGLT-2i of varying selectivity on the neurological deficit severity and the brain damage volume in a transient focal brain ischemia model in rats without DM.

Design and methods. Male Wistar rats were divided into groups (n = 10 each) depending on the therapy received: “EMPA” (empagliflozin per os 2 mg/kg once daily), “CANA” (canagliflozin per os 25 mg/kg once daily), “LIRA” (liraglutide 1 mg/kg s. c. once daily), “DULA” (dulaglutide 0,12 mg/kg s. c. every 72 hours), “SEMA” (semaglutide 0,012 mg /kg s. c. once daily), “MET” (metformin per os 200 mg/kg once daily — comparison group), “Control” (administration of 0,9 % NaCl solution s. c. once daily). After 7 days, all groups underwent transient focal 30-minute filament middle cerebral artery occlusion. After 48 hours of reperfusion, neurological deficit was assessed using the Garcia scale, then the brain was collected and sections were stained with 1 % triphenyltetrazolium chloride solution to calculate the damage volume.

Results. Neurological deficit severity in the “LIRA” (14,50 (12,25; 15,25) points) and “SEMA” (14,00 (13,50; 18,00) points) groups was significantly less than in the “Control” group (11.00 (6,75; 12,00) points). The use of both SGLT-2i, as well as metformin, had no effect on the neurological status. At the same time, therapy with all study drugs had an infarct-limiting effect, compared with the “Control” group (damage volume 24,50 (14,69; 30,12) % of the total brain volume). At the same time, the brain damage volume in the “MET” group (12,93 (6,65, 26,66) %) was greater than that in the “EMPA” (6,08 (2,97, 7,63) %), “CANA” (5,11 (3,96; 8,34) %), “LIRA” (3,40 (2,09; 8,08) %), “DULA” (4,37 (2,72; 5,40) %), “SEMA” (5,19 (4,11; 7,83) %) groups.

Conclusions. SGLT-2i of varying selectivity and GLP-1RA of varying duration of action have a similar infarct-limiting effect in acute experimental brain ischemia. At the same time, GLP-1RA neuroprotective potential is higher, as it is characterized by an additional positive effect on the neurological status.

Objective. The aim of the study was to compare the parameters of lipid profile, arterial stiffness and endothelial function in patients with arterial hypertension (HTN), examined before the COronaVIrus Disease-2019 (COVID-19) pandemic, and patients with HTN who underwent COVID-19.

Design and methods. In total, 133 people were included: 72 patients with HTN examined in 2010–2015, 61 patients with HTN who survived after COVID-19. A biochemical blood test was performed to determine the level of glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol. The level of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol was calculated. The parameters of arterial stiffness were assessed using volume sphygmography, endothelial function was determined based on the values obtained in the sample with post-occlusive reactive hyperemia.

Results. According to the results of a biochemical blood test, a significantly higher level of total cholesterol and non-high-density lipoprotein cholesterol was noted in patients with HTN who underwent COVID-19. In the compared groups, comparable indicators of endothelial function were registered with post-occlusive reactive hyperemia. At the same time, according to volume sphygmography, the highest values of arterial stiffness indicators (pulse wave velocity in the aorta, pulse wave velocity in elastic arteries, cardio-ankle vascular index on the right and left) were found in patients with HTN who had undergone COVID-19. A univariate regression analysis was carried out, which confirmed a significant negative effect of the transferred COVID-19 on the parameters of arterial stiffness.

Conclusions. Patients with HTN in the post-COVID period represent a particularly vulnerable cohort of the population in terms of the risk of developing and progressing cardiovascular pathology, including vascular events. The inclusion of volume sphygmography in the list of examinations will probably allow early detection of an increase in arterial stiffness with subsequent drug correction.

Objective. To study the peculiarities of COVID-19 course and gender differences in patients with arterial hypertension (HTN) in the conditions of the Arctic watch.

Design and methods. In the settlement of Yamburg (Nadym district), 517 case histories were retrospectively analyzed by random sampling: 359 men (M) and 158 females (F) treated as inpatients at the medical unit of GAZPROM DOBYCHA YAMBURG LLC in the period 2019–2021. Of these, a diagnosis of COVID-19 was verified in 233 M (with HTN — 150 M (64 %) and 77 F (with HTN — 51 F (66 %)); and those without COVID-19: 126 M (with HTN — 77 M (61 %) and 81 F (with HTN — 38 F (47 %)). The diagnosis of COVID-19 was based on the detection of SARS-CoV-2 RNA by polymerase chain reaction. Retrospective analysis was performed as part of routine clinical practice; patients gave written informed consent for data processing according to the order No. 36/1 dated 29.01.2020 and the approved informed consent form.

Results. M and F groups who survived after COVID-19 were significantly older than those who did not. The largest number of COVID-19 patients among M and F were from the group of interregional watch — rotations from temperate regions without crossing the time zone (Tyumen, Ufa, Tobolsk), the smallest — from the group of intraregional watch (coming on a rotation from the Far North — cities Nadym, Novy Urengoy). Correlation analysis showed direct significant relationships between COVID-19 and age (p = 0,009), northern experience (p = 0,006), and history of HTN (p = 0,002). Patients with HTN who survived after COVID-19 were significantly more likely to have grade II obesity. M with HTN compared to F and M with normal blood pressure (BP), had a significant decrease in saturation (94,8 (5,0) % vs 95,9 (3,0) %, p = 0,038) and had an increase in the number of individuals with a severe course (11 % vs 4 %, p = 0,041). In 6 M with HTN who survived after COVID-19, atrial fibrillation was registered for the first time. Myocardial repolarization disorders, blockade changes (incomplete right bundle branch block), sinus tachycardia were registered more often in HTN subjects.

Conclusions. Thus, our analysis showed that patients with HTN, overweight or obesity were more likely to be infected with COVID-19 under the conditions of the Arctic watch. In 65 % of cases, COVID-19 was accompanied by moderate changes in the lungs of the CT1 type, due to the timely hospitalization of patients. M compared to F more often had a severe course of COVID-19 with a significant decrease in saturation and more frequent electrocardiography changes. Observation and being on a 2-week quarantine before the watch had no significant success in limiting the incidence of COVID-19.

Background. During the recent years, there has been a steadily growing interest in the problems of microcirculatory disorders (MD) in patients with cardiological and rheumatological profile that is determined by a significant role of microcirculatory in the pathogenesis of these diseases.

Objective. Analysis of the MD special features in patients with hypertension (HTN) and rheumatoid arthritis (RA).

Design and methods. Patients matching the inclusion criteria by age (58,6 ± 6,4 years), debut (aged 45–64 years) and RA experience (7,2 ± 2,1 years) and HTN duration (11,2 ± 1,6 years) were divided into three groups: I group — 277 patients with stage II HTN; II group — 142 patients with stage II HTN and RA (in clinical and laboratory remission); group III — 112 patients with stage II HTN and RA (in clinical and laboratory exacerbation). The study of the microcirculatory bed was performed on an outpatient basis by laser Doppler flowmetry according to a standard technique. Results. Microcirculatory bed analysis in patients with HTN and RA showed the variability of indicators depending on gender characteristics, body weight and microcirculatory type. The study of the amplitude-frequency spectrum in women with stasis, in men with spastic and normocirculatory types of microcirculation showed an increase in neurogenic tone, endothelial activity and some decrease in the amplitude of oscillatory processes at the periphery.

Conclusions. In patients with HTN and RA, changes at the microcirculatory level were determined, they manifested by an increase in adrenergic tone, spastic phenomena, endothelial activation, some decrease in blood flow variability and more pronounced vasomotor dysfunction that is not only the result of RA presence but its activity. RA in this situation could be regarded as a surrogate marker for the unfavorable course of HTN.

Background. Wake-up stroke (WUS) is often combined with sleep-disordered breathing and may potentially have a more unfavorable course.

Objective — to evaluate the association between the time of stroke onset and the pattern of sleep-disordered breathing, as well as the effect of wake-up stroke on stroke recovery and stroke severity in patients with ischemic stroke.

Design and methods. We included patients 18–85 years old with acute ischemic stroke admitted within 24 hours of symptom onset to the neurological resuscitation unit, and performed polygraphy within the first day of hospitalization to assess the parameters and severity of sleep-disordered breathing. In 2018–2023, 2122 patients were screened, polygraphy was performed in 639 patients, and data from 292 patients were included in the final analysis. Stroke severity was assessed using the NIHSS scale, stroke type was determined using the TOAST classification. WUS was considered when symptoms were detected upon awakening. Functional status was assessed by the Barthel index, and rehabilitation outcomes by the modified Rankin scale. The cumulative end point included death from any cause, new nonfatal myocardial infarction, new nonfatal stroke/transient ischemic attack, emergency revascularization, or emergency hospitalization due to exacerbation of cardiovascular disease.

Results. WUS was detected in 101 patients (34,6 %). The WUS group had more frequent diabetes mellitus and higher NIHSS (p = 0,021) and Barthel index (p = 0,026) at discharge, less frequent thrombolytic therapy and emergency endovascular procedures (p = 0,007) which in most cases was associated with hospitalization in time beyond the therapeutic window (p < 0,001). Endpoints were reached in 21,6 % with a median follow-up of 209 days. No significant differences were found in the main indices of sleep-disordered breathing in groups of different severity and pathogenetic type of stroke. The most significant factors related to Barthel index were stroke severity at discharge (p < 0,001) and age (p < 0,001). Stroke severity at discharge was most influenced by thrombolytic therapy (p = 0,006) and stroke severity on admission (p < 0,001).

Conclusions. Our study did not show the previously described higher incidence of sleep-disordered breathing in WUS. The best outcomes were in subjects who received reperfusion therapy. Patients with WUS should be hospitalized in a hospital where reperfusion therapy is available. Lower Barthel index values at discharge of patients with WUS may characterize their lower rehabilitation potential.

Objective. To assess the possibility of obtaining and the degree of additional antihypertensive effect, the dynamics of vascular wall stiffness parameters, vascular age indicators in patients with uncontrolled hypertension (HTN) when transferring from previous therapy to a fixed combination of amlodipine/indapamide in typical outpatient practice.

Design and methods. Twenty-five patients with 1–3 degree HTN who got a prescription of a fixed combination of amlodipine/indapamide (ARIFAM 5/1,5 or 10/1,5 mg, Servier) were included in the study. The follow-up duration was 2 months and included the following methods: clinical assessment (systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate), with titration of the drug dose every two weeks; double assessment (at the beginning and at the end of the study) of arterial stiffness based on the determination of the cardio-ankle vascular index (CAVI), biological age of vessels using the VaSeraVS‑1500N volumetric sphygmography device, as well as quality of life indicators (SF‑36 questionnaire). The reliability of changes in the studied parameters during active outpatient management of patients was assessed.

Results. Combined pharmacotherapy using a fixed combination of amlodipine/indapamide was well tolerated by all patients. We recorded a significant decrease in SBP on average by 31,0 ± 10,6 mmHg, DBP by 11,0 [7,0; 20,0] mmHg, and the achievement of the target SBP level at the end of the 2nd month was shown in 17 (68 %) patients, the target DBP level was found in 100 % of patients. A significant decrease in vascular wall stiffness parameters was shown as a decrease in the CAVI index (p = 0,034), a decrease in AI (p = 0,0001) and the PEP/ET ratio of the Veissler coefficient (p = 0,009), as well as in the calculated vascular age indicator (p = 0,00001). Significant (p = 0,0001) changes were recorded for most data of quality of life (SF‑36) in patients with HTN, with the exception of the social functioning scale.

Conclusions. Combined pharmacotherapy of patients with 1–3 degree HTN with the inclusion of a fixed combination drug amlodipine/indapamide with prolonged release has a clear positive effect, i. e. improved hemodynamic parameters, a significant reduction in vascular stiffness, a decrease in vascular age and improved quality of life.