The article reviews monogenic forms of hypertension, data on the role of heredity of essential hypertension and candidate genes, as well as genome-wide association studies. Modern approach for the role of genetics is driven by implementation of new technologies and their productivity. High performance speed of new technologies like genome-wide association studies provide data for better knowledge of genetic markers of hypertension. The major goal nowadays for research is to reveal molecular pathways of blood pressure regulation, which can help to move from populational to individual level of understanding of pathogenesis and treatment targets.

Pulmonary arterial hypertension (PAH) is a rare and severe form of pulmonary hypertension, which is characterized by pulmonary vascular remodeling, as well as metabolic and functional alterations in the right ventricular myocardium. The proven metabolic shift towards anaerobic glycolysis in the heart and lungs can be quantitatively and qualitatively evaluated with a molecular imaging technique — 2-[18F] fluoro-2-deoxy-Dglucose (FDG) positron emission tomography (PET). This review is devoted to the analysis of foreign scientific publications. There are presented research results that prove the diagnostic value of fused PET/computer tomography (CT) (PET/CT) images with FDG and other promising radiopharmaceuticals in patients with PAH. This tool allows estimation of the severity of the disease, to determine the clinical prognosis and monitor the effectiveness of treatment in each case. Furthermore, the methods of molecular visualization allow the analysis of the PAH pathogenesis and description of the new biologic targets, such as development factors of endothelial dysfunction and remodeling of pulmonary vasculature.

The COVID-19 pandemic has had a huge impact on the health of millions of people around the world on an unprecedented scale. Unfortunately, the process of creating effective antiviral drugs and vaccines is being delayed. Therefore, drugs that are already available and may have an effect on COVID-19 are being investigated. Due to the fact that viral infection often affects the cardiovascular system, causing myocardial infarction, viral myocarditis, tachyarrhythmias and stress cardiomyopathies, a theory was put forward that HMG-CoA reductase (3-hydroxy-3methyl-glutaryl-CoA reductase) inhibitors (statins) can reduce the risk of cardiovascular complications in these patients. In recent years, this class of drugs has been proposed, including for viral infections, such as the influenza virus or MERS-CoV. The review discusses both the latest clinical data on the efficacy of statins in COVID-19 and the pleotropic mechanisms of statins that can limit the pathogenic effect of viruses. In particular, statins can act on lipid cell rafts (subdomains of the plasma membrane), decreasing their lipid concentration; limiting the interaction of the virus with the receptors of angiotensin-converting enzyme-2 and CD-147. Statins have an antiinflammatory effect (blocking the molecular mechanisms of inflammation, including NF-κB and NLRP3), limit the development of a “cytokine storm” in severe patients with COVID-19; can inhibit SARS-CoV-2 basic protease; influence coagulation, limit sympathetic activity and have other effects. In two large cohort observational studies (n = 96032 and n = 13981), hospitalized patients with COVID-19 who were taking statins showed a decrease in hospital mortality and mortality 28 days after the admission to the hospital. Thus, statins can play a role in the treatment of COVID-19.

Objective. To study the role of gene-gene and gene-environment interactions of polymorphisms of matrix metalloproteinases with obesity and smoking in the formation of hypertension (HTN) in women. Design and methods. The study included genotyping data for seven polymorphic loci of MMPs — rs3025058, rs11568818, rs1320632, rs11225395, rs652438, rs243865 and rs17577 in 375 patients with HTN and 209 women in the controls. Genetic and environmental interactions involved in the HTN formation were detected using the Multifactor Dimensionality Reduction (MDR) method in Model-Based-MDR modification (MB-MDR vers. 2.6). The results were visualized in the MDR vers. 3.0.2 (http://sourceforge.net/projects/mdr). Results. Eight models of genegene interactions associated with the HTN formation in women (p_perm ≤ 0,05) have been identified which are based on SNPs rs652438 MMP12, rs1320632 MMP8, rs3025058 MMP3 and rs11568818 MMP7. Eight models of interactions of locuses of MMPs with obesity and smoking (p_perm < 0,002) were identified. Most of models include the polymorphic locus rs243865 MMP2. For the identified models, combinations of high (β = 0,76–2,06) and low (β = –0,37 — –1,23) risk of developing HTN were established. Conclusions. Our findings suggest that the polymorphic variants of MMPs and environmental factors have a synergistic effect in the formation of susceptibility to HTN.

Objective. To assess and compare the impact of physical training (PT) on functional and hemodynamic characteristics in patients with chronic heart failure (CHF) depending on continuous inotropic support. Design and methods. Prospective randomized study included 120 men aged 18–65, admitted to the Almazov National Medical Research Center (St Petersburg, Russia) from 2014 to 2019 due to decompensated CHF of III–IV functional class (FC), with left ventricular ejection fraction (LVEF) ≤ 30 %; blood pressure (BP) ≥ 90/60 mmHg (with or without inotropic therapy). Patients receiving dopamine or dobutamine for ≥ 2 weeks were randomized into two groups: group 1 participated in program of physical training (PPT), and group 2 did not participate in PPT. Patients of group 3 had CHF of III–IV class without inotropic therapy and participated in PPT. Initially, all groups were comparable by clinical, functional and hemodynamic parameters. The follow-up lasted 6 months. During months 3 and 6, hemodynamic parameters — BP and heart rate (HR), respiration rate (RR) at rest and peak of exercise, echocardiographic and central hemodynamics at rest, parameters at rest, number of arrhythmias were evaluated. Results. Patients of group 1, after 3 and 6 months, showed no increase in systolic (BPs) and mean BP (BPm) at peak of exercise, in contrast to patients of group 3 who demonstrated a significant increase in BPs (p ≤ 0,002) and BPm (p ≤ 0,005) after 3 months, and BPs (p ≤ 0,001) and BPm (p ≤ 0,002) after 6 months. By 6-month follow-up, intergroup analysis did not show significant changes in HR, LVEF, end-diastolic volume, stroke volume and pulmonary pressure. Initially, ECG monitoring showed a higher number of unstable ventricular tachycardia (VT) in group 1 compared with group 3 (p = 0,01), after 3 and 6 months in all groups the number of VT was comparable. During 6 months, implantable cardioverter defibrillator (ICD) shocks were compared in all groups: 2 per group (5 %). Conclusions. “Inotrope-dependent” survivors with CHF at peak of exercise did not significantly increase BPs and BPm in contrast to “inotrope-independent” patients. Individually developed aerobic PPT of low and intermediate intensity in “inotrope-dependent” survivors did not influence negatively on echocardiographic parameters, parameters of hemodynamics at rest and during the peak of exercise, did not increase mortality and number of life-threatening cardiac arrhythmias and ICD shocks.

Objective. To describe the technical issues and safety of renal denervation (RD) when using a multielectrode radiofrequency (RF) bipolar balloon catheter, a multielectrode unipolar RF spiral catheter, and an electrophysiological (EP) 3,5-mm RF ablation catheter. Design and methods. Between 2016 and 2019, 54 patients undergoing renal artery (RA) denervation were included into a prospective observational study: 27 procedures were performed using the balloon technology, 21 — using the spiral; and 6 — using a steerable irrigated EP catheter under three-dimensional electroanatomical guidance. In 50 patients RD was performed due to resistant arterial hypertension, and in 4 — due to intractable ventricular tachyarrhythmias. Results. The use of the spiral catheter was associated with a higher number of RF points in the RA, when compared with balloon ablation and EP catheter ablation (22,3 ± 9,6 vs. 13,4 ± 5,5 vs. 8,7 ± 2,1, p < 0,01). In the balloon ablation group, a direct correlation between the number of RF points and the sharpest RA angle was found (correlation coefficient — 0,82). We observed the following complications: in the balloon ablation group — 1 dissection of the RA and 1 aneurysm of the right femoral artery (7,4 %); in the spiral ablation group — 1 aneurysm and 1 pulsating hematoma of the right femoral artery (9,5 %); in the electrophysiological electrode ablation group — 1 dissection of the RA, 1 aneurysm of the right femoral artery (33,4 %). Conclusions. The use of the spiral multielectrode catheter is associated with the higher number of RF applications, including ablation inside distal branches. The number of RF points depends on the artery tortuosity when performing balloon-based ablation. Manipulations inside the RA using the EP catheter might not be safe.

Objective. The aim of this study was to investigate the long-term effect of renal denervation (RDN) on MRIcharacteristics of renal artery (RA) wall in diabetic patients with resistant hypertension (RHTN). Design and methods. We included 19 diabetic patients with RHTN (mean age 61,9 ± 6,8 years; 6 men; HbA1c 6,6 ± 1,4 %; mean blood pressure (BP) 24h 159,5 ± 18,9 / 82,2 ± 13,7 mm Hg) who underwent MRI of the RA before and 12 months after RDN. The measurement of signal intensity (SI) of RA wall based on two-dimensional T1-weighted spin-echo images was done before and after the administration of a gadolinium-based contrast agent. The index of enhancement (IE) was calculated as ratio of SI post-to-precontrast enhancement. All patients underwent ambulatory 24-hour (24h) BP monitoring, lab tests (serum hsC-reactive protein (CRP), tumor necrosis factoralpha (TNF-α)) at baseline and 12-month follow-up. On average, patients were taking 4 (3–6) antihypertensive drugs. The mean number of ablations was 13 ± 1,8 (10–16). Patients were instructed not to change the treatment regimen throughout the study. At 12-month follow up MRI of RA was available for 16 patients. Results. After RDN there was a significant comparable decrease in IE of RA wall for both sides (IE mean values for right and left sides: from 1,7 ± 0,4 to 1,4 ± 0,3, p = 0,02 for the main RA; from 1,7 ± 0,5 to 1,4 ± 0,2, p = 0,04 for the middle parts of RA; from 1,9 ± 0,4 to 1,4 ± 0,3, p = 0,001 for distal branches of RA). In addition, RDN reduced the 24h BP (systolic / diastolic) by –15,1/–10,0 mm Hg, p < 0,001 as well as reduced the level of TNF-α (from 4,6 ± 3,8 to 3,4 ± 2,5 pg/ml, p = 0,03) and the level of hsCRP (from 6,5 ± 3,4 to 5,9 ± 3,2mg/L, p = 0,003). There was no direct relation between the IE and BP reduction. At the same time, the change in IE of middle part of RA after RD was directly related to decrease in both hsCRP level (R = 0,62, p = 0,03) and TNF-α level (R = 0,56, p = 0,04). Conclusions. The beneficial effect of RDN on the RA wall is associated with the attenuation of systemic subclinical inflammation.

Background. Metabolic syndrome and diabetes mellitus (DM), as well as a number of environmental factors increase the risk of cardiovascular diseases, which are the leading causes of mortality among working population. Objective. To assess the levels of specific autoantibodies in individuals with vibration disease and type 2 DM. Design and methods. People with vibration disease (group I), patients with type 2 DM (group II), and patients with vibration disease and type 2 DM (group III) were examined. The serum level content of autoantibodies related to vascular state was studied using enzyme immunoassay. Results. More than a quarter of all examined patients had elevated levels of antibodies to the РАРР-А. The changes in the serum level of cardiospecific autoantibodies indicate endothelial damage, alterations of thrombus formation and vascular inflammation. People with vibration disease showed increased incidence of hypoimmunoreactivity of antibodies to collagen, nitric oxide synthase, platelet membrane components, neutrophil and endotheliocyte cytoplasm. Patients with DM had the highest levels of autoantibodies to collagen, nitric oxide synthase, and platelet membrane components. In these patients, increased level of specific autoantibodies to nitric oxide synthase and collagen were found more common. Patients with comorbid pathology showed similar changes: higher rate of reduced level of antibodies to platelet membrane components, nitric oxide synthase and increased level of autoantibodies to nitric oxide synthase and collagen.

Objective. The role of Cl^– -transport in ATP-dependent regulation of contractile activity of rat pulmonary artery (PA) smooth muscle cells was studied. Design and methods. The study was performed on endotheliumdenuded ring segments of the PA of male Wistar rats. Mechanical tension was measured using organ bath technique. Contractions of the PA segments were induced by high-potassium solution (30 mM KCl), hyposmotic solution (40 mM NaCl), as well as restoration of the medium osmolarity (120 mM NaCl) after incubation in hyposmotic solution. Inhibitor of Na⁺ , K⁺ , 2Cl^– cotransport (NKCC) bumetanide (10 μM, 30 minutes preincubation), nonselective Cl^– -channel blocker SITS (100 μM) and Ca2⁺ -activated Cl^– channels blocker niflumic acid (NA, 10 μM) were used to modulate the Cl^– -transport. Results. ATP (10–500 μM) did not affect vascular tone of PA segments incubated in Krebs solution (120 mM NaCl), while 500 and 1000 μM ATP led to the development of transient contractions, the amplitude of which decreased in the presence of bumetanide, SITS and NA. Incubation of PA segments in a hyposmotic medium (40 mM NaCl) caused the development of transient contraction. Subsequent recovery of the medium osmolarity (120 mM NaCl) induced another transient contraction — isosmotic striction. ATP (500 μM) eliminated the relaxation phase of hyposmotic striction, and completely suppressed the development of isosmotic striction. Bumetanide did not affect the action of ATP during isosmotic striction, but restored the relaxation phase of hyposmotic striction. SITS and NA eliminated the effect of ATP on hypo- and isosmotic striction. Conclusions. The constrictive effect of ATP on the smooth muscle cells of the PA is associated with the activation of mechanisms of transmembrane Cl^– -redistribution, in which NKCC and Ca2⁺ -activated Cl^– channels are involved.

Objective. To assess the relationship between heart rate variability (HRV), blood pressure (BP) and heart function in patients with essential hypertension (EH) who are undergoing medical treatment (EH-1) and are simultaneously regularly involved in kinesitherapy (EH-2). Design and methods. In patients, blood pressure (BP) was measured and echocardiography was performed to determine the end-systolic and end-diastolic volume (ESV and EDV) of the left ventricle (LV), cardiac minute volume (CMV), stroke volume (SV) of the LV, left ventricular myocardial mass (LVM), LVM index (LVMI), post-systolic shortening (PSS), and ejection fraction (EF). To assess the characteristics of HRV, photoplethysmography (PPG) was applied. Information on the variability of the RR intervals was extracted from the pulse component of the PPG signal, and HRV indicators were calculated: HR — heart rate, LF — power in the Low Frequency range (sympathetic activity), HF — power in the High Frequency range (parasympathetic activity), LF/HF — general sympatho-vagal balance, CVI — cardiac vagal index, CSI — cardiac sympathetic index. Results. EH-1 patients have a negative relationship between LF and mean BP. In EH-2 women, positive relationships between LF and pulse BP, HF and systolic and pulse pressure were found. In patients with EH-1, there is a negative relationship between VLF and CMV, and CSI with LVMI. In patients with GB-2, there are positive correlations between SDNN and EDV, LF and EDV, SV and CMV, as well as LF/HF with EDV, SV and CMV, CSI and CVI with PSS. Conclusions. In women of the EH-1 group, there is an imbalance in the activity of the autonomic nervous system (ANS), while the activity of the sympathetic and parasympathetic sections of the ANS in patients with EH-2 is strictly balanced.

The aim of the study is to analyze the structure of acquisition of antihypertensive drugs in six regions of the Far East Federal District at the cost of a monthly course of therapy. Design and methods. The following indices were analyzed: level of the average per capita income, a living wage, morbidity of the population of Kamchatka Krai, Sakhalin Region, Republic of Saha, Jewish Autonomous Region, Republic of Buryatia, Zabaykalsky Krai. We analyzed data from 6 regions out of 11. We used the data from three regions with the largest and three regions with the lowest indicators of income of the population. We applied the intragroup marketing analysis of the pharmaceutical market (52 pharmaceutical organizations) based on defined daily doses (DDD) in quantitative and monetary equivalents, and the statistical analysis (descriptive statistics, intermediate results, dispersive analysis, coefficient of correlation of Spearmen, criteria Mann–Whitney). Results. Regions of the Far Eastern Federal District are characterized by differences in distribution of an indicator “income level / a living wage” from 3,3 to 1,7, to average in Russian Federation — 2,9. The highest rates of drug acquisition (over 40 %) was found in a segment with the cost of a 30-day course of therapy till 100 rubles at regions with the low income of the population, and over 35 % — in regions with high income. In total over 50 % packages of used drugs are within the range “till 300 rubles per monthly treatment”. Differences in quantitative and monetary value between two groups are not statistically significant. The highest sales in a money equivalent was in a segment of “100–300 rubles” in the regions with low level of income of the population and “500–1000 rubles” — in the regions with high income. The average cost of a 30-day course of antihypertensive therapy in regions varies from 350–450 rubles. Conclusions. The cost of a monthly course of antihypertensive therapy correlates with acquisition by patients of medicines in regions, both with low, and with high level of income of the population. Our data show the need for consideration of the patient’s expenses when prescribing the drugs and forming the assortment in the pharmaceutical organizations in regions of the Far Eastern Federal District.

As defined by the World health organization, a paramedic (from German feldscher) is a medical professional who provides various medical services, limited to emergency treatment and the practice of ambulance. In Russia, on the one hand, the need for a paramedic is minimal and not relevant in big cities, on the other hand, this profession is in demand in remote areas and in rural areas due to the shortage of doctors there. This contradiction can be resolved when training a paramedic in the framework of higher education at the bachelor’s level “General medicine”. The purpose of this work was to structure the qualification characteristics of a paramedic, for which we analyzed the international experience of training and assessing the professional qualifications of a paramedic, the work functions performed by a paramedic and a general practitioner and the prospects for the development of a paramedic’s competence, prepared within the framework of the educational program bachelor’s degree “General medicine”.