We review main issues of early diagnostics of kidney damage in patients with essential hypertension. The remodeling of renal vessels and the underlying mechanisms are discussed. The evidence-based data are reviewed to substantiate the use of laboratory methods for the kidney damage diagnostics (calculation of glomerular fltration rate and microalbuminuria). We discuss the role of Doppler methods in the assessment of intrarenal hemodynamics (the resistance index and blood flow acceleration time) for timely detection of changes in renal vessels and the choice of management strategy.

The review analyzes the structure of cardiovascular risk factors in patients with hypertension in Mongolia. According to the WHO data from 2014 the prevalence of hypertension in Mongolia is high among men and above medium level among women. In adults (≥ 18 years old), the prevalence of hypertension constituted 28,7% (25,8 % among men and 22,9 % among women), and when adjusted for age it achieved 31,8% (34,8% and 28,8 %, respectively). The most important modifable (non-nutritious food, low physical activity, smoking, alcohol abuse, obesity, hyperglycemia) and non-modifable risk factors of cardiovascular diseases are considered. We perform a comparative analysis of the Mongolian data with the data of the World Health Organization, the Russian Federation and other countries.

Histology studies fnd organized thrombi in small pulmonary arteries in 57% patients with idiopathic pulmonary arterial hypertension (PAH). This evidence justifed a rationale for the widespread use of oral anticoagulants (OAK) in patients with PAH of various etiologies. In recent years, the concept of OAK therapy in PAH patients has changed due to the novel data from clinical retrospective and prospective studies involving patients with PAH of various etiologies who have received anticoagulants. The present review discusses possible risk factors for thrombosis and bleeding in patients with PAH, indications, effcacy, and safety of OAK therapy in diverse PAH etiologies.

Objective. To evaluate the plasma levels of metalloproteinases (MMP) and their inhibitor in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (DM2) and their relationship with renal blood flow and kidney function.

Design and methods. The study included 18 patients with RHTN and DM2 and 16 individuals with RHTN without DM, who underwent offce and 24-h ambulatory blood pressure measurements, renal Doppler ultrasound, and laboratory tests (daily albuminuria, estimated glomerular fltration rate calculated by CKD-EPI formula, HbА1c and basal glycaemia levels, MMP-9, MMP-2, tissue inhibitor of MMP type 1 (TIMP1), MMP/TIMP-1 ratios).

Results. Patients with RHTN and DM2 and subjects with RHTN without DM were comparable by mean levels of metalloproteinases, TIMP-1, and their ratios. The frequency of increased MMP-9 level was similar in both groups (61 % for RHTN + DM2 group and 75 % for RHTN without DM, p > 0,05). In patients with RHTN and DM2 the increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio were associated with a reduction in renal resistive indices (MMP-9 and RI in the main renal arteries: right-sided R = –0,60, p = 0,009, left-sided R = –0,60, p = 0,008; in segmental arteries: R = –0,49, p = 0,038 on the right and R = –0,59, p = 0,012 on the left; for TIMP-1/MMP-9 and segmental arteries: R = 0,51, p = 0,028 on the right; and R = 0,46, p = 0,04 on the left). The eGFR and MMP-9 signifcantly correlated (R = 0,55, p = 0,023). Patients with increased albuminuria showed higher values of TIMP-1/MMP-2 ratio than patients with normal albuminuria (2,97 ± 0,82 и 1,58 ± 0,33 ng/mL, respectively, p = 0,03). There was a direct correlation between TIMP-1/MMP-2 ratio and basal glycaemia (R = 0,59, p = 0,018).

Conclusions. Patients with RHTN and DM2 had comparable MMP levels and their inhibitor to those in patients with RHTN without DM, which may partly reflect that extracellular matrix formation is independent from carbohydrate disorders in RHTN. In patients with RHTN and DM2 an increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio may be adaptive, since it is accompanied by improved intrarenal blood flow and renal fltration function. The increase in basal hyperglycemia is associated with the suppression of the proteolytic activity of MMP-2 related to the progression of albuminuria.

Background. The high prevalence of cardiac damage in resistant hypertensive patients signifcantly increases the risk of cardiovascular complications. Despite the antihypertensive effcacy of renal denervation (RDN), the cardioprotective effect has not been suffciently studied.

Objective. To study the changes in left ventricular mass (LVM) and volume of myocardial damage after the RDN and to detect a possible connection of the studied parameters with blood pressure (BP) reduction after RDN.

Design and methods. RDN was applied to 84 patients with resistant hypertension. Initially, at 6 and 12 months after treatment, patients underwent the measurements of the “offce” BP, 24-h BP, echocardiography and cardiac contrast-enhanced magnet-resistance tomography.

Results. At baseline, “offce” BP averaged 175,3 ± 22,1 / 100,4 ± 16,1 mmHg and the prevalence of left ventricular hypertrophy (LVH) was 84,5 %. “Offce” BP reduced signifcantly at 6 month by –27,5 (–74,0; 12,0) / –14,2 (–39,4; 10,3) mmHg (p < 0,001), at 12 month by –31,6 (–78,7; 8,3) / –15,5 (–43,3; 10,2) mmHg (p < 0,001). 24-h BP reduced signifcantly at 6 month by –13,0 (–45,2; 17,6) / –6 (–27,8; 8,9) mmHg (p < 0,001), at 12 month by –14,3 (–52; 25) / –7,3 (–26; 15,0) mmHg (p < 0,001). At 12 month after RDN LVM decreased by 6,9% (p = 0,015), LV mass index by 5,5 % (p = 0,020). According to MR study, subendocardial damage was detected in 100% of patients in the absence of coronary atherosclerosis. A volume of subendocardial damage signifcantly reduced by 29 % at 6 month (p = 0,031) and by 41,4% at 12 months after RDN (p = 0.008). LVM reduced signifcantly by 18,3 % (р = 0,008). LVM also reduced signifcantly in non-responder’s group at 6 month after RDN (р = 0,046). The regression of subendocardial damage correlated with the change in systolic BP at 12 months after RDN (р = 0,034). There was no signifcant correlation between LVH regression and baseline BP and its change after RDN.

Conclusions. One year after RDN, LVH decreased independently from the BP change. Subendocardial damage was detected in 100% patients, regressed at 6 months after RDN and correlated with the regression of systolic BP at 12 month after the RDN.

Objective. To study the association of polymorphic loci rs243865 MMP2, rs17577 MMP9, rs652438 MMP12 with the development of arterial hypertension (HTN) in women of the Central Chernozem Region of Russia.

Design and methods.A total of 584 women were examined: 375 HTN patients and 209 controls. Analysis of the polymorphic loci of metallоproteinases was performed using real-time polymerase-chain reaction (PСR). Statistical analysis was carried оut using software “STATISTICA for Windows 10.0”. The prediсtive value of the non-synоnymous single nucleotide polymorphism (SNP) wаs estimatеd using the Sorting Tolerant From Intоlerant software (http://sift.jcvi.org/). The regulatorу potential of polymоrphic loci was analyzеd in the HaplоReg software (v4.1) (http://archive.brоаdinstitute.оrg). The effect of SNP on gene expression was studied using thе data of the Genоtype-Tissue Expressiоn project (http://www.gtexportal.оrg/).

Results. We found an association of the locus rs652438 MMP12 with the occurrence of HTN in women. Polymorphic variant G (odds ratio (OR) = 1,86, 95 % confdence interval (CI) = 1,02–3,45, p = 0,04) and genotype GA (OR = 2,04, 95 % CI = 1,06–3,98, p = 0,03) of rs652438 are associated with the high risk of HTN development. The genotype AA rs652438 demonstrates a protective effect regarding the risk of HTN occurrence (OR = 0,50, 95% CI = 0,26–0,95, p = 0,03). We assume that the epigenetic effects of rs652438 MMP12 underlie the identifed associations. The locus rs652438 MMP12 is nsSNP and has a SIFT Score = 0,01. This polymоrphism is lоcated in histоnes regiоn marking prоmoters (H3K9 ас) and enhаncers (H3K4me1, H3K27 ас). The locus is in linkage disequilibrium (r 2 = 0,95) with SNP that affect the expression level of the MMP12 gene

Objective. The purpose of our study was to research specifc features the daily changes of the vascular stiffness (VS) in patients with end-stage renal disease (ESRD) and to assess the feasibility of using the 24-hour vascular index Pulse Time Index of Norm (PTIN) (the percentage of the 24-hour period during which the pulse wave velocity (PWVao) does not exceed 10 m/second) in the management of arterial hypertension (HTN) in patients after renal transplantation (RT).

Design and methods. We examined 158 people, divided into 4 comparable age groups: those receiving program hemodialysis (PGD), patients after RT, patients with essential HTN and healthy volunteers. All of them underwent 24-hour blood pressure (BP) monitoring with a daily evaluation of VS indices and central BP. At follow-up, 27 patients from the PG group underwent all assessments also 1 week and 6 months after transplantation.

Results. Patients with ESRD compared with patients with essential HTN had elevated PWVao, night central BP and decrease PTIN. PTIN changes were the most signifcant. In 27 patients a week after the RT a decrease in the PTIN was found in most cases. After 6 months the mean PTIN in the whole group increased again. Our study demonstrates HTN persistence after kidney transplantation can be predicted. Two PTIN states could be predicted by the cutoff PTIN value that was determined in the study: a state of improvement and a state of decline/unchanged state. PTIN cutoff value at 45 % was characterized by 69 % sensitivity, 76 % specifcity and AUC of 0,65. Therefore, baseline PTIN ≥ 45 % (before RT) is associated with its further growth, and a favourable course of HTN.

Conclusions. Patients receiving replacement therapy, compared to patients with essential HTN, showed a marked increase in the daily VS and the night central BP. The daily PTIN is the most accurate predictor of the changes in the VS index, the PTIN values before the RT at the PG stage allow predicting the course of HTN after the RT

Background. Hypertension (HTN) is associated with impaired skin microcirculation. Laser Doppler flowmetry is an objective, quantitative, instrumental method that allows evaluating skin microcirculation. However, the method was not widely used clinically due to high variability of perfusion and small difference between healthy people and HTN patients and, as a consequence, low diagnostic signifcance.

Objective. To provide the grounds for the approaches increasing the informative value of skin microcirculation measurement by laser Doppler flowmetry in HTN patients.

Design and methods. The study involved HTN patients (n = 13, the median age was 60 (49; 63) years) and young otherwise healthy volunteers without HTN (n = 12, the median age 26 (25; 27) years). Microcirculation measurement was performed by laser Doppler flowmetry using LAKK-02 device. Registration of microcirculation on the forearm skin was carried out during the occlusionheating test. The Mann-Whitney test was used to compare the parameters in two groups. The diagnostic accuracy of the method for the inverse classifcation of the subjects was evaluated using ROC analysis.

Results. In HTN patients, the median baseline perfusion was 3,1 (1,84; 4,31) perfusion units (PU), in healthy volunteers — 4,29 (3,66; 8,14) PU (p = 0,04). The median area under the microcirculation curve for the frst 2 minutes of heating in HTN patients was 1206,7 (813; 1449) PU × s, in healthy volunteers — 1552,3 (1310; 1624) PU × s (p = 0,035). In healthy volunteers, the heating increased the perfusion by 596 % (386%; 878%), and in HTN patients perfusion increased only by 265% (180 %; 318%) (p = 0,01). The relative increase in perfusion during postocclusion hyperemia with continued heating compared with the baseline in healthy volunteers was 651% (493 %; 999%), and in HTN patients — 302 % (182 %; 436%) (p = 0,005). Thus, when comparing the average parameters for each period in the occlusion-heating test, only basic perfusion showed signifcant differences. However, when changed from absolute to relative parameters (the increase in microcirculation in relation to the vasodilating effects), the difference was signifcant. Moreover, sensitivity achieved was 75 % and specifcity — 84,6% (the inverse classifcation of groups).

Conclusions. The physiological (the local heating of the forearm skin at a rate of 2 degrees Celsius per second, a combination of vasodilating effects) and mathematical (the transition from absolute to relative values) approaches provided an increase of the informative value of the laser Doppler flowmetry, as well as its sensitivity and specifcity.

Objective. To compare the cardioprotective effcacy of a preservation solution based on Krebs–Henseleit buffer and HTK solution in the model of heterotopic heart transplantation in rat.

Design and methods. A study was conducted on 12 Wistar rats. The animals were divided into groups depending on the preservation solution used: 1) Krebs–Henseleit buffer-based solution (n = 7), 2) HTK (n = 5). Each experiment consisted of collecting donor heart, preserving it with an appropriate cardioplegic solution, heterotopic transplantation into a recipient rat followed by explantation and evaluation of left ventricular contractility using the Langendorff model and histochemical assessment of the irreversible myocardial damage. Coronary blood flow in the donor heart was assessed in vivo using ultrasound doppler flowmetry. After 3 hours, the donor heart was explanted and connected to the Langendorff apparatus to assess left ventricular contractility, and the myocardium was subjected to histochemical staining with 1 % triphenyltetrazolium chloride for the assessment of the irreversible myocardial damage.

Results. In the group of Krebs–Henseleit buffer-based cardioplegic solution, 7 experiments were performed. Myocardial infarct size was 3,5 ± 1,2%, the coronary flow rate was 4,5 ± 1,3 ml/min, and the developed left ventricular pressure of the donor heart was 70 ± 6,3 mmHg at diastolic left ventricular pressure of 10 mmHg. In the HTK solution group (n = 5), in all of the experiments after the start of blood flow, the transplanted heart did not begin to contract, and all 5 hearts remained in an asystole state. Therefore, after the end of the 3-hour reperfusion period, the assessment of the contractility of the left ventricle using the Langendorff apparatus was not carried out. Coronary flow rate was only 0,4 ± 0,1 ml/min, probably resulting from inadequate cardioprotection with HTK solution. Due to the lack of adequate reperfusion, the accurate assessment of the irreversible myocardial damage was impossible in the HTK solution group.

Conclusions. The technique of heterotopic heart transplantation in rats is adequate and informative for the study of ischemia-reperfusion myocardial damage as well as for the study of the effectiveness of cardioplegic and cardiac preservation solutions. Cardioplegic solution based on Krebs– Henseleit buffer demonstrated greater cardioprotective effectiveness in our model compared to HTK solution.

Objective. To assess the clinical signifcance of auscultatory gap (AG) found by the 24-hour ambulatory blood pressure monitoring (ABPM) using the Korotkoff’s sounds (KS) and its potential causes.

Design and methods. 24-hour ABPM was performed in 60 patients (mean age 51,3 years, range 22–85 years), including 24 women and 36 men. In 24 patients, hypertension was diagnosed. In total, 2333 blood pressure (BP) measurements without “noise contamination” were selected for subsequent analysis (38,9 measurements per patient; from 28 to 73 measurements). The simultaneous recording of electrocardiogram (ECG), brachial cuff pressure, and KS phonograms on the right hand, as well as continuous recording of non-invasive BP curve in the left fnger using the volume clamp technique were performed in 10 patients with AG.

Results. Based on the 24-hour ABPM, AG was shown in 43 of 60 subjects (71,7%). The AG was found to be associated with a decreased amplitude of fluctuations of the cuff pressure; upon its termination, the amplitude recovered. The above synchrony of changes in KS and amplitude of pressure fluctuations was found in all 124 cases which demonstrated AG during BP measurement. We assume that AG is a true variation of BP rather than a feature of KS, as the fluctuation amplitude depends on the ratio of BP and cuff pressure but does not depend on the KS phase. To test the hypothesis, the cuff pressure and KS were compared to the continuously monitored arterial pressure. When the systolic arterial pressure exceeded the cuff pressure, the KS appeared. Later on, the BP fluctuations led to a decrease in systolic BP; the arterial pressure did not reach the cuff pressure and, therefore, KS were not recorded. Subsequent decrease in the cuff pressure led to re-appearance of KS.

Conclusions. The auscultative gap phenomenon is associated with true (mostly respiratory) variations of systolic BP rather than with features of KS in individual patients. The initial and repetitive KS occur at certain systolic BP levels depensing on the BP respiratory fluctuations and may indirectly indicate the amplitude of fluctuations.

Objective. We performed a cross-sectional study of risk factors and biomarkers of cardiovascular diseases among young women with hypertensive disorders during pregnancy in comparison with women without hypertension during pregnancy.

Design and methods. Altogether 117 women were enrolled, 33 were included in the group of hypertensive disorders during pregnancy, and 44 formed the group without hypertension during pregnancy. The control group consisted of 40 patients. The time interval after delivery was on average 5 to 19 years.

Results and conclusions. Women with hypertension during pregnancy developed changes in carbohydrate and lipid metabolism associated with hypertension and abdominal obesity, which are the components of the cluster of the metabolic syndrome. These changes are also accompanied by insulin resistance, hyperinsulinemia, adipokine imbalance, changes in fbrinolysis and more pronounced remodeling of the heart and vessels as target organs in hypertension.

The problem of arterial hypertension (HTN) in pregnant women is very important due to its high prevalence and severity of consequences for the mother and fetus. In Russia, hypertension is diagnosed in 5–30% pregnant women, with the increasing trend in the past decades. HTN is a risk factor for complications, both for the mother, the fetus and newborn, so HTN remains the leading cause of maternal, fetal and neonatal mortality. HTN in pregnant women is a signifcant predictor of cardiovascular disease in the future. It is also a social problem considering the increase in the cost of treatment, i.e. related to the repeated hospitalizations after childbirth. In 2018, new European recommendations on cardiovascular diseases during pregnancy and European recommendations on HTN (the latter ones include special sections devoted to hypertension in pregnant women) were published. These recommendations provide the latest data on the classifcation, diagnosis and treatment of HTN in pregnant women. Currently, methyldopa is still the frst-line drug for the treatment of HTN in pregnant women, which has proved to be an effective and safe medication in pregnant women.