Aim. To assess the functional state of the sympathetic nervous system according to β-adrenergic reactivity of erythrocyte membranes (EM) in patients with refractory (rfHTN) and resistant hypertension (rHTN) in relation to target organ damage. Material and methods. The cross-sectional comparative study included 78 patients with uncontrolled hypertension (mean age, 57,4±9,3 years (33 men)) with 24-hour blood pressure (BP) (systolic/diastolic) of 160,0±18,8/88,1±17,3 mm Hg. Thirty-nine (50%) patients had type 2 diabetes (T2D). At baseline, patients were divided into 2 groups depending on the phenotype of uncontrolled hypertension. The first group consisted of patients with rfHTN (n=26 (33,3%)), the second — with rHTN (uncontrolled BP with 3-4 agent therapy) (n=52 (66,7%)). In all patients, office and mean 24-hour blood pressure, EM β-adrenergic reactivity and target organ damage were assessed. Results. The compared groups did not differ in sex and age composition, prevalence of T2D and basic clinical data. However, despite comparable levels of office and mean 24-hour blood pressure, the incidence of left ventricular (LV) hypertrophy according to echocardiography in rfHTN was significantly higher than in rHTN (96,2% vs 76,9%, p=0,027, respectively). An increase in EM β-adrenergic reactivity (>20 conventional units) was documented in 87,1% of patients in the general group. Moreover, the mean EM β-adrenergic reactivity in the rfHTN group was significantly higher than in the rHTN group (51,5±18,7 vs 39,3±18,2, p=0,008). According to ROC analysis, the threshold value of EM β-adrenergic reactivity corresponding to rfHTN was ≥44,8 conventional units (sensitivity — 69,2%, specificity — 64,5%, area under the ROC curve — 0,687). The mean EM β-adrenergic reactivity in the rfHTN group did not have a direct relationship with the LV mass index, but correlated with increased pulse pressure. Conclusion. RfHTN is associated with higher EM β-adrenergic reactivity values than in patients with rHTN, which may indirectly confirm more pronounced sympathetic activity and explain the higher prevalence of LVH, realized through an increase in vascular stiffness and load on the LV.

Arterial hypertension (AH) remains a global problem of modern healthcare, since, despite advances in clinical pharmacology and the use of modern antihypertensive drugs, it continues to be a major risk factor for cardiovascular complications. This necessitates a more in-depth study of the pathogenetic mechanisms of this disease and the development of new pathogenetically based methods of its treatment. Every year more and more studies are published, the results of which indicate the significant role of autonomic imbalance in the pathogenesis of the disease. The article presents the main modern data concerning the study of this problem. A detailed analysis of works devoted to the role of sympathetic hyperactivation in a sustained increase in blood pressure (BP) and the development of pharmacotherapy-resistant forms of hypertension (RAH) was carried out. Particular attention is paid to the influence of modern endovascular methods on changes in the severity of immunoinflammatory processes, through the activation of which the hypertensive effects of increased activity of the sympathetic nervous system are realized. Possible mechanisms of the therapeutic effectiveness of renal denervation and prospects for further clinical application of the method are described.

Aim. To study the features of regression of left ventricular hypertrophy and magnetic resonance changes of cardiac fibrosis in patients with resistant hypertension (RH) 1 year after renal denervation (RDN) in relation to changes in blood pressure (BP), the level of high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinases 2, 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1). Material and methods. The study included 42 patients with true RH. The mean age of the patients was 59 (51; 62) years, while half were men. All patients took 3 or more antihypertensive drugs. At baseline and after 12 months, creatinine, hsCRP, MMP-2, MMP-9, TIMP-1 were determined, as well as 24-hour blood pressure monitoring, assessment of left ventricular mass (LVM) and contrast agent accumulation according to cardiac MRI. RDN was performed using Symplicity Fleх (n=18) and Symplicity Spyral (n=24) catheters in accordance with the manufacturer's instructions. Results. A year after RDN, a significant antihypertensive effect and a decrease in heart rate were noted. Sixteen patients (38,1%) reached the target office BP level. After 1 year, a significant decrease in the levels of hsCRP from 2,05 (1,04; 3,28) to 1,64 (0,96; 2,25) mg/l (p=0,045) and MMP-2 from 278,2 (240,9; 353,4) to 265,2 (221,2; 293,2) ng/ml (p=0,018) was detected. There was a trend towards an increase in TIMP-1 and a decrease in MMP-9. According to MRI 1 year after RDN, there was a tendency to increase the contrast agent volume, and there was a pronounced LVM decrease from 228 (180; 295,2) to 204 (169,8; 277) g (p=0,029). Correlation analysis revealed a direct connection between a decrease in LVM and a decrease in SBP and DBP levels, MMP-2 and MMP-9 levels. There was a relationship between a decrease in the contrast agent volume and an increase in TIMP-1 level (r=-0,64; p=0,04). Conclusion. A year after RDN, patients with RH show regression of left ventricular hypertrophy with a pronounced antihypertensive effect and a decrease in collagen production, which could also be significant for suppressing the myocardial fibrosis.

Aim. To assess awareness of blood pressure (BP) level, adherence to therapy and achievement of target BP in residents of Russian regions as part of the 2023 hypertension (HTN) screening campaign. Material and methods. During May 2023, 4613 participants from 23 cities of Russia took part in the screening. Participation was voluntary without restrictions on sex. All patients aged over 18 years. During screening, BP and pulse were measured three times using automatic or mechanical BP monitors, and a questionnaire about behavioral risk factors, concomitant diseases and therapy was filled out. HTN was diagnosed with systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg and/or taking antihypertensive therapy (AHT). Results. The analysis included data from 4585 respondents aged 18 to 95 years with an average age of 45 [28;59] years, of which 1729 were men (37,7%). The proportion of hypertensive patients was 49,6%. Among them, 62,8% took AHT and achieved target BP in 76,6% and 45,7% with the target BP criterion <140/90 mm Hg and <130/80 mm Hg, respectively. Most patients took dual AHT (37,4%), while monotherapy and triple therapy was registered in 27,5% and 23,4%, respectively. Initiation of therapy was performed with combination AHT in 43,7% of patients with HTN and 41,4% are currently using fixed-dose combination therapy. On-demand therapy was the most common reason for skipping medications and was more common in women, while men more often cited the high drug cost and a history of adverse reactions. Among patients with HTN, home BP measurement was associated with a higher prevalence of achieving target BP as follows: 1000 (60%) vs 100 (17%), p<0,001. Conclusion. The data obtained indicate, on the one hand, a continuing insufficient level of awareness about high BP and the use of antihypertensive drugs among the population, but there is a tendency to improve the effectiveness of the treatment of hypertension, including the use of fixed-dose combinations of antihypertensive drugs.

Objective. To study possible correlations between the quantitative characteristics of fat depots in the abdominal and perirenal regions according to magnetic resonance imaging (MRI) data with metabolic and immunoinflammatory parameters, renal function, blood pressure (BP), as well as anthropometric data in patients with resistant hypertension (RH). Design and methods. Sixty-three patients (26 men) with RH aged 60 [54; 64] years who were receiving individual treatment with antihypertensive medication (mean, 4,3 ± 1,1 drug per day) were included in the study. Systolic/diastolic/pulse BP (SBP/DBP/PBP) was 157,7 ± 15,4 / 86,3 ± 13,6 / 71,3 ± 14,5 mm Hg. Mean body mass index (BMI) 34,1 [31,0; 38,5] kg/m2, waist circumference (WC) 108 [102; 113] cm (95,2 % with abdominal obesity). Diabetes mellitus type 2 suffered 51,6 %, chronic kidney disease C3–30,6 %. Clinical and laboratory examinations were performed. Creatinine level with estimated glomerular filtration rate (CKD-EPI), biomarker levels were assessed by ELISA. MRI was performed in a high-field tomograph with a magnetic field induction on 1,5 T. Mean parameter values in apparently healthy volunteers were considered normal. The area of visceral adipose tissue (S VAT) and subcutaneous adipose tissue (S SAT) was determined at the L4-L5 level (normal 123,5 [101,0; 169,0] and 216,5 [167,0; 287,0] cm2, respectively); kidney diameter — the anterior-posterior size of the kidney at the level of the renal vein (normal 5,0 [4,4; 5,4] cm); the thickness of perirenal adipose tissue (PRAT) as the difference between the distance between the sheets of Gerota’s fascia at the level of the renal vein and the diameter of the kidney (normal 1,2 [0,9; 2,4] cm); thickness of anterior subcutaneous adipose tissue (SATT) at the level of the umbilicus (normal 2,7 [1,8; 3,8] cm), the ratio of PRAT/SATT (normal 0,72 ± 0,61). Results. An increase was observed in all fat depots: S VAT 271,2 ± 104,4 cm2, S SAT 309,5 [236,0; 400,0] cm2, PRAT 2,7 [1,8; 3,9] cm, SATT 3,0 [2,3; 3,7] cm. Anthropometric parameters were associated with S VAT and S SAT. The thickness of PRAT correlated only with weight (r = 0,44) and WC (r = 0,41), whereas SATT correlated with BMI (r = 0,49). The PRAT/SATT ratio was not dependent on BMI. S VAT was associated with the level of PBP (r = 0,30). The following associations were observed with metainflammatory markers: TNF-α with S VAT (r = 0,31) and S SAT (r = 0,43) and with BMI (r = 0,32) and WC (r = 0,38); hsCRP with S SAT (r = 0,30), PRAT thickness (r = 0,34), and SATT (r = 0,34); leptin level correlated only with subcutaneous adipose tissue (S SAT, r = 0,60 and SATT, r = 0,69) and BMI (r = 0,51). Kidney size was 5,5 [5,0; 6,0] cm and was not associated with BMI. A decrease in kidney size was associated with a decrease in estimated glomerular filtration rate (r = 0,36). Glomerular filtration rate was associated with PRAT, as was creatinine (r = 0,43), which was also correlated with S VAT (r = 0,32). No correlations were found between renal function and anthropometric data. Conclusions. In patients with RH, there is an increase in the size of fat depots in the abdominal and perirenal regions according to MRI, which are closely related to anthropometric parameters and markers of inflammation. A direct correlation between the serum concentration of leptin and the size of subcutaneous adipose tissue has been established. An increase in the ratio of PRAT/SATT indicates an increase in the predominantly visceral component of adipose tissue and is associated with an increase in PBP, which reflects vascular stiffness. The decrease in the filtration function of the kidneys is correlated with an increase in the size of perirenal fat depots in the absence of direct links with dimensions of subcutaneous adipose tissue and anthropometric characteristics.

Aim. To evaluate the severity of coronary atherosclerosis and its association with biochemical markers of fibrosis in patients with coronary artery disease (CAD) and resistant hypertension (RHT). Material and methods . The study included 39 patients with CAD and RHT. All patients underwent 24-hour blood pressure (BP) monitoring, office BP numbers were measured. Laboratory diagnostics included routine tests, as well as determination of serum lipocalin, plasma concentration of matrix metalloproteinases 2 and 9 (­MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinases-1 (TIMP 1). Coronary atherosclerosis in patients was assessed retrospectively according to medical records with an assessment of the protocols of invasive coronary angiography and multislice computed tomography, performed no more than a year ago from the moment of inclusion in the study with no clinical signs of CAD progression. Obstructive atherosclerosis was considered a coronary artery narrowing by more than 50%. Results. Considering the results of previous coronary angiography, the patients were divided into two groups. In the first group (n=20), coronary artery stenosis was <50%, in the second (n=19) >50% (p<0,05). The compared groups of patients were comparable in sex, age, duration of hypertension, blood pressure level, and the number of antihypertensive drugs taken. There were no differences in blood lipid profile, basal glycemia, uric acid levels, and the frequency of previous cerebral accidents. However, the incidence of diabetes in group 2 was significantly higher (p<0,05). Additionally, there was a significant difference in serum levels of lipocalin and MMP-2 with higher values of these indicators in patients with coronary atherosclerosis stenosis (p=0,02). Conclusion. In patients with RHT with symptoms and signs of myocardial ische­­mia, the incidence of obstructive coronary atherosclerosis according to coronary angiography is 50%. Diabetes in this category of patients indicates a more frequent obstruction of coronary bed. An increase in the level of MMP-2 and lipocalin in this category of patients is associated with more severe coronary damage and can be considered as an indirect indicator of obstructive coronary atherosclerosis.

Aim. To study brain magnetic resonance imaging (MRI) changes in patients with resistant hypertension (HTN) after renal denervation (RD) and its cerebral protection effectiveness. Material and methods. The study included 111 patients, of whom 50 were men (45%) and 61 were women (55%), who underwent RD. The mean number of antihypertensive drugs taken regularly was 4,1±1,1. All patients underwent brain MRI and 24-hour ambulatory blood pressure monitoring before and after renal denervation. The data were statistically processed using Statistica 10,0 software. Results. After RD, a pronounced antihypertensive effect was observed with a significant reduction in systolic and diastolic blood pressure by 10,3/5,5 and 13,1/7,3 mm Hg at 6 and 12 months, respectively. Office blood pressure, daytime, and nighttime blood pressure levels also decreased (p<0,001). According to MRI data after RD, a decrease in the relative number of patients with I and II degree cerebrospinal fluid circulation changes and an increase in the proportion of patients without detected pathology were noted, but no significant difference in the obtained results was found. A decrease in the linear dimensions of brain ventricles was observed, including a reduction in the size of the left posterior horn of the lateral ventricle (p=0,03) and the third ventricle diameter (p=0,02) at 6 months after RD. At 12 months, the sizes of the anterior horn (p=0,04) and left lateral ventricle body (p=0,017) decreased. A positive effect of RD on the linear dimensions of cerebrospinal fluid system was noted, manifested by a decrease in the mean size of frontal subarachnoid spaces (p=0,028). No significant changes in the frequency and degree of focal lesions and lacunar infarcts were observed after RD (p>0,05). Conclusion. RD contributes to a significant decrease in blood pressure levels and exerts a cerebral protective effect by reducing lateral brain ventricles, subarachnoid spaces, and absence of ischemia progression and intracranial hypertension after intervention.

Hypertension remains the main risk factor of cardiovascular diseases despite the improvement of pharmacotherapy methods. This provides rationale for an in-depth study of pathogenetic mechanisms and development of new methods for the treatment of hypertension. There is increasingly more evidence for the essential role of immune-inflammatory disorders in the pathogenesis of hypertension. The article reviews the current state of knowledge on this problem. The authors provide a detailed analysis of the studies focusing on the role of abnormal factors of cellular immunity essentially associated with cell abilities to produce pro-inflammatory cytokines. Particular attention is paid to the effects of state-of-the-art methods of endovascular treatment on the changes in degree of severity of immune-inflammatory processes in patients with pharmacotherapy resistant form of hypertension. Possible mechanisms of the therapeutic action of renal denervation and the prospects for further clinical use of this method are discussed.

Aim To study renal hemodynamics in patients with resistant arterial hypertension (RAH) in combination with type 2 diabetes mellitus (DM2) and to identify factors involved in the increase in intrarenal vascular resistance.Material and methods This study included 59 patients (25 men) with RAH in combination with DM2. Mean age of patients was 60.3±7.9 years; 24-h blood pressure (24-BP) (systolic, diastolic, SBP/DBP) was 158.0±16.3 / 82.5±12.7 mm Hg during the treatment with 4.3 [4.0;5.0] antihypertensive drugs; glycated hemoglobin (HbA1c) was 7.5±1.5 %; estimated glomerular filtration rate (eGFR) was 73.1±21.8 ml/min / 1.73 m2 (CKD-EPI equation). Measurement of office BP, 24-h BP monitoring, renal artery (RA) Doppler, routine lab tests including determination of GFR (CKD-EPI), 24-h urine albumin excretion, and ELISA measurement of blood lipocalin-2, cystatin C, high-sensitive C-reactive protein (hsCRP), and asymmetric dimethylarginine (ADMA) were performed for all patients.Results Incidence of increased RA resistive index (RI) was 39% despite the high rate of vasodilator treatment (93% for renin-angiotensin-aldosterone system inhibitors, 78% for calcium antagonists). According to a correlation and regression analysis, RA RI values were correlated with the kidney function (r=-0.46, p<0.001 for eGFR, r=0.56; p=0.006 for lipocalin-2), age (r=0.54, p<0.001), increases in concentrations of hsCRP (r=0.35, p<0.001) and ADMA (r=0.39, p=0.028), the increase in vascular stiffness (r=0.59, p<0.001 for pulse BP (PBP) as well as DM2 duration, and HbA1c (r=0.33, p<0.001 for both). The independent association of RA RI with the age, PBP, and duration of DM2 was confirmed by the results of multivariate regression analysis. According to the ROC analysis, the threshold level of RA RI corresponding to a decrease in GFR <60 ml / min / 1.73 m2 was ≥0.693 conv. units.Conclusion In more than one third of patients with RAH in combination with DM2, increased renal vascular resistance was documented, which was closely associated with impaired kidney function, age, DM2 duration and severity, and markers of low-grade inflammation, endothelial dysfunction, and vascular stiffness. The value of RA RI ≥0.693 conv. units was a threshold for the development of chronic kidney disease (CKD).

Introduction. Patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) are characterized by sympathetic hyperactivity. A promising method for the assessment is a measurement of erythrocyte membrane beta-adrenergic reactivity (β-ARM). However, little is known about β-ARM in patients with RHTN and T2DM.Purpose. To investigate the properties of β-ARM of erythrocytes in patients with RHTN and T2DM in relation to clinical, laboratory, and instrumental data.Material and Methods. The cross-sectional study comprised 38 patients with RHTN combined with T2DM with mean age of 62.1 ± 7 years (25 women (65.8%)), 24-hour systolic/diastolic blood pressure (24-BP) (SBP/DBP) of 160.3 ± 14.2/90.8 ± 10.5 mm Hg, and glycated hemoglobin (HbA1c) of 7.2 ± 1.4%. The comparison group comprised 24 patients with RHTN without T2DM, which did not significantly differ in sex and age. General clinical examinations, measurements 24-BP and office blood pressure, β-ARM, HbA1c, 24-hour urine, echocardiography, and 24-hour electrocardiography with the assessment of heart rate variability (HRV) with low-frequency (LF) and high-frequency (HF) components were performed in all patients.Research Results. In both groups, β-ARM was significantly higher than the normal value corresponding to 20 conventional units (CU): 45.9 ± 21.9 and 41.3 ± 18.9 for patients with RHTN+T2DM and RHTN without T2DM, respectively, p = 0.39. The incidence of increase in β-ARM was comparable: 82% in RHTN with T2DM patients and 88% in RHTN without T2DM patients, χ2 = 0.38, p = 0.537. The β-ARM values correlated with duration of hypertension (R = 0.31), SBP-24 variability (R = 0.36), LF (R = 0.60), and HF (R = –0.53)) values according to HRV, 24-hour urine volume (R = –0.32), left ventricular parameters (ejection fraction (R = 0.42), ventricular efficiency (R = –0.36), arterioventricular coupling (R = –0.40)), duration of T2DM (R = –0.45), and HbA1c level (R = –0.55).Conclusions. RHTN patients were characterized by a high frequency of β-ARM increase, whether or not T2DM was present, although a long and severe course of T2DM was associated with lower values of this indicator. According to the data from instrumental studies, β-ARM in patients with RHTN and T2DM was quantitatively related to the markers of sympathetic activity, which correlated with the duration of hypertension and parameters of renal and left ventricular functional status.

Objective. To assess the changes in subclinical MRI signs of brain damage in relationship with the changes in blood pressure, proinflammatory cytokines, and endothelial function one year after renal denervation (RDN) in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM).Material and Methods. The prospective interventional study (ClinicalTrials.gov identifiers NCT02667912 and NCT01499810) analyzed qualitative brain MRI imaging data from 39 patients with RHTN and T2DM. All patients underwent 24-h ambulatory blood pressure monitoring (ABPM), brain MRI scan (1.5 T), blood tests for high-sensitivity C-reactive protein (hsCRP), and brachial artery flow-mediated dilation (FMD) measurements by high-resolution ultrasound. Patients were taking an average of 4.5 (3–6) antihypertensive drugs and were instructed not to change the therapy regimen throughout the study. A total of 29 patients completed the one-year follow-up.Results. A significant decrease in average daily systolic/diastolic blood pressure by 12 [95% CI 4.1; 19.8]/5.9 [95% CI 0.4; 11.3] mmHg (p = 0.004/0.038) according to 24-h ABPM, increase in FMD (p = 0.008), and a decrease in hsCRP level (p = 0.04) were observed one year after RHTN. Over half of patients (57%) had a decrease in 24-h systolic blood pressure by ≥ 10 mm Hg; target level of blood pressure was achieved in 38% patients. No changes in the MRI signs of brain damage (linear dimensions of liquor systems, white matter lesions [WMLs], brain damage MRI score, and intensity of MRI signal from the basal nuclei and WMLs) were observed except for a decrease in the severity of liquorodynamic disturbances. Reduction or stabilization of WML degree was observed in 24 patients (86%). No relationships were found between the dynamics of WMLs and the changes in blood pressure, FMD, and hsCRP.Conclusion. Administration of RDN to patients with RHTN and T2DM allowed to limit the WMLs in most cases and reduce the severity of liquorodynamic disorders during one-year of follow up.