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ObjectiveTo investigate the sex differences in the efficacy of renal denervation (RDN) in patients with resistant hypertension (RHT) concerning the size of abdominal fat depots, changes in biomarkers of sympathetic activity, and renal function.Materials and methods24 men (56.5 ± 7.8 years) and 33 women (59.5 ± 8.4 years) with RHT were enrolled in the study and underwent RDN. 24-h ambulatory blood pressure (BP) [systolic/diastolic (SBP/DBP)], serum creatinine (with eGFR calculation), serum adipocytokines (leptin, adiponectin, resistin), serum metanephrines and normetanephrines were measured baseline and 12 months after RDN. The size of subcutaneous, visceral, and perirenal adipose tissue (SAT, VAT, and PRAT) was assessed using MRI.ResultsAfter RDN, BP decreased, leptin increased, and adiponectin, resistin, and metanephrine levels did not change in both sexes. There was a decrease in normetanephrine levels in women and a similar trend in men. In men, the eGFR did not change. In women, the eGFR remained unchanged only in those with chronic kidney disease (CKD) (n = 10) and decreased in the absence of CKD (n = 23) from 79.7 ± 14.1 to 72.1 ± 12.0 ml/min/1.73 m2 (p = 0.011). Men had larger visceral fat depots, and women had larger subcutaneous fat depots. After RDN, the size of adipose tissue in men remained unchanged, and in women, the PRAT thickness decreased from 2.36 ± 1.23 to 2.10 ± 1.17 cm (p = 0.002). Lowering BP in women was associated with increased leptin levels after RDN (r = −0.47 for SBP, r = −0.48 for DBP). Dependence of BP reduction on baseline eGFR was observed in men only [r = 0.44 for SBP, r = 0.48 for pulse pressure (PP)]. Additionally, in men, the decrease in SBP and PP depended on VAT areas (r = −0.44 and r = −0.58, respectively). In women, the SBP reduction showed an inverse correlation between baseline weight (r = −0.35) and waist circumference (r = −0.38).ConclusionsThe magnitude of the antihypertensive effect of RDN depends on signs of visceral obesity and, in men, also on the presence of CKD. Renoprotective effects of RDN in men are obtained regardless of the initial kidney function, while in women, it was observed only in individuals with CKD. Additional beneficial effects of RDN in women include a decrease in normetanephrine levels and a reduction in PRAT size.

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.

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 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 (p0,05).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.

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% (p

BACKGROUND: Diabetes mellitus (DM) and hypertension are risk factors for cerebral stroke, which are exacerbated by the combination of these diseases. Identifying the factors involved in the development of subclinical brain damage could change the therapeutic strategy for protecting the brain.AIM: to study severity of MRI- sings of brain damage and to identify factors associated with their development in patients with type 2 diabetes and RHTN.MATERIALS AND METHODS: 46 patients with type 2 DM and RHTN were included in a single-center observational uncontrolled study. Patients underwent brain MRI (1.5 Tesla) with calculation of Evans’s index (EI), clinical and lab examinations (HbA1c, glucose, insulin, C-peptide, leptin, resistin, TNF- α, hsCRP, blood aldosterone, insulin-like growth factor-1 (IGF-1)), measurement of the office and ambulatory blood pressure (BP), assessment of peripheral and cerebral vasoreactivity (test with hyperventilation and breath holding).RESULTS: The most frequent MR brain changes were white matter lesions (WML) in periventricular region (PVR) (89%), focal WML (52%) and expansion both of the ventricles (45%) and subarachnoid spaces (65%). Multiple direct correlations were revealed between parameters of carbohydrate metabolism with the degree of WML in PVR and the density of the MR-signal in the basal nucleus (BN), as well as with EI. Adipokines had a direct relationship with the size of the chiasmatic cistern and IE (for resistin), as well as with the density of the MR signal from the BN and IE (for leptin), that was also directly related to the IGF-1 level. The aldosterone level positively correlated with the size of III ventricle. An increase in TNF-α and hsCRP was accompanied by an increase in the density of the MR-signal in the PVR. Impairment of cerebrovascular reactivity is associated with an increase in the density of the MR-signal in PVR and with indirect signs of cerebral atrophy (increase in EI, the size of cisterns and lateral ventricles). Impairment of peripheral vasoreactivity had direct relationship with EI and the expansion of the III ventricle. There were no direct correlations between the severity of MR-sings of brain damage and BP levels.CONCLUSION: The combination of type 2 DM with RHTN is characterized by a high frequency of WML and liquorodynamics disturbances, which related with metabolic, neurohormonal and hemodynamic factors in the absence of a direct relationship with the degree of BP increase

Aim. To determine the prevalence of refractory hypertension (RfH) in patients with and without type 2 diabetes mellitus (DM), as well as to evaluate whether diabetic patients with RfH significant differ from those with uncontrolled resistant hypertension (RH) in clinical phenotype, metabolic profile and endothelial function. Materials and methods. The study included 193 patients with RH: RH 74 patients with diabetes and 119 patients without DM. Uncontrolled RH and RfH were defined by the presence of uncontrolled blood pressure BP (140 and/or 90 mm Hg) despite the use of 3 but 5 antihypertensive drugs (for RH) and 5 antihypertensive drugs, including a mineralocorticoid receptor antagonist (for RfH). Clinical examination, lab tests were performed. Flow-mediated dilation (FMD) and vasoreactivity of middle cerebral artery (MCA) using both breath-holding and hyperventilation test were measured by high-resolution ultrasound. Results. The prevalence of refractory hypertension in patients with and without DM was similar (30% vs 28%, respectively). No differences in BP levels, data of echocardiography and clinical phenotype were found between the diabetic groups, but value of HOMA index, plasma resistin level and postprandial glycaemia were higher in patients with RfH. FMD and MCA reactivity to the breath-holding test were worse in patients with RfH, and they had a more pronounced vasoconstrictor response of MCA to the hyperventilation test compared to patients with RH. Conclusion. The prevalence of RfH is the same in patients with and without diabetes. Diabetic patients with refractory hypertension have a more unfavorable metabolic profile and greater impairment of endothelial function than patients with uncontrolled resistant hypertension.

Aim. To study the long-term outcomes of renal denervation (RDN) within 3-year follow-up with an assessment of blood pressure (BP) changes, the severity of target organ damage and the levels of pro- and anti-inflammatory cytokines in patients with resistant hypertension (RH), taking into account sex characteristics.Material and methods. A total of 42 patients with RH were examined at baseline, 1, 2, and 3 years after RDN on the background of antihypertensive therapy. Twenty-four-hour BP monitoring, echocardiography, assessment of creatinine level and estimated glomerular filtration rate (eGFR), as well as determination of some cytokines (interleukin (IL)-1β, 6, 10, tumor necrosis factor-α) were performed.Results. There was a persistent BP decrease in men and women for three years compared with the initial level by an average of 17 [4; 31]/10 [0; 18] mm Hg (p0,05), IL-10 — from 5,8 [3,2; 8,2] to 2,8 [2,6; 2,9] pg/ml (p=0,000), correlating with IL-6 dynamics.Conclusion. Three years after RDN, there is a persistent decrease in mean 24-hour BP, regardless of sex. In women, a more pronounced BP variability decrease is observed, while in men — regression of left ventricular mass. There is no significant decrease in eGFR in the long-term period. The decrease in proinflammatory cytokines maintains, and in some cases becomes more pronounced within three years after RDN.

Aim. To study the long-term effect of renal denervation (RDN) on left ventricular mass (LVM) and inflammatory markers in resistant hypertensive patients.Material and methods. Forty-one patients with resistant hypertension and 24-h blood pressure (BP) 158,7±15,8/87,3+14,6 mmHg, aged 56,6+10,2 years, were enrolled in the study and undergone RDN. Mean 24-h BP, left ventricular mass (transthoracic echocardiography), high sensitivity C-reactive protein (hsCRP), interleukin- 1β (IL­1β), IL-6, IL-10) and tumor necrosis factor alpha (TNF- α) were assessed at baseline and 2 years after the RDN.Results. A baseline prevalence of left ventricular hypertrophy (LVH) was 90,2%. Two years after RDN LVM and interventricular septum (IVS) decreased significantly (p0 g) was documented in 24 patients. The regression of LVM was accompanied by a significant decrease in levels of inflammatory markers — hsCRP by 38,3% (p=0,031), TNF-α by 60,7% (p=0,009), IL- 1β — by 71,1% (p=0,001), and IL-10 by 58,2% (p=0,001). In patients in the absence of LVM regression only TNF-α decreased significantly (-68,8%, p=0,001). There was no correlation between changes of LVM and the inflammatory markers at 24 months after RDN.Conclusion. The RDN in RH patients may have long-term cardioprotective effect in terms of significant regress of LVH, which may be partly attributed to the regress in systemic or myocardial inflammation.

Aim. To compare cardioprotective effects of two renal denervation (RD) techniques: main renal artery or its branches after bifurcation in patients with resistant hypertension (RH).Materials and methods. This randomized double-blind clinical (ClinicalTrials. gov. identifier: NCT02667912) study with a follow-up of 12,3±1,6 months included 55 patients with RH, which was divided into 2 groups: group 1 (n=27) — main renal artery denervation; group 2 — RD of branches. Mean age of patients was 57,3±9,5 and 56,4±9,3 years, respectively. We assessed structural and functional cardiac characteristics using two-dimensional speckle-tracking echocardiography (STE).Results. Initially, the patients in the groups did not differ in terms of studied parameters and therapy. After RD in both groups, the levels of myocardial stress significantly decreased; 95% confidence interval: after main renal artery denervation — systolic [-4802; -2896], diastolic [-3264; -2032] dyne/cm2; after RD of branches — [-6324; -5328] and [-4021; -2521] dyne/cm2, respectively (p=0,001 and 0,024, respectively). After main renal artery denervation, there was a decrease in the left ventricular (LV) wall thickness (interventricular septum [1,06; -0,62] and posterior wall [0,12; -0,62]) in comparison with RD of branches ([-0,68; -1,28] and [-0,68; -1,06], respectively). These differences were significant: p=0,023 and 0,021, respectively. After distal RD, decrease in the LV mass was observed more often by 21,2%, an increase in the LV mass was 2 times less frequent. Restoration of diastolic function was more common in patients after distal RD than main renal artery denervation (26% vs 13%, respectively). According to pilot analysis, STE parameters was also improved.Conclusion. Twelve months after distal RD, compared with the main renal artery denervation, the LV wall thickness, number of patients with LV hypertro -phy, and diastolic dysfunction decreased significantly greater. Two-dimensional STE revealed improvement of cardiac parameters. The results require further research.

Aim. To study the effectiveness of using the anatomically optimized distal renal denervation (RDN) in comparison with the standard approach for reducing myocardial damage and left ventricular (LV) hypertrophy in patients with resistant hypertension (HTN).Material and methods. The randomized double-blind study of the efficacy and safety of distal RDN compared to conventional main renal artery intervention (ClinicalTrials.gov NCT02667912) for the treatment of resistant HTN included 26 patients. All patients were divided into two groups: group 1 (n=16) — distal RDN, group 2 (n=10) — conventional RDN. In addition to 24-hour blood pressure (BP) monitoring, initially and 12 months after the intervention, contrast- enhanced cardiac magnetic resonance imaging was performed to determine the left ventricular mass and non-coronary myocardial damage area. All patients signed informed consent. Twenty-four patients completed the present study.Results. After 12 months, the mean 24-hour BP significantly decreased after both distal RDN (from 167,2±28,5/93,2±19,3 to 147,0±13,7/81,5±9,3 mm Hg (p

Aim. To define and develop a procedure that can select patients with resistant hypertension (RH) for a renal sympathetic denervation (RSD) procedure, by being orienting to the specific initial values of β-adrenoreactivity (β-AR) and systolic blood pressure (SBP). Subjects and methods. The analysis included 23 RH patients receiving the maximally tolerable doses of 4 antihypertensive drugs. The investigations involving BP control and a Russian spectrophotometric procedure for determining β-AR in terms of the change in the osmoresistance of erythrocyte membranes (EM) were performed at baseline and 4 and 24 weeks. RSD was carried out using endovascular radiofrequency ablation of the renal arteries. The therapy was not changed during the observation. Results. If SBP was >170 mm Hg and β-AR of EM >40 conditional units (CUs) at baseline, ΔSBP was 17.68±3.24 mm Hg and the efficiency of RSD was 100%. When SBP was

Aim. To study the relationship of 24-hour BP patterns in patients with AH resistant to drug treatment and structural-functional changes in heart before and after sympathetic denervation of the kidneys.Material and methods. The study included 53 patients (25 women and 28 men) with a diagnosis of II stage hypertension, resistant to drug therapy. Mean quantity of continuous drug compounds taking is 4,09±1,16. baseline office SBP for all patients — 176,3±19,9 mmHg, by ABPM — 158,2±14,5 mmHg, left ventricle myocardium mass (LVMM) — 275,3±91,9 g. All patients under the informed consent conditions underwent renal denervation with endovascular catheter. We analyzed the data from 46 patients (87%), studied in 6 months after ablation. All patients before and after the procedure underwent 24-hour BP monitoring and echocardiography Results. Depending on the grade of hypotensive effect after denervation all patients were divided into groups of responders (35 persons), non-responders (11 patients). In responders we found higher level of office SBP and DBP at baseline as variability of BP. In 6 months after ablation variability of SBP and DBP, level of mean daily SBP and DBP, and office values of SBP and DBP were significantly higher than in non-responders. Comparing ABPM parameters with the patterns of echocardiographic changes of the heart there were no significant differences between the groups of responders and non-responders.Conclusion. The data obtained makes evident that the decrease of hypertrophy of the left ventricle in the patients with resistant AH by sympathetic renal denervation is predefined at first by a grade of mean daily levels of BP by the data of 24-hour monitoring and also significantly by the dynamics of 24-hour BP index.

Aim. To assess the dynamics of left ventricular (LV) longitudinal deformation and blood flow velocity in the distal segment of anterior descending coronary artery (ADCA) among patients with resistant arterial hypertension (AH) 12 months after renal artery denervation.Material and methods. In seven patients with resistant AH (mean age 52,00±6,59 years), bilateral renal artery denervation was performed. Five out of seven patients had concentric LV hypertrophy. The complex clinical and instrumental examination included the assessment of office and 24-hour blood pressure (BP) levels, echocardiography, speckle tracking imaging (2D strain), and transthoracic visualisation of the distal segment of ADCA.Results. Twelve months after renal artery denervation, office BP levels decreased by 31/20 mm Hg. Mean 24-hour, mean daytime, and mean nighttime BP levels reduced by 15,58/14,62 mm Hg, 17,1/14,9 mm Hg, and by 21,1/14,47 mm Hg, respectively. There was an increase in global longitudinal LV deformation and local LV deformation (basal septal segment, basal and middle segments ofanterior and posterior walls, and middle and apical segments of lateral wall). The improvement in longitudinal systolic LV function was associated with reduced linear velocity of diastolic blood flow in the distal ADCA segment, without similar systolic changes.Conclusion. Our results suggest that renal artery denervation is linked to improved LV function; therefore, this method could be widely recommended for the management of patients with resistant AH.