Введение. Ренальная симпатическая денервация (РДН) для лиц с резистентной артериальной гипертонией (РАГ) показана как дополнительный инвазивный способ лечения при неэффективности медикаментозной терапии [1, 2]. Несмотря на противоречивые результаты эффективности РДН [3–6], в безопасности метода научное общество, как правило, не сомневается. Однако исследований, направленных на изучение состояния почек после РДН, недостаточно. Зачастую оценка функции почек на основе сывороточного креатинина, альбумина и их соотношения не отражает выраженности изменений в паренхиме почек, и длительное время могут носить компенсаторный характер [7]. В свою очередь современные возможности МРТ за счет высокой тканевой дифференцировки позволяют выявлять структурные изменения почек, такие как фиброз и гиперплазия, предшествующие функциональным показателям [8]. Целью исследования стало определение показателей, совокупность которых у пациента с РАГ поможет спрогнозировать сохранность объема почечной паренхимы, оцененной с помощью МРТ, через год после РДН.

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently. AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF. MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA 1c , creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines. RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes. CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes.

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 (p 0 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 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 (p 0,05), 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.

Background. Diabetic patients with resistant hypertension (RHT) are characterized by a high rate of annual decline in estimated glomerular filtration rate (eGFR) (up to 14 mL/min/1.73 m 2 ). The distal approach to sympathetic renal denervation (RD) reduces blood pressure (BP) to a greater extent compared with standard RD. However, the long-term effect of distal RD on the renal function remains unknown. comparison) despite a more powerful decrease in 24-h systolic BP in the distal RD group relative to that in conventional RD group (–25.3 ± 15.3 vs. 4.4 ± 22 mmHg, p = 0.04). The degrees of annual decline in GFR did not differ between the distal RD group and conventional RD group ( p = 0.9) and were –2.7 ± 2.4 mL/min/1.73 m 2 /year and –2.7 ± 4.0 mL/min/1.73 m 2 /year, respectively. No significant changes in renal blood flow, albuminuria, MRI-based kidney size, and the number of patients with albuminuria and renal dysfunction were found during the study. Conclusions. Distal RDN in diabetic patients with RHT had a three-year safety profile and nephroprotective efficacy similar to those when the standard method was used despite a more significant reduction of blood pressure. Both modes of RD are likely to slow the progression of renal dysfunction in these patients.

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/cm 2 ; after RD of branches — [-6324; -5328] and [-4021; -2521] dyne/cm 2 , 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.

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.

Резюме Цель исследования. Разработать способ, позволяющий проводить отбор пациентов с резистентной артериальной гипертонией (РАГ) для процедуры симпатической денервации почек (СДП), ориентируясь на конкретные исходные показатели β-адренореактивности (β-АР) и систолического артериального давления (САД). Материалы и методы. В анализ включили 23 пациентов с РАГ, получавших максимально переносимые дозы 4 антигипертензивных препаратов. Исследования, включая контроль АД и отечественный спектрофотометрический метод определения β-АР по изменению осморезистентности эритроцитарных мембран (ЭМ), проведены исходно, через 4 и 24 нед. СДП осуществляли путем эндоваскулярной радиочастотной абляции почечных артерий (ПА). Терапия в процессе наблюдения не менялась. Результаты. В случае, если исходно САД >170 мм рт.ст. и β-АР ЭМ >40 усл. ед., то ΔСАД составило –17,68±3,24 мм рт.ст., а эффективность СДП 100%, при исходном САД 0,05) и эффективность СДП была низкой. Заключение. Суммарная оценка исходных САД и β-АР ЭМ у больных РАГ позволила определить целесообразность проведения процедуры СДП с целью снижения АД. Предлагаемый способ дает возможность оптимизировать подбор пациентов и повысить эффективность применения СДП при лечении РАГ.

Design and methods. The office and ambulatory blood pressure (BP) were assessed at baseline, 1 week, 6 and 12 months after RD in patients with resistant essential hypertension who underwent bilateral transcatheter radiofrequency RD in single-arm prospective clinical study (ClinicalTrial.gov, NCT01499810). Results. Fifty three patients were included (aged 53,8 ± 9,6 years, 28 males), 46 (87 %) and 39 (74 %) patients completed 6 and 12 months follow-up, respectively. Office BP at baseline was significantly higher than mean 24-h BP: 176,3/102,4 vs 158,2/93,3 mmHg, for systolic and diastolic BP, respectively, but rapidly decreased to its level 1 week after RD: 143,6/86,9 vs 145,9/87,3 mmHg. During the rest of follow-up period the office and ambulatory BP remained almost equal: 149,1/88,2 vs 148,5/87,2 mmHg at 6 months and 146,4/87,3 vs 145,7/85,6 mmHg at 12 months follow-up. Both office and ambulatory BP decreased significantly after RD, however, the effects were substantially different: -32,7/-15,5 vs -12,9/-7,0 mm Hg (office vs mean 24-h BP) at 1 week, -27,1/-13,3 vs -10,3/-6,2 mmHg at 6 months and -30,9/-15,1 vs -12,2/-7,8 mm Hg at 12 months after RD. At all follow up assessments the difference was almost equal to the baseline WCE. Conclusions. Besides true BP reduction sympathetic RD also leads to the inhibition of WCE in patients with resistant hypertension. The difference between the decreases of office and ambulatory BP after RD may be totally explained by the elimination of significant baseline WCE. Inhibition of excessive BP reactivity to psychoemotional stress may have additional benefits.

Comparative study results revealed some difference in the treatment effect between beta-blockers cardvedilol and bisporolol. Blood pressure, metabolic parameters, early brain damage were monitored by MRI in 51 patients having arterial hypertension and diabetes mellitus of the type 2. Both drugs had significant antihypertensive effect but it was more prominent in bisoprolol treatment. Improvement in liquorodynamics disturbances was concluded to be caused by decreased blood pressure.

The aim of our work was studying influence of calcium antagonist felodipine on the blood pressure (BP) daily index (DI) in patients with arterial hypertension. 24-h BP monitoring was performed at 29 patients with essential hypertension initially and after 1, 2, 3 and 6 months of felodipine therapy in a dose of 2,5-15 mg per day. Significant reduction of the office BP and 24-h monitoring BP was noted. Favourable influence of felodipine on DI in patients with DI abnormalities was revealed as well. The revealed peculiarities of felodipine allow to recommend it for preventive maintenance of cardiovascular complications in patients with DI complications.

Study results of evaluating MRI detectable structural changes in the brain of hypertensive patients with the 2-nd type diabetes mellitus and comparing them with structural changes in hypertensive patients without the 2-nd type diabetes mellitus are given in the article. Hypertensive patients with the 2-nd type diabetes mellitus were shown to DM have more prominent MR detectable signs of cerebrovascular pathology.

Dynamics of hypertensive encephalopathy signs and brain perfusion under influence 6-month therapy by felodipine was estimated. The study included 29 patients having hypertension of the II stage. The treatment with felodipine resulted in decreased arterial pressure and signs of intracranial hypertension and increased blood flow in the area of periventricular edema. It is concluded that felodipine has expressed cerebroprotective efficacy besides its hypertensive action.

The study results of formation cerebrovascular peculiarities and of factors which define changes of cerebral microcirculation in 51 patients aged 51,7±4,6 years having arterial hypertension and the 2-nd type diabetes mellitus are given in the article. It was established that in patients with arterial hypertension and the 2-nd type diabetes mellitus, signs of cerebral disturbances were revealed already in the early disease stages; in vast majority of cases (94%) focal damages of white substance of the brain were seen. Increased level of von Willebrand factor from 145,5±10,5%was noted to be accompanied by increased number of hypoperfused sectors (R2=0,623, df (7,12), F=2,918, p=0,049).