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.

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.

Clinical-echocardiographic parameters of LV in 92 patientsaged from 24 to 72 years who underwent primary anterior MI based upon follow-up (5 years) data using serial ultrasound study were assessed. The follow-up mortality was revealed to be 21%; 2/3 of patients died in the latter 2 years of the period studied. Early (to one month) left ventricular dilatation is supposed to be the manifestation of acute compensatory reaction.

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.