Resistant Arterial Hypertension Research Articles

The Role of Immunohistochemistry in Managing Clinical Hypertension and Other Chronic Inflammatory Processes

Immunohistochemistry (IHC) is a pivotal technique in the visualization of specific proteins within tissue samples, leveraging antigen-antibody interactions to elucidate protein presence, distribution, and abundance. In clinical hypertension, IHC is instrumental in unraveling disease mechanisms, identifying biomarkers, and fostering targeted therapies. This review delves into IHC’s contributions to managing hypertension by examining its role in understanding the pathophysiology and identifying key proteins like those in the renin-angiotensin-aldosterone system. Elevated angiotensin II type 1 receptors in vascular walls, detected via IHC, correlate with hypertension and vascular remodeling. Additionally, IHC identifies inflammatory markers such as interleukin-6 and tumor necrosis factor-alpha, linking chronic inflammation to hypertension. The technique is vital for discovering biomarkers like endothelial nitric oxide synthase and vascular endothelial growth factor, essential for assessing endothelial function. IHC also detects oxidative stress markers, aiding in understanding oxidative mechanisms in hypertension. Evaluating antihypertensive therapies at a molecular level, IHC shows how interventions affect protein expression and vascular health, guiding therapeutic strategies. By revealing proteins differentially expressed in hypertensive tissues, IHC identifies new therapeutic targets, enhancing treatment efficacy. Furthermore, this review explores the application of IHC in other chronic inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease, highlighting its broader relevance in disease management. Recent advancements include the development of new drugs targeting specific molecular pathways, such as endothelin 1 receptor antagonists like aprocitentan, approved by the FDA in March 2024 for the treatment of resistant arterial hypertension. Overall, IHC significantly advances both research and clinical practice, promising improved health outcomes through continued methodological advancements.

MODERN VIEW ON RADIOFREQUENCY DENERVATION OF RENAL ARTERIES

Today, arterial hypertension is one of the most important health problems. It is also the main cause of cardiovascular complications and death. Despite significant success of modern antihypertensive pharmacotherapy, 10 % of the entire patient population with high blood pressure have extremely low sensitivity to core drugs aimed at BP correction. According to large clinical studies, the risk of myocardial infarction, stroke and other adverse cardiovascular outcomes in individuals with resistant hypertension is several times higher than in patients with controlled blood pressure. The purpose of this work is to analyze scientific literature on the history of development, effectiveness and safety of catheter radiofrequency denervation of renal arteries in patients with resistant arterial hypertension. The authors used articles from Pubmed, eLIBRARY, etc. for their analysis. The results of clinical studies show that patients with resistant arterial hypertension, in contrast to patients with controlled blood pressure, have more pronounced sympathetic activity. Hyperactivity of this part of the nervous system may be one of the main pathogenetic factors causing development of resistance to pharmacotherapy. Thus, radiofrequency renal denervation, modulating the tone of the sympathetic nervous system, is of particular interest.

Aprocitentan: a novel option for treatment of resistant arterial hypertension.

Aprocitentan: a novel option for treatment of resistant arterial hypertension.

Оценка чувствительности методов диагностики в выявлении гемодинамически значимых односторонних стенозов почечных артерий

Objective. Assessment of renal artery stenosis significance in patients with resistant arterial hypertension using non-invasive diagnostic methods and to compare them with the results of selective angiography and methods of physiological assessment of renal artery stenoses.Materials and methods. Prospectively, 156 patients with drug-resistant arterial hypertension and signs of renal artery stenosis detected by doppler ultrasonography of renal arteries were included in the study. Subsequently, 25 patients were excluded from the study due to multiple variant renal blood supply and bilateral renal artery stenosis. The remaining patients (n=131) underwent selective angiography of renal arteries, and 66 of them additionally underwent CTA of renal arteries with intravenous contrast. If the artery narrowing was 90% or more (n=27) in diameter, the stenosis was considered hemodynamically significant and further stenting of the affected artery was performed, and in case of 60-90% stenosis (n=52) additional assessment of functional significance of the stenosis was performed by measuring translesional pressure gradient, fractional blood flow reserve, instantaneous blood flow reserve (iFR) and Pd/ Pa ratio. Results. Among all patients (n=131), in whom the doppler ultrasonography of renal arteries showed signs of unilateral renal artery stenosis, after angiography combined with additional methods of functional significance assessment, hemodynamically significant renal artery stenosis was confirmed in 41% of cases (n=54). Thus, the sensitivity of doppler ultrasonography of renal arteries in detection of hemodynamically significant stenoses was 74%, prognostic value of positive 78% and negative result 64% (p<0,001). According to CTA (n=66) renal artery stenosis was confirmed in 56 patients. The results of CTA of renal arteries in 88% of cases coincided with the results of selective angiography, and using additional functional methods hemodynamically significant stenosis was confirmed in 32 (48%) patients. The sensitivity of CTA in detection of hemodynamically significant stenoses of renal arteries was 69%, specificity 91%, prognostic value of positive and negative results was 91 and 68% respectively. According to selective angiography, out of 131 patients, 24 patients had no renal artery stenosis, 28 patients had stenosis <60%, 27 patients had renal artery stenosis >90% and 52 patients had stenosis 60-90%. Patients with stenosis <60% were not considered candidates for renal artery stenting.

Renal denervation for the management of refractory ventricular arrhythmias

Abstract Background While catheter ablation (CA) has proven effective in managing ventricular arrhythmias (VA) associated with structural heart disease, a portion of patients continue to experience refractory VA despite medical treatment and multiple CA procedures. In such cases, additional techniques, such as autonomic neuromodulation, have been explored. Renal denervation (RDN), traditionally performed for the treatment of resistant arterial hypertension, inhibits the afferent renal sympathetic pathway, leading to reduced efferent sympathetic overactivation on a systemic level. Due to this mechanism, it has also been studied for the management of arrhythmias, including atrial fibrillation and VA, with favorable results. Objective To assess the effectiveness and safety of RDN for the management of refractory VA storms in high-risk patients. Methods A retrospective analysis of RDN procedures for electrical storms, conducted at a tertiary center between February 2020 and September 2023. We analyzed baseline patient characteristics, procedural details, and acute complications. Recurrence of VA after RDN was assessed at one and six months. Results A total of 7 patients underwent RDN for the treatment of refractory VA. The mean age was 56 ± 10 years (6 male). The primary diagnosis was ischemic cardiomyopathy (n=5), with a mean left ventricular ejection fraction (LVEF) of 20 ± 5%, and no history of resistant arterial hypertension. All patients had an implantable cardioverter-defibrillator (ICD) (two with concomitant resynchronization therapy). Five patients had undergone previous endocardial VA ablation. Of the two patients without prior VA ablation, one had a contraindication because of a large left ventricle thrombus, and the other was submitted to an electrophysiological study, but without inducible ventricular tachycardia. In the four weeks before RDN, patients exhibited a mean of 12 ± 18 sustained VA episodes, meeting the criteria for electrical storm (3 ≥ episodes in 24h). During the procedure, there was a mean of 7 ± 8 radiofrequency applications in the right renal artery and 6 ± 10 in the left renal artery. No acute complications were observed. One month after the procedure, VA episodes were reduced to a mean of 0 ± 1, with only two patients experiencing recurrent VA. After six months, the absence of VA recurrence remained consistent, with only one patient experiencing new episodes. There were no deaths during this period. Conclusion In our pilot study, RDN appeared to be a safe and effective treatment for the management of VA.VA episodes before and after RDN

Is endothelin targeting finally ready for prime time?

The endothelin family of peptides has long been recognized as a physiological regulator of diverse biological functions and mechanistically involved in various disease states, encompassing, among others, the cardiovascular system, the kidney, and the nervous system. Pharmacological blockade of the endothelin system, however, has encountered strong obstacles in its entry into the clinical mainstream, having obtained only a few proven indications until recently. This translational gap has been attributable predominantly to the relevant side effects associated with endothelin receptor antagonism (ERA), particularly fluid retention. Of recent, however, an expanding understanding of the pathophysiological processes involving endothelin, in conjunction with the development of new antagonists of endothelin receptors or adjustment of their doses, has driven a flourish of new clinical trials. The favorable results of some of them have extended the proven indications for ET targeting to a variety of clinical conditions, including resistant arterial hypertension and glomerulopathies. In addition, on the ground of strong preclinical evidence, other studies are ongoing to test the potential benefits of ERA in combination with other treatments, such as sodium-glucose co-transporter 2 inhibition in fluid retentive states or anti-cancer therapies in solid tumors. Furthermore, antibodies providing long-term blockade of endothelin receptors are under testing to overcome the short half-life of most small molecule endothelin antagonists. These efforts may yet bring new life to the translation of endothelin targeting strategies in clinical practice.

#2169 Transplant renal artery stenosis in recipients with resistant arterial hypertension

Abstract Background and Aims Transplant Renal Artery Stenosis (TRAS) is a vascular complication after kidney transplantation. It worsens the prognosis of the graft and the patient's life. The aim was to study the incidence of TRAS as a cause of resistant arterial hypertension in kidney transplant recipients in the Republic of Belarus and the efficiency of its endovascular treatment. Method The study included 187 kidney transplant recipients. Blood pressure of 72 (38.5%) patients was less than 130/80 mmHg without taking antihypertensive drugs. Arterial hypertension was diagnosed in 115 (61.5%) recipients. The study included clinical, laboratory and instrumental methods (24-hour blood pressure monitoring, Doppler ultrasound, graft scintigraphy with captopril). Results 31 (16.6%) recipients needed to take one antihypertensive drug, 43 (23.0%)—2 drugs, 41 (21.9%)—3 or more. 17 (9.1%) recipients did not have target blood pressure correction while taking more than 4 antihypertensive drugs. There was decreased blood flow in the graft artery with a peak systolic velocity > 200 cm/s in 14 (7.5%) cases. These patients were submitted to the graft nephroscintigraphy with caplopril where 8 grafts (4.3%) were diagnosed signs of TRAS. These recipients were submitted to the renal angiography with the injection of 150 (100; 200) ml of contrast agent. 5 (2.7%) recipients were diagnosed with hemodynamically significant TRAS of more than 70 (65; 75) % and received percutaneous transluminal angioplasty and stenting. All these patients had a decrease of glomerular filtration rate and resistant arterial hypertension before operation. The average age of the patients with TRAS was 57.4 ± 11.0 years, the period after transplantation was 11 ± 3 months. Their blood tests did not show dyslipidemia, but 4 out of 5 cases had diabetes mellitus. Their postoperative period had no complications. The patient was placed on dual antiplatelet therapy with aspirin and clopidogrel. There was an increase in glomerular filtration rate by 27 ± 7 ml/min/1.73 m2 and a decrease in systolic blood pressure by 40 (40; 45) mm Hg in the early postoperative period. Graft artery stenting allowed reducing the number of antihypertensive drugs to one tablet in 4 out of 5 patients. Conclusion Transplant Renal Artery Stenosis is a rare but significant complication of the late postoperative period that may cause resistant hypertension in kidney transplant recipients. Timely identification and stenting of the graft artery improves the graft functioning and reduces blood pressure.

FOLLOW-UP OF SURVIVAL PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION

Objective: Resistant arterial hypertension (RAH) contributes to high mortality worldwide. Aim of the study: to assess 7-year follow-up survival and development of a composite end point (CEP) in patients with RAH. Design and method: The analysis includes 50 patients with RAH who were discharged from hospital. After 7 years discharge from the hospital, the patients underwent office BP measurement. Adverse events or death were reported as the composite endpoint (CEP). The average age of patients as of 2016 was 57.89 ± 11.81 y.o. 16% had type 2 diabetes (n=8). Results: After 7 years, in 32% (n=16) developed CEP, and 10% (n=5) of them died. The BMI increased from 30.87 ± 6.30 to 33.80 ± 6.90 kg/m2 (p<0.05). 20% had smoke (n=10), but 8% (n=4) (quit smoking after developing CEP). After 7 years, 48.88% of patients (n=22) controlled office blood pressure below 140/90 mmHg and 51.11% did not (n=23). Among patients who reached the target office BP (130.73 ± 6.61/81.59 ± 4.13 mmHg), there was a decrease in the number of drugs from 3.76 ± 0.19 to 2.85 ± 0.14, p<0.05. 45% (n=10) from the group took fixed combinations. Among patients who did not reach target office BP (148.04 ± 7.49/92.17 ± 4.66 mmHg), there was also a decrease in the number of drugs from 3.52 ± 0.18 to 2.50 ± 0.13, p<0.05 – patients decision. After regression analysis the main factors that were associated with the occurrence of CEP in patients with RAH were: the presence of diabetes (β= 5,237, p= 0,032) smoking (β=4,326, p= 0,037), increased body weight (β =3,423, p=0,024), failure to achieve target blood pressure levels (β =4,152, p=0,041) Conclusions: Mortality among patients with RAH were 10% during 7 years. The total composite endpoint were 32%. Did not reach the target office BP in patients with RAH the factors for the development of combined end point was diabetes mellitus, smoking and weight gain.

FOLLOW-UP OF RENAL DENERVATION IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION

Objective: Aim. Determining the long-term efficacy and safety of RDN the results of a 10-year follow-up Design and method: We selected 1146 patients with resistant arterial hypertension (RAH) who received 3 or more antihypertensive drugs. 16 patients were selected for renal artery denervation. RDN was performed in 8 patients (0.70%). 8 patients refused the procedure. The age was 52.13 ± 3.88 years (40–66), the duration of hypertension was 16.75 ± 2.17 (12–25) years. The number of antihypertensive drugs was 5.5 ± 0.18 (patients was in refractory hypertension). Office SBP/DBP on optimization of therapy was 156.88/95.00 ± 2.98 mm Hg and heart rate - 68.88 ± 3.28 beats/min. 24SBP/DBP was 149.16 ± 5.40/86.98 ± 5.08 mm Hg. 24HR was 70.12 ± 2.94 beats/min. All patients tolerated the procedure well. Results: The decrease in office SBP/DBP in the dynamics of 1 month, 12 months, 2 years, 5 years and 10 years were -12,59/-10,0, -11,17/-2,57, -20,31/-11,71, -27,71/-13,33 and -30,21/-16,67 mm Hg, respectively. The office heart rate (HR) decreased, its dynamics were -3.74 bpm, -4.68 bpm, -1.45 bpm, - 2.13 bpm. -4.21 bpm, - 3.88 bpm., respectively. The decrease in 24SBP/DBP was -14,45/-6,95, -8,70/-10,01, -19,45/-12,37, -19,91/-11,24, -29,93/-13,61 and -26,13/-23,35 mm Hg. (p<0.05 for all values). 24HR dynamics: -3.16 bpm, - 4.19 bpm, + 1.43 bpm. -1.51 bpm, -4.46 bpm, and -5.49 bpm, respectively. After 2, 5, and 10 years, all patients reached the target blood pressure level both in the office and with ABPM. Patients reduced the number of antihypertensive drugs from 5.50±0.18 to 3.50±0.30 - after 5 years and 3.67±0.18 - after 10 years after RDN. GFR change over 10 years from 76.10±5.62 to 64.60±1.93 ml/min/1.73m2, p>0.05. One patient died of thyroid cancer 2 years later. All other patients are alive and have not had any cardiovascular event or death during 10 years. Conclusions: Long-term results of renal artery denervation showed no cardiovascular events or cardiovascular death over 10 years. RDN contributed to a reduction in the number of antihypertensive drugs from 5.5 to 3.67 after 10 years of therapy. All patients achievement of the target BP level.

EFFECT OF RENAL DENERVATION ON 24H BLOOD PRESSURE PATTERN

Objective: Endovascular renal denervation (DRN) is a therapeutic approach for resistant arterial hypertension (RH). The aim of this study was to assess the effects of RDN on 24h blood pressure. Design and method: A retrospective evaluation of ABPM data at baseline and after 6 months from RDN in patients undergoing DRN between 01/01/2011 and 31/12/2021 in the Arterial Hypertension Center of Turin. Mean 24h, Daytime, Nighttime BP and HR values and short term 24h, daytime and nigthtime BP and HR varability parameters (standard deviation, dipping and coefficient of variation) were calculated. Results: The series included 14 subjects, of which 8 (57%) were female and with an average age 54±10 years. The number of antihypertensive drugs before renal denervation was 5.7±1.0. At baseline office BP was 188/113±22±18 mmHg and ABPM 24h BP was 150/92±21±16 mmHg. Patients were considered as responders if a reduction of least 10 mmHg in systolic blood pressure (PAS) at 24h Blood Pressure Monitoring at six months from RDN was obtained. From a safety point of view, there were no short-term or long-term complications. The responders at six months were 66%. Non-responders showed an increased blood pressure variability compared to responders at baseline and only one was dipper. The responders had a statistically significant redution of SD24h after DRN, an increased average nocturnal blood pressure drop and a lower pressure variability. While in non-responders no redution in SDnight, SDday and coefficient of variation was found, by contrast all of them become dippers because mean daytime SBP increase. Conclusions: In conclusion, pressure variability (SD24h and coefficient of variation) is globally reduced in the denerved patients, this trend is particularly present in responders. The non-responders have an increased BP variability at baseline without decreasing after DRN. These results suggest that, when effective, DRN can reduce both BP levels and BP variability, thus may have an important effect in reducing cardiovascular risk.

Features of The Dynamics of Profibrotic Markers and Regression of Left Ventricular Hypertrophy After Renal Denervation in Patients With Resistant Hypertension and Stenosing Atherosclerosis of the Coronary Arteries.

To compare the changes in serum concentrations of matrix metalloproteinases (MMPs) and their tissue inhibitor (TIMP) to the dynamics of blood pressure (BP) and parameters of left ventricular hypertrophy (LVH) 6 months after renal denervation (RD) in patients with resistant arterial hypertension (RAH) and complicated coronary atherosclerosis. In 22 RAH patients with complicated coronary atherosclerosis (revascularization and/or history of myocardial infarction (MI)), 24-hour BP monitoring, echocardiography, and measurement of blood MMPs and TIMP were performed at baseline and six months after RD. The comparison group consisted of 48 RAH patients without a history of coronary revascularization or MI. In 6 months after RD, BP was decreased comparably in both groups. In the group of complicated atherosclerosis, there were no significant changes in profibrotic markers or LVH parameters. Thus, at baseline and after 6 months, the values of the studied indicators were the following: left ventricular myocardial mass (LVMM) 233.1±48.1 and 243.0±52.0 g, LVMM index 60.6±14.5 and 62.8±10 .9 g/m2.7, proMMP-1 4.9 [2.1; 7.7] and 3.6 [2.0; 9.4] ng/ml, MMP-2 290.4 [233.1; 352.5] and 352.2 [277.4; 402.9] ng/ml, MMP-9 220.6 [126.9; 476.7] and 263.5 [82.9; 726.2] ng/ml, TIMP-1 395.7 [124.7; 591.4] and 424.2 [118.2; 572.0] ng/ml, respectively. In the comparison group, on the contrary, there was a significant decrease in LVMM from 273.6±83.3 g to 254.1±70.4 g, LVMM index from 67.1±12.3 to 64.0±14.4 g/m2.7, proMMP-1 from 7.2 [3.6; 11.7] to 5.9 [3.5; 10.9] ng/ml, MMP-2 from 328.9 [257.1; 378.1] to 272.8 [230.2; 343.2] ng/ml, MMP-9 from 277.9 [137.0; 524.0] to 85.5 [34.2; 225.9] ng/ml, and the MMP-9/TIMP-1 ratio from 0.80 [0.31; 1.30] to 0.24 [0.07; 0.76]. The BP dynamics in this group was inversely correlated with MMP-2 at 6 months (r=-0.38), and the MMP-9/TIMP-1 ratio was correlated with LVMM and the LVMM index at baseline (r=0.39 and r=0.39) and at 6 months (r=0.37 and r=0.32). The change in TIMP-1 from 543.9 [277.5; 674.1] to 469.8 [289.7; 643.6] ng/ml was not significant (p=0.060). In RAH patients with complicated coronary atherosclerosis, the dynamics of profibrotic biomarkers and LVH parameters after RD was absent despite the pronounced antihypertensive effect, probably due to the low reversibility of cardiovascular remodeling processes or more complex regulatory mechanisms of the MMP system.

Association between skin lymphangiogenesis parameters and arterial hypertension status in patients: An observational study.

Recent studies have indicated that the skin lymphatic system and interstitium may play a role in the pathophysiology of arterial hypertension (AH). We aimed to determine whether the set of pathway parameters described previously in rodents would allow for the distinction between hypertensive and normotensive patients. Molecular and histopathological parameters from the skin and blood of patients with AH (AH group, n = 53), resistant AH (RAH group, n = 32) and control (C group, n = 45) were used, and a statistical multivariate bootstrap methodology combining partial least squares-discriminant analysis (PLS-DA) and selectivity ratio (SR) were applied. The C vs RAH model presented the best prediction performance (AUC test = 0.90) and had a sensitivity and specificity of 73.68% and 83.33%, respectively. However, the parameters selected for the C vs AH group model were the most important for the pathway described in the rodent model, i.e., greater density of the skin lymphatic vessels (D2-40 expression) and greater number of macrophages (CD68 expression), higher expression of the messenger ribonucleic acid (mRNA) of nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGFC) and podoplanin (PDPN) in the skin, greater concentration of hyaluronic acid (HA) in the skin, and lower serum concentration of VEGF-C. Our study suggests that the NFAT5/VEGF-C/lymphangiogenesis pathway, previously described in rodent studies, may also be present in human HA. Further experiments are needed to confirm our findings.

Predictors of cardiovascular and renal complications in patients with resistant arterial hypertension during long-term follow-up

The aim – to evaluate the incidence of cardiovascular and renal complications and its predictors in resistant hypertensive (RH) patients during the long-term follow-up.Materials and methods. The frequency of cardiovascular and renal events was studied in 240 true resistant hypertensive patients. The duration of observation was 5.1±0.1 years. The comparison group consisted of 228 patients with controlled arterial hypertension (CAH) on a triple combination antihypertensive therapy. Cardiovascular endpoints included stroke/transient ischemic attack, myocardial infarction, cardiovascular death, myocardial revascularization, development of atrial fibrillation, hospitalization due to heart failure, and lower limb arterial disease. Kidney outcomes included dialysis or GFR decline by 40 % or greater. All the endpoints formed a composite primary endpoint. New cases of type 2 diabetes mellitus were also estimated.Results and discussion. The patients with resistant hypertension on multi-component antihypertensive therapy and significant reduction in arterial blood pressure (BP) levels (achievement of controlled office BP in 49.6 % of patients, office and ambulatory BP in 34.2 % of patients), maintained a higher risk of cardiovascular and renal events compared to patients with controlled arterial hypertension. It was found that the frequency of occurrence of the composite primary endpoint in resistant hypertensive patients was four times higher than in the group of patients with controlled hypertension – 30.0 % (72/240) versus 7.0 % (16/228) (p=0.001). The frequency of new cases of type 2 diabetes mellitus in patients with RH exceeded compared to CAH patients by 3.7 times (p=0.03).Conclusions. Independent predictors of the risk of cardiovascular and renal complications in patients with RH were the initial indicators of circulating endothelial progenitor cells if their concentration in the blood was ≤ 1818 cells/ml (HR 0.41; 95 % CI (0.21–0.79); p=0.007), the content of citrulline in the blood is more than 68 μmol/l (HR 1.13; 95 % CI (1.07–1.20); p<0.001); value of initial average daily systolic BP > 163 mm Hg (HR 1.10; 95 % CI (1.03–1.18); p=0.008).

A brief overview of modern approaches to the therapy of resistant arterial hypertension

Resistant hypertension is associated with increased mortality and morbidity. The optimal drug therapy for resistant hypertension has not been fully clarified, there are few studies on this issue in the literature. We compared the efficacy of nebivolol 5 mg, a third-generation beta-blocker, with spironolactone 25 mg in patients with resistant hypertension.
 81 patients with resistant hypertension were included in the study. Resistant hypertension was defined as the presence of official blood pressure ≥ 140/90 mm Hg. when patients received 3 or more antihypertensive drugs, including diuretics. Blood pressure was recorded in office and outpatient settings at baseline and after 8 weeks of treatment.
 Office systolic blood pressure and diastolic blood pressure at 24-hour ambulatory blood pressure monitoring were significantly lower compared to baseline values in the nebivolol and spironolactone groups. The decrease in 24-hour mean systolic and diastolic blood pressure in the nebivolol group was 14.9±19.8 mm Hg. Art. and 9.3±12.7 mm Hg. Art. compared to 19.5±16.4 mm Hg. Art. and 13.7±10.8 mm Hg. Art. in the spironolactone group, respectively. The reduction in 24-hour mean systolic and diastolic blood pressure was not significantly different between the nebivolol and spironolactone groups (P = 0.338 and P = 0.153).
 Therefore, nebivolol is an effective treatment option for resistant hypertension, and the antihypertensive effect of this drug is similar to low doses of spironolactone.

Association between Resistant Arterial Hypertension, Type 2 Diabetes, and Selected microRNAs.

In recent years, a very close relationship between miRNA and cardiovascular diseases has been found. RAH and T2DM are accompanied by a change in the microRNA expression spectrum. This study aimed to evaluate the clinical characteristics and expression of selected microRNAs in patients with idiopathic RAH and T2DM. A total of 115 patients with RAH were included in this study. Among them were 53 patients (46.09%) with T2DM. miRNA levels were determined using quantitative real-time polymerase chain reaction. The expression of the examined genes was calculated from the formula RQ = 2-ΔΔCT. Analysis using the Mann-Whitney U test showed a statistically significant (p < 0.05) difference in the expression of MIR1-1 (p = 0.031) and MIR195 (p = 0.042) associated with the occurrence of T2DM in the subjects. The value of MIR1-1 gene expression was statistically significantly higher in patients with T2DM (median: 0.352; mean: 0.386; standard deviation: 0.923) compared to patients without T2DM (median: 0.147; mean: -0.02; standard deviation: 0.824). The value of MIR195 gene expression was statistically significantly higher in patients with T2DM (median: 0.389, mean: 0.442; standard deviation: 0.819) compared to patients without T2DM (median: -0.027; mean: 0.08; standard deviation: 0.942). The values of MIR1-1 and MIR195 gene expression were statistically significantly higher in patients with RAH and T2DM compared to patients with RAH and without T2DM. Further studies are necessary to precisely clarify the roles of miRNAs in patients with RAH and T2DM. They should demonstrate the utility of these genetic markers in clinical practice.

Resistant arterial hypertension: modern view of the problem

In clinical practice, uncontrolled arterial hypertension remains a difficult but solvable task, given the available arsenal of antihypertensive drugs. However, resistant arterial hypertension is diagnosed in 10%–15% of these cases. A significantly higher risk of cardiovascular complications indicates the extreme importance of the successful treatment of this pathology. Resistant hypertension is defined as above-goal high blood pressure in a patient despite concurrent use of three antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a renin–angiotensin blocker (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. All antihypertensive drugs should be administered at maximum or maximally tolerated doses. Resistant hypertension also includes cases in which blood pressure targets are achieved with ≥4 antihypertensive medications. The diagnosis of resistant hypertension requires assurance of antihypertensive medication adherence and exclusion of the “white-coat effect” (office blood pressure above goal but out-of-office blood pressure at or below the target). Once antihypertensive medication adherence is confirmed and out-of-office blood pressure recordings exclude a white-coat effect, the evaluation includes the identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. The management of resistant hypertension includes the maximization of lifestyle interventions, correction of sleep disorders, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower blood pressure if blood pressure remains high.

Pediatric hypertension as an early manifestation of cardiovascular disease in children.

In adults, cardiovascular events associated with arterial hypertension (AH) have a major impact on morbidity and mortality. In light of recent findings, AH in children has been interpreted as early cardiovascular disease (CVD), while exposure to CV risk factors in children proves to be a predictor of subclinical CVD in adults. The American College of Cardiology/American Heart Association has recently updated the classifications for measuring blood pressure (BP) in adults and children. Primary AH in children is generally asymptomatic, and it is associated with a family history of AH, overweight/obesity, and normal morphofunctional characteristics of the urinary system. The younger the child and the higher the BP, the greater the likelihood of secondary AH. The investigation into the etiology of AH begins with a detailed anamnesis, which should include clinical information and details on the use of medication, smoking, and alcohol consumption from the perinatal period to the time of consultation. Modifying risk factors by reducing weight, decreasing alcohol consumption and increasing vegetable intake from childhood to adulthood has been associated with the resolution of AH in the childhood-adulthood transition, and with the reversal of cardiometabolic adverse effects in non-obese adult individuals. Pharmacological therapy should be initiated in cases of symptomatic AH, AH secondary to chronic kidney disease or diabetes mellitus, presence of target organ lesions, stage 2 AH with no modifiable cause and resistant AH unresponsive to lifestyle changes.

Renovascilar hypertension against the background of multifocal atherosclerosis: impact of endovascular methods of correction on its course and optimization of remedial measures

The course of renovascular (resistant) arterial hypertension was analyzed in 60 patients (45 men, 15 women) with isolated atherosclerotic stenosis of the renal artery of more than 75% (group 1), and in 30 patients (26 men, 4 women) who, in addition to unilateral stenosis of the renal artery of more than 75%, also had stenoses of the brachiocephalic arteries up to 60% of the vessel diameter (group 2). The mean age of the examined patients in group 1 was 52.4 ± 6.9 years, and in group 2 it was 53.2 ± 7.4 years. Endovascular correction of hemodynamically significant stenosis of the renal artery leads to a significant decrease in systolic and diastolic blood pressure levels, a reduction in the number of antihypertensive drugs from 5-4 to a 3-component scheme in most cases, and an improvement in the functional state of the kidneys. At the end of the 2-year observation period, in patients with multifocal lesions of the renal and cerebral arteries (group 2), both systolic and diastolic blood pressure levels corresponded to “high normal” values, while in group 1 (isolated renal artery lesions) they corresponded to “normal” blood pressure levels. Patients in group 2 had metabolic disorders such as atherogenic dyslipidemia, hyperuricemia, and significant signs of renal dysfunction. The multifocal nature of atherosclerotic vascular lesions contributes to a more “severe” course of the disease, which should be taken into account when conducting treatment measures.

Case Report: Transcatheter treatment of aortic coarctation in a 58-year-old patient with LACHT syndrome and left lung agenesis

LACHT (Lung Agenesis, Congenital Heart, and Thumb anomalies) syndrome is an extremely rare congenital anomaly and presents significant challenges in adults due to its poor survival rates. Herein, we report a case of late diagnosis and successful transcatheter treatment of aortic coarctation in a 58-year-old male patient with LACHT syndrome, medically resistant arterial hypertension, and left lung agenesis. Baseline CT angiography showed isthmic aortic coarctation and left lung agenesis, with compensatory right pulmonary artery and vein thickenings. The patient underwent balloon dilation and subsequent implantation of a covered NuMED 45 mm 8-ZIG CP stent with satisfactory outcomes. The pressure gradient decreased from 43 to 23 mmHg. The arterial pressures normalized during the follow-up with fewer medications. Genetic testing identified a heterozygous mutation (c.6583C &amp;gt; T) in the FBN2, supporting the diagnosis of variant Marfan syndrome.

G894T of nos3 gene polymorphism and resistant arterial hypertension in Uzbek population

Abstract Aim To estimate the influence of G894T polymorphism of NOS3 gene on the risk of developing resistant arterial hypertension (AH) in the Uzbek population. Materials and Methods The study included 176 patients with AH I-III degree (ESH / ESC, 2018) of both sexes of Uzbek population. The mean age of the patients was 57.12 ± 11.03 years, the mean duration of AH was 9.58 ± 5.76 years. Resistant hypertension was defined in uncontrolled BP, even though ≥ 3 drugs of different classes were taken. Genotyping of the G894T polymorphism of NOS3 gene was performed using real-time PCR using gene-specific primers of allele-specific probes, followed by fluorescence detection of the corresponding alleles. Relative risk (RR) was calculated using genetic models. Calculations were performed using the online program "Calculator for calculating statistics in case-control studies". The results of all studies were considered statistically significant at p&amp;lt;0.05. Results All patients were divided into two groups: group 1 - patients with resistant hypertension (cases, n=61) and group 2 - patients with controlled hypertension (controls, n=115). Among patients of group 1, the following distribution of the G894T polymorphism of the NOS3 gene was revealed: GG genotype - determined in 45.9% of patients, GT genotype - in 44.3%, TT genotype - 9.8%, χ2=22.770, p=0.000 . The allelic distribution showed the predominance of carriage of the G allele: G allele - 68.0%, T allele - 32.0%, χ2=30.311, p=0.000. Among patients of group 2, the allelic distribution was with a significant prevalence of the G allele: G allele in 80.9%, T allele in 19.1%, respectively, χ2=172.878, p=0.000. The ratio of GG:GT:TT genotypes was as follows: 67.8% : 26.1% : 6.1%, χ2=102.704, p=0.000. An analysis using genetic models of inheritance revealed a protective effect of the G allele G894T of the NOS3 gene polymorphism on the risk of developing resistant hypertension in the Uzbek population: among 115 patients with controlled hypertension of group 2, the G allele was significantly more common than in patients with resistant hypertension of group 1 (80.9%; χ² = 7.29 P=0.007; OR=0.50, 95% CI 0.30-0.83) and only 19.1% of patients had the T allele (χ²=P=0.007; OR=1.99 95% CI 1.20-3.28). The general model of inheritance demonstrated a significant accumulation of the GG genotype among patients of group 2 67.8% (χ² = 8.01; P = 0.02; OR = 0.40, 95% CI 0.21-0.76), while the GT genotype was less common in 26.1% cases and the TT genotype is even rarer in 6.1% of cases. Whereas in 1st group of patients GG and GT genotypes were found in the same ratio: 45.9%: 44.3%, respectively. Conclusion The results obtained indicate a significantly greater accumulation of the G allele G894T of NOS3 gene polymorphism among patients with controlled hypertension. Carrying the G allele and GG genotype G894T of NOS3 gene polymorphism is associated with a low risk of developing resistant hypertension in Uzbek population.