In most countries worldwide, hypertension (HTN) occupies a leading position in the structure of modifiable risk factors for cardiovascular diseases and their complications. One of the main reasons for this trend is the increasing prevalence of obesity, which is becoming an important risk factor for high blood pressure (BP). The results of numerous epidemiological studies showed an association between obesity (assessed by body mass index (BMI)) and BP levels, as well as a prognostic role of BMI in relation to the development of HTN. However, there is currently no consensus on the obesity criterion that most accurately predicts the risk of HTN and associated complications. Data from prospective observational studies showed a greater prognostic value of indirect and direct indicators of abdominal and ectopic visceral adipose tissue.These facts stimulated research aimed at revealing the pathophysiological mechanisms of HTN in patients with overweight and obesity, which are reviewed in this article.

Epicardial obesity (EO) can lead to lipotoxic myocardial damage with the development of myocardial fibrosis, which underlie the impairment of left ventricular (LV) diastolic function. The identification of markers of lipotoxic myocardial damage is important at an early preclinical stage for preventive measures. Objective. To study the relationship of plasma levels of markers of insulin resistance and lipotoxic fibrosis with the parameters of LV mechanics in patients with EO. We hypothesized that there are significant differences in plasma levels of markers of insulin resistance and myocardial fibrosis and that they are associated with the parameters of LV mechanics in EO. Design and methods. The study included 143 men. Inclusion criteria: general obesity I–III degree. Exclusion criteria: type 2 diabetes mellitus, hypertension, LV diastolic dysfunction based on echocardiography (Echo). Patients were divided into 2 groups: EO (+) with epicardial fat thickness (tEAT) ≥ 7 mm (n = 70); EO (–) with tEAT < 7 mm (n = 31). All patients were assessed for glucose, blood insulin, profibrotic factors and free fatty acids (FFA) using enzyme-linked immunosorbent assay. HOMA-IR insulin sensitivity index was calculated as (insulin × glucose)/22,5. With the help of speckle-tracking Echo, the mechanics of LV were studied (LV twisting, LV twisting ratio, time to LV twisting peak, LV untwisting ratio, time to LV untwisting peak). Results. The patients with EO (+) showed a statistically significant increase in the level of FFA up to 0,82 (0,39; 1,30) mmol/L (< 0,0001) and HOMA-IR index up to 3,89 (2,02; 5,76) (< 0,0001) in comparison with the group EO (–). There was a statistically significant effect of tEAT on the level of FFA (F = 7,90; p = 0,006) and on the development of insulin resistance (F = 14,85; p < 0,001). The correlation analysis in the EO (+) group showed the relationship between FFA and type III collagen (r = 0,29, p = 0,01) and procollagen type I carboxy-terminal propeptide (PICP) (r = 0,26, p = 0,03), as well as between HOMA-IR and MMP-3 (r = 0,30, p = 0,01). In the EO (–) group, the relationship of profibrotic factors with the level of FFA and HOMA-IR was not found. There was also a significant relationship between LV untwisting ratio and level of FFA (r = 0,24, p = 0,04) in the group EO (+). Conclusions. Thus, an increase in the level of FFA in patients with EO may be accompanied by an increase in the level of some profibrotic factors and a LV untwisting violation determined by speckle-tracking Echo. Our data supports the need for assessing the FFA level and speckle-tracking Echo for the early diagnosis of LV diastolic dysfunction in patients with EO.

Objective. The purpose of the study was to determine the dynamics of the metabolically healthy obesity (MHO) status according to the Meigs criteria, and to establish the predictors of the transformation of healthy obesity phenotype into an unhealthy (MUHO) one in the population of residents of St Petersburg (Russia) at 6,5-year follow-up. Design and methods. Within the epidemiology study ESSE-RF a random sample of 1600 St Petersburg inhabitants stratified according to gender and age was formed. Examination of participants included anthropometry with measurement of waist circumference and calculation of body mass index (BMI), measurement of blood pressure (BP), fasting blood glucose, insulin (index of insulin resistance was calculated), creatinine, cortisol, lipid spectrum, C-reactive protein, adiponectin, leptin, and uric acid. Meigs MHO criteria (2006) were used in obese subjects (BMI > 30 kg/m²). Obese patients, who were identified as metabolically healthy in 2012–2013, were invited for follow-up in 2018–2019. Results. At the first stage obesity was diagnosed in 430 (26,9 %) participants, according to the BMI, 116 (27,0 %) of them were metabolically healthy according to the Meigs criteria. At follow-up, 44,4% individuals with the MHO phenotype transformed to the MUHO category on average after 6,5 years. Individuals who retained the MHO phenotype over time had significantly lower baseline systolic BP and diastolic BP levels, more favorable lipid levels and lower levels of uric acid, insulin, and index of insulin resistance. Glucose increase by every 0,5 mmol/l and higher was associated with elevated probability of transformation MHO to MUHO phenotype by 10,9 times (adjusted for sex and age). Conclusions. Significantly higher levels of BP, insulin resistance, low density lipoprotein and uric acid at baseline, as well as an increase in glucose levels over time, were associated with the transformation of the metabolically healthy to the unhealthy phenotype in obese individuals at 6,5-year follow-up. In all individuals with the MHO phenotype, there was a significant increase in waist circumference over time, accompanied by an increase in BMI only in those who transformed into the MUHO status.

This article presents an analysis of data on the mechanisms of antihypertensive effect of β-adrenergic receptor blockers. The article describes the effectiveness of cardiotropic action of drugs to reduce high blood pressure (BP) with short-term and long-term action of compounds, the effect of blockers on the activity of plasma renin. The influence of β-blockers on the central mechanisms of blood circulation regulation is considered. Information on the effect of β-blockers on myogenic mechanisms of vascular tone regulation is presented. The possibilities of blockade of β-adrenergic receptors of endothelium-dependent hyperpolarization of smooth muscles of resistive arteries, violation of the NO-cGMP pathway and blockade of Ca²⁺ channel currents as factors providing expansion of resistive vessels and reduction of high BP are analyzed.

Aortic stenosis (AS) is one of the most common cardiovascular diseases. The prevalence of AS and vascular stiffness are significantly associated with age. Elevated arterial stiffness is an independent risk factor for cardiovascular events. The pathogenetic and clinical relationship of degenerative AS and aortic stiffness is poorly known. This review reflects the current understanding of the relationship between degenerative AS and aortic stiffness. The existing evidence on the effects of surgical and endovascular correction of the defect on aortic stiffness is described. The potential predictors of AS prognosis and outcomes of valve replacement are discussed. Unresolved issues and directions for further research are clarified.

Improving the effectiveness of drug therapy and reducing the risk of adverse cardiovascular and renal outcomes in patients with resistant hypertension (HTN) remains an unsolved problem of cardiology. The results of the PATHWAY-2, PATHWAY-3 and ReHOT studies have shown the clinical efficacy of spironolactone, amiloride and, to a lesser extent, the antiadrenergic drugs clonidine, bisoprolol and doxazosin in improving blood pressure (BP) control in this patient population. However, the inclusion of spironolactone and other known drugs in antihypertensive therapy does not ensure the achievement of target BP level in a significant proportion of these patients. The review presents the results of clinical studies of new approaches aimed at increasing the effectiveness of drug therapy in resistant HTN including sodium-glucose cotransporter type 2 inhibitors, brain aminopeptidase A inhibitors, and new antagonists of endothelin receptors.

Objective. Renal sympathetic denervation (RDN) is one of the invasive treatment options for the patients with hypertension (HTN) who are resistant to antihypertensive therapy (AHT). The short-term efficacy of RDN has been proven in a number of randomized clinical trials, but remains controversial, the data on its long-term efficacy are limited. The aim of our study was to evaluate the natural course of HTN, to assess long-term major adverse cardiovascular events (MACE) and other outcomes, as well as AHT efficacy and its features in patients with resistant HTN after bilateral RDN during extended prospective follow-up. Design and methods. We included 22 patients with truly resistant HTN (median 57 y. o., 9 males), in whom RDN was performed during 2012–2015 in the clinical center of excellence. We assessed initial and further (after 1 year and after ≥ 5 years) clinical, laboratory and anthropometric parameters, as well as detailed AHT history. Long-term MACE and other clinically significant outcomes were recorded. At baseline and follow-up, the quality of life (QoL) was determined with the use of EQ-5D questionnaire at all time points. Multiple linear regression was used to find possible predictors of the efficacy of RDN. Results. A significant and sustained drop in office and ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed at 12 months after RDN compared to baseline values (∆ –24 and –12 mm Hg, p < 0,005; ∆ –10 and –7 mm Hg, p < 0,05, respectively). There were 7 patients with office SBP on-target, and 12 patients were considered responders (∆ SBP > 10 mm Hg). These numbers increased to 10 and 14 patients after ≥ 5 years after RDN. A causal relationship between changes in office SBP was found only for the baseline SBP (β -0,6, p = 0,02). No differences in the number of medications were noted during follow-up (4,4; 4,1 and 4,1 drugs, p = 0,41). During the follow-up 10 MACE occurred and 5 patients were diagnosed with various types of cancer; there were no fatal outcomes. The QoL significantly improved a year after RDN (+9,7 points, p = 0,01), however, a negative trend was observed in the next 5 years with return to reference level. No association was observed between BP and QoL changes at two timepoints. Conclusions. The RDN shows a pronounced clinical effect in patients with resistant HTN up to 5 years, and is not accompanied by an AHT intensification, but is not associated with QoL changes. The initial positive trend for QoL completely harked back after 5 years which may be associated with the development of MACE. The only predictor of RDN positive effect is baseline SBP level.

Objective. To evaluate the role of computed tomography in the assessment of chronic thromboembolic pulmonary hypertension (CTEPH) severity. Design and methods. We included 41 patients. Chest dual-energy CT-computed tomographic angiography was performed according to the standard protocol and in some cases Dual Energy mode was used. The patients were divided into 2 groups: with proximal and distal types of pulmonary artery lesions. Results. Quanadli index and Score index showed a significant negative correlation with the value of cardiac output (CO) (r = –0,591, p < 0,05; r = –0,531, p < 0,001, respectively), mixed venous blood saturation (SvO2) (r = –0,457, p = 0,065; r = –0,595, p < 0,001, respectively). For the Score index, significant negative correlations were established with both the CO value: r = –0,531, p < 0,001, the SvO2 r = –0,595, p < 0,001, and with the N-terminal pro-B type natriuretic peptide (NTproBNP) value (r = –0,537, p = 0,003). Correlations are also found in the analysis within the compared groups. The Quanadli index correlated with the mean pressure in the pulmonary artery in the group with the proximal type of lesion (r = 0,825, p = 0,012). Pulmonary artery aneurysms were detected in 39 % (n = 16) patients. There was a positive correlation between the presence of a pulmonary artery aneurysm and the functional class of CTEPH (r = 0,526, p = 0,007) in patients with the distal lesion. Conclusions. Quanadli and Score indices are promising tools for CTEPH severity assessment.

Background. Low plasma concentration of L-homoarginine (hArg) is associated with the progression of cardiovascular disease. However, the association between plasma hArg and cardiovascular complications in hypertension is not established. Objective. To assess and compare hArg levels as a biomarker of cardiovascular risk in hypertension. Design and methods. We included 60 hypertensives with moderate (n = 12), high (n = 16) and very high (n = 32) cardiovascular risk. Blood plasma tests including hArg were assessed. The control group included 30 age-matched regular donors. Results. The level of hArg was significantly lower in hypertensives compared to ocontrols (р < 0,001). There were negative correlations between hArg and echocardiography parameters of left ventricular hypertrophy. In the higher cardiovascular risk groups hArg was lower (р = 0,042). ROC-analysis showed AUC 0,860 (95 % confidence interval 0,787–0,933) with the threshold for hArg ≤ 1,69 µM, sensitivity 72,0 % and specificity 93,3 %. Conclusion. The hArg plasma level is associated with the expression and enzyme activity of the protein arginine: glycinamidinetransferase in various tissues. The hArg level ≤ 1,69 µM can be considered a cumulative laboratory biomarker of high cardiovascular risk. Further studies of prognostic and diagnostic role of hArg are needed.

Objective. The aim of the study was to analyze cognitive functions, emotional disorders, the quality of life with the application of the International Classification of Functioning (ICF) in patients with chronic cerebrovascular diseases, dyscirculatory (vascular) encephalopathy II stage in the Komi Republic. Design and methods. In the clinics of the Komi Republic, we examined 126 people (mean age — 65,8 ± 10,1 years; women comprised 76 participants, 60,3 %, p ≤ 0,05) with dyscirculatory (vascular) encephalopathy. Complaints and anamnesis were analyzed, somatic and neurological status, cognitive functions, emotional status, and sleep were assessed. Results. Out of 126 patients, 44,5 % patients are employed (56 people). Among non-working patients with an established group of disability, 35,7 % (in 14,3 % disability 2^nd degree (10 people), in 21,4 % — disability 3^rd degree (15 people), p ≤ 0,05). Among the workers, 3 people (5,3%) had disability 3^rd degree. Hypertension (HTN) I stage was detected in 10,6 %, HTN II stage — in 44,4 %, HTN III stage — in 45 % (p ≤ 0,05); 27,8 % had history of ischemic heart disease, 7,2 % — myocardial infarction, 19,1% — cerebrovascular accident, 8,6% — heart rhythm disturbances, 15,8 % — significant stenosis of the brachiocephalic arteries. Based on memory function assessment by ICF, none demonstrated normal results. Mild cognitive impairment was usually found, and there was no case of dementia. Dysfunction in the domain of blood pressure function was found in all patients. The dysfunction of blood vessels was found in all patients with chronic cerebral ischemia II stage. Daily activities were reduced due to the physical dysfunction. According to the total assessment of health status by the SF-36 scale, the physical and mental components of health were similarly decreased. Conclusions. The SF-36 (questionnaire for assessing the quality of life) and ICF (International Classification of Functioning, Disabilities and Health) complement each other. Cognitive scales are the basic tools for examination of patients with chronic cerebral ischemia, making diagnosis according to ICF, and treating cognitive, physical and emotional disorders in dyscirculatory (vascular) encephalopathy.

Objective. To assess the effect of antihypertensive therapy with ramipril and indapamide on the elasticity of the vascular wall of the large arteries in relation to insulin resistance and chronic low-intensity inflammation in patients with hypertension (HTN) and non-alcoholic fatty liver disease (NAFLD). Design and methods. An open prospective controlled study was conducted: 30 patients with HTN stage I–II in combination with NAFLD (Fatty Liver Index (FLI) > 60) at the age of 45–65 years were included. Washout period was scheduled 5–7 days before the baseline examination, followed by the prescription of one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg), depending on the required dosage (Konsilar-D 24 VERTEX AO, Russia) and were given recommendations on lifestyle changes and weight loss. A clinical examination was carried out, indicators of daily blood pressure (BP) monitoring and central aortic pressure (CAP), pulse wave velocity (PWV), lipid and carbohydrate metabolism, chronic low-intensity inflammation and the severity of insulin resistance before and after treatment were analyzed. Results. After 24-week therapy with a fixed combination of ramipril and indapamide at an average dosage of 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively, 100% of patients with HTN and NAFLD achieved target BP levels. According to 24-hour BP monitoring data, a significant decrease in systolic BP (SBP) and diastolic BP (DBP) was observed, both in the daytime (Δ12 mm Hg, р = 0,0001; Δ5,5 mm Hg, р = 0,0019, respectively), and at night (Δ13,5 mm Hg, р = 0,0006; Δ5,5 mm Hg, р = 0,0054, respectively). In addition, there was a significant decrease in CAP in the daytime (SBPao p = 0,0011, DBPao p = 0,0022) and night hours (SBPao p = 0,0015, DBPao p = 0,00124), and a statistically significant decrease in augmentation index (day p = 0,0460, night p = 0,0182). When evaluating clinical data and bioimpedance measurements, a decrease in waist circumference (p = 0,0000), hip circumference (p = 0,0001), the proportion of subcutaneous (p = 0,0134) and visceral (p = 0,0019) fat was found, which may indicate a decrease in the severity of visceral obesity. Also, during treatment, there is a decrease in the severity of insulin resistance (and the concentration of tumor necrosis factor alpha (TNF-α) (p < 0,0001) and CRP (p = 0,0002) in blood plasma. Finally, fixed combination of ramipril and indapamide led to a significant decrease in vascular stiffness (p = 0,0166) and a decrease in the proportion of patients with PWV paradoxical test (p = 0,0320). Correlation analysis showed that increased stiffness of the large arteries in patients with HTN and NAFLD is closely related to insulin resistance and lipid metabolism. At the same time, after 24-week therapy by a fixed combination of ramipril and indapamide, a decrease in the vascular stiffness in patients with HTN and NAFLD significantly correlated with the TNF-α concentration. Conclusions. A 24-week therapy by the fixed combination of ramipril and indapamide iin patients with HTN and NAFLD is associated with the persistent decrease in BP and CAP, both during the day and at night. There was a decrease in the vascular rigidity in muscular arteries. The treatment and recommendations for changing the lifestyle are associated with the decrease in the severity of abdominal obesity and insulin resistance, as well as the decrease in the severity of low-intensity systemic inflammation in patients with HTN and NAFLD, and a significant correlation was established between a decrease in TNF-α and an increase in the vascular elasticity of muscle and elastic type arteries.

The combined effect of dyslipidemia and high blood pressure largely contributes to the development and progression of cardiovascular diseases, and therefore the control of these risk factors should be a priority strategy both within primary and secondary prevention. A concept of a polypill, which provides effective control of both blood pressure and lipid profile, is a promising strategy. It allows of controlling several factors of the cardiovascular continuum, and contributes to a higher patient adherence to treatment. Therefore, the wider implementation of a polypill strategy will improve patients’ prognosis and quality of life.