Objective. To estimate changes in clinical status, quality of life, structural and functional myocardial parameters in patients with early stages of chronic heart failure with preserved ejection fraction (EF) with the combination treatment by calcium antagonist and renin-angiotensin-aldosterone system blocker (angiotensin converting enzyme inhibitor or angiotensin II receptor blocker). Design and methods. We examined 104 patients with chronic heart failure with preserved EF (EF > 50 %). All patients were divided into three groups: the first group (n = 37) was treated by combination of amlodipin (average dose 6,9 ± 2,1 mg/day) and perindopril arginine (average dose 12,3 ± 2,9 mg/day), the second group (n = 37) — by combination of S (-) amlodipin (average dose 3,2 ± 1,1 mg/day) and valsartan (average dose 130,8 ± 38,8 mg/day), the third control group (n = 30) — by standard therapy of chronic heart failure. All patients underwent full examination at baseline and in 12 weeks, including clinical status, the level of N-terminal brain natriuretic propeptide, quality of life by Minnesota questionnaire, 6-minute walk test, electrocardiogram monitoring, and heart ultrasound. Results and conclusions. Decrease in clinical manifestations and symptoms of chronic heart failure, improvement of exercise tolerance, increase in quality of life, regress of myocardial hypertrophy were found in all groups. Increased exercise tolerance and reduction in the degree of myocardial hypertrophy was the most expressed in the first group (calcium antagonist + angiotensin II receptor blocker), improvement of diastolic function — in the second group (calcium antagonist + angiotensin converting enzyme inhibitor).

Objective. To evaluate patient-oriented endpoints and antihypertensive effectiveness of blood pressure (BP) monitoring and distant counseling (TMDC) among outpatients with uncontrolled hypertension (HTN). Design and methods. Programs of TMDC with different duration of follow-up (1, 3, 6, 12 months) were developed (with obligatory initial and final clinic visits). The demand in TMDC was assessed by a preliminary survey among cardiologists (n = 73) and hypertensive patients (n = 540) referred to Almazov National Medical Research Centre. Patients with uncontrolled HTN who signed informed consent were enrolled in the study being assigned to TMDC or to the age, sex and BP level-matched control group; the latter ones were given standard recommendations (outpatient visits once every 3 months). None of the patients had any serious comorbidities requiring frequent face-to-face visits. On a baseline clinic visit TMDC patients were given detailed technical instructions on BP selfmonitoring and request for counseling through web-site and mobile application. Office BP levels were evaluated twice, at baseline and at the final clinic visit. In the TMDC group BP level, the frequency and reasons for the consultations were assessed. For evaluation of patient-reported outcomes questionnaires of the Hospital Anxiety and Depression Scale («HADS») and «SF-36» were provided at the first and final visits. Results. According to initial survey, 12 (16 %) of 73 cardiologists and 184 (34 %) among 540 patients at Almazov National Medical Research Centre gave a positive opinion regarding TMDC. Most patients (n = 129; 70 %) chose a three-month TMDC plan. Of these, 110 patients (74 men, mean age 51,2 ± 17,0 years) completed follow-up period; control group consisted of 80 sex-, age- and BP-matched patients. TMDC group demonstrated a more pronounced decrease in office systolic (SBP) and diastolic (DBP) BP levels as compared to the control group: Δ –22 ± 12,4 versus Δ –8,6 ± 22,4 mmHg for SBP (p = 0,005) and Δ –13,6 ± 10,8 versus Δ –7 ± 11,3 mm Hg for DBP (p = 0,02). At final visit target office BP level (< 140/90 mmHg) was achieved in 82 patients (75 %) and 16 patients (20 %) in the TMDC and control groups, respectively (χ 2 = 20,8; p < 0,01). For the entire follow-up period, everyone in TMDC group required at least 1 remote doctor’s advice and in 36 cases (33 %) antihypertensive therapy correction was necessary. Aside, TMDC group showed reduction in anxiety and depression according to HADS (–1,2 and –1,8 score, respectively, p < 0,05) and improvement in physical HRQoL (+ 9 ± 3,3 points SF-36, p = 0,04). Conclusion. Results demonstrated that a simple and safe telehealth tool for patients with uncontrolled HTN is easily applicable in routine daily clinical practice, provides additional antihypertensive effect and improves patientreported outcomes. However, it needs additional support measures for higher acceptance in routine practice.

Objective. To study the impact of cardiometabolic risk factors and polymorphic variants rs2290149 and rs10838692 of the MADD gene on myocardial remodeling in the elderly patients with hypertrophic cardiomyopathy (HCM). Design and methods. We enrolled 257 patients with left ventricular hypertrophy (LVH) of various origin (mean age 57,7 ± 11,2 years; men — 5 %, women — 48 %): HCM (n = 154) and LVH caused by cardiometabolic risk factors (n = 103). The control group included 288 healthy donors. A standard clinical (laboratory and instrumental) diagnostic methods were applied. Genotyping for SNPs rs2290149 and rs10838692 of the MADD gene was performed using real time polymerase chain reaction (PCR). Results. Pre-obesity and obesity in patients with HCM were associated with increased left ventricular (LV) posterior wall thickness (14,82 ± 3,6 versus 12,77 ± 3,69 mm, respectively, p = 0,01), but not with the LV mass index and the interventricular septum. Obese HCM patients had greater detection rate of the symmetrical LVH (64 versus 10 % in non-obese HCM patients, p = 0,001). We observed a significant increase in frequency of TT genotype of rs2290149 and rs10838692 of the MADD gene in patients with LVH of various origin compared to healthy group: 81,6 vs. 71,5 % (ТТ : ТС+СС, p = 0,007) and 54,1 vs. 43,1 % (ТТ : ТС+СС, р = 0,002), respectively. The allele frequency also differs for rs2290149 (T : C = 89,6 : 10,4 % vs. 82,3 : 17,7 %; odds ratio (OR) = 1,864, 95 % confidence interval (CI) 1,306 to 2,660; p = 0,01) and for rs10838692 (T : C = 72,6: 27,4 % vs. 62,2 : 37,8 %; OR = 1,611, 95 % CI 1,246 to 2,082; p = 0,01). We found a significant increase in frequency of TT genotype of rs10838692 of MADD gene in patients with HCM 55,2 % (ТТ : ТС+СС, р = 0,019) and LVH caused by cardiometabolic risk factors — 52,4 % (ТТ : ТС+СС, p = 0,014) compared to healthy group (43,1 %). We also detected a trend towards the predominance of the TT genotype in rs2290149 of the MADD gene in patients with LVH caused by cardiometabolic risk factors (80,4 %) (ТТ : ТС+СС, р = 0,097), reaching a statistical significance in the HCM group (82,5 %) (ТТ : ТС+СС, р = 0,025) compared to healthy group (71,5 %). The allele frequency also differs for rs2290149 (T : C = 89,9 : 10,1 %, p = 0,01 in HCM; 89,2:10,8 %, р = 0,04 in LVH caused by cardiometabolic risk factors) versus 82,3 : 17,7 % in control group and for rs10838692 (T : C = 72,4 : 27,6 %, p = 0,01; 72,8 : 27,2 %, р = 0,01, respectively) versus 62,2 : 37,8 % in control. Conclusions. Pre-obesity and obesity in patients with HCM led to a greater LV posterior wall thickness and symmetrical myocardial remodelling. The T allele and TT genotype of SNPs rs10838692 and rs2290149 of the MADD gene were associated with the presence of LVH of various origin in the older subjects, but do not affect the degree of myocardial hypertrophy. Patients with HCM showed greater frequency of simultaneous carriage of the TT genotype and сombined carriage of the T allele of the polymorphic variants rs10838692 and rs2290149 of the MADD gene compared to the control group. The presence of obesity/overweight in patients with combined carriage of the TT genotype and simultaneous carriage of the T allele is associated with a greater thickness of the LV posterior wall, an increase in the left atrium size and the LV end-diastolic dimension.

Background. Dyspnea is the most frequent, but not specific manifestation of the chronic heart failure (CHF). The arterial hypertension (HTN) is one of the causes of CHF. Its verification requires an echocardiography with tissue Doppler, which is not always available in routine practice. Identification of easily estimable CHF predictors in hypertensive patients with dyspnea is an important task. Objective of our study was the identification of the predictors of CHF with preserved ejection fraction (EF) among hypertensive outpatients with dyspnea. Design and methods. We included 116 outpatients with HTN and dyspnea over 60 years old with EF ≥ 50 %. Exclusion criteria were concomitant diseases which might lead to CHF. All patients performed the 6-minute walk test and echocardiography with tissue Doppler. Results. CHF was confirmed in 52,6 % patients. Palpitations, right-sided heaviness below the ribs, swollen feet, as well as reduced tolerance to physical activity were more frequent in older patients with HTN and dyspnea and did not allow to confirm CHF. Patients with confirmed CHF showed higher levels of systolic blood pressure (SBP). They had longer disease anamnesis and lower financial resources. Conclusions. Among elderly hypertensive outpatients with dyspnea every second one has no echocardiographic signs of CHF. SBP ≥ 140 mm Hg according to home measurements is associated with the 6-fold higher probability of CHF with preserved ejection fraction. In the elderly hypertensive outpatients with dyspnea, the duration of HTN more than 20 years and limited financial resources for medications are associated with the increased probability of CHF.

Background. Registries are the most accurate tool for assessing the status of real clinical practice. The registries help to identify deficiencies in the management of patients, to determine the most optimal ways to improve the quality of treatment. In 2015, the Republican Specialized Center of Cardiology organized and initiated the Registry of acute coronary syndrome (ACS) and acute myocardial infarction (AMI) in one of the districts of Tashkent city (RACSMI-Uz Registry). In the present work, which is a fragment of the RACSMI-Uz study, the main clinical and laboratory characteristics of patients with ACS/AMI were collected and analyzed, depending on the presence or absence of arterial hypertension (HTN). Design and methods. We analyzed the registry database of 432 patients who survived ACS/AMI. Results. In HTN patients survived after ACS/AMI, such accompanying pathologies as 1–2 stage obesity, myocardial infarction in past, type 2 diabetes mellitus, etc. were registered more often and the rate of stenotic (> 50 %) narrowing of the coronary arteries was greater. The heart rate > 80 beats/min was 1,5-times greater among HTN patients than among non-HTN subjects. Lipid metabolism in patients after ACS/AMI with concomitant HTN was characterized by hypertriglyceridemia and relatively safe low values of total cholesterol level. Compliance with medications was 2 times higher in HTN patients with ACS/AMI than among those without HTN.

The main causes of ischemic stroke (IS) include arterial hypertension (HTN) and cerebral atherosclerosis. Based on the recent evidence, vascular endothelium is considered a target organ in patients with HTN and atherosclerosis, as well as an effector in their pathogenesis. The concept of endothelial dysfunction includes structural and functional changes in the endothelium. The level of circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in the blood allows us to judge about degree of endothelial damage and its reparative activity. The article presents data on the diagnostic value of assessment of CECs and EPCs by flow cytometry for predicting the course and outcomes of IS in hypertensive patients.

Objective. To evaluate diastolic function of the left ventricle and anthropometric parameters in patients with abdominal obesity (AO). Design and methods. We examined 438 patients aged 30 to 55 years (44,8 ± 0,3 years) with AO (IDF, 2005) and 115 patients (40,3 ± 0,8 years) without AO (comparison group). Two-dimensional transthoracic echocardiography was performed (GE Vivid 7 Dimension) in 2D mode, in M-mode, also Doppler studies were performed using pulsed, continuous-wave, color and tissue regimes of Doppler. Results. Based on echocardiography, 126 patients with AO and arterial hypertension (HTN) (28,8 %) (94 women and 32 men) had type I left ventricular diastolic dysfunction (LVDD). In patients with AO and without HTN, the E/A ratio and the E’ value were lower, and the DT and isovolumic relaxation time (IVRT), the E/E’ and LAVI ratio are higher than the same parameters in the comparison group (p < 0,0001). Only the ratio E/E’ was in accordance with the criteria for type 1 LVDD. We found positive correlations between the body mass index (BMI) and the IVRT (r = 0,3, p = 0,0001), BMI and the E/E’ ratio (r = 0,4, p = 0,0001), BMI and LAVI (r = 0,4, p = 0,0001), between the waist circumference (WC) and the IVRT (r = 0,3, p = 0,001), the WC and the E/E’ (r = 0,3, p = 0,0001), WC and LAVI (r = 0,4, p = 0,0001) in female with AO without HTN. In patients with AO and without HTN, there is a 3,7-fold increase in LVDD risk in case of BMI ≥ 30,0 kg/m 2 (odds ratio: 3,7, 95 % confidence interval: 1,2–9,0, p < 0,0001). Conclusions. The type I LVDD was found in patients with AO and HTN. in patients with AO without concomitant HTN, the risk of LVDD increases by 3,7 times with a threshold of body mass index ≥ 30,0 kg/m 2.

Objective. To evaluate myocardial function in patients with chronic heart failure with preserved left ventricular ejection fraction (CHF-PEF) by speckle tracking echocardiography. Design and methods. We examined 56 patients aged from 50 to 69 years with verified CHF-PEF, NYHA (New York Heart Association) class I–IIa and stage A–C of the ABCD classification of the American College of Cardiology, and 15 healthy persons. CHF-PEF was associated with arterial hypertension and coronary artery disease. The results of 6-minute walk test, echocardiography and speckle-tracking echocardiography were analyzed. Results. The average left ventricular ejection fraction measured by Simpson’s method was 61,7 ± 5,28 %. According to the 6-minute walk test the patients were divided as followed: 26,7 % — stage A, 48,2 % — stage B, 25,1 % — stage C. All patients with CHF-PEF had the diastolic dysfunction: in 48 patients abnormal relaxation pattern was found, and in 8 pseudonormal pattern was shown. Patients with CHF-PEF had reduced global longitudinal strain (GLS –16,6 ± 2,58 %) and GLS rate (GLSR –0,74 ± 0,12 s) of the left ventricle. Also they had reduced strain and strain rate in basal anteroseptal (–13,2 ± 3,24 % and –0,75 ± 0,03 s-1) and basal anterolateral (–14,16 ± 3,29 % and –0,83 ± 0,12 s-1) segments. Conclusions. Patients with CHF-PEF have abnormal relaxation pattern and pseudonormal pattern of the diastolic dysfunction. They also have reduced global and segmental strain and strain rate of the left ventricle.

Background. Endothelial dysfunction underlies the development of chronic complications in type 2 diabetes mellitus. Glucose-lowering drugs with additional protective effects on endothelium are required. Objective. To study endothelial protective action of liraglutide in patients with type 2 diabetes mellitus and to detect its relation with glycemic control. Design and methods. The study was held in patients with type 2 diabetes mellitus with glycated hemoglobin 7,5–9,0 % who received metformin monotherapy. Metformin dose had been titrated for 3 months. Patients who reached glycated hemoglobin level less than 7,5 % were included in the group 1 — they had received metformin monotherapy for next 6 months. Patients with glycated hemoglobin over 7,5 % after 3 months formed the group 2, and they received liraglutide in addition to metformin for the following 6 months. At baseline, at 3, 6 and 9 months, endothelium-dependent vasodilation was evaluated by forearm microcirculation dopplerography with 0,3 % acetylcholine solution ionophoresis. Results. At baseline, patients of groups 1 and 2 showed impaired endothelium-dependent vasodilation (decrease of the reaction to acetylcholine, curve form change). There was no significant change in the linear blood flow parameters in the group 1 when euglycemia was reached by metformin monotherapy. Additional administration of liraglutide in the group 2 led to the increase in the amplitude and favourable change of the curve form. These changes were more prominent after 6 months of combined therapy. Endothelium-dependent vasodilation amplitude reached values observed in healthy subjects after 9 months from the study beginning. Conclusions. The improvement of glycemia control (euglycemia) does not have endothelial protective properties on its own. Liraglutide has its own endothelial protective action independent of glycemia control.

Objective. Metabolic syndrome (MS) increases the risk of atrial fibrillation (AF). The probability of the incident AF increases in case of atrial fibrosis and remodeling. Transforming growth factor beta 1 (TGF-β1, encoding gene TGFB1) induces myocardial fibrosis, in particular, in the atria. We analyzed the distribution of CC, CG and GG genotypes G/C+915 polymorphism of TGFB1 gene in patients with MS and AF. Design and methods. We included 426 subjects (30–65 years old): 222 patients with MS, including 115 patients with paroxysmal and permanent AF. The control group included 209 healthy individuals without cardiovascular disease and metabolic disorders. Genomic DNA was isolated from the venous blood. Allelic variants were identified by polymerase chain reaction followed by restriction analysis with endonucleases BglI. Results. GG genotype G/C (+915) TGFB1 gene in patients with MS and AF is more frequent than in MS patients without AF (97,4 and 87,9 %, respectively; χ 2 = 6,19, p = 0,013) and in healthy individuals (97,4 and 86,6 %, respectively; χ 2 = 8,77, p = 0,003). GG genotype is associated with an increased the risk of AF in patients with MS (odds ratio (OR): 5,74, 95 % confidence interval (CI): 1,71–19,33, p = 0,012). There were no differences in GG genotype G/C (+915) TGFB1 gene in MS patients without AF and healthy individuals. GC genotype G/C (+915) TGFB1 gene in healthy individuals was found more frequently than in MS with AF (12,4 and 2,6 %, respectively; χ 2 = 7,63, p = 0,006) and more frequently in MS patients without AF (12,1 and 2,6 %, respectively; χ 2 = 6,19, p = 0,013). C allele (genotype GC+CC) gene TGFB1 is associated with the decreased risk of AF in patients with MS (OR = 0,19, 95 % CI 0,05–0,70, р = 0,001). Conclusions. We found an association of G/C (+915) TGFB1 gene with the risk of AF in patients with MS. C allele (СС and CG genotypes) seems to be protective and is associated with the 5,3-fold reduction in the risk of AF in patients with MS. We suggest that increased expression of gene TGFB1 causes heterogeneity of conduction and contributes to the AF in patients with MS.

Objective. We performed post-hoc analysis of results of multicenter open-label randomized comparative trial on antihypertensive efficacy and safety of fimasartan and losartan in parallel groups for adult outpatients with mildto-moderate hypertension (HTN) during 12 weeks of treatment in order to determine characteristics associated with better treatment efficacy. Design and methods. Post hoc analysis included ITT (intention-to-treat) population: 89 patients from fimasartan group and 90 patients from losartan group. We assessed associations between change from baseline in “office” sitting systolic and diastolic blood pressure and gender, age, anthropometric parameters, duration and severity of hypertension, previous antihypertensive treatment, clinical and laboratory parameters on study visits, and doses of studied drugs. Statistical package R (version 3.0.2, The R Foundation for Statistical Computing 2013) was used for analysis. Results. Fimasartan and losartan provided comparable blood pressure lowering effect in gender, age subgroups, in patients with different duration and severity of hypertension, risk factors profiles. There was a trend toward higher blood pressure decrease in patients with body mass index (BMI) ≥ 30 kg/m 2 in fimasartan group. In the overall population BMI ≥ 30 kg/m 2 was associated with 2-fold increase of risk of dose change at any visit: odds ratio (OR) = 2,1 (95 % confidential interval (CI): 1,08–3,91). However, study groups analysis demonstrated that it was true only for losartan: OR = 2,75 (95 % CI: 1,1–6,88; р = 0,036). Fimasartan was equally effective in both obese and normal weight patients: OR = 1,50 (95 % CI: 0,63–3,93; р = 0,356). Conclusions. Hypertensive patients with BMI ≥ 30 kg/m 2 may benefit more from fimasartan treatment. This fact needs confirmation in further studies with larger sample size.

Coronary heart disease is one of the most important clinical problems of modern medicine, which is associated with its high prevalence, low quality of life, poor prognosis and high mortality. Chronic heart failure (CHF) is one of the cardiovascular continuum endpoints, which starts from the risk factors of arterial hypertension (HTN) and leads to the development of atherosclerosis, myocardial infarction and subsequent reduction of the pumping function of the heart. According to the Framingham study, systolic blood pressure > 140 mm Hg is associated with a 4-fold increase in the risk of CHF and the normalization of blood pressure allows a 50 % reduction in the risk of CHF. Early diagnosis of HTN and risk assessment will allow to interrupt the cardiovascular continuum. Recently the serum biomarkers have been recognized as important toll for the diagnosis of heart failure and cardiovascular events. They reflect various pathophysiological aspects. In particular, the following biomarkers are produced in CHF: biomarkers of apoptosis (tumor necrosis factor α, Fas), remodeling of extracellular matrix metalloproteinase, inflammation and fibrosis (galectin-3, ST2, transforming growth factor beta 1). The review presents a brief description of the above biomarkers and their effects on the development of CHF and cardiovascular events.

Objective. Target blood pressure (BP) is achieved only in 1/3 of patients with arterial hypertension (HTN). The target is most difficult to achieve in elderly patients. Systolic BP (SBP) in elderly patients is the strongest prognostic factor of cardiovascular complications. Thiazide/thiazide-like diuretics and calcium antagonists are effective drugs for reducing SBP and pulse pressure (PP). They also show positive impact on aortic BP, which is associated with high arterial stiffness and is common in elderly people. The combination of a thiazide diuretic and a calcium antagonist is recommended by the current algorithms and guidelines for HTN, but due to the lack of a fixed combination, it has not yet been widely applied in clinical routine practice. Recent data on the efficacy, safety of indapamide retard and amlodipine suggest that their combination may become an alternative treatment option for HTN patients, especially in patients with high SBP and PP, in elderly patients and other groups of patients with high arterial stiffness.