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Clinical and hemodynamic aggravation of heart failure with preserved ejection fraction (HFpEF) is largely due to progression of left ventricular (LV) diastolic dysfunction. The key role in the normal maintenance of diastolic function is played by a high level of activity of the intracellular signaling axis, cyclic guanosine-monophosphate-protein kinase G, the activity of which is significantly reduced in HFpEF. The activity of this axis can be increased by increasing the bioavailability of natriuretic peptides by blocking the enzyme neutral endopeptidase (neprilisin), which is responsible for the destruction of natriuretic peptides.This review presents experimental and clinical data on the use of neprilysin inhibitors in HFpEF and addresses prospects of this treatment.

Актуальность. Остеопороз и атеросклероз заболевания, имеющие сходство в патогенезе и общие звенья в механизме действия вы1 сокоэффективных препаратов для их лечения: бисфосфонатов и статинов. Цель. Оценить возможности потенцирования эффектов комбинированной терапии алендронатом и розувастатином по влиянию на артериальную жесткость, концентрацию общего холесте1 рина (ОХС), липопротеидов низкой плотности (ЛПНП), маркера костного обмена (С1концевого телопептида коллагена I типа (CITP), минеральную плотность костной ткани (МПКТ). Материал и методы. Обследованы 48 пациентов (средний возраст 64 (5672) года) с высоким риском сердечно1сосудистых осложнений и остеопенией (T1критерий от 1 до 2,5 SD по результатам денситометрии, DEXA), преимущественно с гипертонической болезнью n42 (88) и достигнутым целевым уровнем артериального давления (АД). Пациенты были рандомизированы в 2 группы: А (n26) комбинированная терапия розувастатином (средняя доза 197 мг) и алендронатом (70 мг 1 раз в неделю) и Б (n22) терапия розувастатином (средняя доза 147 мг). Исходно и через 12 мес. определены уровни центрального систолического и центрального диастолического артериального давления (цСАД, цДАД), каротидно1феморальной скорости пульсовой волны (СПВкф), аппланационная тонометрия, сердечно1лодыжечный сосудистый индекс (СAVI) (обьемная сфигмография), ОХС, ЛПНП, маркера костной резорбции (С1концевого телопептида коллагена I типа, CITP), МПКТ (DEXA). Результаты. Средняя доза розувастатина, исходные и финальные значения уровня ОХС, ЛПНП в группах сравнения не отличались. В группе А наблюдали статистически значимую динамику СПВкф (p0,01), составившую 11(11,8 10,2) м/си CAVI10,3(11,4 0),(p0,05), в группе Б динамики СПВкф и CAVI не произошло. В группе А в отличие от группы Б произошел статически достоверный прирост МПКТ шейки бедра (p0,05). Уровень CITP статистически значимо снизился в группе А c0,37 (0,160,57) до 0,23 (0,150,35)г/мл, p0,05 в группе Б динамики CITP не отмечено. Выявлена стати1 стически значимая корреляция динамики уровня CITP со снижением цСАД в группе А (r0,399, p0,05). Заключение. Комбинированная терапия алендронатом и розувастатином у пациентов с высоким риском развития сердечно1сосудистых осложнений и остеопенией сопровождалась увеличением МПКТ, снижением СПВкф, CAVI и отсутствием дополнительного влияния на уровни ОХС, ЛПНП в крови. Выявлена ассоциация между динамикой уровней CITP и цСАД.Introduction: Osteoporosis and atherosclerosis are diseases linked by pathogenesis and have similar mechanism of actionof high effective drug agents: bisphosphonates andstatins. Objectives: to investigate whether is a synergistic activity of alendronate and rosuvastatin in the regression of arterial stiffness level, serum holesterol, low density lipoproteins (LDL), C1terminal telopeptide collagen type I (CITP) concentrations in high cardiovascular risk (HCVR) patientswith osteopenia. Methods: 48 HCVR patients average age of 64(5672) years with osteopenia (T1score from 1 to 2.5SD (dual1energy X1ray absorptiometry (DEXA), mostly with arterial hypertension (n42 (88)) and with target blood pressure achieved were randomized into two groups:А1group with rosuvastatin (197 mg) alendronate (70 mg/week) combination treatment (n26) and B1group with rosuvastatin (147 mg) treatment (n22). Carotid1femoral pulse wave velocity (PWVcf, applanation tonometry), CAVI (volume sphygmography), serum holesterol, serum holesterol, LDL and CITP levels, bone mineral density (BMD (DEXA)) were measured. Results: No significant difference in doses of rosuvastatin, baseline and final LDL levels between groups A and B were found. In group A, there was a significant dynamics of PWVcf11 (1.8... 0.2) m/s (p 0.0) and CAVI 0.3 (1,4... 0) (p0.05). In group B, the dynamics of PWVcf and CAVI did

Not only “classic” risk factors such as age, sex, smoking status, blood pressure (BP) and cholesterol (HS) levels, but also additional factors, one of which is the psychological status of the patient, need to be considered to improve the prediction of cardiovascular complications. This is especially true for low/moderate risk patients on the SCORE scale, whose risk of cardiovascular complications (CVC) is often underestimated. Aim To assess the contribution of psychological status of hypertensive patients and SCORE Materials and methods In 2009, 142 hypertensive patients with SCORE risk Results At the time of inclusion in the study, the age of the patients was 50, 9±8.2 years. At the first visit systolic BP (SBP) level was 130.0 (128.4; 133.7) mm Hg and diastolic BP (DBP) 80.0 (81.3; 84.5) mm Hg. The HS level was 6.1 (5.9; 6.3) mmol/L, triglycirides 1.4 (1.5:1.8) mmol/L, low dencity lipoproteins 3.8 (3.6; 4.0) mmol/L, high density lipoproteins 1.3 (1.4; 1.5) mmol/L. Level of anxiety (A) was 7.0 (7.0; 8.2) points, depression (D) – 5.7 (5.2; 6.2) points. The patients without the expressed symptom of D (0–7 points) – 76.8% (n=109), A (0–7 points) – 52% (n=74). The patients with clinically significant D (>11 points) – 8.5% (n=12), A (>11 points) – 18.3% (n=26). 2 CVD occurred in the observed group in 10 years (1.4%), 6 MI, 12 percutaneous coronary intervention (8 acute coronary syndrome), 4 strokes, 34 cardiovascular hospitalizations. 14 new onset cases of coronary artery disease (9.6%). Thus 31.7% of observed patients had CVC. Comparison of the initial data of the group with CVC with the group without CVC revealed a difference only in the level of D: 7.0 (5.6; 7.3) points in patients with CVC vs 5.0 (4.7; 5.8) p=0.04) – Fig. 1. The patients were comparable in sex and age. BP, lipid profile, glucose, heart rate, smoking status, levels of A did not differ significantly. Multi-factor regression analysis has demonstrated that depression levels D is an independent predictor of the development of complications in a model involving age, sex, BP, HS and A (β=0,218, p=0,03). Conclusion Level D is an independent risk factor development of CVC in hypertensive patients low/moderate risk on SCORE. Funding Acknowledgement Type of funding source: None

Background The low efficiency of recommended therapy for reducing cardiovascular risk (CV) in patients with arterial hypertension even with an effective blood pressure decrease is often due to the persistence of high blood cholesterol and arterial stiffness. Among the effective ways to achieve the goal of therapy is considered the changing to a single-pill combinations (SPCs) of two antihypertensive drugs and statin. Aim To assess influence of fixed combination consisted of amlodipine, lisinopril and rosuvastatin to the dynamic of lipid spectrum, blood pressure level and elastic properties of arteries in patients with arterial hypertension and high risk of cardio-vascular complications being transferred from their preceding antihypertensive therapy. Materials and methods 113 patients with atherosclerosis of brachiocephalic arteries (BCA) receiving antihypertensive and partially taking statins therapy were assessed cholesterol, low-density lipoprotein cholesterol (LDL-C), peripheral and central blood pressure, carotid-femoral pulse wave velocity (PWV) initially and after 12 months of taking amlodipine + lisinopril + rosuvastatin (A+L+R) SPCs. Results The administration of A+L+R SPCs for 12 months was associated with an increasing of number of patients with the achieved target blood pressure.

Dry carbon dioxide baths have a positive effect on blood pressure, the number of blood platelets, blood rheological properties of weather-dependent patients with arterial hypertension. The obtained results justify the possibility of dry carbon dioxide baths applying for treatment and prevention of meteopathies at patients with arterial hypertension.

Rationale: The influence of drugs on adaptation to high temperatures and seasonal variability of cardiovascular disease factors is one of the most important issues of treatment raised during re-cent heat waves. The safety of calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) use during heat waves is quite controversial. Aim: To assess the seasonal variability of hemodynamic parameters, vessel wall stiffness, lipid, carbohydrate and electrolyte metabolism in patients with arterial hypertension (AH) and to as-sess safety and effectiveness of fixed combination of Losartanum and Amlodipinum (Lortenza® KRKA) use according to one-year follow-up results. Materials and methods. The study included 26 patients with stage 1 and 2 AH aged from 42 to 81 years. Office blood pressure measurement, electrocardiography, volumetric sphygmography (pulse-wave velocity, cardio-ankle vascular index), serum chemistry, blood osmolarity tests were performed. Visual Analog Scale (VAS), Heat Questionnaries and self-control diaries were also assessed. The baseline visit took place in spring of 2016, the first visit - in May-June 2016, the second - during the heat wave, the third - in September-October 2016, the fourth - in January-February 2017, and the fifth - in April-May 2017. Results. The treatment resulted in systolic and diastolic blood pressure decrease (р=0.000) to target value which persisted during the follow-up period. According to the self-control diaries 81% of patients did really control BP. During the heat wave only 58% of patients succeeded in BP control, in autumn - 63%, in winter and spring - 81% and 86%, respectively. By the third visit the heart rate decreased on -6.0 (-11.1; -2.8) beats per minute, p=0.007. The decrease in pulse-wave velocity from 15.2±3.4 m/s to 13.6±2.7 m/s, p=0.01 and CAVI on -2.1 (-2.9; -0.65), p=0.01 was observed on the third visit. Decrease in uric acid level (р

Actuality. The effect of drugs on adaptation to abnormal temperatures is one of the most important questions put to practical medicine by the heat waves of recent years. One of the controversial issues - safety of use during the heat wave of calcium channel blockers (ACC) and blockers of receptors for angiotensin II (ARBS). The goal is to evaluate the efficacy and security of treatment of patients with arterial hypertension (AH) during the heat wave of a fixed combination of ARBS+ACC (Lortenza, KRKA). Materials and methods. Included 26 patients with hypertension 1 and 2 degrees from 42 to 81 years. All patients underwent measurement of office blood pressure, electrocardiography, body sphygmography with the determination of the pulse wave velocity and selectively CAVI, biochemical analysis of blood, estimation of osmolarity of blood, questionnaire: visual analogue scale, a questionnaire for patients exposed to heat, the test of adherence to treatment Moriscos-Green. Estimated diaries of self-control of blood pressure. The inclusion visit took place in spring 2016, 1st visit was in May - June 2016, 2nd - during heat waves, 3rd - September - October 2016. Results. The observed decrease in systolic blood pressure and diastolic blood pressure (p=0.000) to the target values, preserved for the whole period of observation. According to the diaries of self-control of blood pressure controlled blood pressure 81% of patients. During a heat wave, this value decreased to 58%, in autumn - to 63%. The 3rd visit achieved a reduction in heart rate at -6.0 (-11.1; and 2.8) beats/min; p=0.007. A noticeable decrease of the pulse wave velocity from 15.2±3.4 to 14.4 V±3.0 m/s; p=0.01 and CAVI in of-2.1 (to -2.9; -0.65); p=0.01; the decline in uric acid level c of 415.3 to 346.2 mmol/l (p=0.04) and creatinine on the 2nd visit compared to baseline (p=0.02). Electrolyte shifts and increasing the osmolarity of the blood during heat waves have not been identified. There is a growing commitment therapy (p=0.04) and quality of life to 20.0 (7.4; 23.3); p=0.000 by visual analogue scale. Conclusion. Fixed combination of losartan and amlodipine (Lorenza) is an effective, safe and may be recommended for patients receiving AG in the hottest period.

Background The contributions of the effectively treated hypertension on blood viscosity remain unclear, as well as impact of clinical and demographic parameters, biochemical variables, level of anxiety. Aim Aim of the study is to research viscosity state in patients with effectively treated hypertension and to reveal factors affecting blood viscosity. Materials 58 treated hypertensive patients (36 females and 24 males aged 62,9±9,7 years) with achievement of target blood pressure (BP) level (systolic BP was 130,9 (126,6; 135,4), diastolic BP - 81,4 (79,7; 83,1) mmHg. 71.7% of patients were treated with beta-blockers, 46.7% - angiotensin converting enzyme inhibitors (ACE inhibitors), 31.7% - angiotensin II receptor blockers, 38.3% - calcium channel antagonists, 18.3% - diuretics, 71.3% - statins, 60% - acetylsalicylic acid. Coronary heart disease (CHD) were presented in 24 (40%). The average cholesterol level was 5.11 (4.76; 5.46) mmol/l, creatinine 71.83±12.6 mmol/l, sodium 143.4 (143.0; 143.9) mmol/l. The level of anxiety disorders determined on Sheehan's Patient-Rated Anxiety Scale (SPRAS) was 33.7 (23.1; 39.2) points. Methods Whole blood viscosity at high (η1) and low (η2) shear rates, plasma viscosity (ηpl) were measured by a rotational viscometer. Aggregation of erythrocytes (η2/ η1) was studied also. The statistical analysis was carried out by nonparametric method of Spearman and multivariate regression analysis with STATISTICA 6. Results Hemorheological profile was as follows: η1 4,7 (4,7; 5,0) sec–1, η 2 24,6 (23,5; 26,5) sec–1, η2/η 1 5,4 (4,9; 5,3), η pl 1,52 (1,51; 1,55) sec–1. Blood viscosity in men was higher than in women in all indices studied: η1 5,4 (5,1; 5,7) sec–1 in men vs 4,6 (4,6; 5,0) sec–1 in women (p Conclusion In effectively treated hypertensive patients the level of anxiety, indirectly reflected the activity of the sympatho-adrenal system, proved to be an independent predictor of a higher value of η2/η1.

To study the impact of cold waves on disease course, hemodynamics, lipid and carbohydrate metabolisms, oxidative stress, and blood rheological properties in patients with cardiovascular diseases (CVD).24 men and 36 women (their mean age was 62.9±9.7 years) were examined; coronary heart disease (CHD) and hypertension were present in 40 and 95% of the patients, respectively; selected therapy remained unchanged throughout the entire period. The investigators measured blood pressure and pulse wave velocity (PWV), carried out biochemical blood tests, estimated plasma oxidized low-density lipoproteins (oxLDL) and malondialdehyde (MDA) and erythrocyte superoxide dismutase (SOD) activity, calculated a MDA/SOD ratio, determined blood viscosity; as well as assessed quality of life using a visual analogue scale (VAS) and a specially developed questionnaire.Female sex, CHD, type 2 diabetes mellitus (DM-2) were independent predictors of cardiovascular events (CVEs) in the frost period. The persons who had experienced CVEs in frost had higher baseline PWV. CVEs, such as hypertensive crisis, emergency calls, cardiac arrhythmias, and the larger number of adverse reactions, were more commonly recorded in frost. There was an increase in blood glucose levels, a decrease in oxLDL, a rise in η2/η1, and a reduction in plasma viscosity during frost and elevated glycation end product levels at visit 2. Conclusion. The cold wave is associated with the larger number of CVEs in some patients with CVD during selected therapy. CHD, DM-2, female sex are independent predictors of CVE in patients with CVD during the winter period. In this period, there were increases in the levels of glucose, glycation end products, and erythrocyte aggregation, and a reduction in plasma viscosity.Цель исследования. Изучение влияния волн холода на течение заболевания, а также на гемодинамику, липидный и углеводный обмен, окислительный стресс и реологические свойства крови у больных сердечно-сосудистыми заболеваниями (ССЗ). Материалы и методы. Обследовали 24 мужчины и 36 женщин (средний возраст 62,9±9,7 года), ишемическая болезнь сердца (ИБС) имелась у 40%, артериальная гипертония - у 95%, подобранная терапия оставалась неизменной весь период. Измеряли артериальное давление, скорость пульсовой волны (СПВ), проводили биохимический анализ крови, оценку окисленных липопротеидов низкой плотности (окЛПНП), малонового диальдегида, (МДА) в плазме, активность супероксиддисмутазы (СОД) в эритроцитах, рассчитывали отношение МДА/СОД, оценивали вязкость крови, а также качество жизни с помощью визуальной аналоговой шкалы (ВАШ) и специально разработанного опросника. Результаты. Независимыми предикторами сердечно-сосудистых осложнений (ССО) в период морозов явились женский пол, наличие ИБС и сахарного диабета 2-го типа (СД-2). У лиц, перенесших ССО в мороз, СПВ исходно была выше. Таких ССО, как гипертонический криз, вызов скорой медицинской помощи, нарушений ритма сердца, число нежелательных явлений отмечено больше в мороз. Выявлено увеличение в крови уровня глюкозы, уменьшение окЛНП, увеличение η2/η1, уменьшение вязкости плазмы в мороз; увеличение конечных продуктов гликирования на 2-м визите. Заключение. Волна холода ассоциируется с увеличение числа ССО у части больных ССЗ на фоне подобранной терапии. Наличие ИБС, СД-2, женский пол - независимые предикторы ССО у больных ССЗ в зимний период. В этот период отмечаются увеличение уровня глюкозы, конечных продуктов гликирования, агрегации эритроцитов, уменьшение вязкости плазмы.

The study shows that addition of statins to osteoporotic therapy in postmenopausal women with different cardiovascular risk beside desired hypolipidemic effect and reduction of arterial stiffness also elevates BMD at femoral neck by 4,9% from the baseline (p

to evaluate of the effectiveness of switching from beta-adrenoblockers (BAB) non-included into the guidelines for the management of chronic heart failure (CHF) to nebivolol and bisoprolol for outpatients.The study included 67 patients with stable Functional Classes (FC) II and II CHF who received the standard therapy and BAB non-included into the guidelines for the management of CHF. The patients were randomized to the groups taking bisoprolol (n = 35) or nebivolol (n = 32) in doses of 1.25 to 10 mg/day. Before and 6 months after therapy, the investigators assessed the patient's clinical status and quality of life (QL), performed a six-minute walk test and echography, and determined the blood level of the N-terminal fragment of brain natriuretic peptide prohormone (NT-proBNP).The switching to bisoprolol and nebivolol was followed by a significant clinical improvement, a larger covered distance, and better QL. Left ventricular ejection fraction was increased along with a reduction in mean FC CHF. There were no significant changes in NT-proBNP in the total patient group, but it was significantly decreased in the subgroup of those with the baseline high level of the peptide.The switching of patients with stable CHF from therapy with BAB not included into the guidelines for the management of CHF to nebivolol or bisoprolol yields positive results and improves left ventricular systolic function (which is attended by the reduction in NT-proBNP levels) and may be recommended for treatment in the outpatient setting.