In the first part of review we present some issues regarding the choice of antihyperglycemic agents in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. In particularly, patients with chronic heart failure are discussed. In the management of high-risk patients with type 2 diabetes mellitus, the individualized choice of glycosilated hemoglobin target level (which is higher) is very important. We analyze the safety profile of biguanides, meglitinides, alpha-glucosidase inhibitors, insulin, and sulfonylurea drugs. Evaluation of randomized clinical trials and meta-analyses regarding cardiovascular safety of antyhyperglycemic agents showed, that in high-risk patients with type 2 diabetes mellitus, biguanides (metformin) are the first line treatment (as monotherapy or combined, depending on baseline glycosilated hemoglobin level) due to their favorable prognostic profile. Few types of insulin lead to poorer prognosis in patients with cardiovascular diseases. Insulin glargine shows favorable cardiovascular safety profile. Sulfonylurea drugs (except for gliclazide), meglitinides, alpha-glucosidase inhibitors are not recommended for high-risk patients with type 2 diabetes mellitus due to the proven negative prognostic impact, or lack of evidence regarding cardiovascular safety, or contradictory data. The choice and administration of “novel” antihyperglycemic agents will be discussed further, in the second part of the review.

Background. Pre-eclampsia is a frequent and serious complication of pregnancy associated with arterial hypertension (HTN). The underlying mechanisms remain unclear. At present time, reliable early predictors are lacking, as well as the precise criteria to assess the safety and effectiveness of its treatment and prevention are absent. the aim of the study was to identify additional predictors of pre-eclampsia of pregnant women with high blood pressure (BP). design and methods. The study included 223 pregnant women. Among them 63 (28.3 %) pregnant women had HTN: in 31 (49.2 %) pregnant women chronic HTN was diagnosed, and 32 (50.8 %) had gestational HTN. Women with secondary and non-classified HTN were not included. Depending on the presence of BP elevation, pregnant women with pre-eclampsia were retrospectively divided into two groups. The first group included 50 pregnant patients with HTN without signs of pre-eclampsia, and the second group was formed by 13 hypertensive women who reported pre-eclampsia symptoms during pregnancy. results. Dynamics of office BP throughout pregnancy did not differ between groups. The higher risk of pre-eclampsia at 30 weeks correlated with more pronounced morning BP surge, higher average pulse BP, SBP time index in the morning, BP variability at night, and high frequency of DBP “non-dipping” profile. Left ventricular diastolic dysfunction and reduced glomerular filtration rate (CKD-EPI) in the third trimester of pregnancy associated with HTN correlated with increased frequency of pre-eclampsia. In the first and third trimesters of pregnancy, cystatin C level was higher (p = 0.01; p = 0.005, respectively), and the levels of matrix metalloproteinase (MMP) –2 (p 0.001; p < 0.001) and MMP-9 (p < 0.001; p = 0.002) were lower in women with pre-eclampsia. conclusions. Increased concentrations of cystatin C and reduction of MMP-2 and –9 in the early stages of pregnancy in women with HTN can be considered as early predictors of risk of pre-eclampsia.

High prevalence of arterial hypertension (HTN) in the population remains one of the most significant health and social problems. There are three main approaches for HTN diagnostics: office blood pressure (BP), 24-h ambulatory BP monitoring (ABPM) and home BP monitoring. The current European recommendations for the diagnosis and management of HTN (2013) state that 24-h ABPM is the most accurate for individual assessment and helps to distinguish the following BP phenotypes: sustained normotension, HTN, «white coat» hypertension, masked hypertension (MHT). The prevalence of MHT in the population averages from 13 to 24 %, it is associated with male sex, increased body mass index, smoking, stress, elevated office systolic BP, diabetes mellitus, left ventricular hypertrophy and diastolic dysfunction. The cardiovascular risk is comparable in patients with «masked» and primary HTN. The latent HTN is high prevalent in patients with comorbidities, in particular, in chronic kidney disease (27.8–32.8 %), diabetes mellitus (29.3 %), rheumatoid arthritis (RA) (10 %). In our study, MHT was found in 28.3 % of patients with RA, confirming the relevance of the topic. ABPM is recommended for early diagnosis of HTN in RA patients with high cardiovascular risk. This will allow to improve the prognosis of patients with RA and to optimize their treatment.

Objective. To estimate the effectiveness of combination antihypertensive therapy, including the direct renin inhibitor aliskiren, in resistant hypertension (RHTN) and abdominal obesity (AO) according to gender and salt sensitivity.

Design and methods. The study included 161 patients with RHTN and AO, 78 (48.4 %) men and 83 (51.6 %) women. All patients at baseline and after 48 weeks of therapy as well as clinical and anthropometric study, electrocardiography and ambulatory blood pressure monitoring (ABPM) («Petr Telegin» BPLab Vasotens, Russia). Based on the V. I. Kharchenko’s test, all patients were divided into 4 groups: group 1 m (n = 38) and 1 w (n = 42) — «salt sensitive» men and women, and group 2 m (n = 40) and 2 w (n = 41) — «salt resistant» men and women. All patients received combination therapy: enalapril (renitek 20 mg/day, MSD, Switzerland),  amlodipine (normodipin 10 mg/day, Gedeon Richter, Hungary), hydrochlorothiazide (hydrochlorothiazide 12.5 mg/day, Gedeon Richter, Hungary) and direct renin inhibitor aliskiren (rasilez 150 mg/day, Novartis, Switzerland). After 3 weeks, aliskiren dose was increased up to 300 mg/day in case of low efficiency, followed by the repeated evaluation 3 weeks later. The data were processed using nonparametric statistics (Statistica 6.1, StatSoft Inc, USA). results. After 6 weeks of antihypertensive therapy including aliskiren (daily dose of 150/300 mg), target blood pressure (BP) < 140/90 mm Hg was detected in 31 (81.6 %) men and 32 (76 %) women in salt sensitive group, and in 31 (77.5 %) men and 39 (95.1 %) women in salt resistant group. Target BP < 140/90 mm Hg was registered more frequently among salt resistant women compared to salt resistant men (p = 0.02) and salt sensitive women (p = 0.01). All treatment groups showed a significant decrease in office systolic (SBP) and diastolic BP (DBP), and heart rate. Regardless of salt sensitivity and gender, there was a significant positive changes of ABPM indicators after 48 weeks of treatment. However, in salt sensitive men and women, the change in ABPM parameters was comparable, while salt resistant women showed more marked changes in comparison with salt resistant men positive, including changes in 24-mean and daily values of SBP and DBP, SBP and DBP time index and variability during the day, as well as the time and the speed of morning surge in SBP and DBP. After 48 weeks of therapy, «dipper» BP profile was found in 17 (54.8 %) of 31 men and 17 (53.1 %) of 32 women in the salt sensitive group. In salt resistance group, «dipper» type was more prevalent among women than among men (51.3 and 35.5 %, respectively, p = 0.048). conclusions.

Results of the study demonstrated a significant efficiency of aliskiren as part of combination antihypertensive therapy in both men and women with RHTN and AO regardless of salt sensitivity. At the same time, in salt sensitive men and women antihypertensive effects of aliskiren were comparable regardless of gender, whereas among salt resistant patients women showed higher benefit compared to men.

Objective. To investigate the role of leptin, its soluble receptors, free leptin index and resistin in development of metabolic syndrome (MS) and to estimate the efficiency of a diet modification. design and methods. Altogether 90 patients with arterial hypertension (HTN) 1–2 degrees without any preceding antihypertensive therapy were enrolled: a group of obese subjects (n = 70), patients without obesity (n = 20); 25 normotensive patients with obesity but without other metabolic disturbances; 30 almost healthy individuals (average age — 48,2 ± 2,4 years). Insulin level, HOMA-IR, leptin, leptin receptors, resistin, free leptin index (FLI = leptin × 100/sLR).) were determined. All patients had followed a diet for 6 months.

Results. The leptin, FLI, НОМА-IR and resistin levels were higher, while sLR was lower in MS group compared to controls. In the group of patients with HTN without obesity a significant increase in the resistin level was found compared to normotensive subjects. The FLI was directly related to triglyceride (R = 0,42; р = 0,04), uric acid levels (R = 0,39; р = 0,03), and LDL levels (R = 0,39; р = 0,03), and HOMA-IR (R = 0,42; р = 0,04). Resistin correlated with blood pressure (R = 0,36; р = 0,04), triglycerides (R = 0,42; р = 0,04), and HOMA-IR (R = 0,37; р = 0,04).

Conclusions. Blood pressure in obese patients is associated with increased level of resistin, leptin resistance and low plasma level of soluble leptin receptors. The free leptin index is a more accurate marker for leptin resistance. The resistin can be considered as an unfavorable marker of metabolic disturbances in hypertensive patients, regardless of the presence of obesity.

Background. The prevalence of arterial hypertension (HTN) increases with age, but the causes of HTN in elderly and young age are different. The contribution of the specific parameters of high blood pressure (BP) in the pathogenesis of organ damage in the elderly has not been studied enough.

Objective. We assessed the effect of BP variability (BPV) on left ventricular (LV) remodeling and vascular stiffness in patients with HTN developed at age before and over 65 years. design and methods. Altogether 122 elderly patients were enrolled and divided into 3 groups: group 1–45 patients with newly diagnosed HTN 1–2 degree at the age over 65 years (21 males, 24 females, the average age — 71,7 ± 2,6 years), group 2–39 subjects with newly diagnosed HTN 1–2 degree under 65 years old (18 males, 21 females, the average age — 68,4 ± 2,4 years). The 3rd control group, comprised 38 elderly subjects without HTN (20 males, 18 females, the average age — 67,5 ± 2,0 years). At baseline, none of the patients achieved target BP. At admission to the hospital, two-component antihypertensive therapy was prescribed to all patients, it included a blocker of the renin-angiotensine-aldosterone system (RAAS) — an angiotensin-converting enzyme inhibitor or angiotensin receptor antagonist) and calcium channel blocker (amlodipine in all cases). Short-term BPV was assessed by ambulatory BP monitoring (ABPM), medium-term BPV — based on the BP monitoring for 7 days, and long-term BPV — based on the 3-month self-monitoring of BP. Central aortic pressure was also measured. LV myocardial mass index and LV relative wall thickness (2T/DD) were assessed by 2D-echocardiography, and early diastolic flow velocities E, A and the ratio E/A were evaluated by spectral Doppler. Pulse wave velocity, cardio-ankle vascular index (R-CAVI and L–CAVI), ankle-brachial index (ABI) and the biological arterial age were assessed by sphygmomanometry.

Results. Increased BPV seems to be an indicator in elderly, as elderly patients without HTN show increased SBP and DBP short-term variability. However, the maximum rate of BPV increase was found in patients with the HTN development in the age over 65 years. In the same group, the correlation between BPV and LV and vascular remodeling was the most severe. The increase in visit-to-visit DBP variability had the greatest impact on the arterial wall stiffness, while visit-tovisit SBP variability affected LV remodeling. The increase in the mediumand long-term BPV was found to be a more powerful predictor of cardiovascular remodeling compared to the increase in short-term BPV assessed by ABPM. Thus, arterial stiffness may be an important factor leading to the increase in both short-term and longterm BPV.

Conclusions. BPV measurement should be widely implemented for the assessment of cardiovascular risk and the overall effectiveness of antihypertensive therapy.

Objective. To study a circadian profile of blood pressure (BP), heart rate variability, and structural and functional remodeling of the left ventricle (LV) in patients with arterial hypertension (HTN) and hypothyroidism, as well as to evaluate the efficiency of various schemes of antihypertensive therapy. design and methods. The study included 150 patients aged 52–75 years: the main group — 31 patients with HTN and primary hypothyroidism in the decompensation stage, the first comparison group — 30 patients with HTN without hypothyroidism, the second comparison group — 22 patients with primary decompensated hypothyroidism without HTN, the third group — 73 patients with HTN and compensated hypothyroidism, and the control group — 14 people without cardiovascular disease, HTN and thyroid disease. Patients with HTN and compensated hypothyroidism received the following antihypertensive therapy for 12 weeks: patients of the 1st subgroup (n = 25) — ramipril and metoprolol succinate, 2nd  subgroup (n = 24) — ramipril and amlodipine, 3rd  subgroup (n = 24) — metoprolol succinate and amlodipine. At baseline and at follow-up, the levels of thyroid-stimulating hormone and free thyroxine, ambulatory BP monitoring, Holter ECG monitoring, echocardiography were performed.

Results. Hypertensive patients with primary decompensated hypothyroidism compared to those without hypothyroidism demonstrated: 1) significantly higher values of systolic and diastolic BP, the time index and the square index at all time intervals, BP variability, and a higher rate of nocturnal hypertension; 2) an increase in the vagal activity, compared to the sympathetic activation in hypertensive patients with compensated hypothyroidism; 3) more pronounced changes in the LV structure and function, higher prevalence of LV concentric remodeling (71 %). Combination therapy of ACE inhibitors and beta-blocker in hypertensive patients with compensated hypothyroidism led to a persistent decrease in BP, as well as to positive changes in LV structure and function, and to an improvement in heart rate variability.

Conclusions. Our findings can be used for optimization of HTN in patients with primary hypothyroidism and different thyroid function level.

Objective. To evaluate vasomotor endothelial function, biochemical markers of endothelial dysfunction (ED) and heart rate variability (HRV) in patients with arterial hypertension (HTN) and HTN combined with coronary artery disease (CAD).

DEsign and methods. The present study included 121 patients aged between 40 and 70 years. The control group accounted for 18 people without HTN and CAD, the HTN group included 56 patients, the group with the HTN combined with CAD — 47 subjects. The assessment of vasomotor endothelial function, HRV and biochemical ED indicators such as endothelin-1 (ED-1), nitrites, lipid peroxidation was performed. results. Both hypertensive patients and patients with HTN and CAD the signs of ED demonstrated a decrease in endothelium-dependent vasodilation (EDVD) (less than 10 %) and endothelium-independent vasodilation (EIVD) (less than 18 %) compared to the control group. Severe deterioration of vasomotor endothelial function was detected in male patients with HTN combined with CAD and obesity. In HTN patients the negative dynamics of biochemical ED markers was found, manifested as reduced levels of nitrites, ED-1 increase, imbalance of antioxidant protection (AOP) and processes of lipid peroxidation in comparison with the control group. In patients with HTN combined with CAD and increased levels of ED-1, there was a complete reduction of AOP and reduced activity of lipid peroxidation. Decrease in sympathetic and parasympathetic activity was found in hypertensive patients compared to the control group. The most evident sympathetic-parasympathetic imbalance manifested as relative decline of all HRV indices was observed in patients with HTN combined with CAD. These changes were more significant in males and elderly patients.

Conclusions. Reduction in vasomotor endothelial function, dysregulation of biochemical markers of ED, imbalance of antioxidant protection and lipid peroxidation, significant reduction in parasympathetic heart regulation as a result of the increased sympathetic activity, interrelation between HRV and ED, evidence the common mechanisms in HTN and CAD. The male gender has the most significant impact on the ED development and progression in hypertensive patients, while the age is a more important factor in patients with HTN combined with CAD.