One of the key regulators of vascular tone is the vascular endothelial growth factor (VEGF), which can enhance the production of nitric oxide, a potent vasodilator, and reduce vascular resistance by generating new vessels. Both mechanisms contribute to blood pressure decrease. The implementation of a new class of antitumor therapy — inhibitors of VEGF signaling pathway — results in the growth of cardiovascular complications such as arterial hypertension (HTN). The paper analyzes the causes of HTN development, approaches to the timely diagnosis of HTN and the correct assessment of cardiovascular risk before administration of VEGF inhibitors and during the treatment. We also review the features of the approaches of elevated blood pressure management in patients receiving targeted therapy.

Oral  appliances  (ОА)  are  one  of  the  leading  methods  of  effective  treatment  of  sleep-related  breathing disorders. Obstructive sleep apnea (OSA) is a widespread disturbance in the general population. It is closely associated with many cardiovascular diseases (hypertension, cardiac arrhythmias, chronic heart failure, ischemic heart disease). Timely detection and treatment of OSA is an important task in the process of reducing the number of cardiac complications. Modern devices for the treatment of OSA are custom-made devices which allow to change the position of the mandible and its extension providing personalized treatment of snoring and sleep apnea. Changing the degree of the mandible extension, the ОА retains the upper respiratory tract in open position and indirectly stimulates the muscles, determining their tone. The effectiveness of the ОА is evaluated by the complete elimination of all respiratory events (snoring, upper airway resistance syndrome, OSA and hypopnea), as well as the influence on the sleep structure and the wakefulness functioning (excessive daytime sleepiness). The effects of ОА on cardiovascular diseases are of great importance, as they showed a decrease in both systolic and diastolic blood pressure, as well as a positive effect on the impaired endothelial function. Among all the treatment options, ОА take the leading positions, only slightly inferior in effectiveness to noninvasive ventilation, so called CPAP therapy. Regarding the long-term adherence to therapy (which is especially important in the cardiovascular prevention) оral appliances exceed CPAP therapy. Thus, the OA therapy is one of the leading therapeutic directions in modern sleep medicine for obstructive sleep-related breathing disorders.

Objective. To evaluate the effect of 24-week atorvastatin therapy on the lipid profile, structure and functions of the large arteries in patients with ST-elevation myocardial infarction (STEMI) with single-vessel hemodynamically significant stenosis of the coronary arteries. Design and methods. We enrolled 85 patients with STEMI aged 33 to 66 years (51,9 ± 9,3 years), 75 men (88 %), and 10 women (12 %). Inclusion criteria were: age from 30 years to 70 years, STEMI confirmed by electrocardiogram and increased troponin I and creatine kinase-MB, the presence of a significant stenosis of the infarct-related artery, stenosis of other arteries less than 50 %, and the stenosis of the trunk of the left coronary artery less than 30 %. Patients underwent laboratory (lipids) and instrumental examination at baseline (7–9 days from the symptoms onset) and 24 weeks after the therapy was started. We assessed carotid atherosclerosis by the ultrasound scanner MyLab 90 (“Esaote”, Italy). Central pressure parameters and arterial stiffness were evaluated using the applanation tonometry (SphygmoCor, “AtCorMedical”, Australia). Results. After 24 weeks of treatment patients from the control group demonstrated a decrease in total cholesterol by 26 %, low density lipoproteins — by 40,5 % and high density lipoproteins — by 3 %. Patients receiving atorvastatin 80 mg/day showed similar reduction of the parameters: by 45 %, 55 % and 14 %, respectively. Patients who took lower dose of atorvastatin showed no change in intima-media thickness (IMT), but there was a positive change of the coefficient of transverse extensibility — DC, which increased by 25 % (p < 0,05). In the same cohort of patients, locPsys and locPdia increased by 5,4 and 3,6 mm Hg, respectively, and there was a 3,5-fold increase in the augmentation index (p < 0,05). In the group of high-dose atorvastatin therapy carotid IMT decreased by 11 % after 24 weeks (p < 0,05). The coefficient of transverse compliance (CC) increased by 11 % (p < 0,05), the stiffness indices α and β significantly decreased by 11 % and 13 %, respectively (p < 0,05). There was also a decrease in pulse wave velocity (PWV) measured locally in the carotid arteries by 6 % (p < 0,05). We found a 3-fold increase in augmentation pressure (AP) and augmentation index (Aix) after 6 months of therapy (p < 0,05). Conclusions. Patients who receive the maximum daily dose of atorvastatin develop a more significant improvement of lipid profile compared to the control group. Our results are consistent with the statement of the American Association of Cardiologists proving that high-dose statin therapy can reduce the level of low density lipids by more than 50 % compared to the baseline values. Using the radiofrequency analysis of the ultrasound signal (echotracking), we analyzed the stiffness parameters α and β, the compliance and distensibility coefficients, which reflect the vascular wall rigidity, regardless of the arterial pressure level. When comparing two schemes of atorvastatin therapy, intensive therapy showed a more evident favourable effect on carotid stiffness.

The aim of the study was to analyze the influence of the baseline systolic blood pressure (SBP), the length of beat-to-beat interval (RR) and the components of the heart rate variability (HRV) spectrum on the development of vasorenal hypertension in the model “2 kidneys, 1 clamp” in Wistar rats. Also we investigated the relationship between anxiety and parameters of hemodynamics in intact animals using the “open field” test and the correlations between SBP level, RR duration and the components of the HRV spectrum in both intact animals and animals with renal artery ischemia. Design and methods. We recorded hemodynamic parameters on the tail of awake rats. In the HRV analysis, a low-frequency component (LF), a high-frequency component (HF) and a sympathetic-vagal balance (LF/HF) were calculated. Results. In normotensive rats the normal high SBP is accompanied by tachycardia and increased anxiety in “open field” test. The baseline values of SBP, RR interval and HRV spectrum components do not influence the development of unilateral vasorenal hypertension. In the development of unilateral vasorenal hypertension, weakened parasympathetic effects on cardiac function were observed, as evidenced by a decrease in the RR interval duration and HF component of the HRV spectrum in animals with developed hypertension, as well as an increase in the LF/HF component of HRV in clamped rats. Сonclusions. Individual increased anxiety of normotensive animals does not affect the development of vasorenal hypertension in the model “2 kidneys, 1 clamp”.

Objective of our study was to assess the ambulatory blood pressure monitoring (ABPM) in young people with different office blood pressure (BP). Design and methods. We included 981 students of a medical university at the age of 20–29 years (536 men, 445 women). ABPM was performed using the device “Kardiotekhnika 4000” (Inkart, Russia), the data were processed using the program “KT Result2” (Inkart, Russia). Results. The optimal BP during office measurement was recorded in 220 patients (22,4 %, group 1), normal — in 488 (49,8 %, group 2), high normal — in 134 (13,6 %, group 3), hypertension (HTN) 139 (14,2 %, group 4). The proportion of males was significantly higher in groups 3 and 4 (96,6 % and 85,6 %) compared with groups 1 and 2 (47,7 % and 40,2 %, respectively, p < 0,001). The median systolic BP (SBP) was 123 (110; 126) mm Hg, diastolic BP (DBP) — 85 (84; 87) mm Hg. According to the ABPM, the parameters of SBP and DBP correlated with the corresponding office BP parameters. A strong direct correlation was found for both SBP (r_s = 0,87) and DBP (r_s = 0,85). Daytime variability of SBP was significantly higher in individuals with high normal BP and HTN (15,9 ± 2,6 and 17,2 ± 4,2 mm Hg) compared to groups 1 and 2 (9,2 ± 4,4 and 9,9 ± 3,0, respectively, p < 0,05). The majority of young people had normal BP decrease at night (dipper), non-dipper profile was also frequent. Over-dipper and night-peaker profiles were rarely recorded. In the groups 3 and 4, a larger number of non-dipper patients were observed compared with groups 1 and 2 (23,9 % and 34,6 %, compared with 10,0 % and 11,1 %, respectively, p < 0,001). The prevalence of white-coat hypertension (WCH) among the young people was 0,31 % (95 % CI 0,06–0,75 %), among subjects with office HTN 2,2 % (95 % CI 0,4–5,3 %). The prevalence of masked hypertension (MHTN) in the studied population was 1,4 % (95 % CI 0,8–2,3 %), among normotensive subjects — 1,7 % (95 % CI 0,9–2,6 %), among subjects with high normal BP — 10,4 % (95 % CI 5,8–16,2 %). Conclusions. ABPM in young hypertensive patients is characterized by higher variability of daytime SBP. The majority (56,1 %)of HTN subjects had normal BP decrease at night. The prevalence of WCH among young people is 0,31 % (95 % CI 0,06–0,75 %). The prevalence of MHTN among young people is 1,4 % (95 % CI 0,8–2,3 %).

Objective. To study the changes in mRNA expression level of two main protein kinase C substrates — MARCKS and NAP-22 — in rats with spontaneous hypertension (SHR rats) and in normotensive control rats (WKY rats) in renal cortex, renal medulla and total kidney. We also aimed at the identification of possible interstrain differences between the mRNA expression levels. Design and methods. We assessed the level of MARCKS and NAP-22 mRNA by real-time polymerase chain reaction in male SHR and WKY (as a normotensive control) rats. Results. In SHR rats, MARCKS mRNA expression level in renal cortex was 1,5 times higher than in renal medulla (p = 0,0001) and also higher than in total kidney (p = 0,001), in renal medulla it was lower than in total kidney (p = 0,002). In WKY rats, MARCKS mRNA expression level in renal cortex was higher than in renal medulla (p = 0,0005). There was no differences neither between renal cortex and total kidney (p = 0,011), nor between renal medulla and total kidney (p = 0,716). In SHR rats, NAP-22 mRNA expression level in renal cortex was twofold higher than in renal medulla (p = 0,001), in renal medulla it was lower than in total kidney (p = 0,005), the differences between renal cortex and total kidney were less significant (p = 0,011). In WKY rats, NAP-22 mRNA expression level in renal cortex was 1,5 times higher than in renal medulla (p = 0,001), while in renal medulla it was lower than in total kidney (p = 0,002). There was no significant difference in NAP-22 mRNA expression level between renal medulla and total kidney (p = 0,011). There were no significant interstrain differences in the animal groups either in the levels of MARCKS mRNA expression in renal cortex (p = 0,872), in renal medulla (p = 0,024) or in total kidney (p = 0,520). Neither there were differences in the levels of NAP-22 mRNA expression in cortex (p = 0,028), in medulla (p = 0,028) and in total kidney (p = 0,978). Conclusions. In both SHR and WKY rat strains, the level of MARCKS and NAP-22 mRNA expression in cortical and medullary kidney layers is different, in WKY rats these differences are less pronounced. At the same time, interstrain differences in NAP-22 and MARCKS mRNA expression levels in cortical, medullary layers and in total kidney of SHR and WKY rats were not found.

Objective. To evaluate the morphologу of focal formations of the adrenal glands after adrenalectomy. Design and methods. We analyzed the adrenal glands of 44 patients who underwent the surgery in the Research Institute of Fundamental and Clinical Urinephrology of Saratov in 2004–2016. Renovascular hypertension was the exclusion criterion. Results. The majority of the examined patients (72,7 %) had adrenal hypertension, caused by hormonally active adrenal tumors: pheochromocytoma, corticosteroma and aldosterome. Hormonally inactive tumors were found in 12,5 % patients with adrenal hypertension. Therefore, essential hypertension was diagnosed in these cases. In total 27,3 % patients underwent resection of the incidentalomas, among them 16,7 % were diagnosed as “silent” chromaffin tumors which do not lead to the blood pressure elevation. Conclusions. In the majority of cases (87,5 %), patients who undergo surgery due to adrenal focal formation demonstrate adrenal hypertension related to a hormonally active tumor. Adrenal hypertension is more often diagnosed in middle-aged women, who show higher blood pressure, smaller adrenal glands compared to those who have hormonally inactive adenomas. Based on the morphological study, asymptomatic pheochromocytoma was diagnosed in 16,7 % cases.

Background. The International Society of Hypertension and World Hypertensive League therefore joined forces to organize a concerted global effort by expanding World Hypertension Day to May Measurement Month 2017 (MMM17). The campaign was aimed to improve hypertension awareness and blood pressure control in participants with hypertension. Russian Society of Cardiology supported initiative — blood pressure measurement was performed in 11 Russian cities. Objective. The aim of our study was to estimate Russian population awareness about blood pressure in terms of campaign MMM17. Design and methods. During May 2017 we screened 1532 participants in 11 Russian cities: St Petersburg (119 participants), Moscow (102), Belgorod (28), Bryansk (405), Kemerovo (142), Krasnoyarsk (154), Samara (67), Saratov (59), Stavropol (269), Ulyanovsk (50), Surgut (137). All subjects participated voluntarily. Inclusion criteria was age age older than 18 years old. Blood pressure (BP) was measured three times with automated and manual sphygmomanometers. Questionnaire regarding diabetes mellitus, cardiovascular diseases, smoking and alcohol intake was filled in. Respondents provided information about weight and height. Results. We examined 1532 participants aged 39,3 ± 18,7 years (from 18 to 90 years old), among them 509 (33,2 %) males and 1023 (66,8 %) females. All participants were divided into 3 groups according to the date of the last BP measurement: group 1 — BP has never been checked before (n = 188, 12,3 %), group 2 — less than one year ago (n = 630, 41,1 %), group 3 — more than one year ago (n = 714, 46,6 %). Conclusions. About half of Russian participants checked blood pressure last time more than one year ago. Insufficient awareness, low compliance to antihypertensive medication and poor blood pressure control were found in Russian population independently of gender and age in both primary and secondary prevention.

Background. Advantages of the two-component drugs are well-known and described in the professional standards and guidelines. However, in clinical practice their application is often limited, despite the increase in the variants of full-doses combinations. Objective. To analyze the dynamics of sales of the fixed-doses antihypertensive combinations in regions of the Far Eastern federal district. Design and methods. We present the results of the pharmacoepidemiological study of the regional pharmaceutical market of the antihypertensive fixeddoses combinations in Khabarovskii, Primorskii region and the Sakhalin region in 2015–2017. Results. In the studied regions of the Russian Federation, combinations of angiotensin-converting-enzyme inhibitors and diuretics are the most popular. Leading ones appeared to be enalapril + hydrochlorothiazide and perindopril + indapamide. Combinations of angiotensin-converting-enzyme inhibitors with dihydropyridine derivatives calcium channel blockers were acquired seldom. The most popular combinations were perindopril + amlodipine and lizinopril + amlodipine. Among combinations of angiotensin II antagonists with diuretics losartan + hydrochlorothiazide and valsartan + hydrochlorothiazide showed the greatest sales. Combinations including sartan and calcium channel blockers were acquired more seldom, despite the wide range of international non-proprietary variants in drugstores. Atenolol + chlortalidone was in the most popular demand among combinations of β-blockers with diuretics. In 2016 three-component combinations were presented by only four trade names, and their demand is still limited. Nevertheless, a nonsignificant growth of purchases was observed. Conclusions. Our data show low demand of fixed-doses combinations. In regions, as a rule, there is an increase in sales of generic more affordable combinations which proves the significance of both antihypertensive efficiency and the price.

The article presents current knowledge of рro- and antihypertensive mechanisms involved in the development of hypertension (HTN), and antihypertensive management strategies. Particular attention is paid to the angiotensin converting enzyme inhibitor lisinopril and thiazide-like diuretic indapamide. The mechanisms and effects are described. The paper discusses the results of multicenter randomized clinical trials, and the antihypertensive effects of lisinopril and indapamide and their impact on myocardial hypertrophy in hypertensive patients. The potential advantages of fixed combination of lisinopril and indapamide in the treatment of patients with HTN are also discussed.

Objective. To determine the frequency of markers of chronic kidney disease (CKD) in hypertensive patients, and to assess their relationship with the circadian blood pressure (BP) profile and intrarenal vascular resistance. Design and Methods. We studied 70 patients with medically-controlled hypertension (63,2 ± 8,3 years, m — 48,6 %, office BP was 130,5 ± 13,7 / 78,1 ± 8,5 mm Hg), 40 patients were recruited from the Russian multicentre program CHRONOGRAF. Measurement of the office BP, ambulatory BP monitoring were performed. Glomerular filtration rate (GFR) was calculated using the CKD-EPI formula, and albuminuria (AU) was determined as albumin/creatinine (A/Cr) ratio in the morning portion of urine (n = 40) or 24-hour urinary albumin excretion (UAE) (n = 22). Intrarenal vascular resistance was estimated by renal duplex Doppler ultrasound. The resistive index (RI) levels in the main renal arteries (MRA) and intrarenal arteries (IRA) were calculated. Results. Markers of CKD (GFR < 60 ml/min/1,73 m² and/or A/Cr > 30 mg/g and/or UAE > 30 mg/day) were detected in 31,4 % of patients with well-medically-controlled hypertension: average values of BP-day and BP-night were normal. The frequency of markers of CKD was 44,4 % in patients with BP-night ≥ 120/70 mm Hg (40,9 %) and 28,2 % in patients with BP-night < 120/70 mm Hg (58,1 %). A/Cr ratio was positively associated (Rs = 0,3550, р = 0,0266), GFR was negatively associated (Rs = –0,3795, р = 0,002) with systolic BP-night. RI in the segmental intrarenal arteries correlated with GFR (Rs = –0,4232, p = 0,0005). Renal RI were higher in CKD-patients vs. non-CKD-patients. During the ROC-analysis, the threshold value of RI in segmental IRA 0,725 to the detection of CKD markers (sensitivity of 71,4 %, specificity of 68,9 %, AUC = 0,699) was established. Among the diabetic patients, there were more marked disturbances of renal hemodynamic in the presence of CKD markers: RI in arcuate IRA reached 0,73 (0,68–0,75). Conclusions. The high frequency of markers of CKD (31,4 %) was identified even in patients with well-medically-controlled hypertension, it was associated with systolic BP-night. The negative correlation was found between GFR and RI. Renal hemodynamics was significantly disturbed in the presence of CKD markers, especially in patients with type 2 diabetes mellitus. The cut-off point of RI in segmental IRA indicating the CKD markers is 0,725.