Objective. Evaluate leptin gene expression in epicardial adipose tissue in males with coronary heart disease (CHD). Design and methods. We enrolled 106 males: 57 males with CHD aged 61,3 ± 1,1 years old and 49 males without CHD aged 57,3 ± 1,3 years old (p > 0,05). Epicardial adipose tissue (EAT) specimens were obtained in 65 males (57 males with CHD and 8 males with valvular heart disease without CHD) undergoing cardiac surgery. Serum leptin was measured by immune enzyme assay (IEA). Leptin mRNA (messenger ribonucleic acid) level in EAT was assessed by real-time polymerase chain reaction. All patients underwent coronaroangiography and echocardiography. Results. Leptin mRNA level in EAT was significantly higher in males with CHD and atherosclerosis of main coronary arteries. Patients with multivessel (3 and more coronary arteries) atherosclerotic lesions showed higher leptin mRNA level in EAT than in subjects with lesions of 1–2 coronary artery and in patients without CHD: 2,84 ± 0,04 (RU), 1,91 ± 0,03 RU and 1,41 ± 0,02 RU, respectively (р < 0,05). Conclusions. Paracrine activity of epicardial adipose tissue plays a role in the pathogenesis of coronary atherosclerotic lesions in males

The review presents data on the role of natriuretic peptides in the pharmacodynamics of LCZ696 (sacubitril/valsartan) and the results of clinical studies evaluating its clinical efficacy in patients with arterial hypertension (HTN), including those with impaired renal function. LCZ696 when administered as monotherapy at doses 200–400 mg/day for 8 weeks causes a clinically significant antihypertensive effect in patients with essential HTN 1–2 degree, as well as when used in combination therapy in HTN 3 degree. Short-term use of the drug is not accompanied by angioedema occurrence or other side effects. These results apply mainly to patients with primary HTN with relatively preserved kidney function and without diabetes mellitus, as subjects with serum creatinine > 133 micromole/L and patients with type 1 and 2 diabetes mellitus were excluded. Available data show that LCZ696 at doses 200–400 mg/day for 8 weeks also provides obvious antihypertensive effect and a moderate decrease in albuminuria in patients with HTN 1–2 degree and chronic kidney disease 3–4 stage. The long-term, large-scale clinical trials are needed for a more complete assessment of the clinical efficacy and safety of LCZ696 in hypertensive patients, including patients with impaired renal function.

Objective. To study the changes of impedance agregatometry indicators in patients with a history of stroke receiving antiplatelet therapy. Design and methods. We analyzed 324 medical records of patients with cerebrovascular events in past. Among them 252 patients (77,7 %) took aspirin, 53 patients (16,4 %) — clopidogrel and 19 patients (5,9 %) received in dual antiplatelet therapy. Simultaneously, all patients were treated with standarddose antihypertensives and statins for secondary prevention. In all patients the impedance agregatometry was performed (CHRONO-LOG, USA, Model 590). The platelet function in whole blood was evaluated with the use of adenosine diphosphate (ADP, final concentration — 10 pM/ml) and collagen (2 mg/ml) as inductors. The results were compared with the reference values intervals used in the diagnostic laboratory of urban advisory diagnostic center № 1 of St. Petersburg. Results. The patients treated with aspirin show an increase in time of the beginning of platelet aggregation up to 74,0 ± 1,1 (71,8–76,2) s and a platelet aggregation area under curve (AUC) decrease to 53,8 ± 1,1 (51,7–55,9) om × s when collagen is used as an inducer. The patients receiving clopidogrel 75 mg once daily demonstrate a decrease in amplitude of platelet aggregation to 8,8 ± 0,8 (7,1–10,5) om and AUC to 37,6 ± 3,5 (30,5–44,7) om × s when adenosindiphosphate (ADF) is used as the inductor. Also clopidogrel (75 mg/day) therapy is associated with the prolongation of time of aggregation onset (Lag Time) to 76,9 ± 5,3 (66,3–87,5) s, and with the decrease in AUC to 53,6 ± 2,9 (47,4–59,5) om × s when collagen is used as the inductor. Conclusions. The impedance agregatometry may be used to assess the impact of antiplatelet drugs on platelet aggregation in out-patients with a history of stroke.

Objective. The subanalysis of the study “PANDA” (the study of renal function in patients with acute nonspecific pain in lower back during therapy with nonsteroidal anti-inflammatory drugs (NSAID)) is the study of renal-associated escape effect of antihypertensive therapy in patients with arterial hypertension (HTN) receiving NSAID. Design and methods. We included 407 patients receiving one of the following NSAIDs for 14 days: meloxicam (15 mg/day), etoricoxib (60 mg/day), nimesulide (200 mg/day) or celecoxib (200 mg/day). Five visits were performed. During the visits blood pressure (BP), glomerular filtration rate (GFR), blood levels of cystatin C were assessed. Results. At first step, all parameters were evaluated in the whole group (n = 407). As the second step, we analyzeds the indicators in 4 groups depending on the NSAID type. At the third stage (subanalysis) we allocated 3 groups of patients: 1 group (n = 62) — patients with a history of HTN and diabetes mellitus, group 2 (n = 173) patients with HTN, and group 3 (n = 172) — patients without HTN and diabetes mellitus. Conclusions. In patients with acute nonspecific back pain, with a history of HTN, NSAID intake is associated with the certain changes in BP, GFR and cystatin-С. Therefore, we can discuss a renal-associated escape effect of antihypertensive therapy. It is the most evident on the 7th day of NSAID therapy. All changes of the studied parameters should be considered as a class-effect adverse reactions of NSAIDs, without any benefits in relation to specific medications.

Objective. To study cardio-hemodynamic disorders of the left ventricle (LV) in males with gout depending on the renal function and presence of arterial hypertension (HTN). Design and methods. We evaluated 105 patients with gout (average age — 49,5 ± 8,5 years old). All the patients underwent 24-hour BP monitoring (24-h BPM, BPLab “Petr Теlegin”, Russia), and echocardiography (EchoG) to assess LV geometry and diastolic function (Atrida pro Tochiba). The stage of chronic kidney disease (CKD) was diagnosed according to the 2012 National Guidelines based on the calculation of glomerular filtration rate by CKD-EPI method. Statistical analysis was processed by Software program Statistica 6.0 (Stat Soft). Results. All the patients were divided into 2 groups according to data of 24-h BPM: the main group consisted of 75 males with HTN (71,4 %), the control group included 30 patients without HTN (28,6 %). The patients with gout associated with HTN showed mainly concentric LV hypertrophy (49,3 %; р < 0,05). The normotensive patients more often demonstrated normal LV geometry and eccentric hypertrophy (69,9 %; р < 0,05). Most of the patients with gout develop CKD, and its incidence is higher than in hypertensives. The patients with gout and CKD demonstrated either eccentric or concentric LV hypertrophy as predominant variants of heart remodeling. Left ventricular diastolic dysfunction (LVDD) was registered more often in hypertensive patients with CKD. We found correlations between hyperuricemia, elevated C-reactive protein and indicators of 24-h BPM, EchoG indices of LV hypertrophy, and the kidney function. Conclusions. We found the relation between HTN, renal filtration function and LV remodeling and LVDD. Thus, our data suggest the contribution of gout associated with HTN in renal hemodynamic disorders, LV remodeling and heart failure development.

Objective. To study the renal function in relation to fibrosis, inflammation and left ventricular ejection fraction in patients with essential hypertension (HTN) and atrial fibrillation (AF). Design and methods. The main group included 69 males with HTN and AF, the control group consisted of 17 hypertensive males without AF. The average age was 55,0 (50,0–57,0) and 52,0 (45,0–56,0) years old, respectively. We identified firstmorning urine albumin, plasma creatinine, cystatin C, high-sensitivity C-reactive protein (hsCRP), and matrix metalloproteinase-2 (MMP-2). Glomerular filtration rate (GFR) was calculated by the CKD-EPI formula based on creatinine and cystatin levels. Left ventricular ejection fraction (EF) was determined by echocardiography. All the parameters were compared in the study groups, as well as in patients with different forms of AF. We also evaluated fibrosis and inflammation severity as well as cardiac function in relation to renal function. Results. In the main group the level of cystatin C was higher and GFR lower than in the control one (1,4 (1,2–1,7) and 1,2 (1,0–1,4) mg/l, p = 0,015; 62,2 (54,9–73,2) and 73,2 (66,1–78,6) ml/min/1,73 m 2, p = 0,01). The groups differed in the incidence of GFR < 60 ml/min/1,73 m 2 (40,6 and 11,8 %, respectively; p = 0,025). Paroxysmal AF was diagnosed in 29 men (42,0 %), persistent AF — in 17 (24,6 %), and permanent AF — in 23 cases (33,4 %). Cystatin C level increased from 1,3 (1,1–1,4) mg/l in paroxysmal AF up to 1,7 (1,2–1,8) mg/l in persistent AF and up to 1,5 (1,3–1,7) mg/l in permanent AF (p = 0,006). Plasma MMP-2 level was higher in AF patients than in the control group (16,4 (13,9–19,3) and 11,3 (9,8–12,1) ng/ml, respectively; p < 0,001). It also increased from 14,6 (12,1–18,4) ng/ml in paroxysmal AF up to15,5 (12,9–16,5) ng/ml in persistent AF and to 18,0 (16,4–21,6) ng/ml in permanent AF (р = 0,009). In the main group mean EF was lower than in the control group (65,0 (60,0– 68,0) and 68,0 (66,0–71,0) %; p < 0,001). The following correlations were found in HTN patients with AF: hsCRP with cyctatin C (r = 0,34, р = 0,004) and GFR (r = –0,28, р = 0,02); EF with cyctatin C (r = –0,34, р = 0,004) and GFR (r = –0,34, р = 0,004). No significant correlations between MMP-2 and renal indicators were found. Conclusions. In HTN patients with AF compared to HTN patients with sinus rhythm, MMP-2 and cystatin C serum levels are higher while GFR is lower. Renal dysfunction and fibrosis severity increase in patients with permanent AF compared to persistent and paroxysmal forms. Deterioration of renal function at AF is associated with inflammation increase and left ventricular EF decline in the absence of MMP-2 level change. 

Objective. To study the role of cystatin C and collagen type IV as early diagnostic markers of chronic kidney disease in patients with arterial hypertension (HTN) and obesity. Design and methods. We included 170 people aged 25–55 years old: 90 patients with obesity, metabolic disorders and HTN (“the group of complicated obesity”), 50 — with obesity without metabolic disturbances (“metabolically healthy obesity”), and 30 hypertensive subjects without obesity. Control group consisted of 50 healthy individuals without obesity. We assessed clinical and biochemical indicators, leptin levels, resistin, adiponektin, cystatin C in blood and urine, albuminuria, and collagen IV. Results. In groups of hypertensive patients we found associations between cystatin C level with triglycerides, blood pressure (BP), leptin, resistin, insulin resistance index and albuminuria. Glomerular filtration rate calculated by Hoek’s formula showed decreased kidney function while eGFR by CKD-EPI formula was optimal. Serum cystatin C level correlated with degree of obesity, while urinary excretion of cystatin C showed no association. Patients with «metabolically healthy obesity» showed increased urinary excretion of cystatin C while GFR and albuminuria were within normal values. Hypertensive patients demonstrated higher urinary excretion of collagen type IV and its association with albuminuria, BP level and cholesterol level. Conclusions. In HTN, serum cystatin C concentration is associated with adipokyne levels that confirms the role of hormonal activity of adipose tissue in the development of glomerular and tubular kidney dysfunction. Increased urinary excretion of collagen type IV in hypertensive patients indicates nephrosclerosis, which is augmented in obesity.

Objective. To investigate changes in NAP-22 messenger RNA (mRNA) expression level and the level of NAP-22 protein, as well as the level of MARCKS protein in kidney cells cytosole in spontaneously hypertensive rats after long-term high salt consumption which is a dietary factor of arterial hypertension (HTN). Design and methods. We evaluated SHR and WKY male rats before and after 10-day consumption of 1 % NaCl instead of drinking water. NAP-22 mRNA level was estimated using real time polymerase chain reaction (PCR), and the content of NAP-22 and MARCKS proteins was evaluated by dot immunoblotting or electerophoresis with subsequent immunoblotting. Results. In spontaneously hypеrtensive rats, the renal level of NAP-22 mRNA expression was significantly increased as compared with WKY group. High NaCl consumption definitely diminished NAP-22 mRNA expression in the both rat lines, however, its level was still higher in hypertensive rats than in normotensive rats. The NAP-22 protein level decreased, too. Similar changes were observed in the level of MARCKS protein in renal tissue. Conclusions. Unlike the long-term exogenous calcium deficiency, the salt load leads to the decrease of both RNA expression and the content in major protein kinase C (PK C) substrate proteins (NAP-22 and MARCKS). This indicates a potential change in the functioning of renal PK C system with an increased consumption of NaCl.

Objective. To study the impact of psycho-emotional stress (PES) on the correlation between blood pressure (BP) and plasma sodium and potassium ions, and their renal excretion in patients with arterial hypertension (HTN). Design and methods. We examined 18 men with normal BP and 20 men with HTN of the second stage (mean age in both groups — 57 ± 3 years) who were exposed to PES. All the subjects responded by the increase in BP, pulse, diuresis, natriuresis, renal excretion of K+, clearance from Na+-CNa+. We evaluated Na+ and K+ by the flame photometer Flafo-40 (Germany), and the activity of plasma Na+ and K+ by potentiometric method with ion-selective minielectrodes ISE-M-K and the ISE-M-Na. Results. At PES, neither normotensives nor HTN patients showed any correlation between BP and either plasma sodium ions or their renal excretion. BP correlated negatively only with renal excretion of potassium ions in normotensives: the higher systolic (SBP) and diastolic (DBP) BP at all stages of the experiment (5 ties: –0,57, –0,52, –0,64, –0,56, –0,54) the lower renal excretion of potassium after PES. Normotensive subjects showed no correlation between BP and plasma potassium ions. Unlike the normotensive subjects, patients with HTN had no correlation between BP and renal excretion of potassium ions. However, patients with HTN showed negative correlation between BP (especially systolic) and plasma potassium ions: the higher SBP at baseline and at PES exposure (–0,42, –0,51), the lower the baseline concentration of plasma potassium. The higher SBP at all three stages of the experiment, the lower active potassium at baseline and at PES exposure (5 relations: –0,52, –0,45, –0,46, –0,53, –0,48). The higher SBP and DBP during and after PES exposure, the lower the coefficient of activity of potassium at PES (4 relations, –0,58, –0,47, –0,58, –0,45). Conclusions. 1) Correlation between BP and plasma sodium ions and renal sodium excretion was absent in both normotensives and HTN patients at PES exposure. 2) BP elevation negatively correlated with the renal excretion of potassium ions in normotensive subjects during PES exposure. 3) BP increase negatively correlated with the plasma potassium ions (potassium ions, active potassium and its coefficient of activity) in hypertensive patients during the PES. 4) In normotensive subjects BP negatively correlated only with the renal excretion of potassium ions during the PES. In HTN patients BP correlated negatively only with potassium ions, active potassium and potassium coefficient of activity. 5) Potassium ions play a significant role in the BP regulation and the mechanisms are different in normotensive and hypertensive individuals.

Objective. To determine the levels of circulating microRNA-21-5p in various fractions of blood plasma in children with type 1 diabetes mellitus (DM1) and to study their relationship with the clinical and laboratory characteristics. Design and methods. The study included 12 patients with confirmed DM1 (mean age 12 years, boys/girls = 6/6). The control group consisted of 12 healthy children without diabetes mellitus and other metabolic disorders) (mean age 9 years, boys/girls = 5/7). Ultracentrifugation was used to separate blood plasma into the exosome fraction and the fraction without membrane vesicles. A quantitative analysis of the levels of mature microRNA-21-5p in plasma fractions was carried out by real-time polymerase chain reaction. Results. In the control group, age is not associated with either the levels of microRNA-21-5p in the exosome fraction, or with the levels of microRNA-21-5p in the supernatant fraction. In patients with DM1, the age is not associated with the level of microRNA-21-5p in the exosome fraction. In the supernatant fraction, the level of microRNA-21-5p negative correlated with the age of patients with DM1 (r = –0,75; p = 0,005), as well as with the glycated hemoglobin level (r = –0,59, p = 0,045). In children with DM1 aged 10 years and older, a 1,6-fold decrease (p = 0,026) in the levels of microRNA-21-5p from the supernatant fraction compared to the control group is observed. There were no differences in the levels of microRNA-21-5p between the sex-different cohorts of children, both in the control group and among patients with diabetes mellitus. Conclusions. In 2–16-year-old children with DM1, levels of circulating extravesicular microRNA-21-5p correlate with age and the level of glycated hemoglobin. DM1 is accompanied by a decrease of circulating extravesicular microRNA-21-5p levels in 10–16 years old children.

Objective. The aim of this work was to study the impact of seasons on the incidence of the experimental arterial hypertension. Design and methods. We applied the model of vasorenal hypertension “2 kidney, 1 clip” in Wistar male rats in standard laboratory conditions. We compared the following parameters in the groups with clipped arteries in autumn, winter and spring: systolic blood pressure, beat-to-beat interval, low- and high-frequency components of heart rate variability. Results. The risk of vasorenal hypertension occurrence was higher in spring (56 %). More seldom vasorenal hypertension developed in winter (20 % of animals), and an increase in density of low and high-frequency components of heart rate variability was observed after applying renal artery clamp in the winter group. There was a clear correlation between an increase in the average monthly variability of atmospheric pressure and a decrease in the frequency of vasorenal hypertension occurrence. Conclusions. We conclude that the season has an impact on the development of hypertension, which probably is due to the seasonal changes in sympathetic and parasympathetic activity. We assume that clear seasonal dynamics of atmospheric pressure variability causes the seasonal variations in the functioning of the cardiovascular and autonomic nervous systems in standard laboratory conditions.

Objective. To examine combinations of risk factors (RF) and incidence of cardiovascular events (CVE) in an unorganized population of Orenburg city based on the 3-year prospective study. Design and methods. We surveyed 1,600 people divided into groups depending on the number of cardiovascular RF (arterial hypertension (HTN), smoking, impaired carbohydrate and lipid metabolism). Three years later all patients were re-evaluated, and the following parameters were assessed: life status, new CVE, the newly onset diabetes mellitus (DM) and cancer. Results. In individuals without RF only 1 (0,6 %) event which appeared to be a CVE was registered. In the group with 1 RF only 21 (4,9 %) events occurred, including 19 (4,5 %) CVE. Patients with two or three RF reported 74 (11,4 %) and 70 (21,4 %) total events, respectively, and 59 (9,1 %) and 45 (13,8 %) CVE, respectively. In patients with 4 RF, 1 (2,8 %) event occurred, which appeared to be a CVE. Conclusions. This large cohort study demonstrated that the frequency of total events, and in particular CVE, in patients with newly onset DM depend on the number of RF and their combinations.