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Aim      To evaluate cardiometabolic effects of empagliflozin in patients with ischemic heart disease and type 2 diabetes mellitus (DM) following elective percutaneous coronary intervention (PCI).Materials and methods Patients meeting the inclusion/non-inclusion criteria were randomized into two groups of equal number using simple randomization with successively assigned numbers. Group 1 included 37 patients (18 men and 19 women) who gave their consent for the treatment with empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy. The drug administration started one month prior to the elective PCI and continued for the next 11 months (treatment duration, 12 months). Group 2 (comparison group) consisted of age- and DM duration-matched patients (37 patients; 18 men and 19 women) who continued on their hypoglycemic therapy previously prescribed by endocrinologists during the entire study period. Before the study, 36.11 % patients of the empagliflozin group and 27.03 % of the comparison group had unsatisfactory glycemic control as shown by the level of glycated hemoglobin (HbA1c).Results At 6 and 12 months of the study, fasting glycemia and HbA1c were significantly lower in the empagliflozin treatment group. The groups were comparable by the incidence of adverse outcomes: 8 (22.24 %) patients in the empagliflozin group and 10 (27.04 %) patients in the comparison group (р=0.787). The 12-month empagliflozin treatment reduced total cholesterol (C) by 5.56 % (p<0.05), low density lipoprotein (LDL) C by 3.67 % (p<0.05), visceral adipose tissue area (VATA) by 5.83 % (p<0.05), and subcutaneous adipose tissue area (SATA) by 3.54 % (p<0.05).Conclusion      The empagliflozin treatment for 30 days prior to and after elective PCI can enhance the effectiveness of myocardial revascularization due to the demonstrated beneficial cardiometabolic effects.

Aim: To assess the relationship between the prevalence of visceral obesity (VO) and the severity of coronary calcification (CC) in patients with verified coronary artery disease (CAD)., Materials and Methods: 125 patients with CAD were examined. Assessment of the morphometric characteristics of visceral adipose tissue (VAT) and CC was perform using multislice computed tomography (MSCT). The calcium index (CI) of the coronary arteries (CA) was determine by the Agatston method. Statistical analysis was perform using Statistica 10.0., Results: VO was detect in 82 (65.6%) patients with CAD. In the presence of VO, higher CC values were observed in the projection of the envelope (p=0.00014), right coronary (p=0.00002) arteries, total CI (p=0.0003), and the prevalence of massive CC. Correlation analysis showed the relationship between the area of VAT and the CC of all the studied localizations. According to the ROC analysis, VO is a significant predictor of massive CC (area under the ROC curve AUC 0.72, 95% CI 0.560.89), in contrast to body mass index BMI (AUC 0.56, 95% CI 0.310.82)., Conclusion: The index of the ratio of VAT to subcutaneous adipose tissue (VAT/SAT), but not BMI, had a direct correlation with CC. Morphology of VAT may be a significant diagnostic sign of massive CC in patients with CAD, as a factor affecting treatment and prognosis.

Aim      To study possible correlations between echocardiography (EchoCG) indexes and markers of myocardial fibrosis, procollagen I C-terminal propeptide (PICP) and procollagen III N-terminal propeptide (PIIINP) during one year following ST-segment elevation myocardial infarction (STEMI).Material and methods  120 patients with STEMI were evaluated. EchoCG was used to assess dimensions and volumes of heart chambers, left ventricular (LV) systolic function, mean pulmonary arterial pressure (mPAP), and indexes of LV diastolic function (Em, early diastolic lateral mitral annular velocity; e', peak early diastolic septal mitral annular velocity; E / e', ratio of peak early diastolic transmitral inflow velocity and mitral annular velocity  -, Е / А, ratio of peak early and late transmitral inflow velocities; DT, deceleration time of LV early diastolic filling). EchoCG indexes and serum concentrations of PICP and PIIINP were determined at 1 (point 1) and 12 (point 2) days of disease and one year after STEMI (point 3). The sample was divided into two groups: group 1 (n=86; 71.7 %) included patients with a LV ejection fraction (EF) ≥50 % and group 2 (n=34; 28.3 %) consisted of patients with LV EF ≤49 %.Results At one year, the number of patients with signs of diastolic dysfunction increased by 10% in group 1 whereas myocardial systolic dysfunction worsened in both groups. LV EF decreased in 15 (17.4%) patients of group 1 and in 4 (11.8%) patients of group 2. Concentrations of PIIINP were correlated with Em, E / e', mPAP, PICP, e', and LV EF.Conclusion      Direct correlations between PIIINP concentrations and Em, E / e', and mPAP were found in the group with LV EF ≥50 %. In the group with LV EF <50 %, correlations were observed between PICP concentrations, LV EF, and e'. Also, in this group, the increase in PIIINP was statistically more significant. These results indicate continuing formation of myocardial fibrosis in a year following MI, which may underlie progression of chronic heart failure.

Aim To evaluate the effect of empagliflozin on glycemia and renal filtration function in patients with stable ischemic heart disease (IHD) and type 2 diabetes mellitus (DM2) who underwent a percutaneous coronary intervention (PCI).Materials and methods This study included 40 patients with stable IHD and DM2 (age, 63 (58; 65) years; DM2 duration, 7 (4; 15) years) who had indications for an elective PCI. At baseline in the total sample, the level of glycated hemoglobin was 7.2 (6.5; 8.3)%; 48.7 % failed to achieve glycemic goals. A decrease in glomerular filtration rate (GFR) to below 60 ml/min/1.73 m2 was observed in 10.3 % of patients. All patients were divided into two group by simple randomization with successively assigned numbers. The main group consisted of 20 patients who received empagliflozin 10 mg/day in addition to their previous hypoglycemic therapy irrespective of their baseline glycemic control. Patients of the comparison group (n=20) continued on their previous hypoglycemic therapy as prescribed by their endocrinologist. The follow-up duration was 6 months. Statistical analysis was performed with the Statistica 10.0 software.Results The empagliflozin treatment improved the glycemic control; in the comparison group, no significant changes in glycemic control were observed. In both groups, GFR significantly decreased during the follow-up period; median decreases in GFR were -6.0 (-16.0; 4.0) and -8.4 (-26.5; 2.5) ml/min / 1.73 m2 in the main and comparison groups, respectively (p = 0.646). No significant changes in 24-h proteinuria were observed for patients taking empagliflozin. In the control group, the 24-h urinary protein excretion significantly progressed (p=0.011) during the follow-up period.Conclusion In patients with DM2 and stable IHD who underwent a PCI, addition of empagliflozin 10 mg/day to their current hypoglycemic therapy was associated with a significant improvement of glycemic control. The decrease in GFR during the empagliflozin treatment did not significantly differ from the value for patient receiving the other hypoglycemic therapy.

The incidence of obesity is steadily increasing worldwide, reaching the epidemic. Obesity is associated with cardiometabolic diseases through the complex interactions between genetics and epigenetics predisposition, the environment, diet, and lifestyle. However, the molecular mechanisms and factors influencing these processes are not fully known. MicroRNAs are a new class of important regulatory determinants in many biological and pathological processes. There is increasing evidence of the role of miRNAs in the regulation of the functional activity of adipose tissue and the development of obesity. A change in the expression of MicroRNAs can lead to changes in the activity of genes that control a number of biological processes, including inflammation, lipid metabolism, and adipogenesis. Understanding the role of miRNAs in the regulation of adipogenesis and the development of obesity will establish therapeutic targets for the development of new and effective drugs, which will lead to a breakthrough in the fight against obesity and related diseases. This review presents current data on the role of miRNAs in the regulation of the functional activity of adipose tissue, including adipogenesis of white, beige and brown adipocytes, as well as the prerequisites for using miRNAs as biomarkers of obesity and the possibility of therapeutic use., Competing Interests: The authors declare no conflict of interest.

Aim: To determine the dependence of adiponectin gene expression by subcutaneous, epicardial and perivascular adipocytes on the degree of coronary lesion in coronary heart disease., Materials and Methods: 84 patients with coronary artery disease were examined. Of these, 39 people showed a moderate degree of atherosclerotic lesion of the coronary bed (less than or equal to 22 points) on the SYNTAX Score scale, 20 severe (2231 points), and 25 extremely severe (more than 32 points). Upon admission to the hospital, all patients underwent an echocardiographic study (Echocardiography, Acuson, Germany) with the calculation of the ejection fraction (EF) of the left ventricle (LV) to assess its systolic function. During a planned surgical intervention (coronary bypass surgery, CABG), adipocytes of subcutaneous, epicardial (EAT) and perivascular adipose tissue (PVAT) were taken. Adiponectin gene expression was evaluated by polymerase chain reaction (real-time PCR) using TaqMan probes. Statistical analysis was performed using Statistica 9.0., Results: The maximum level of adiponectin expression was detected in adipocytes of PVAT, and the minimum EAT. With an increase in the degree of atherosclerotic lesion of the coronary bed, the expression of the adiponectin gene in adipocytes of local depots significantly decreases r=-0.82; p=0.023. Moreover, the low level of gene expression in EAT correlated with a decrease in LV EF by r=0.73; p=0.03. In adipocytes of subcutaneous and especially PVAT, gene expression was the highest in patients with a moderate degree of coronary lesion., Conclusions: Low adiponectin gene expression in EAT is associated with an increase in the degree of atherosclerotic lesion of the coronary bed and a decrease in LV EF.

Almost all known stress stimuli, including inflammatory agonists, chemotherapeutic agents and saturated fatty acids, cause the synthesis of ceramide and its metabolites. In recent studies, it has been shown that excessive synthesis of ceramides causes the development of various metabolic diseases, such as obesity, diabetes and cardiovascular diseases. Currently, the role of cеramids in the development of obesity and diabetes has been studied quite well. At the same time, studies devoted to the study of lipid data in the development of cardiovascular disease are not large. In this review, we generalize the data on this new class of bioactive lipids for understanding their role in the development of cardiovascular diseases., Competing Interests: The authors declare no conflict of interest.

Aim: To study polyvascular disease in patients with myocardial infarction (MI) and chronic kidney disease (CKD)., Materials and Methods: A total of 954 patients older than 18 years old with ST-segment elevation MI (STEMI) up to 24 hours of pain onset were included in the study. Clinical and demographic data were collected for all patients, including physical examination, 16-lead electrocardiogram recording, echocardiography, laboratory assessment with the measurements of cardiospecific enzymes and serum creatinine. Glomerular filtration rate (GFR) was estimated according to the CKD-EPI equation. Of them, 771 (81%) underwent coronary angiography, duplex scanning of the brachiocephalic (BCA) and lower extremity arteries (LEA). Patients with stage 1-4 CKD diagnosed according to the criteria provided by the Russian Society of Nephrologists were allocated into a separate group (n=281; 36.5%). CKD stages were determined with the level of GFR. Patients with stage 5 CKD were excluded from the study. Renal dysfunction was defined as the presence of an estimated GFR less than 60 ml/min/1.73 m2., Results and Discussion: The results of the study indicate a high prevalence of PolyVD in patients with CKD. Every second patient had LEA stenosis (p.

Ghrelin is a multifunctional peptide hormone, mainly synthesized by P / D1 cells of the stomach fundus mucosa. Its basic effect, which is realized via GHS-R1 α receptor in the arcuate and the ventromedial nucleuses of hypothalamus, is stimulation of the synthesis of pituitary hormones. Ghrelin is involved in control of appetite and energy balance, regulation of carbohydrate and lipid metabolism, cell proliferation and apoptosis, as well as modulation of functioning of gastrointestinal, cardiovascular, pulmonary and immune systems. It was found that cardiomyocytes are able to synthesize ghrelin. High concentrations of GHS-R1α in the heart and major blood vessels evidence for its possible participation in functioning of cardiovascular system. Ghrelin inhibits apoptosis of cardiomyocytes and endothelial cells, and improves the functioning of the left ventricle (LV) after injury of ischemia-reperfusion mechanism. In rats with heart failure (HF) ghrelin improves LV function and attenuates development of cardiac cachexia. In addition, ghrelin exerts vasodilatory effects in humans, improves cardiac function and reduces peripheral vascular resistance in patients with chronic HF. The review contains of the predictive value of ghrelin in the development and prevention of cardiovascular disease.

The purpose of the study was to investigate the features of expression and adiponectin content in the adipocyte culture of subcutaneous, epicardial, and perivascular adipose tissue and the effect of various doses of rosuvastatin on these processes. 29 patients with coronary artery disease were examined. Adipocytes were isolated from the samples of SAT, EAT and PVAT which were taken during coronary artery bypass surgery, followed by cultivation in the presence of rosuvastatin and evaluation of gene expression and adiponectin concentration. Adipocytes SAT, EAT and PVAT differed in the level of adiponectin secretion and expression of its gene. On day 1 of cultivation the expression of the adiponectin gene in the EAT was 2.3 times lower than in the PVAT. On day 2 of cultivation the expression of the adiponectin gene was reduced both in the EAT and the PVAT as compared to the SAT. When rosuvastatin was added at a concentration of 1 mmol/L, adiponectin gene expression in PVAT was higher than when rosuvastatin was added at a concentration of 5 mmol/L, in the adipocyte culture of SAT effect was opposite. Thus, the adipocytes of EZhT and, to a greater extent, PAS, can be a therapeutic target for statins in the case of the pathological activation of adipose tissue.

The fatty tissue is an endocrine organ secreting biologically active factors called adipokines that have systemic and local features. The adipokines play an important role in development of complications caused by obesity. nowadays, retinol-binding protein 4 (RBP4), one of adipokines identified recently, is considered as a connecting link between obesity and its complications. Adipokine participates in development of resistance to insulin and correlated with cardio-metabolic markers at chronic inflammatory diseases, including diabetes mellitus type II, metabolic syndrome and cardio-vascular diseases. It is considered that inflammation, produced by RBP4, induces resistance to insulin and cardio-vascular diseases. It seems that RBP4 is an adipokine that both induces resistance to insulin and participates in pathogenesis of other metabolic complications of obesity. This is confirmed by a tight relationship between RBP4 and atherogenic lipoproteins, atherosclerotic affection of vessels and cardio-vascular diseases. However, an important restriction in certain studies related to RBP4 is that they included patients who received medicinal therapy (sugar lowering and hypo-lipidemic pharmaceuticals) or had renal and hepatic insufficiency. The mentioned factors impact concentration of RBP4 in blood and hence can distort the results. In spite of that, the established potential metabolic role of RBP4 requires a further investigation. Besides further carefully planned studies are required focusing on establishing is RBP4 a molecular participator of molecular alterations or it is only a dynamically volatile "witness". The present review summarizes actual knowledge concerning the role of RBP4 under obesity, in development of dyslipidemia, insulin resistance and cardio-vascular diseases. The purpose of the study is to summarize data of studying of inflammatory and immune effects of RBP4 especially in case of cardio-vascular diseases and also establishment of perspective of applying retinol-binding protein as a potential biomarker of cardiovascular risk., Competing Interests: The authors declare no conflict of interest.

Aim: To compare dynamics of biological marker concentrations with echocardiographic data in patients with ST elevation myocardial infarction (STEMI) and preserved LV function during the hospitalization period., Materials and Methods: The study successively included 100 patients with diagnosis of STEMI and LV ejection fraction.

The ST2 is a member of family of receptors of interleukin I (IL-I) and consists of two isoforms: a trans-membrane of cellular one (ST2L) and soluble or circulating one (sST2). The ST2 is a receptor of IL-33 that represents IL-I like cytokine. The IL-33 manifests its cellular functions binding receptor complex consisted of accessory protein ST2L and IL-IR. The system IL-33/ST2 is activated in cardiomyocytes and fibroblasts in response to mechanical irritation or damage. It was demonstrated that interaction between IL-33 and ST2L is a cardioprotective one. The experimental models were used to demonstrate decreasing of myocardium fibrosis, prevention of development of hypertrophy of cardiomyocytes, decreasing of apoptosis and amelioration of functional capacity of myocardium at interaction of IL-33 and ST2L. In particular, the positive effects of IL-33 are related to receptor of ST2L. In turn, sST2 by binding with IL-33 sets blocking of interaction between IL-33/ST2L hence eliminating cardioprotective effects. During last years, the knowledge about the role of ST2 in pathophysiology of cardio-vascular diseases broadened and now the role of ST2 is related to myocardium dysfunction, fibrosis and remodeling. The system IL-33/ST2L, besides its myocardial role, can play an additional role in development and progressing of atherosclerosis. The system IL-33/ST2L can have a therapeutic potential in case of myocardial overload or trauma. On the contrary, sST2 acts as a false receptor of IL-33 blocking cardioprotective effects of interaction of IL-33/ST2L., Competing Interests: The authors declare no conflict of interest.

The purpose of study is to evaluate peri-operational parameters of testing of generation of thrombin and its relationship with indices of coagulation hemostasis, fibrinolytic system and anti-coagulants in patients with ischemic heart disease under coronary bypass surgery in conditions of artificial blood circulation. The examined sampling included 200 patients with ischemic heart disease. The planned primary operation of coronary bypass surgery in conditions of artificial blood circulation was applied to all of them. The testing of generation of thrombin was implemented using automated analyzer CEVERON-ALPHA (Technoclone, Vienna, Austria). The indices of testing of generation of thrombin were compared with common techniques of evaluation of hemostasis (INR, PTT, fibrinogen, Qick's prothrombin testing, thrombin time, AT-III, protein C, factor VIII), von Willebrand factor, inhibitor of activation of plasminogen type I (PAI-I), tissue and urokinase plasminogen activator. It is demonstrated that application of testing of thrombin generation duplicates enumerated indices and permits at the same time instant to detect both pro-coagulation and anti-thrombotic shifts. The advantage of testing of thrombin generation is in evaluation of thrombin potential that is most actual in cardiologic practice., Competing Interests: The authors declare no conflict of interest.

Aim: To monitor the hemostatic system during platelet concentrate transfusions using low-frequency piezothromboelastography in patients with coronary bypass surgery given aspirin therapy., Materials and Methods: The study involved 148 patients with coronary bypass surgery, with 76 ones undergoing intraoperative transfusion of platelet concentrate and 72 treated without transfusion. The control group consisted of 20 healthy individuals. In the perioperative period indicators of vascular-platelet, coagulation, anticoagulant and fibrinolytic components of hemostasis were evaluated by low-frequency pezotromboelastography using the ARP-01M "Mednord" hardware and software system (Russia)., Results: It was shown that the antiplatelet effect of aspirin in the preoperative period was manifest as inhibition of the initial stage of blood coagulation accompanied by increased thrombin potential, the total gain of anticoagulant and fibrinolytic activity of the blood. Heart-lung bypass was accompanied by structural and chronometric anticoagulation, reduction of anticoagulation and increase of blood fibrinolytic activity. In the postoperative period, structural and chronometric anticoagulation was more pronounced in patients who did not undergo transfusion of platelet concentrate than in the group of patients with transfusion. Donor platelets further increased the blood hemostatic potential by neutralizing the antiplatelet effect of aspirin. Perioperative thrombohemorrhagic complications were absent in both groups., Conclusion: Low-frequency piezothromboelastography provides a tool for real-time monitoring the functional state of hemostasis system. Transfusion of platelet concentrate is not advisable given that the thrombin potential is preserved as confirmed by the results of low-frequency piezothromboelastography.

Aim: to assess value for inhospital and 1 year prognosis of unfavorable course of ST-elevation myocardial infarction (STEMI) of blood serum galectin and markers of renal dysfunction (RD)., Material and Methods: Standard laboratory and instrumental examination, calculation of glomerular filtration rate using MDRD formula and by cystatin C level, determination of galectin in blood serum were carried out in 128 patients with STEMI. According to GFR by cystatin C level on day 12 of STEMI patients were divided into 2 groups - with normal renal function (GFR more or equal 60 ml/min/1.73 m2, n=47) and with RD (GFR <60 ml/min/1.73 2, n=81)., Results and Conclusion: In patients with STEMI presence of RD (lowering of GFR by cystatin C, by blood serum creatinine <60 ml/min/1.73 2, creatinine clearance <60 ml/min), and elevation of galectin concentration >17.8 hg/ml on day 12 of STEMI were independent predictors of unfavorable 1 year prognosis. Elevation of galectin level directly correlated with presence of early postinfarction angina.

Purpose of Study: To detect level ST2 in blood serum of patients with myocardium infarction in dynamics of hospital period and their relationship with remodeling of myocardium., Materials and Methods: The study sampling included 87 patients (65 males and 22 females) with myocardium infarction and the ST-segment elevation and average age of 59 years. All patients were allocated in two groups: with adaptive alternative of remodeling of myocardium (67 patients) and deadaptive alternative (20 patients). The control group consisted of 30 individuals. At the first and twelfth days after myocardium infarction in blood serum content of ST2 and NT-proBNP were detected using immune-enzyme technique with application of test-systems produced by Critical Diagnostics (USA) and Biomedica (Slovakia) correspondingly. The data statistical analysis was processed using non-parametric criteria., The Results: He content of ST2 and NT-proBNP at the first day of myocardium infarction increased in 2.4 and 4.5 times correspondingly as compared with control group. The patients with deadaptive remodeling were characterized by in 1.5 times higher content of ST2 at the first day than in group of adaptive remodeling and in 5.3 times higher that in control group. In the end of hospital period (twelfth day) in both groups decreasing of level of ST2 was observed. The concentration of NT-proBNP at the first day was increased in 1.8 times in patients of both groups and decreased at twelfth day. At that there were no differences between both groups. The high level of ST2 at the first day increases the risk of development of deadaptive remodeling in 4.5 times, NT-proBNP only in 2.3 times., Conclusion: The high level of stimulant growth factor ST2 at the first day of myocardium infarction was associated with deadaptive alternative of post-infarction remodeling that permits using ST2 as prognostic marker with high sensitivity and specificity., Competing Interests: The authors declare no conflict of interest.

Aim: To evaluate the prognostic impact of chronic kidney disease (CKD) during hospital stay in patients with ST-segment elevation myocardial infarction (STEMI) and to specify factors showing a negative impact of CKD., Subjects and Methods: 954 patients with STEMI were examined. The diagnosis of CKD was verified in 338 (35.4%). In all the patients, glomerular filtration rate (GFR) was calculated using the CKD-EPI formula with regard to serum creatinine levels on admission and before discharge (on days 10--12). In the patients who had undergone X-ray contrast intervention, serum creatinine levels were additionally determined on days 2--3 of this procedure in order to identify contrast-induced nephropathy (CIN). Cardiovascular events were assessed in the hospital period., Results: Endovascular interventions into the coronary vessels were made much more rarely in the patients with CHD; but CIN cases were twice more commonly recorded. Nonfatal cardiovascular events were 1.5 times more frequently observed in the CKD patients in the hospital period. The odds of fatal outcomes in both the total sample of STEMI patients and in those with CKD increased by 3.5 and 3.1 times, respectively, in the over 60 age group and by 7.9 and 5.8 times in the presence of Killip Classes II--IV clinically relevant acute heart failure (AHF). In the total sample, the independent predictors for a fatal outcome were a decreased admission GFR less than 60 ml/min/1.73 m(2), CIN, and Killip II--IV AHF. The hospital nonfatal complications were also associated with a decreased admission GFR less than 60 ml/min/1.73 m(2)., Conclusion: The independent predictor of a poor hospital period of STEMI, including fatal outcomes, was a decreased admission GFR less than 60 ml/min/1.73 m(2); the presence of CKD was of no independent value.

Aim: To comparatively assess formulas for estimating glomerular filtration rate (GFR) in the prediction of poor outcomes in patients with type 2 diabetes mellitus (DM) within one year after myocardial infarction (MI)., Materials and Methods: The investigators examined 89 patients with ST-segment elevation myocardial infarction (STEMI) within 24 hours after the onset of clinical symptoms of the disease. All the patients underwent standard laboratory and instrumental tests. GFR was calculated using the Modified of Diet in Renal Diseases (MDRD) formulas in terms of serum creatinine levels, the Hoek equation: GFR [ml/min/1.73 m2] = (80.35/cystatin C [mg/l]) - 4.3 (CKD-EPI), as well as from cystatin C levels, and the creatinine clearance rate was determined using the Cockcroft and Gault formula (ml/min). During a year after STEMI, the investigators recorded cardiovascular events (CVEs), such as death, recurrent MI, progressive angina pectoris, emergency coronary revascularization, and decompensated chronic heart failure (CHF). The examinees were divided into two groups: 1) 70 (78.6%) patients with MI and no DM; 2) 19 (21.3%) patients with MI and DM., Results: Comparative analysis revealed a tendency towards a difference in the detection rate of GFR <60 ml/min/1.73 m2 calculated using the Hoek formula from cystatin C levels: 42.1% in Group 2 and 21.4% in Group 1 (р=0.067). There were no great differences in the GFR estimated using other formulas. Logistic regression analysis was carried out to determine the most sensitive formula for estimating GFR to assess the risk of CVEs in the patients within a year after MI concurrent with and without type 2 DM. A univariate analysis showed that GFR calculations using the CKD-EPI (odds ratio (OR), 13.5; p=0.046) and MDRD (OR, 6.5; р=0.040) formulas and creatinine clearance estimation (OR, 2.4; p=0.025) were most sensitive in selecting MI patients without DM and with poor outcomes. This analysis revealed that GFR estimates using the Hoek formula from cystatin C levels (OR, 6.15; p=0.018) were most sensitive for patients with MI concurrent with type 2 DM. In both models, multivariate analysis included none of the analyzed indicators., Conclusion: To estimate cardiovascular risk in the long-term post-infarction period, the CKD-EPI formula in the patients without type 2 DM and the Hoek formula from cystatin C levels were noted to be of the greatest prognostic value in patients with DM.

Aim: To estimate thrombin generation test parameters in patients with coronary heart disease during coronary artery bypass surgery under extracorporeal circulation after transfusion of donor platelet concentrates during long-term therapy with acetylsalicylic acid (ASA)., Subjects and Methods: A total of 148 patients with coronary heart disease who had undergone elective primary coronary artery bypass surgery under extracorporeal circulation during preserved therapy with ASA (75-100 mg/day) were examined. According to donor platelet concentrate transfusion, all the patients were divided into 2 groups: 1) 76 patients undergoing donor platelet transfusion and 2) 72 without this procedure. A control group consisted of 20 apparently healthy individuals. At the pre-, intra-, and early postoperative stages, the investigators evaluated the following thrombin generation test parameters: lag time (min); peak thrombin concentration (nM/l); time to peak (min); the area under the thrombin generation curve (nM), and thrombin generation rate (nM/min)., Results: During long-term ASA therapy, the patients were found to have an activated endogenous thrombin potential in the pre- and intraoperative periods, as evidenced by the high peak concentration of thrombin and the increased rate of its generation. At the same time, the time of prothrombinase complex activation and that of thrombin generation were longer than those in the control group. In the early postoperative period, the patients who had not been transfused with platelet concentrates with a further increase in the temporal parameters, showed a decreased hemostatic potential, reaching the control level, whereas donor platelet transfusion stimulated endogenous thrombin generation: the time to initiate clotting and that to reach the peak were shorter; in this case, the thrombin generation rate and concentrations increased, but the preoperative level was not reached. No perioperative (hemorrhagic or thrombotic ischemic) events were noted in the examined groups., Conclusion: The hemostatic potential was preserved in patients receiving long-term therapy for ASA. Taking into account laboratory and clinical findings, platelet concentrate transfusions are unnecessary for preventive purposes. The appropriateness of donor platelet transfusion should be strictly individually approached with regard to the laboratory parameters of the thrombin generation test, by minimizing the risk of perioperative ischemic and hemorrhagic events in each specific patient.

Aim: To determine the concentration of the stimulating growth factor ST2 and its relationship to the clinical course of myocardial infarction (MI) over time during hospitalization., Materials and Methods: Eighty-eight MI patients whose mean age was 59±8.36 years were examined. On days 1 and 12 of MI, the serum levels of ST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were determined by ELISA. A control group consisted of 30 people., Results: On day 1 of hospitalization for MI, the concentrations of ST2 and NT-proBNP were higher 2.4 and 4.5 times, respectively, than those in the controls; by day 12, there was a statistically significant decrease in the level of ST2 while that of NT-proBNP was unchanged. During hospitalization, the investigators recorded MI complications, according to which the patients were divided into favorable and unfavorable MI groups. On day 1 of hospitalization, the level of ST2 in the patients with unfavorable MI was twice higher than in those with favorable MI and 3.7 times higher than in the control group. On day 12, both favorable and unfavorable MI groups showed a reduction in the level of the marker. On day 1 of MI, the concentration of NT-proBNP in the patients with a poor prognosis was 6.8 times greater than in the controls and 1.8 times more than in the patients with a good prognosis. On day 12, NT-proBNP levels remained elevated in both groups. Logistic regression analysis revealed that the determination of ST2 in combination with NT-proBNP increased their diagnostic significance (odds ratio, 1.92; 95% CI, 1.7-3.2; area under characteristic curve, 0.89; p=0.004)., Conclusion: The level of ST2 was a more sensitive indicator of hospitalization for MI than that of NT-proBNP. The combined use of ST2 and NT-proBNP was found to have a high diagnostic sensitivity and specificity.

Purpose: To elucidate association of renal dysfunction (RD) with unfavorable outcomes of in-hospital and long-term (1 year) treatment stages of patients with ST-elevation (STE) myocardial infarction (MI) and concomitant diabetes mellitus (DM)., Material and Methods: We enrolled in this register study 954 patients (65% men, 35% women, mean age 63.4 [62.6-64.2] years) with STE acute coronary syndrome. Mean age of men was 60.3 (59.4-61.1), of women - 69.2 [68.1-70.4] years. DM was verified in 175 patients (18.3%) basing on history data and values of fasting and postprandial glycaemia. Glomerular filtration rate (GFR) was calculated by MDRD formula using serum creatinine level determined at admission., Results: Four groups of patients were distinguished depending on the presence of DM and RD: with DM and RD (n=82), with DM without RD (n=93), without DM with RD (n=269) and without DM and RD (n=510). Presence of RD in acute period of MI was associated with 3.3-fold increase of risk of in-hospital and annual mortality, while the presence of DM was associated with 1.6-fold increase of in-hospital mortality without significant impact on annual mortality., Conclusion: RD had a significant impact on realization of poor outcomes in STEMI patients with concomitant DM. Prognostic significance of combination of DM and RD was proved to be higher than that of isolated DM.

Unlabelled: PURPOSE. To elucidate association of renal dysfunction (RD) with unfavorable outcomes of in-hospital and long-term (1 year) treatment stages of patients with ST-elevation (STE) myocardial infarction (M) and concomitant diabetes mellitus (DM)., Material and Methods: We enrolled in this register study 954 patients (65% men, 35% women, mean age 63.4 [62.6-64.2] years) with STE acute coronary syndrome. Mean age of men was 60.3 (59.4-61.1), of women--69.2 [68.1-70.4] years. DM was verified in 175 patients (18.3%) basing on history data and values of fasting and postprandial glycaemia. Glomerular filtration rate (GFR) was calculated by MDRD formula using serum creatinine level determined at admission., Results: Four groups of patients were distinguished depending on the presence of DM and RD: with DM and RD (n = 82), with DM without RD (n = 93), without DM with RD (n = 269) and without DM and RD (n = 510). Presence of RD in acute period of MI was associated with 3.3-fold increase of risk of in-hospital and annual mortality, while the presence of DM was associated with 1.6-fold increase of in-hospital mortality without significant impact on annual mortality., Conclusion: RD had a significant impact on realization of poor outcomes in STEMI patients with concomitant DM. Prognostic significance of combination of DM and RD was proved to be higher than that of isolated DM.

The present study was motivated by the lack of data on the role ofvariations in the levels of leptin and its soluble receptors and their interaction with proinflammatory factors in the development of acute coronary syndrome. The study included patients suffering myocardial infarction with and without type 2 diabetes mellitus. Hyperleptinemia and its relationship with myocardial necrosis markers (creatine phosphokinase, creatine phosphokinase-MB, troponin) give reason to suggest the important role of leptin in the development of inflammatory process associated with myocardial infarction in patients with and without diabetes mellitus. The results of the study provide a basis for the elaboration of a new therapeutic strategy for the correction of metabolic disorders in patients with acute coronary syndrome.

The index and structure of allosensibilization of patients according transfusion dangerous antigens of erythrocytes were identified. The purpose of action was to evaluate risk of development of post-transfusion hemolytic complications under application of hemotransfusions during operative interventions on heart and vessels. The immune anti-erythrocytes antibodies were detected in 81 cases (1.7%) and their main percentage formed antibodies of Rhesus system (67.7%). The antibodies to antigens of other systems like anti-K (10%), anti-S (2.5%), anti-Jka (1.2%), anti-Fya (1.2%), anti-Lea (3.7%) were more rarely detected. The estimated index of sensitization in patients made up to 1.7% that testifies higher degree of alloimmunization of examined patients and potential risk of development of post-transfusion complications of hemolytic type under hemotrasfusions. The received data was used as a background to develop and to implement algorithm of immune hematologic examination of patients of cardiosurgery profile. This approach permits minimizing risk of alloimmunization of recipients, to forecast and to prevent development of complications under transfusion of erythrocyte-containing components of donor blood that significantly enhances quality of transfusion therapy.

Aim: To evaluate the most informative parameters of adipokine, anti-inflammatory, and prothrombogenic status associated with diabetes mellitus., Materials and Methods: The study included 200 patients with myocardial infarction (MI) in whom markers of adipokine status, grelin, anti-inflammatory factors, CRP and plasminogen activator inhibitor were measured by biochemical methods on days 1 and 12 after admission., Results: In the period of acute MI, the adipokine status was disturbed, FFA and grelin levels decreased, pro-inflammatory and thrombotic potential increased. Patients who developed diabetes within 1 year after MI were characterized by more pronounced changes of the parameters of interest., Conclusion: Adiponectin, retinol-binding protein, grelin, TNF-α, and plasminogen activator inhibitor are the most informative biochemical parameters associated with diabetes mellitus developing 1 year after MI.

The sampling included 133 patients with diagnosis of cardiac infarction with peak of segment ST. After a year after old cardiac infarction, in 38 patients were established such unfavorable outcomes of disease as progressive stenocardia, decompensation of cardiac failure, repeated cardiac infarction and lethal outcome. It is established that among all indicators of lipid profile detected at hospital period of cardiac infarction only three indicators are prognostically significant in groups of patients with different outcomes--levels of free fatty acids, oxidized modified lipoproteins of low density and antibodies to them. During hospital period, augmentation of concentration of free fatty acids, oxidized modified lipoproteins of low density and antibodies to them increases risk of development of distant complications of cardiac infarction. The mathematical model is proposed comprising as predictors free fatty acids and antibodies to oxidized modified lipoproteins of low density. This model makes it possible on the basis of biochemical data obtained during hospital period, to calculate individual cumulative risk and to develop long-term prognosis of probable outcome of cardiac infarction.

Aim: To identify predictors of contrast-induced nephropathy (CIN) and evaluate its significance for the hospital prognosis of myocardial infarction with elevated ST segment., Materials and Methods: 722 (75.7%) of the total 954 patients underwent X ray examination with the use of contrast material (coronary angiography (CAG) and/or transcutaneous coronary intervention (TCI)) within 24 hr after the appearance of symptoms. In all cases, serum creatinine level was determined and glomerular filtration rate (GFR) calculated by the MDRD formula at admission, 2-3 days after CAG/TCI, and 10-14 days after hospitalization. CIN was defined as a more than 25% (44 mcmnol/l) rise in the creatinine level compared with the initial one within 48-72 hr after intravascular administration of contrast material in the absence of an alternative cause. The endpoints (adverse cardiovascular effects) were evaluated at the hospital stage of the study., Results: Significantly more patients with CIN (n=52; 7.2%) had the history ofdiabetes mellitus (DM) and chronic renal disease (CRD), clinically manifest Killip class II-IV acute cardiac failure (ACF), and reduced left ventricular ejection fraction (LVEF) compared with the patients having normal renal function. The risk of RAEF in the presence of CIN increased by 2.5 times (95% CI 1.26-5.05), that of MI by 5.4% (95% CI 2.69-10.64), life-threatening and other complications by 4.1% (95% CI 1.99-8.29) and 5.1% (95% CI times 2.85-9.17) times respectively. The presence of Killip class II-IV ACF increased the risk of CIN and DM by afactor of 2.2., Conclusion: CIN was diagnosed in 7.2% of the patients with myocardial infarction and elevated ST segment; it is associated with the history of DM, CRD, pronounced Killip class II-IV ACF and decreased LVEF DM and clinically manifest ACF were independent predictors of CIN in patients with myocardial infarction and elevated ST segment.

The article presents the assessment of prognostic value of perioperative level of C-reactive protein in the development of post-operative cardio-vascular complications in patients with ischemic heart disease and underwent coronary artery bypass grafting. The sample consisted of 99 patients with stable forms of ischemic heart disease and underwent the planned coronary artery bypass grafting. The average age of patients was 58 +/- 4.19 years. All patients were applied direct revascularization of myocardium in conditions of artificial blood circulation. The patients were divided on the groups depending on occurrence of post-operational cardio-vascular complications. The group I consisted of 42 patients with non-complicated post-operational period (42%). The group 2 consisted of 57 patients with cardio-vascular complications and included the subgroup of 24 patients with fibrillation of atriums developed in post-operational period. The concentration of C-reactive protein was analyzed in blood serum one day before the operation and at first and seventh days after operation. The post-operative period after application of coronary artery bypass in conditions of ischemic heart disease is characterized by activation of inflammation reaction evaluated by concentration of C-reactive protein. The pre-operation level of C-reactive protein can be used as prognostic marker of development of cardio-vascular complications, post-operative fibrillation of atriums after application of coronary artery bypass in particular

The shortage of data concerning the character of changes of leptin concentration and its role information of insulin resistance under development of acute coronary events determined the appropriateness of the present study. The cardiac infarction patients with and without diabetes type II were examined. The identified hyperleptinemia, its relationship with basal and post-prandial hyperglycemia and with increase of C-peptide concentration and free fatty acids made possible to consider leptin both as one of the important components in the series of carbohydrate and lipid metabolism disorders and the additional marker of development of insulin resistance under cardiac infarction. These study results can be applied to patients with diabetes anamnesis and to patients without this concomitant pathology. The study results can be used as a foundation for new diagnostic and therapy tactics of metabolic disorders correction in patients with acute coronary vascular pathology.

Aim of the study was to assess prognostic role of high sensitivity C-reactive protein (CRP) in progression of atherosclerosis in patients with ischemic heart disease (IHD) in a year after coronary artery bypass grafting (CABG). We examined 49 patients with stable IHD subjected to elective CABG (45 with and 4 without without cardiopulmonary bypass). In a year after surgery patients were divided into 2 groups: with (group 1, n=18, 36.7%) and without (group 2, n=31, 63.3%) progression of atherosclerosis of any localization. Contribution of various clinical and instrumental factors, type of intervention, CRP level before and in 1 year after surgery was analyzed. Before CABS CRP level was 3 times higher in group 1 compared with group 2 (=0.03). Increase of intima-media thickness was registered in a year after CABS in both groups, but it was significant only in patients with atherosclerosis progression (=0.04). Other clinical factors, gender characteristics of groups, type of intervention exerted no significant influence on progression of systemic atherosclerosis.

Aim of the study was to investigate role of matrix metalloproteinases (MMP) in assessment of prognosis of repetitive cardiovascular events during hospital stay of patients with ST-elevation (STE) myocardial infarction (MI). We consecutively included into this study 175 patients with diagnosis of STEMI. Content of MMP-1, MMP-3 and MMP-9 in blood serum was measured at admission and on day 12 after onset of disease. Levels of all MMPs on day 12 were 1.1-1.6 times higher than on day 1 of MI (<0.05). Comparison of groups of patients with favorable and unfavorable outcome showed that patients with unfavorable outcome had higher median concentrations of MMP-3 and MMP-9 on day 1; this tendency was maintained on day 12. However these differences were significant only for MMP-9. Compared with patients with favorable outcome levels of this marker in patients with unfavorable outcome were higher by 19.4% (=0.04) on day 1 and by 48.8% (=0.03) on day 12. At logistic regression analysis for MMP-9 and unfavorable outcomes during hospital stay area under ROC-curve did not exceed 0.5. But when only inhospital deaths were considered 2 for MMP-9 (day 1) was 14.3 (<0.0001) while area under ROC-curve was 0.72 (0.64; 0.78; =0.02). Thus in patients with STEMI high concentrations of MMP-9 on day 1 of STEMI can come forward as independent marker of unfavorable outcome during hospital stay.

Aim: The estimate insulin resistance in myocardial infarction., Patients and Methods: The study involved 200 patients with myocardial infarction, in which on the 1st and 12th day of hospitalization measured glucose, insulin, insulin resistance index (IR), lipid profile, the concentration of adipokines and ghrelin., Results: IR was detected in 77% of patients and was associated with a history of factors of cardiovascular risk, adverse clinical course of the disease, lipid disorders. The most important marker was the level of free fatty acids. High risk associated with increased in 9 times the concentration of free fatty acids in blood plasma. Patients with IR observed increased concentrations of leptin, resistin, and reduced the protective effect of adiponectin. The high specificity and sensitivity characteristic of the concentration of ghrelin: its reduction by 4 times in the acute phase of myocardial infarction increases the risk of MI by 78%., Conclusions: Significant risk factors for MI myocardial infarction, along with insulinemia and glycemia, is to increase the concentration of free fatty acids and the disbalance in the system adipokines against deficiency of ghrelin in acute and early recovery periods of the disease. Free fatty acids and ghrelin are promising markers to stratify the risk of insulin myocardial infarction. resistance in patients with myocardial infarction.

High mortality of patients with myocardial infarction (MI) determines pursuit of novel markers of risk as well as predictors of development of unfavorable outcome. The question of the role glycemia in development of cardiovascular complications in patients with acute coronary syndrome remains open. Analysis of in hospital mortality revealed U-shaped relacion ship between level of glycemia at admission and mortality in patients with ST elevation MI combined with diabetes mellitus (DM), and presence of direct linear relation - in patients without DM. Episodes of hypoglycemia registered in patients with MI and DM at hospital stage of treatment do not determine in hospital prognosis, but allow to distinguish a group of patients with unfavorable course of remote postinfarction period.

Diabetes mellitus (DM) is not only an independent risk factor (RF) of development of atherosclerosis, but it substantially worsens prognosis of patients with acute myocardial infarction (MI). Results of this study evidence that presence of disturbances of carbohydrate metabolism (DM or impaired glucose tolerance (IGT) in patients with ST elevation MI manifests with higher activity of the inflammatory process compared with patients with MI without abnormalities of carbohydrate metabolism. Unfavorable 1 year prognosis in patients with ST elevation MI is associated with higher concentrations of inflammation markers assessed on days 10-14 from onset of the disease: in patients with DM and IGT- of sCD40 ligand, in patients without disturbances of carbohydrate metabolism - C-reactive protein, in all patients irrespective of presence of carbohydrate metabolism abnormalities - interleukin 12.

According contemporary conceptions, the key role in the development of atherosclerosis play the low density oxidative modified lipoproteins and its antibodies. The purpose of the study was to discover the characteristics of changes in lipid metabolism indicators, including the low density oxidative modified lipoproteins and their antibodies. The factors of oxidative status in patients with cardiac infarction with complicated and non-complicated course were considered. It is established that the development of cardiac infarction is followed the increase of concentration of low density oxidative modified lipoproteins and their antibodies both during the first day after acute pain syndrome and stabilization period. The evaluation of content of low density oxidative modified lipoproteins and their antibodies broaden the possibilities of diagnostics, prognosis and decrease of risk of development both acute and recurrent coronary events.

Basing on complex evaluation of clinical, angiographic, and laboratory data we revealed predictors of stent thrombosis in patients with ST-elevation acute coronary syndrome (ACS) subjected to percutaneous coronary interventions (PCI). Among studied sample of patients (n=124) we distinguished a group of patients with proven stent thrombosis at various stages of follow-up (n=22, group 1) and a group of patients with favorable outcome (n=102, group 2). Unifactorial analysis revealed unfavorable prognostic influence (p=0.025) of hemodynamically significant stenosis of proximal segment of anterior distending artery, disturbances of rhythm and conduction (p=0.0002), as well as degree of heart failure (HF) according to Killip on day 1 of development of symptoms of ACS, and also of high selectin P level on day 10 (p=0.031). With the aim of assessment of prognostic significance of revealed factors we conducted stepwise discriminant analysis according to results of which most significant parameter affecting development of stent thrombosis in patients with ST-elevation ACS appeared to be high Killip class of HF (p&lt;0.0003), to a lesser degree - elevated level of sP-selectin on day 10 of observation (p=0.005). Parameter for which prognostic significance was not revealed as a result of multifactorial analysis was lesion in proximal segment of anterior descending artery (p=0.496). Probability of correct classification of the model was 88.7% at p&lt;0.0001.

It was established that insulin caused a reduction in the parameters of collagen-induced platelet aggregability in healthy donors; this effect of insulin on platelets was not found in patients with type 2 diabetes mellitus. In the healthy donors, joint incubation of platelets with insulin and L-arginine (a NO synthase substrate) resulted in an even more pronounced decrease in collagen-induced platelet aggregability while the group of patient showed a reduction in the degree and rate of the aggregability only along the light scattering curve. In the healthy individuals, addition of the NO synthase blocker LNMMA to the incubation medium containing platelets and insulin, as well as that of insulin and L-arginine eliminated insulin antiaggregability. The effect of insulin on platelet aggregation seems to be displayed with the involvement of platelet NO synthase and NO-dependent mechanisms. The change in the antiaggregability of insulin in patients with type 2 diabetes mellitus may be due to both lowered platelet NO synthase activity and insulin receptor dysfunction.

The aim of the study was to obtain a comparative evaluation of antihypertensive efficacy, tolerability and influence of combine therapy on myocardium mass, diastolic function of a left ventricle, lipid and carbohydrate exchange in patients with arterial hypertension in metabolic syndrome. Out of 40 examined cases 20 patients took enalapril and long-acting nifedipin and 20 ones--enalapril and moxonidine. All examination were been performed before administration of drugs and 6 months after the therapy. The dynamics of indices of ambulatory blood pressure monitoring, echocardiography, cycle ergometry, anthropometry, lipid, carbohydrate exchange and tolerability of conducted therapy was been evaluated. The use of this combination of the drugs may be recommended to be included in the treatment of arterial hypertension within the bounds of metabolic syndrome, as in most of cases they promote an achievement of target blood pressure level, have a cardioprotective action, high tolerability and favorable metabolic profile. The combination of enalapril and long-acting nifedipin has a more evident antihypertensive activity but a therapy with enalapril and moxonidine has a positive effect on the indices of carbohydrate exchange.

The state of lipid transport function of the blood, blood contents of stable nitrogen metabolites, and proinflammatory cytokines (TNF-a and IL-1b) during therapy with simvastatin were studied in 29 patients receiving combination antihypertensive therapy with angiotensin converting enzyme inhibitors (ACEI) and verapamil. Lipid lowering action of simvastatin was realized just in 1 month of treatment and remained sustained for half a year (average duration). 6 months after addition of simvastatin to antihypertensive therapy substantial (58.4%, p=0.044) rise of plasma content of stable nitrogen metabolites took place. At the same time therapy with metoprolol in a similar group of patients exerted no considerable effect on blood plasma concentration of nitrate and nitrite anions. Lowering of median values of TNF-alpha from 20.13 (12.67-52.80) to 11.34 (3.31-31.29) pg/ml (p<0.0038) was also noted at the background of combination antihypertensive therapy. This happened without distinct affair with degree of lipid lowering action of simvastatin. The results of the study document positive effect of half year treatment of patients with concomitant hypertension and diabetes with simvastatin (10-20 mg/day) in combination with ACEI and verapamil on metabolism of nitric oxide and plasma content of TNF-alpha which realizes independently from degree of hypolipidemic action of simvastatin.

The oxidant resistance of low-density lipoproteins was shown in patients with metabolic cardiovascular syndrome to be reduced versus healthy donors. A changing total antiradical activity of blood serum is an important factor for such reduction of the antioxidant resistance in the above pathology. The level of tocopherol in blood serum could be the most significant chain determining the mentioned activity in patients with metabolic cardiovascular syndrome.