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Atherosclerosis is a major risk factor for cardiovascular disease (CVD), which is the leading cause of death worldwide. Atherosclerosis is initiated by endothelial activation, followed by a cascade of events (accumulation of lipids, fibrous elements, and calcification) triggering vasoconstriction and activation of inflammatory pathways. This review focuses on the various stages in the development of atherosclerosis, ranging from endothelial dysfunction to plaque rupture. In addition, disorders of lipid, glucose and amino acid metabolism in atherosclerosis are considered here. The key pathological stages of metabolism disruption and their role in atherosclerosis are considered in detail which may be helpful for the more better understanding of atherosclerosis pathogenesis. Finally, some therapeutic approaches aimed at modulating lipid metabolism will also be presented which show the therapeutic targets (enzymes and transport proteins) which modulation can prevent further deterioration of patients symptoms.

The aim : to evaluate the incidence of obstructive lesions of the coronary arteries during routine coronary angiography (CAG) before carotid endarterectomy (CEA) and the incidence of perioperative complications. Materials and Methods : We examined a continuous sample of 498 patients before CEA who underwent an invasive evaluation of the coronary bed during CAG. Depending on the hemodynamic significance of coronary artery lesions, the patients were divided into three groups: group I-obstructive coronary artery disease (≥70%) ( n = 309, 62.0%); group II-non-obstructive lesions of the coronary arteries (<70%) ( n = 118, 23.7%); group III-intact coronary arteries ( n = 71, 14.3%). The groups were compared with each other according to the data of the preoperative examination (clinical and anamnestic parameters, laboratory data and results of echocardiography), as well as according to the immediate results of the operation. In the hospital period, adverse cardiovascular events were assessed: death, myocardial infarction (MI), stroke, arrhythmias, atrial fibrillation or flutter (AF/AFL) and combined endpoint. Results : The groups differed significantly in the presence of symptoms of angina pectoris, myocardial infarction and myocardial revascularization procedures in their medical history and in the presence of chronic ischemia of the lower extremities. However, in the group of intact coronary arteries, the symptoms of angina were in 14.1% of patients, and a history of myocardial infarction was in 12.7%. Myocardial revascularization before CEA or simultaneously with it was performed in 43.0% of patients. As a result, it was possible to reduce the number of perioperative cardiac complications (mortality 0.7%, perioperative myocardial infarction 1.96%). Conclusions : The high incidence of obstructive lesions in the coronary arteries in our patients and the minimum number of perioperative complications favor routine CAG before CEA.

Aim    To analyze long-term outcomes by results of the prospective part of the Kuban registry of patients with an implantable cardioverter defibrillator (ICD).Material and methods    A prospective analysis of the incidence of hard endpoints and changes in the condition was performed for 260 patients with ICD successively added to the Registry of Patients with Implantable Cardioverter Defibrillator" from 2015 through 2019.Results    At the time of ICD implantation, all patients had chronic heart failure (CHF), mostly of ischemic etiology with a low left ventricular ejection fraction (LVEF); median LVEF was 30 (25; 36.5) %. 54 of 266 (21.9 %) patients died by 2021;  17 of them (31.5 %) died in the hospital; in 76.5 % of cases, death was caused by acute decompensated heart failure (HF). 139 (53.5%) patients were readmitted; 66 (25.4 %) hospitalizations were related with ICDs (lead revision or reimplantation); acute cardiovascular events developed in 38 (14.6 %) patients; 12 (4.6%) patients underwent percutaneous coronary interventions; orthotopic heart transplantation was performed for 4 patients. ICD shocks were recorded in 27 (10.4 %) patients. After the ICD implantation, median LVEF remained unchanged, 31 (25; 42) vs. 30 (25; 36.5) % (р&gt;0.05). However, both objective and subjective HF symptoms worsened. Thus, the number of patients with IIB stage CHF increased from 29.6  to 88.8 % (р&lt;0.01) and with NYHA III CHF from 24.2  to 34.5 % (p&lt;0.05). 80 (30.8%) patients visited cardiologists on a regular basis. Only 7.3% of patients received an optimal drug therapy. During the observation period, the rate of beta-blocker treatment considerably decreased, from 90.6  to 64.3 % (р&lt;0.01), and the rate of the mineralocorticoid receptor antagonist treatment decreased from 50.8  to 17.4 % (р&lt;0.01). The rate of the diuretic treatment was inconsistent with the severity of patients' condition.Conclusion    Most of the problems the patients encountered after the ICD implantation were related with an inadequate treatment of the underlying disease. Since the majority of patients with ICD have a low LVEF, it is essential to focus on prescribing an optimal drug therapy and maintaining compliance with this therapy.

Aim: To assess the possibilities of using comorbidity indices together with the GRACE (Global Registry of Acute Coronary Events) scale to assess the risk of hospital mortality in acute coronary syndrome (ACS)., Materials and Methods: The registry study included 2,305 patients with ACS. The frequency of coronary angiography was 54.0%, percutaneous coronary intervention (PCI) 26.9%. Hospital mortality with ACS was 4.8%, with myocardial infarction 9.4%. All patients underwent a comorbidity assessment according to the CIRS system (Cumulative Illness Rating Scale), according to the CCI (Charlson Comorbidity Index) and the CDS (Chronic Disease Score) scale, according to their own scale, which is based on the summation of 9 diseases (diabetes mellitus, atrial fibrillation, stroke, arterial hypertension, obesity, peripheral atherosclerosis, thrombocytopenia, anemia, chronic kidney disease). All patients underwent a mortality risk assessment using the GRACE ACS Risk scale., Results: It was found that the CDS and CIRS indices are not associated with the risk of hospital mortality. With CCI3, the frequency of death outcomes increased from 4.1 to 6.1% (2=4.12, p=0.042). With an increase in the severity of comorbidity from minimal (no more than 1 disease) to severe (4 or more diseases) according to its own scale, hospital mortality increased from 1.2 to 7.4% (2=23.8, p0.0001). In contrast to other scales of comorbidity, our own model more efficiently estimates the hospital prognosis both in the conservative treatment group (2=8.0, p=0.018) and in the PCI group (2=28.5, p=0.00001). It was in the PCI subgroup that the comorbidity factors included in their own model made it possible to increase the area under the ROC curve of the GRACE scale from 0.80 (0.740.87) to 0.90 (0.850.95)., Conclusion: CCI and its own comorbidity model, but not CDS and CIRS, are associated with the risk of hospital mortality. The model for assessing comorbidity on a 9-point scale, but not CCI, CDS and CIRS, can significantly improve the predictive value of the GRACE scale.

Aim        To study gender aspects of comorbidity in evaluating the risk of in-hospital death for patients with acute coronary syndrome (ACS) after a percutaneous coronary intervention (PCI).Material and methods        The presented results are based on data of two ACS registries, the city of Sochi and RECORD-3. 986 patients were included into this analysis by two additional criteria, age &lt;70 years and PCI. 80% of the sample were men. Analysis of comorbidity severity was performed for all patients and included 9 indexes: type 2 diabetes mellitus, chronic kidney disease, atrial fibrillation, anemia, stroke, arterial hypertension, obesity, and peripheral atherosclerosis. Group 1 (minimum comorbidity) consisted of patients with not more than one disease (n=367); group 2 (moderate comorbidity) consisted of patients with 2 or 3 diseases (n=499), and group 3 (pronounced comorbidity) consisted of patients with 4 or more diseases (n=120). In-hospital mortality was 2.7 % (n=27).Results   Significant data on the effect of comorbidity on the in-hospital prognosis were obtained only for men of the compared groups: 0.6, 1.8, and 8.8 %, respectively (χ2=21.6; р&lt;0.0001). At the same time, among 44 women with minimum comorbidity, there were no cases of in-hospital death, and the presence of moderate (n=110) and pronounced comorbidity (n=40) was associated with a similar death rate (7.3 and 7.5 %, respectively). Noteworthy, in moderate comorbidity, the female gender was associated with a 4-fold increase in the risk of in-hospital death (odd ratio, OR 4.3 at 95 % confidence interval, CI from 1.5 to 12.1; р=0.003). In addition, both in men and women with minimum comorbidity, even a high risk by the GRACE scale (score ≥140) was not associated with increased in-hospital mortality, which was minimal (0 for women and 1 % for men). At the same time, in the patient subgroup with moderate and pronounced comorbidity, a GRACE score ≥140 resulted in a 6-fold increase in the risk of in-hospital death for men (OR 6.0 at 95 % CI from 1.7 to 21.9; р=0.002) and a 16-fold increase for women (OR 16.2 at 95 % CI from 2.0 to 130.4; р=0.0006).Conclusion            This study identified gender-related features in predicting the risk of in-hospital death for ACS patients with comorbidities after PCI, which warrants reconsideration of existing approaches to risk stratification.

Analysis of the relationship between the epicardial fat with adipokine and system ST2/IL-33 in-hospital period, and also with the extent of fibrosis of the atrial myocardium through the year after myocardial infarction in patients with visceral obesity. Examined 88 patients with myocardial infarction (MI). Visceral obesity (VO) is established by computed tomography. In fact the presence VO the patients divided into two groups. Determined the concentration of leptin, adiponectin, stimulating growth factor (ST-2) and interlekin-33 (IL-33) in serum on 1st, 12-day in-hospital period and 1 year after MI. Thickness epicardial adipose tissue (EAT) and the percentage of cardiovirus of the myocardium was measured by the method MRI, respectively, on the 12th day of hospitalization and a year after MI. The control group consisted of 30 people. Statistical analysis of data was performed using nonparametric tests. Patients with MI is associated with an increase in the thickness of EAT, imbalance of adipokines with increased leptin, decreased adiponectin in early in-hospital period and development of cardiovirus. Higher values of IL-33 and ЅT2 in the early in-hospital period MI patients with no accompanied by a lower prevalence of cardiovirus in the post-hospital period. The thickness of epicardial fat is directly dependent on the prevalence of myocardial fibrosis, the concentrations of IL-33 and in inverse proportion to the concentration of ЅT2. The degree of cardiovirus is in inverse proportion to the concentration of IL-33 and directly dependent on the concentration of ST2. The increase in EAT closely linked to the development of fibrosis of the atrial myocardium after year. The thickness of EAT more patients MI, which is most pronounced imbalance of adipokines. The metabolic activity of EAT correlated with increased IL-33 and ST2 decrease., Competing Interests: The authors declare no conflict of interest.

The aim of the study was to identify the features of the genetic structure of myocardial infarction (MI) susceptibility depending on age ("early MI" denoting individuals who had the first MI before the age of 60 years, and "late MI" the group of patients with the first "MI after 60 years"). A total of 355 patients were examined (n = 121 early MI and n = 234 late MI) and 285 residents of the Siberian region (as a control group). Genotyping of 58 single nucleotide variants (SNPs) was performed using mass spectrometry using the Agena (ex Sequenom) MassARRAY® System. Statistical analysis was performed using Statistica 8.0 ("StatSoft Inc.", USA), as well as the "stats" and "genetics" packages in the R environment. The regulatory potential of SNPs was evaluated using the rSNPBase online service (http://rsnp.psych.ac.cn/). eQTL loci were identified using data from the Genotype-Tissue Expression (GTEx) project (http://www.gtexportal.org/) and the Blood eQTL online service (https://genenetwork.nl/bloodeqtlbrowser/). The GG genotype of ITGA4 rs1143674, the CC genotype of CDKN2B-AS1 rs1333049, and the CC genotype of KIAA1462 rs3739998, are generally associated with MI. The AA genotype of ADAMDEC1 rs3765124 (OR = 2.03; 95% CI 1.23-3.33; p = 0.004) and the GG genotype of AQP2 rs2878771 (OR = 2.24; 95% CI 1.23-4.09; p = 0.006) are associated with the development of MI at an early age, and the TT genotype of TAS2R38 rs1726866 (OR = 1.82; 95% CI 1.11-2.89; p = 0.009) was the high-risk genotype for the late MI. Genetic variants associated with MI are regulatory SNP (rSNP) and affect the affinity of DNA binding to transcription factors, carry out post-transcriptional control of gene activity and change the level of gene expression in various tissues. Thus, early and late MI are based on both common genetic variants of ITGA4, CDKN2B-AS1, KIAA1462 genes and specific ones (ADAMDEC1 and AQP2 for early MI and TAS2R38 for late MI).

In the review article are provided the approaches to the therapy for improvement of prognosis in patients with peripheral and multifocal atherosclerosis which are available now; some limitations and a real situation are designated for the antithrombotic therapy in this category of patients. According to the clinical trial COMPASS the prospects of wide use of a combination of acetylsalicylic acid and a rivaroxsaban of 2.5 mg 2 times a day in the patients with chronic coronary heart disease and/or symptom peripheral atherosclerosis are designated.

Purpose: to assess drug therapy and achievement of target parameters of treatment in patients with ischemic heart disease (IHD) during 3-5 years of follow-up aſter coronary bypass surgery., Materials and Methods: From the initial sample of the coronary bypass surgery registry (n=680) we selected for this study 111 men (mean age 61 [55; 65] years) hospitalized in 2011 with clinical picture of IHD for coronary artery bypass graſting (CABG)., Results: Mean duration of follow-up was 4.2 years. Mortality was 11.7 % (n=13), 11 deaths were cardiovascular, 2 - from unknown causes. End points defined as repeat hospitalizations and IHD progression were registered in 18 of 98 patients (18.4 %). Only in 25 % of patients during 3-5 years of observation aſter CABG there were no clinical signs of angina. Five patients (5.1 %) developed new type 2 diabetes. Drug therapy: 80 patients (81.6 %) received acetylsalicylic acid, 60 (61.2 %) - angiotensin converting enzyme inhibitors, 80 (81.6 %) - β-adrenoblockers. Eighty-one men (82.6 %) received statins, but only 20 of 98 re-examined patients (20.4 %) took high doses. Target levels of low density lipoprotein cholesterolConclusion. Data of clinical practice illustrate insufficient quality of basic and antianginal therapy in patients with IHD aſter CABG. Indicators of control of angina, heart rate, achievement of target levels of parameters of lipid metabolism remain unsatisfactory.

On April 9, 2018, the national advisory board "Improvement of outcomes in patients with recent ACS: the place of PCSK9 inhibitors" was held in Moscow. Leading Russian experts in the field of atherosclerosis and lipid-lowering treatment attended the board. The purpose of the Board was to determine the place of PCSK9 inhibitors in the improvement of outcomes in patients with recent (less than 1 year) acute coronary syndrome (ACS). During the Board, three major aspects of lipid-lowering treatment were discussed: 1) issues in reaching the target levels of LDL cholesterol in real clinical practice among patients with recent ACS; 2) the results of ODYSSEY OUTCOMES study and their role in the improvement of outcomes in patients with recent ACS; 3) treatment with PCSK9 inhibitors in the management of patients with recent (less than 1 year) ACS in everyday clinical practice, the role of lipid centers.

This Conclusion of the Board of experts is devoted to the analysis of the evidence base, the position in modern clinical guidelines, the efficacy and safety analysis as well as the options of combined therapy with statins and ezetimibe (Otrio, JSC "AKRIKHIN") in various categories of patients in routine clinical practice in theRussian Federation. Cardiovascular diseases (CVD) continue to lead in the structure of morbidity and mortality inRussia. Hypercholesterolemia is one of the main modifiable risk factors for CVD. Administration of HMGCo-A-reductase inhibitors (statins) remains the basis for the prevention and treatment of the main complications of atherosclerosis, but the achievement of target levels of LDL-C on of statin monotherapy in Russian practice among different categories of risk does not exceed 50%. Proportion of patients (up to 12%) does not tolerate statin therapy, which requires the search for alternative therapies. To optimize the control of the level of LDL-C, combination therapy with statins and ezetimibe is used. Ezetimibe is an effective lipid-lowering drug, an inhibitor of intestinal absorption of cholesterol, which was investigated in many international and Russian studies, the results of which have demonstrated good tolerability, safety and efficacy (reduction of LDL-C levels by 18% in monotherapy). It was noted that the combined therapy with low/medium doses of statins and ezetimibe effectively reduces the level of LDL-C by 44-53%, which is comparable to the effect of high doses of statins and reduces CV risk in patients with CKD and ACS. Otrio (INN Ezetimib) tablets 10 mg ( JSC "AKRIKHIN",Russia) has demonstrated bioequivalence to the original drug Ezetrol tablets 10 mg (Schering-plough Labo N. V,Belgium). Broad use of a new generic product Otrio in combination with different statins will significantly increase the frequency of achievement of target lipid levels in patients with high and very high CV risk, including patients with chronic renal failure, type 2 diabetes and in patients with high hypercholesterolemia (LDL-C &gt; 5 mmol/l) and, ultimately, reduce the burden of CV disease and mortality in Russia.

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.

Purpose: Determination of clinical and instrumental predictors of progressive course of multifocal atherosclerosis (MFA) in patients one year after myocardial infarction (MI), initially having hemodynamically insignificant stenoses of carotid arteries., Materials and Methods: From database of patients with acute coronary syndrome treated in the Kemerovo Regional Clinical Cardiac Dispensary in 2009-2010 we selected for this study 141 patients with verified diagnosis of MI and hemodynamically insignificant lesions in the internal carotid artery (ICA) (stenosis up ≤ 55 %). All patients had coronary atherosclerosis verified on coronary angiography at admission because of MI. A multivariate analysis of possible predictors of the progressive course of multifocal atherosclerosis was made based on assessment of the development of cardiovascular complications (CVC) (death, MI, stroke and transient cerebral circulatory attacks [TIA]), as well as revascularizations and negative dynamics of parameters of color duplex scanning (CDS) of ICA during one year after MI., Results: One year after MI the overall incidence of CVC was 16.3 % (n=23). Structure of registered events was as follows: death from MI 7.1 % (n=10), deaths from stroke 2.1 % (n=3) and other causes 2.1 % (n=3), non-fatal MI 5.0 % (n=7), non-fatal stroke / TIA 2.1 % (n=3), carotid revascularization 2.8 % (n=4), coronary revascularization 14.9 % (n=21). CDC of ICAs was repeated in 125 patients. There were 17 (13.6 %) cases of progression of carotid atherosclerosis in the form of de novo bilateral stenoses in 14 (11.2 %) patients, stenoses in the left and right ICA 1 patient and 2 patients, respectively. The following predictors of progression of atherosclerosis of cerebral arteries were identified: family history of cardiovascular diseases (CVD),ICA stenosis ≥45 %, baseline circular atherosclerotic plaque (ASP). Predictors of high risk of stroke were family history of CVD, history of stroke,ICA stenosis ≥45 %, heterogeneous hypoechoic ASP. As predictors of lethal outcome, we identified history of MI, high functional class of angina preceding the index MI, severe coronary vascular bed involvement (SYNTAX score &gt;23), presence of any bilateral atherosclerotic lesion in ICAs, and heterogeneous hypoechoic ASP. Assessment of the contribution of adherence to therapy in the prognosis 1 year after hospital discharge was fulfilled in 125 alive patients. It allowed to conclude that patients with progression of atherosclerosis and nonfatal CVC were characterized by insufficient adherence to standard therapy., Conclusion: Predictors of the progressive course of multifocal atherosclerosis during one year after MI were identified in this study. It is necessary to strengthen therapeutic and preventive measures aimed at minimization of the impact of these factors in this category of patients.

Purpose: to study the relationship between degree of calcification of coronary arteries, osteopenic syndrome, and clinical course of ischemic heart disease (IHD) during 3-5 years of follow-up in men after coronary artery bypass grafting (CABG). Materials and methods. We included in this prospective study 111 men admitted for CABG under cardiopulmonary bypass. All patients underwent color duplex scanning (CDS) of brachiocephalic arteries (BCA), coronary angiography, multislice computed tomography (MSCT) of coronary arteries (CAs) to assess the degree of calcification, densitometry of femoral neck. Cardiac calcium score of the vessels was assessed by the Agatston method. After 3-5 (mean 4.2) years we assessed dead or alive status of 111 patients. Mortality during followup was 11.7 % (n=13). In 59 of 98 survived patients we repeated CDS of BCA and MSCT of CAs with calculation of CA calcification scores., Results: Significant CA calcification prior to CABG was detected in more than half of the patients (57.6 %). Among all clinical and anamnestic factors only one risk factor - smoking was associated with mortality (odds ratio [OR] 9.8, 95 % confidence interval [CI] 1.2-78.1, χ2=6.6, р=0.01). There were no association of mortality with index of CA calcification, Syntax score, osteopenic syndrome and BCA involvement. In the group of patients with baseline coronary calcification index &gt;400 there were more smokers (р=0.026) and patients with lesions in &gt;3 CAs (р=0.037) compared with the group with values ≤400. At the preoperative stage we revealed associations of CAs calcification index with T-test characterizing presence of the osteopenic syndrome (r= -0.24, р=0.06), Syntax score (r=0.26, р=0.041), and number of affected CAs (r=0.25, р=0.048). At repeated examination 3-5 years after CABG a medium positive correlation was detected between the severity of CA calcification and the severity of BCA stenoses (r=0.28, р=0.029). Linear regression analysis with stepwise selection identified baseline (prior to CABG) higher values of T-test evaluated at femoral bone as the only significant predictor of calcium score increase during 3-5 years of follow-up., Conclusion: Dynamics of calcification of CAs in men with IHD during 3-5 years of follow-up after CABG was multidirectional, but in most cases (66 %) it was progressive. There was correlation between coronary calcification and smoking status and decreased T-test assessed at femoral bone prior to CABG. In the long-term follow-up period the correlation between severity of BCA lesion and severity of coronary  calcification was found. Negative correlation was detected between progression of coronary calcification and baseline impairment of mineral density of femoral bone.

Objectives: To study associations between genes of different functional classes, including fibrogenesis genes, with coronary atherosclerosis and specific features of its course., Methods: We included in this study 404 patients with confirmed chronic ischemic heart disease (IHD) who had undergone coronary artery bypass grafting. Two groups of participants were distinguished - those with (n=188) and without (n=216) history of myocardial infarction (MI). Control group consisted of inhabitants of the Siberia region (n=285). Associations were analyzed using 48 single nucleotide polymorphisms (SNP) located in genes earlier determined as associated with diseases of the cardiovascular continuum (diabetes mellitus, MI, atherosclerosis). Multiplex genotyping was performed using mass spectrometry. For statistical analyses we used Statistica v8.0 and R-language with "stats" and "genetics" packages., Results: We identified several genetic markers contributing to susceptibility to development of atherosclerosis. Same markers were identified as determinants of the character of the course of atherosclerotic disease. Risk of development of atherosclerosis was higher in carriers of the following genotypes: TT of ITGB5 gene (rs1007856) - by 1.6 times (OR=1.59; р=0.0153); GG of ITGA4 gene - by 1.85 times (OR=1.85; р=0.0016); GG of IGFBP7 gene (rs11133482) - by 2.4 times (OR=2.36; р=0.0031). The following genotypes were identified as protective against MI and determining stable course of the disease: AA of TLR4 gene (rs4986790) (OR=0.47; р=0.0104).; CC of LDLR gene (rs2738446) (OR=0,53; р=0.0041); GG of OAS1 gene (rs1131454) (OR=0.50; р=0.0274)., Conclusion: Susceptibility to coronary atherosclerosis and prognosis of disease progression were found to be associated with polymorphism of certain genes, involved in metabolism of the extracellular matrix and processes of fibrogenesis (ADAMDEC1, ITGA4, ITGB5, CDKN2B-AS1, IGFBP7), lipid metabolism (LDLR), immune system functioning (TLR4, OAS1) and DNA repair (LIG1).

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.

Aim: to assess safety and efficacy of single stage complete revascularization by multivessel stenting as primary percutaneous coronary intervention (pPCI) in elderly and middle aged patients with acute ST-elevation myocardial infarction (STEMI)., Material and Methods: We included in this analysis data on 327 of 1690 STEMI patients who had undergone pPCI from 2009 to 2013. Age of 103 patients was more or equal 65 and of 224 less or equal 64 years. Multivessel stenting (MS) during pPCI was carried out in 26 and 65, while strategy of staged revascularization (SR) was implemented in 77 and 129 individuals among older and younger patients, respectively. During follow-up for 12 months we registered deaths, myocardial infarctions, and unplanned target vessel revascularizations., Results: In each age group ( more or equal 65 and less or equal 64 years) there were no significant differences in clinical and demographic characteristics between subgroups of patients subjected to MS and SR. MS appeared to be safe and effective irrespective of age. Mortality during first 30-days was higher among patients aged more or equal 65 years. However, within each age group there were no significant differences in 1 year results between MS and SR subgroups.

Background: The aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI)., Methods: We recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m 2 . After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication., Results: RD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence., Conclusions: Measurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.

Fibrosis is one of the main components in the progression of most cardiovascular diseases, including coronary heart disease, by causing structural changes in the myocardium and vascular wall. The quantitative and qualitative characteristics of fibrosis of the myocardium are responsible for decreasing its elastic properties, developing diastolic dysfunction, impairing myocardial contractility, developing systolic dysfunction and cardiac arrhythmias, and worsening coronary blood flow in patients with heart failure of different etiologies. The important aspect of studying fibrosis is not only its interpretation as a model of the typical pathological process, but also its consideration as a systemic lesion of various organs and tissues. At the same time, the identification of myocardial fibrosis biomarkers that are available for their determination in circulating blood is of particular interest. Since there was evidence for the role of fibrosis in developing dysfunction of various organs and ensuring the systematicity of most diseases, especially at their development stages, the process of fibrosis came to be regarded as a promising therapeutic target. It is relevant to further investigate myocardial fibrosis, which is aimed at increasing the efficiency of its diagnosis and predicting its course and pathogenetically sound therapy.

Purpose: To assess significance of urinary neutrophil gelatinase-associated lipocalin (NGAL) for predicting hospital complications in subjects with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG)., Materials and Methods: The study included 720 subjects who underwent CABG between 03/2011 and 04/2012. Blood serum creatinine level, glomerular filtration rate (GFR) (MDRD formula) and NGAL concentration were measured before and on day 7 after CABG. The following unfavorable outcomes of operative intervention: myocardial infarction (MI), stroke or transient ischemic attack, acute or progression of chronic renal disease, remediastinotomy were registered during in-hospital period. Additive EuroSCORE was calculated for all patients., Results: There were no significant differences in serum creatinine level and GFR both before and on day 7 after CABG between groups of patients with different risk assessed by EuroSCORE, and with complicated and uncomplicated postoperative course. Urine NGAL level before and on day 7 after CABG was significantly higher in high and medium compared with low EuroSCORE risk groups. Preoperative NGAL urine level was significantly higher in patients with than in those without MI or stroke after CABG. NGAL urine level was also higher in patients with development of acute renal failure (ARF) compared with those without ARF. Both pre- and postoperative NGAL urine levels were higher in patients with unfavorable outcome while there were no significant differences in serum creatinine levels and CRF between patients with favorable and unfavorable outcomes., Conclusion: Preoperative measurement of urinary NGAL - a preclinical marker of acute kidney injury - allowed to predict more accurately the hospital risk of development of adverse cardiovascular and renal complications of CABG.

Aim: to assess early (in-hospital) results of percutaneous coronary intervention (PCI) for ST-elevation (STE) myocardial infarction (MI) in different age groups., Materials and Methods: We enrolled in this study 356 patients with STEMI who underwent PCI within 24 hours of the disease during 1 year (2012). According to age all patients were divided into 2 groups: "young" ( less or equal 70 years) and "older" (>70 years)., Results: Compared with young in older group there were more patients with renal (53.84 vs. 19.78%) and myocardial (23.07 vs. 6.83%, =0.0000) dysfunction, hypertension (97.43 vs. 83.81% =0.0018), history of MI (19.23 vs. 10.43%, =0,3736), and acute heart failure at admission (32.04 vs. 13.95%, =0.0003), and less smokers (10.25 vs. 34.53%). Hospital mortality in older group was higher (8.97 vs. 1.43%, =0.0007) despite effective PCI. Rate of hemorrhagic complications (major bleedings+hemotransfusions) was also higher in older group (5.12 vs. 0.71%, =0.0077)., Conclusion: Compared with younger older STEMI patients were characterized by more severe initial clinical condition and worse early results of primary PCI with higher mortality and rate of hemorrhagic complications. Thus the problem of improvement of management of this group of patients during hospitalization remains to be actual.

Background: The aim of this study was to evaluate the plasma levels of bone turnover markers (BTMs) in male patients with stable angina depending on the bone mineral density (BMD), coronary atherosclerosis (CA) and coronary artery calcification (CAC)., Methods: We recruited 112 males with verified stable angina. All the patients underwent coronary angiography, multislice spiral computed tomography, and dual-energy X-ray absorptiometry. Plasma levels of BTMs were measured by enzyme-linked immunosorbent assay., Results: Osteopoenia and osteoporosis were reported in 90 (80.4%) and 34 (30.4%) patients, respectively. Multivessel coronary artery disease, severe CA and CAC, decreased cathepsin K plasma level, and increased osteocalcin plasma level were significantly more prevalent in patients with osteopoenia/osteoporosis compared to the subjects with normal BMD. Patients with severe CA and CAC had significantly reduced cathepsin K plasma levels., Conclusions: We revealed a significant association of osteopoenia/osteoporosis with severe CA and CAC in males with stable angina. Cathepsin K and osteocalcin plasma levels may be suggested as the significant markers of osteopoenia/osteoporosis. In addition, cathepsin K plasma level can be also a valuable marker of severe CA and CAC., (Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objectives: The study aimed to evaluate whether serum inflammatory markers have prognostic value in patients with ST-segment elevation myocardial infarction (STEMI)., Background: The role of cytokine-driven inflammation in the development of postdischarge complications after STEMI is obscured., Methods: We recruited 214 patients who were admitted within 24 h of STEMI onset to our Institute. IL-1α, -6, -8, -10, -12, TNF-α, and CRP serum levels were measured on the 10-14th day after STEMI onset., Results: Serum levels of IL-12, TNF-α, and CRP were significantly higher in patients with 3 affected coronary arteries compared to those with 1 affected coronary artery. However, only Killip class II-IV at admission and IL-12 serum level ≥90.0 pg/mL were defined as statistically significant predictors of adverse outcome after 1 year of follow-up., Conclusion: IL-12 serum level may be suggested as a candidate prognostic marker if measured 10-14 days after STEMI onset., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: to study clinical and prognostic significance of serum neutrophil gelatinase-associated lipocalin (s-NGAL) in patients with ST-segment elevation myocardial infarction (STEMI)., Material and Methods: Patients with STEMI (n=85) of less than 24 hours duration admitted to the Kemerovo Cardiology Dispensary were included in the study. s-NGAL levels (ng/ml) were measured on day 1 and 12 of hospital stay by ELISA using commercial kit. Reinfarction rate and mortality were assessed over 3-year follow-up., Results: Median s-NGAL levels on day1 and 12 were 1.33 (0.36-1.90) and 1.63 (1.25-2.61) ng/ml, that corresponded to a 3.32- and 4.07-fold increase, respectively, compared to reference values. Between days 1 and 12 s-NGAL levels increased by 22.55 % (p=0.0009). Higher values of serum NGAL on day 12 of MI were associated with presence of renal structural lesions, three-vessel coronary artery disease and anterior MI. Patients who underwent percutaneous coronary intervention (PCI) demonstrated only a negligible increase of s-NGAL level by day 12 while in those not subjected to PCI 3-fold increase was observed. Patients with s-NGAL levels >2.6 ng/ml compared with other patients had higher mortality (9.52 vs 31.83%; odds ratio 4.42 [1.30-15.16], p=0.012)., Conclusion: High values of serum NGAL in STEMI patients were associated with severe clinical status. s-NGAL level above 2.6 ng/ml on day 12 of hospital stay was associated with 4- fold increase of all-cause mortality during 3-year follow-up.

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.

Aim: to study associations of polymorphic genetic variants of inflammatory response, endothelial function, lipid metabolism, and blood coagulation with impaired renal function in patients with ST elevation myocardial infarction (STEMI)., Material and Methods: We enrolled in the study 171 patients admitted to the Kemerovo Cardiology Dispensary within 24 hours after onset of STEMI. All patients underwent genotype identification of 25 polymorphic variants of 18 major candidate genes for cardiovascular disease. Genotyping was performed with DNA chip SINKAR-1 (Institute of Medical Genetics and LLC "Genomic Diagnosis"). Glomerular filtration rate (GFR) was estimated using serum creatinine level measured at admission., Results: Comparison of allelic and genotype frequencies of the studied polymorphisms revealed that angiotensin-converting enzyme (ACE) gene rs4291 was associated with decreased GFR: odds ratio (OR) for carriers of rare TT genotype was 2.31 [1.01-5.25], =0.043. Analysis of genotype combinations of ACE rs4343 polymorphism and hepatic lipase gene (LIPC) rs1800588 showed that AA genotype of rs4343 polymorphism in combination with CC genotype of rs1800588 polymorphism was associated with lowest risk of renal dysfunction, whereas GG and AG genotypes of ACE rs4343 in combination with TT and CT genotypes of LIPC rs1800588.

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 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.

We have performed association analysis for mtDNA most common variants and haplogroups with myocardial infarction and some prognostic characteristics in patients. Comparison of patients (N=406) and controls (N=183) has shown higher frequency of HV0 haplogroup in patients (6.9% vs. 2.2%; p=0.033). Patients with early infarction (before age 55), comparing to patiens older than 55 and the first infarction, had higher frequency of 16189C variant (24.1 vs. 12.5%; p=0.008); also, haplogroup U2e was registered only in the subgroup with early infarction (4.4%; p=0.004). On the other side, haplogroup U5 was less frequent in the patients with early infarction (5.1% vs. 15.4%; p=0.002). The patients with recurring cardiovascular incidents during one year follow-up had higher frequency of haplogroup H1 (20% versus 4.5% in the patients without complications, p=0.002) and variant 16189C (30% versus 13.5%; p=0.018). Haplogroup U5 was more frequent in the group of patients with left ventricular ejection fraction less than 40%: 17.1% comparing to 8.2% in the group with ejection fraction>40%; p=0.034. The results suggest that mtDNA polymorphism contributes to coronary atherosclerosis. The associations could be explained by the polymorphism effect on oxidative phosphorylation and reactive oxygen production in mitochondria.

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.

Background: This investigation was aimed at assessing the clinical significance of microalbuminuria (MA) in predicting in-hospital adverse outcomes amongst the patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who have undergone coronary artery bypass graft (CABG) surgery., Methods: We recruited 720 consecutive Caucasian (Russian) patients who underwent CABG surgery during 2011-2012., Results: Patients with renal dysfunction (RD) and without type 2 DM had significantly higher median serum creatinine seven days after CABG surgery compared to patients without RD and type 2 DM. There were no statistically significant intergroup differences regarding glomerular filtration rate. However, the highest median of urine albumin excretion 24hours before and seven days after CABG surgery was detected in patients with RD and type 2 DM whilst the lowest median was noted in patients without RD and type 2 DM. Median of urine albumin excretion 24hours before and seven days after CABG surgery in patients with adverse outcome was significantly higher compared to patients with a favourable outcome., Conclusions: We suggest that the determination of MA before and after CABG surgery may assist in predicting adverse outcomes after CABG surgery., (Copyright © 2015. Published by Elsevier B.V.)

Background: This study has been aimed to assess clinical significance of cystatin C in the prognosis of a risk of hospital complications among the patients with coronary artery disease CAD who have undergone coronary artery bypass surgery (CABG)., Methods: We have recruited 719 consecutive Caucasian (Russian) patients who underwent CABG in 2011-2012., Results: No statistically significant differences in the serum creatinine concentration (sCr) and glomerular filtration rate before and seven days after the surgery have been found among the patients belonging to different EuroSCORE risk groups. A statistically significant elevation of serum cystatin C concentration (sCC) before and seven days after the surgery has been demonstrated in EuroSCORE medium- and high-risk groups in comparison with the low-risk group. In addition, we have revealed increased pre-surgical levels of sCC in patients who had died earlier than seven days after CABG. Regarding the cardiovascular complications, a statistically significant elevation of sCC has been observed in patients with and without myocardial infarction (MI), stroke, or acute kidney injury (AKI) in the postoperative period., Conclusions: We suggest that the determination of sCC before and after CABG surgery may help in the prognosis of adverse cardiovascular and renal outcomes after the CABG surgery., (Copyright © 2014. Published by Elsevier B.V.)

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 initial rate of non-coronary atherosclerosis progression in patients of different age groups before and after myocardial infarction (MI) was studied. 168 patients with ST elevation myocardial infarction (STEMI) were enrolled in the study; the age of 60 was a criterion for patients distribution into the study groups. It is established that one year after MI the patients younger than 60 years of age had recurrent acute coronary syndromes (ACS), and older patients had cerebral vascular accidents. Thus in both younger and older patients a correlation, between the presence and intensity of atherosclerosis progression and the rates of cardiovascular events was observed; however, in older patients atherosclerosis progression is associated not only with higher coronary but also cerebrovascular events rates.

The distribution of the allele and genotype frequency for the TOMM40 gene polymorphic variants rs741780, rs157580, rs1160985, rs2075650, and rs8106922 was analyzed in a sampling of ethnic Russians from the city of Kemerovo. The study of the structure of linkage disequilibrium in terms of five studied polymorphic variants showed the presence ofa haplotype block 2 Kb in length, which includes three polymorphic variants, i.e., rs741780, rs1160985, and rs8106922. The differences in the frequencies of alleles and genotypes in terms of the polymorphic rs2075650 and rs157580 variants between ethnic Russians from the city of Kemerovo and other European populations were detected. It was discovered that polymorphic variants of TOMM40 rs741780, rs1160985, and rs8106922 are associated with serum triglyceride concentrations. In men, the polymorphic variant rs2075650 is associated with low-density lipoprotein cholesterol levels. In women, the polymorphic variant rs741780 is associated with diastolic blood pressure levels.

Aim: To elucidate role of subclinical inflammation in progression of atherosclerotic process in magistral noncoronary arteries in patients during one year after ST-elevation myocardial infarction (MI)., Material and Methods: We examined 168 men with MI (mean age 59.5 years). All patients during hospitalization underwent coronary angiography and color duplex scanning of brachiocephalic arteries. In a year ultrasound study of noncoronary vessels was repeated and progression of atherosclerosis assessed. Parameters of inflammation in blood serum were measured on days 10-14 of MI and after one year., Results: At repeat study most patients demonstrated progression of noncoronary atherosclerosis. Some biomarkers measured during inhospital phase of MI (low concentration of anti-inflammatory interleukin 10 - IL-10, elevated N-terminal pro brain natriuretic peptide) allowed to distinguish group of patients with subsequent progression of noncoronary atherosclerosis. Elevated concentrations of C-reactive protein and 11-10 registered in a year after MI were also associated with more severe progression of atherosclerosis. Serum levels of neopterin and IL-12 remained stable in patients with and decreased in patients without pronounced progression of atherosclerosis.

The present article reviews the issues of medical healthcare provision for acute coronary syndrome (ACS) in the Russian Federation from the perspective of benefits of pharmacoinvasive management for these patients. A brief analysis of clinical trials, promoting and defining pharmacoinvasive management as a preferred therapy that should be implemented in the Federal Health Care Program for ACS, is presented. The data of the STREAM study reported similar results in comparison with primary percutaneous coronary intervention (PCI) in immediate and long-term prognosis in patients with ST-elevation ACS after the initiation of thrombolytic therapy (TLT) with tenecteplase in the early pre-hospital period (< 3 hours from the onset of myocardial 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 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.

Unlabelled: Aim of the study was to determine association between clinical-anamnestic factors and degree of progression of atherosclerotic process in magistral noncocronary arteries during one year after ST-elevation (STE) myocardial infarction (MI)., Material: We included into this study 168 men (mean age 59.5 years) with STEMI subjected during hospitalization to coronary angiography and duplex color scanning of brachiocephalic arteries and main arteries of lower extremities. In a year we performed repeat ultrasound examination of same noncoronary arteries and assessed development of vascular complications., Results: Greatest degree of atherosclerosis progression in noncoronary arteries was registered in patients older than 60 years, with hypertension, presence of atherosclerotic stenoses in noncoronary vascular beds at initial examination, those who had undergone percutaneous coronary intervention or coronary artery bypass grafting, and patients with higher levels of total and low density lipoprotein cholesterol at examination after 12 months post MI.

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.

A sample of 165 patients with myocardial infarction (MI) with ST segment elevation has been studied to construct a prediction model for one-year period complications (recurrent nonfatal IM or cardiac death). Polymorphic genetic markers (n = 32) with confirmed role in pathogenesis of cardiovascular disease were analyzed. The best model to stratify patients by risk of post-IM complications included variants rs4291 (A-240T) in the ACE gene, rs6025 (G1691A, Leiden mutation) in the F5, and rs5918 (Leu59Pro) in the IGTB3. C statistics for the genetic model was 0.75 (0.64; 0.86), p = 0.001, which is comparable with characteristics of the GRACE scale for the same patients' population: 0.73 (0.61; 0.85). Thereby, analysis of a limited number of genetic markers was sufficient to create risk prediction model for post-MI complications with comparable effectiveness to the model, which is currently in use in clinical practice. To confirm the clinical validity, the predictive model obtained in the study should be evaluated in independent samples of MI patients. Association analysis of individual genetic markers with patients' outcomes has revealed that T allele carrier status (AT and TT genotypes) rs4291 of the ACE and CG genotype rs328 of the LPL gene are risk factors for cardiac death during one year after MI; Leiden mutation (rs6025) of the F5 gene is related to the higher risk of recurrent non-fatal MI or death during one year; CC genotype of the rs10811661, located in 9p21 locus has a protective effect against recurrent MI or death within one year after acute event.

Background: Complete following existing guidelines for management of acute coronary syndrome (ACS) is known to be associated with better outcomes. Partly this is explained by lesser adherence to recommendations in high risk patients. Aim of our study was to assess relationship between degree of following current guidelines and in hospital outcomes independently from initial assessment of risk., Methods: Each key recommendation from guidelines issued between 2008 and 2011 (13 for STE ACS, 12 for NSTE ACS) was given weight of 1. Sum of these units constituted index of guideline adherence (IGA). IGA was retrospectively calculated for 1656 patients included in Russian independent ACS registry RECORD-2 (7 hospitals, duration 04.2009 to 04.2011). The patients were divided into 2 groups according to quartiles of IGA distribution: 1) low adherence group (quartiles I-II); 2) high adherence group (quartiles III-IV)., Results: In low adherence compared with high adherence group there were significantly more patients more or equal 65 years (=0.0007), with chronic heart failure [CHF] (<0.0001), previous stroke (<0.0001), atrial fibrillation [AF] (=0.0002), Killip class more or equal II (=0.0065), high risk of death by GRACE score (=0.035). Inhospital mortality was 9.3 and 2.4% in low and high adherence group, respectively (p<0.0001). The following independent predictors of inhospital death were identified: IGA quartiles I-II (odds ratio [OR] 4.0; 95% confidence interval [CI] 2.3-7.1; <0.0001), high GRACE score (OR 3.3; 95% CI 1.8-6.0; <0.0001), admission systolic BP less or equal 100 mm Hg (OR 3.1; 95% CI 1.8-5.4; <0.0001), admission serum glucose more or equal 8 mmol/l (OR 2.9; 95% CI 1.8-4.7; <0.0001), age more or equal 65 years (OR 2.3; 95% CI 1.3-4.0; =0.005), ST elevation more or equal 1 mm on first ECG (OR 1.7; 95% CI 1.1-2.5; =0.013). From groups with low and high adherence to guidelines we selected pairs of patients (n=588) with similar (or close) age, type of ACS, GRACE score, Killip class, presence of other important risk factors (CHF, AF, previous stroke), and formed 2 equal subgroups without significant differences in important demographic, anamnestic, clinical and laboratory data. Hospital mortality was 7.8 and 2.7% in low and high adherence subgroup, respectively (p<0.0001)., Conclusions: In RECORD-2 ACS registry low adherence to guidelines was more frequent among high risk patients and was independent predictor of inhospital death. Association between degree of guidelines adherence and outcomes persisted after equalizing groups by some factors of risk of mortality.

Hypothesis: To evaluate the clinical and prognostic role of haemodynamically insignificant stenosis of the extracranial arteries (ECA) and lower extremity arteries (LEA) among patients with ST-segment elevation myocardial infarction (STEMI)., Patients and Methods: The study sample consisted of 423 patients with STEMI who were consecutively admitted to the Kemerovo Cardiological Centre., Results: The prevalence of polyvascular diseases (PVD), as defined by an increased intima-media thickness (IMT) of the common carotid artery or by stenosis of the ECA or LEA, was 95%. Among patients with ECA or LEA, the case fatality rate of those with stenosis with occlusion of less than 30% of the vessel lumen was 5.7%, whereas the case fatality rate among patients with stenosis with occlusion of more than 30% of the vessel lumen was 15.1% (χ(2) = 13.68, P = 0.003). Using the GRACE score model, together with the determination of additional factors (congestive heart failure, PVD, prior stroke, and smoking status), we developed an improved model (KemScore) for death risk stratification for a 12-month period. The value of the AUC for our model (KemScore) was 0.83 (95% CI = 0.76-0.90), which was significantly higher than the initial GRACE score value of 0.71 (95% CI = 0.63-0.79).

Aim: To assess incidence and severity of renal dysfunction as well as its prognostic value in patients with ST elevation myocardial infarction (STEMI) and multifocal atherosclerosis (MFA)., Material and Methods: We enrolled in this study 529 patients with STEMI in whom we estimated creatinine clearance rate (eGFR) and glomerular filtration rate (eCrCl) using Cockcroft-Gault equation and Modification of Diet in Renal Disease (MDRD) formula, respectively. Duplex ultrasonography of lower extremity and extracranial arteries was performed in 423 patients on day 5-10 of hospitalization. Signs of MFA were found in 95% of patients. Hospital mortality was 10.9%. One year survival of 397 patients was assessed by the telephone contacts. Thirty nine patients (9.8%) died., Results: GFR in 35.5% of patients was 30-60, and in 4.9% - less than 30 ml/min/1.73 m2. At the same time 29.5% of patients had CCr 30 - 60, and 3.0% - less than 30 ml/min. Progressive decreases of eCCr and eGFR were observed in patients with incipient MFA (stenosis <30%); relationship between MFA and eGRF was more close. Presence of renal dysfunction in patients with STEACS and MFA was associated elevation of both hospital and 1 year mortality., Conclusion: Any manifestation of peripheral atherosclerosis and impairment of renal function should be considered as independent predictors of cardiovascular events in patients after STEMI.

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.

At present reperfusion therapy in ST-elevation (STE) acute coronary syndrome (ACS) is carried out in majority of countries not more than in 70% of cases. We analyzed predictors of non-fulfillment of reperfusion therapy in patients with STEACS included into ACS registry conducted in the Kemerovo cardiological dispensary. Reperfusion therapy was not carried out in 154 patients with STEACS (36.2%). Main predictors of non-fulfillment of reperfusion were age older than 75 years (odds ratio [OR] 47.97, 95% confidence interval [CI] 19.47-118.21), admission later than in 12 hours after onset of disease (OR 4.29, 95%CI 1.52-12.13), history of myocardial infarction (OR 2.68, 95%CI 1.11-6.48). Thus there are factors including subjective ones which preclude full-fledged use of contemporary recommendations on the management of patients with STEACS.

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.