Purpose: to study changes of serum levels of nonspecific proteinases, their inhibitors, and proinflammatory cytokines during short term observation of patients with acute myocardial infarction (MI). Materials and Methods. We included in this prospective short-term study 82 patients (27 with uncomplicated non-Qwave MI, 30 with Q-MI complicated by Killip class I-II acute left ventricular failure [ALVF], 17 with Q-MI complicated by Killip class III-IV ALVF, and 8 non-survivors due to development of cardiogenic shock) and 12 healthy controls. Serum levels of interleukin (IL) - 1ß, IL-6 and tumor necrosis factor (TNF)-a were measured by ELISA. Elastase-like (ELA) and trypsin-like (TLA) activities as well as characteristics of proteinase inhibitors (antitrypsin activity and acid-stable inhibitors) were also determined. Blood samples were taken at hospital admission within 24 hours after onset of symptoms. The GUSTO Score at admission was used for risk stratification. Results. All cytokines levels were significantly elevated in MI patients in comparison to controls. Mean concentrations of IL-6 and TNF-a at baseline were higher among patients with MI complicated by ALVF than in the group with uncomplicated MI (27.45 vs 16.04 pikogram/mL, р<0.001, and 24.74 vs 19.58 pikogram/mL, р<0.001, respectively). Mean concentrations of IL-1ß did not differ significantly between these two groups. Non-survivors also showed significantly higher levels of IL-6, TNF-a, ELA and TLA and lower levels of proteinase inhibitors than patients with uncomplicated MI. Conclusions. Elevated levels of IL-6 and TNF-a within 24 hours from the onset of MI are associated with the development of ALVF and unfavorable prognosis. Elevated levels of proteinases and their inhibitors in patients with acute MI are indicative of participation of proteinase-inhibitory system in pathogenesis of MI. Levels of proteinases are significantly elevated in non-survivors compared with patients with uncomplicated MI. On the other hand, low level of proteinase inhibitors should be considered as a marker of imbalance of proteinase-inhibitory system. The data support the role of excessive cytokine-mediated inflammation in worsening of MI course.

Objective: to study associations of polymorphism of the genes MMP9 rs17576, MMP12 rs2276109, MMP20 rs2245803, C0L1A1 rs1800012, C0L1A1 rs1107946 with remodeling of the left ventricle in patients with acute myocardial infarction. Materials and methods. We examined 84 patients with myocardial infarction (MI). Type of early postinfarction left ventricular (LV) remodeling was determined by echocardiography on the third day of the disease. Concentration of matrix metalloproteinases (MMP) was measured by enzyme immunoassay using commercial kits; content of C-terminal telopeptide of collagen type I degradation products (ICTP) was measured by chemiluminescent immunoassay. Polymorphisms of the genes MMP9 rs17576, MMP12 rs2276109, MMP20 rs2245803, COL1A1 rs1800012 and rs1107946 were identified by PCR using primers. Statistical analysis was performed using the language R (http://cran.r-project.org) version 3.4.0, and additional packages (stats, forest plot, ROC). Results. Significant association was found between A allele of MMP 20 rs2245803 and dilation type of LV remodeling (odds ratio [OR] 2.82, 95% confidence interval [CI] 1.186-6.695). The prognostic model containing systolic pulmonary artery pressure (SE=0.339) and G allele of MMP9 rs17576 (SE=1.097) was associated with LV dilation. The model containing C allele of the MMP20 rs2245803 (SE=-0.279) showed its relationship with LV hypertrophy. Combined carriage of the minor allele G of MMP9 rs17576 and C allele of MMP20 rs2245803 (SE=-2.228) was associated with hypertrophic modification of the LV geometry. Conclusion. In this work we revealed association of A allele of MMP20 rs2245803 with formation of dilative type of LV remodeling and established relationship between C allele of MMP20 rs2245803 and the hypertrophic morpho-functional modification of the left ventricle. Carriage of the G allele of MMP9 rs17576, along with other factors, increased the likelihood of LV myocardial hypertrophy. The role of this allele was augmented by co-carrying C allele of the MMP20 rs2245803. Identified gene associations can be used as additional early predictors of LV myocardial remodeling in patients with acute MI.

Background. Literature data on hepcidin (H) level - the main regulator of systemic iron homeostasis in patients with chronic heart failure (CHF) - are contradictory. Relationships of H with markers of inflammation elevated level of which is characteristic of CHF are insufficiently studied. The latter problem remains practically unexplored in elderly and very old patients with CHF. Aim: to study the role of H in formation of anemia of chronic disease (ACD) and iron deficiency anemia (IDA) in elderly and very old patients with CHF. Material and methods. We examined 65 elderly and very old patients with ischemic heart disease (IHD) (35 with CHF and ACD, 10 with CHF and IDA, 20 without CHF, ACD, and IDA [control group]). H level in blood serum was measured using competitive solid-phase immunoenzyme assay. Results and discussion. In patients with CHF and ACD mean H levels were significantly high relative to those in patients with CHF and IDA, while in the latter group H levels were insignificantly low relative to those in patients of control group. High H level, high level of inflammatory tests as well as positive correlations between them, and negative correlation between H and hemoglobin (Hb) are indicative of inflammation as a cause of H level elevation, which in turn facilitates development of anemia in elderly and very old patients with CHF and ACD. Low H level, normal levels of inflammatory tests, absence of links between them, as well as absence of correlation between H and Hb are indicative of lack of H role in development of anemia in these patients with CHF and IDA. We did not study influence on development of anemia of each of possible causes (inflammation, decompensation of CHF) separately, therefore contribution of each of them is unknown. The data obtained also do not exclude effect of other not investigated in this work and presently unknown factors. Received by us data indicate to necessity of precise identification of origin of anemia in every case in an elderly or very old patient with CHF with the aim of elimination of its cause and conduct of pathogenetically valid therapy.

Purpose: to assess prevalence of dyslipidemia in patients with ischemic heart disease (IHD) older than 75 years as well as to evaluate possible associations between serum lipids and various cardiovascular and other diseases in these patients. Methods. We enrolled in this cross sectional study 555 hospitalized IHD patients aged 75-98 years (mean age 86.8 years, 74.5% women). Levels of lipids (total cholesterol [TC], triglycerides [TG], low and high-density lipoprotein cholesterol [LDLC, HDLC]) were measured by enzyme method on the biochemistry analyzer Konelab 60i. Results. Elevated TC; hypertriglyceridemia and elevated LDLC were observed in 13.3, 10.4 and 26.3% of patients, respectively. In the majority of patients severity of dyslipidemia was mild. With increasing age serum levels of TC and LDLC decreased. Negative correlation between TC level and patient’s age was significant (r= -0.13; p=0.001). Mean TC level was 5.43, 5.0 and 4.7 mmol/l in patients aged <80 (group 1), 80-89 (group 2), and >90 (group 3) years, respectively (p=0.001 for differences between groups 1-and 3). Similar results were registered in respect of LDLC: mean LDLC level was 3.7 and 2.7 mmol/l in groups 1 and 3, respectively (p=0.004). Mean concentrations of all lipids in women were higher than in men: TC 5.1 vs 4.5 (p<0.0001), LDLC 3.1 vs 2.5 (p=0.0002), HDLC - 1.26 vs 1.17 mmol/l (p=0.01). Lower lipids levels (especially those of TC) were significantly associated with clinically significant heart failure (p<0.0001) and atrial fibrillation (p<0.0001). Higher TC and TG correlated positively with higher systolic and diastolic blood pressure (p=0.001). Significant positive correlations existed between TG and glucose concentration (p<0.0001) as well as between TG and uric acid level (p=0.001). Higher TG and lower HDLC levels were registered in patients with higher creatinine level (p=0.001 and 0.0003, respectively). Only 11.4% of study patients received statins. Conclusion. The study results evidence for considerable peculiarities of lipid profile in the very elderly patients with IHD. Significant associations between dyslipidemia and a number of diseases were also revealed.

Aim: to study effects of using fixed perindopril/amlodipine combination in complex treatment of patients with combined cardiac pathology in active observation mode, in comparison with other angiotensin converting enzyme (ACE inhibitors) or angiotensin II receptor antagonists (ARA), including free combination with calcium channel blockers (CCB) in conditions of routine outpatient practice. Materials and methods. The design of the study included two stages: I - monitoring effectiveness of pharmacotherapy performed in routine outpatient practice (duration of 2 months), II - “active treatment (management)” - changing the pharmacotherapy scheme in patients who did not reach the target level of “office” blood pressure (BP), monitoring patients for 6 months and carrying out, if necessary, dose correction of the newly appointed treatment regimen. The study included 50 patients aged 45-65 years with combined cardiovascular pathology: II-III degree arterial hypertension, I-III functional class (FC) stable angina pectoris, I-III FC chronic cardiac failure. Results. Number of patients who reached target level of office BP by the end of active observation was 41 (p<0.001 in comparison with routine therapy). During 6-month treatment episodes of ischemic ST-segment depression were eliminated in 37 patients (there were no such patients during routine therapy, p<0.001). At the end of the period of routine pharmacotherapy, 1 and 5 patients had a reduction (more than by 80% from the baseline level) of the number of ventricular and supraventricular extrasystoles, respectively. During 6-month active treatment extrasystoles were additionally eliminated in 14 (p<0.001) and 18 (p<0.010) patients, respectively. During the period of active treatment there occurred significant improvement of parameters of role-physical functioning, vitality, mental health (p<0.05) compared with preceding period of 2 months of routine management. During routine pharmacotherapy, depression and anxiety were eliminated in 14 and 13 patients, respectively. During further active treatment parameters of depression and anxiety were normalized in 23 and 20 patients, respectively (p<0.05 for anxiety and p<0.01 for depression vs. preceding period of treatment in routine conditions). Conclusion. Replacement of free combinations of ACE inhibitors or ARA and CCB with fixed perindopril/ amlodipine combination in the complex pharmacotherapy of patients with combined cardiac pathology, together with adjustment of the entire management regimen in accordance with current clinical recommendations and the use of active observation of patients in comparison with preceding routine outpatient treatment was associated with significant positive effects on daily BP profile, ECG signs of myocardial ischemia and arrhythmic activity, parameters of quality of life, and levels of anxiety and depression

In the clinical practice a physician quite often is at a loss due to “freedom of choice” granted by availability of direct oral anticoagulants (DOAC). If a patient with nonvalvular atrial fibrillation (AF) has indications for therapy with anticoagulants which DOAC should be preferred? What are benefits for a patient with ischemic heart disease and AF when definite NOAC is chosen and what are risks inherent of this choice? Answers to such questions are given in this paper.

In recent years, the issues of choice of an agent for dual antiplatelet therapy (DAPT ) as well as timing of initiation and duration of DAPT in patients with acute coronary syndrome (ACS) have been actively discussed. In this article we present data of major randomized trials of clopidogrel and novel P2Y₁₂ inhibitors - prasugrel, ticagrelor, cangrelor - assessing strategy of administration of anti-aggregants in patients with ACS before coronary angiography/percutaneous coronary intervention. The article also contains analysis of differences between recommendations of the European Society of Cardiology and American College of Cardiology/American Heart Association on therapy with oral P2Y₁₂ inhibitors in the management of patients with ACS.

The article discusses various mechanisms of developmentt and progression of arterial hypertension in young and middle aged adults. It emphasizes the predominant role of hypersympathicotonia in the development of the disease in this category of patients. Various mechanisms are considered, by means of which the increase of activity of the sympathetic nervous system leads to elevation of arterial pressure and potentiates early damage of target organs, first of all, damage of the heart. The data of numerous studies demonstrating pronounced cardioprotective effects of a highly selective representative of the class of ß-blockers bisoprolol in young and middle aged hypertensive patients are presented.

In recent years the number of articles on damages of high-density lipoproteins (HDL) properties in patients with atherosclerosis has sharply increased. First, it concerns their ability to accept cholesterol (CH) from macrophages - the basis of antiatherogenic action of HDL. This ability was assessed ex vivo - by activity of cell cholesterol (CH) efflux to HDL or into patient’s serum. In many works inverse relationship was shown between CH acceptor capacity of HDL and severity of atherosclerotic disease or frequency of its exacerbations during long-term observation, independent from HDL CH concentration. This led to the emergence of the concept of importance of “not only HDL quantity but also of their quality”, i. e. functionality. In this review we consider pathways of cellular CH efflux (mainly mediated by cell proteins), methods used for detection of dysfunctional HDL, and results of relevant studies in various categories of patients. These studies directed to identification of mechanisms of damages of HDL properties by means of analysis of their composition, used various approaches including those of proteomics and lipidomics. However, now there are no proven targets for correction of HDL dysfunctionality. The only factor, that is underlined by many authors, is the significance of HDL phospholipids, which level correlates with activity of cellular CH efflux. This allows to take a fresh look at previously used phospholipid therapy of atherosclerosis. Its mechanism is apparently not lowering of plasma CH, as was previously expected, but the improvement of HDL antiatherogenic properties. For its practical usage it is necessary to elaborate principally novel formulations with high bioavailability of phospholipids - for HDL enrichment by phospholipid and thereby normalization of their ability to remove CH from tissues.

The review is devoted to pharmacotherapy of chronic heart failure (CHF) with preserved left ventricular ejection fraction. In this review we discuss data of meta-analyzes of randomized clinical trials and observational studies, as well as the indications for use of inhibitors of the renin-angiotensin-aldosterone system, ß-blockers, and antagonists of mineralocorticoid receptors in these patients in current clinical guidelines. New approaches to therapy of CHF from the perspective of influence on myocardial fibrosis are considered in this review.

The article considers modern approaches to the secondary prevention of cardiovascular events in patients with stable ischemic heart disease (IHD) and/or atherosclerosis of peripheral arteries (peripheral artery disease - PAD) with the oral anticoagulant rivaroxaban. The results of the first international prospective phase III study COMPASS for the evaluation of efficacy and safety of rivaroxaban including 27395 patients with stable IHD or PAD, are discussed. The results of the study were presented at European Congress of Cardiology 2017. Rivaroxaban reduced of the risk of cardiovascular death, stroke and myocardial infarction by 24%. The results of the study confirm the positive balance of risk/benefit and supplement the previously obtained data on the efficacy of rivaroxaban in patients with cardiovascular diseases.