Dynamics of body weight during lifestyle modification in patients with high cardiovascular risk, depending on the carriage of various variants of thrifty genes

Objective — to study the relationship between the carriage of polymorphic variants PPARG2 (Pro12Ala), ADRB2 (Gln27Glu), ADRB2 (Agr16Gly), ADRB3 (Trp64Agr), FABP2 (Thr54Ala) and changes in anthropometric parameters under the influence of increased physical activity in individuals with high cardiovascular risk. Materials and methods. In total, 205 people were examined during the period of years 2019 — 2021. Patients were advised to use physical activity frequently in the form of regular exercises. Among patients who passed the 2nd observation point, 60.5 % (124 patients) reported that they expanded their physical activity, 39.5 % (81 patients) began regular exercises. The study included patients with high cardiovascular risk. The International Physical Activity Questionnaire (IPAQ) was used to assess physical activity. Assessments included anthropometric parameters (weight, height, body mass index, waist and hip circumference, body composition (Composition Monitor BF511, Omron, China, 2015)), levels of total cholesterol, triglycerides, low‑density lipoproteins. Muscle strength (kg/cm2) was assessed using an electric dynamometer on the wrist Camry EH101 2013 (2018). Isolation and purification of DNA from the whole blood was carried out using a set of reagents «DNA‑sorb‑B» (Amplisens, RF) according to the manufacturer’s instructions. Amplification of DNA and genotyping at polymorphic sites in the genes PPARG2, ADRB2, ADRB3, FABP2 was performed by real‑time PCR using a set of reagents «SNP‑EXPRESS‑SHOT» («Litech», RF) according to the manufacturer’s instructions using the product detection system real‑time CFX96 Touch (BioRad Laboratories Pte.Ltd.). Results. Depending on the changes in anthropometric parameters, patients were divided into 2 subgroups: in subgroup 1 there was no decrease in BMI before 30.69 ± 7.25 kg/m2, after 29.03 ± 6.84 kg/m2; p = 0.436, and in subgroup 2 a significant decrease in BMI before 31.85 ± 3.68 kg/m2, after 26.79 ± 3.91 kg/m2; p = 0.041. It was revealed that the decrease in BMI in subgroup 2 was accompanied by a statistically significant decrease in the proportion of adipose tissue (р = 0.011) and an increase the proportion of muscle tissue (р = 0.030). In both groups, blood pressure significantly decreased. Heart rate (HR) decreased in both groups, but these changes did not reach statistical significance (p = 0.43). Changes in anthropometric parameters were not accompanied by significant changes in total cholesterol, LDL cholesterol, triglycerides levels. A significant increase in HDL cholesterol levels was revealed. It was found that patients with CC and GG variants of the polymorphic locus PPARG2 (Pro12Ala), CG and GG variants of the polymorphic locus ADRB2 (Gln27Glu) and TT variant of the polymorphic locus ADRB3 (Trp64Agr) prevailed in group 2. No significant differences were found for the FABP2 locus (Thr54Ala). In subgroup 1, there were no significant differences in people with various polymorphic variants of genes. Conclusions. Associations have been established between the carriage of CG/CG + GG PPARG2 (rs1801282), AA/AA + AG ADRB2 (rs1042713) and TT ADRB3 (rs4994) and a decrease in body mass index during exercise expansion in individuals with high cardiovascular risk.

Determination of clinical and metabolic features in pre- and postmenopausal women with type 2 diabetes mellitus and osteoarthrosis against the background of visfatin metabolism disorders

Objective — to determine the clinical and metabolic features of pre‑ and postmenopausal women with type 2 diabetes mellitus (DM2) and osteoarthritis (OA) against the background of impaired metabolism of visfatin (VF). Materials and methods. 120 pre‑ and postmenopausal women were selected for the study and divided into 3 groups: group 1 included women with isolated DM2; group 2 — women with isolated OA; group 3 — women with DM2, combined with OA. The control group consisted of 16 healthy women. Investigations included anthropometric measurements, assessment of the indices of lipid and carbohydrate exchange and clinical manifestations of premenopause and postmenopause. Determination of the serum VF levels of patients was performed by enzyme‑linked immunosorbent assay on the analyzer «Labline‑90» (Austria). Results. Investigation of the specific features of the DM2 and OA course in premenopausal women demonstrated violations of carbohydrate and lipid metabolism, defined by the significant (р < 0.001) increase in VF levels up to (3.9 ± 1.2 ng/ml) and (4.2 ± 1.1 ng/ml), respectively. The highest VF level was recorded in the group of comorbid DM2 and OA (5.5 ± 1.0 ng/ml) compared with the levels of relatively healthy women of the same age group (1.8 ± 0.5 ng/ml). Moreover, the high indices of body mass index, waist and hip circumference, systolic and diastolic pressure, as well as of the menopausal index were established at DM2 and OA vs control group. Conclusions. Clinical and metabolic disorders have been identified in pre‑ and postmenopausal women against the background of OA and DM2 based on the significant (р < 0.001) increase in visfatin levels, especially in case of comorbid OA and DM2, as compared to the control group of age‑matched practically healthy women.

Orphan diseases (mucopolysaccharidosis) and damage of the cardiovascular system. Literature review

The paper presents literature data, outlining topical issues of the cardiovascular pathology at mucopolysaccharidosis. It is damage to the heart and blood vessels, one of the cardinal signs of this pathology, that is often fatal. Cardiac pathology is recorded in all types of mucopolysaccharidosis, but it is most significant for patients with three clinical variants of Hurler syndrome, Hunter, and Maroteaux–Lamy syndromes. Typical signs of damage to the cardiovascular system in mucopolysaccharidosis are thickening of the valves with the development of their dysfunction (while the severity of damage to the left‑sided valves is more pronounced), myocardial hypertrophy, conduction disturbance, coronary artery disease, arterial hypertension. Many researchers emphasize the difficulties of clinical and functional examination of the cardiovascular system in patients with mucopolysaccharidosis, which is due to the presence of physical and intellectual limitations in patients, and a gradual symptoms aggravation. For the treatment of cardiovascular pathology at mucopolysaccharidosis, medical and surgical methods are used, including enzyme replacement therapy and stem cell transplantation. Gene therapy is considered one of the priority areas in the treatment of mucopolysaccharidosis. Significant progress in this aspect has been achieved with the use of viral vectors under experimental conditions in mice with mucopolysaccharidosis type VII. The basis of mucopolysaccharidosis prevention is medical and genetic counseling of families with subsequent prenatal diagnosis using molecular genetic methods (eg, DNA diagnosis). Thus, early diagnosis and timely pathogenetic treatment of mucopolysaccharidosis will help to prevent disability and adequate integration into society, and effective medical and genetic counseling of families will significantly reduce the incidence of new cases of these severe inherited diseases.

Human microbiota. Friend? Enemy? Neighbors?

The review is dedicated to the modern ideas about the composition of the human intestinal microbiome, factors that determine the bacterial «landscape» and affect its activity. The main functions of normal microflora have been described, including intestinal motility, protection of intestinal barrier against pathogenic bacteria, parasites, intestinal epithelial regeneration, metabolic and immunological functions, participation in digestive processes, synthesis of amino acids and proteins, antibiotics, vitamins, hormonally active substances, promoting the absorption of minerals and nutrients, preventing the development of pathological conditions. Determination of intestinal microbiota expression of the innate immune system explains the role of microflora in chronic inflammation and diseases such as liver fibrosis, metabolic syndrome, type 2 diabetes mellitus, atherosclerosis, cardiovascular, neurodegeneration and cancer. A promising way is the use of microorganisms with beneficial properties (probiotics), the necessary substrate for them (prebiotics), their metabolites (metabiotics) and complexes of pro‑ and prebiotics (synbiotics) not only to restore and regulate the intestinal microflora, but also as therapeutic agents in some diseases, in particular during eradication therapy of the bacterium Helicobacter pylori. The functions of some species and strains of beneficial bacteria have being discussed, in particular the strain Bacillus causii UBBC‑07, as well as the results of preclinical and clinical trials of its use at antibiotic‑associated diarrhea in the inhibition of Clostridium difficile. The issues of safety and facts of positive impact on human health of probiotic products of Probeez line (Organosyn Ltd.) are considered, which differ in the personification of appointments to certain segments of the population: Probeez®, Probeez® Femina, Probeez® Kids, Probeez® DUO and Probeez® Immuno contain successfully selected live probiotic bacteria. The available range of monocomponent (Probeez® with Kids, Probeez® DUO), multicomponent (Probeez®, Probeez® Femina) and synbiotic (Probeez® Immuno) products allows to choose the best option in specific conditions for their application not only in inflammatory diseases of the gastrointestinal tract, but also in chronic disorders of other systems and organs.

The role of macrophage migration inhibitory factor in predicting left ventricular remodeling in patients with acute myocardial infarction

Objective — to assess the role of circulating markers of inflammation and macrophage migration inhibitory factor (MIF) in the development of left ventricular (LV) remodeling 6 months after acute ST‑segment elevation myocardial infarction (STEMI). Materials and methods. The study involved 120 patients after STEMI and successful primary percutaneous coronary intervention (PCI). Transthoracic echocardiography with Doppler was performed within 24 — 48 hours after PCI and after 6 months of follow‑up to assess LV remodeling. The levels of MIF and inflammatory markers were measured before and after PCI. All patients were divided into two groups according to the median MIF level < 2501 pg/ml (first group, n = 60) and > 2501 pg/ml (second group, n = 60). Results. Patients with the high levels of circulating MIF had a higher frequency of complications in the hospital and long‑term periods (p = 0.024), including newly diagnosed heart failure or decompensation with hospitalizations. High MIF levels in patients of the second group were accompanied by a significant enlargement of end‑diastolic and end‑systolic LV volumes (p = 0.028; p = 0.031, respectively), the development of secondary mitral regurgitation (p = 0.024) and decreased LV systolic function (p = 0.037). MIF threshold values for predicting remodeling > 2694 pg/ml (sensitivity 69.2 %, specificity 71.4 %, AUC = 0.714; 95 % CI 0.509 — 0.870; p = 0.0375) and LV dysfunction > 2484 pg/ml (sensitivity 90.0 %, specificity 58.0 %, AUC = 0.782; 95 % CI 0.675 — 0.867, p = 0.0003) were determined using ROC analysis. According to the results of univariate and multivariate analysis, levels of MIF (p = 0.028) and soluble suppressor of tumorigenesis‑2 (p = 0.042) were most significant predictors of LV remodeling. A correlation between the levels of MIF and white blood cells count (r = 0.33, p = 0.0001), C‑reactive protein (r = 0.19, p = 0.032), troponin (r = 0.44, p = 0.002) has been established. Conclusions. An early increase of MIF levels is associated with the development of adverse structural and functional changes in left ventricle of patients after acute ST‑segment elevation myocardial infarction.

Prominent representatives of the Ukrainian therapeutic school

The article is dedicated to the memory of famous representatives of the Ukrainian therapeutic school of three generations: academician M. D. Strazhesko, professor S. Y. Shteinberg, academician L. T. Mala. The life path of prominent Ukrainian doctors has been highlighted, and their scientific heritage and scientific activities in the area of internal diseases have been analyzed. Achievements of N. D. Strazhesko, S. Y. Steinberg and L. T. Mala forever immortalized their names in the line of the most prominent representatives of medical science in Ukraine.

The algorithm of decision-making in administration of anticoagulant therapy due to COVID‑19. Review

There is a hypothesis that on its late complicated stages, coronavirus disease of 2019 (COVID‑19) represents an endothelial disease. According to Peter’s Libbi data (2020), the endothelial monolayer measures up to 7000 m2 in surface area. The endothelial functions include anticoagulant, antiplatelet, anti‑inflammatory, vasomotion, and structure. The aim of the review was to figure out COVID‑19 logistics from the standpoint of its pathogenesis, in particular its thrombotic complications, to summarize data on the choice of an anticoagulant, its dose and duration of use. COVID‑19 is a new disease with the lack of evidence‑based data, however, its per‑syndrome analysis results in conclusion that the most part of acute and post‑COVID complications refer to thromboembolic ones. According to the recommendations of the European Society of Cardiology on diagnostic and treatment of thromboembolism, the need for thromboembolism prevention is defined in case of respiratory failure, installed intravenous catheters, infection (specifically pneumonia), bed rest, elderly age, etc. The adherence to evidence‑based recommendations will allow one to administer rational anticoagulation therapy without harm to a patient. It concerns both patients, who are on anticoagulant therapy at hospital admission, and those who requires its new administration. The following questions are mostly frequent arising in doctors: How one should manage a patient with active bleeding, or platelet levels < 25 · 109/ L, or with congenital abnormality of coagulation? What types of blood chemistry should be considered when administering anticoagulant? What therapy should be administered at discharge? Compliance with clear anticoagulation algorithms will prevent thromboembolic complications, further damage to organs and systems, and significant bleeding.

Management of patients with myocardial infarction and nonobstructive coronary arteries: literature review and own data

Over the past few years, much attention has been paid to the diagnosis and treatment of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA). Its prevalence achieves 5 — 15 %, and impact of risk factors of cardiovascular disease development on the MINOCA onset has some specific features. The following criteria are required to diagnose MINOCA: compliance with the MI criteria, absence of obstructive coronary artery disease (≥ 50 %) and exclusion of an alternative diagnosis. Myocardial ischemia is the underlying cause of cardiomyocyte damage during MINOCA. It can be caused by coronary artery thrombosis due to the rupture of atherosclerotic plaque (type 1 MI), spasm or spontaneous coronary artery dissection (type 2 MI). The aim of our study was to analyse risk factors and the incidence of MINOCA in patients with acute myocardial infarction. A retrospective analysis has been performed on 1358 histories of patients with MI who were hospitalized in Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery during the period of 2019 — 2020 years. From them, 60 (4.4 %) patients were selected based on MINOCA diagnostic criteria according to the European Society of Cardiology (2018). The mean age of patients was 58.6 ± 14 years. ST‑segment elevation MI (STEMI) was diagnosed in 87.2 %. Cardiac and non‑cardiac comorbidity has been investigated with the following results: atrial fibrillation (AF) was revealed in 13.3 % of patients, hypertension (AH) — in 85 %, history of coronary heart disease (CHD) — in 31.7 %, recurrent MI — in 11.7 %, chronic heart failure (CHF) — in 75 %, atherosclerosis of peripheral arteries — in 33.3 %, type 2 diabetes mellitus (DM 2) — in 20 %, obesity — in 40.7 %. The proportion of smokers was 43.8 %. According to the results of laboratory studies, dyslipidemia was diagnosed in 44.7 % of patients. According to coronary angiography, 55 % of patients had no coronary artery stenosis, 21.7 % had stenosis of one artery, and stenosis of two or more arteries was defined in 23.3 % of cases. The following distribution by lesions’ types was established: irregularities in the contours of arteries or stenosis up to 30 % in 35 % of cases; stenosis ≥ 30 < 50 % in 18.3 %, and slow evacuation of the contrast agent in 16.7 % of cases. Men prevailed in our research, which is inconsistent with the data of large observational studies, probably due to a small quantity of patients. Hypertension, chronic heart failure, tobacco smoking, obesity and dyslipidemia prevailed among the basic risk factors. Patients with MINOCA require careful evaluation to determine the causative agent and appropriate treatment choices. Conduction of large‑scale studies, in particular, randomized controlled observations, is reasonable and necessary to determine the optimal tactics for management patients with MINOCA.

Comorbid conditions at chronic obstructive pulmonary disease: the questions under investigation and discussion

The second part of the review examines in detail the questions of diagnostics and peculiarities of the metabolic syndrome manifestations, which presents the link between most comorbid conditions at patients with chronic obstructive pulmonary disease. The metabolic syndrome is based on the insulin resistance and compensatory hyperinsulinemia, caused by both chronic low‑intensity inflammation and increased adipose tissue, often against the background of aggravated heredity at diabetes mellitus. The authors elucidate aspects of the effects of obesity, cachexia and some endocrine disorders on the disease course. The deficiency of researches on endocrine status, especially thyroid function and related metabolic disorders was emphasized. Possible pathogenetic mechanisms of osteoporosis development in this contingent of patients are considered. The need for further research of the pathogenetic role of vitamin D is discussed. Data on the role of the functional state of kidneys in the development of metabolic disorders in an organism have been presented, though kidney pathology in patients with chronic obstructive pulmonary disease is not currently considered as a comorbid condition. The contradictory literature data on the development of anemia in these patients were analysed. The authors presented data on the development of oncological processes as a systemic manifestation at COPD and performed analysis of common and mutually aggravating mechanisms of the development of these pathological conditions. Attention has been paid to the relationship between gastroesophageal reflux disease, bronchiectasis and obstructive sleep apnea with chronic obstructive pulmonary disease. The prospects of modern genetic research in chronic obstructive pulmonary disease and comorbid conditions have been determined.

Pathogenetic rationale for correction of endothelial dysfunction with quercetin in the complex treatment of non-alcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus

Objective — to determine effects of therapeutical complex, including metformin, rosuvastatin, essential phospholipids and quercetin, on the state of blood lipid spectrum, endothelial function, fibrinolysis system and platelet hemostasis, which are factors in the progression of nonalcoholic steatohepatitis (NASH) and diabetic kidney disease (DKD). Materials and methods. The investigation was performed in the dynamics of treatment of 60 NASH patients with type 2 diabetes mellitus (DM 2) and DKD of stage I — III. Depending on the prescribed treatment patients were randomized into 2 groups. The comparison group 1 (28 subjects) was administered hypocaloric diet with account of dietary restrictions #9, received essential phospholipids 300 mg 2 caps. 3 times a day) during 30 days for the NASH treatment, and antidiabetic and lipid‑lowering therapy with metformin hydrochloride 1000 mg per day, rosuvastatin (5 mg 1 time per day) for 1 month. Group 2 consisted of 32 patients and in addition to the similar 30 days of dietary recommendations, essential phospholipids, hypoglycemic and hypolipidemic therapy, received quercetin and povidone 500 mg intravenously in 100 ml of isotonic sodium 10 mg for 10 days. The mean age of patients was 53.8 ± 3.52 years. The comparison group consisted of 30 healthy age‑matching subjects. Results. Parameters of endothelial dysfunction, fibrinolysis and platelet hemostasis were determined to check the degree of endothelial‑protective effects of Quercetin against the background of the recommended protocol therapy. As a result of treatment, baseline significantly reduced NO levels (in 1.7 times) in patients of group 1 increased insignificantly (p > 0.05), and significantly raised in 1.5 times (p < 0.05) in group 2. This can be explained by effects of Quercetin as an endothelial protector, as well as by metformin effects, which reduces degree of insulin resistance and promotes body weight reduction, as well as reduction of hyperlipidemia level and probability of deposition of subendothelial proatherogenic fractions. Conclusions. Combined therapy of NASH with DM 2 and diabetic kidney disease with the use of essential phospholipids, statins and metformin with addition of Quercetin was more effective than traditional therapy: it significantly reduced the markers of NASH exacerbation, optimized blood lipid spectrum, restored endothelial functional state, eliminated the phenomena of hypercoagulable syndrome without the additional administration of antiplatelet agents.