Prognostic Value of Polymorphism of G-308A Gene of the Tumor Necrosis Factor-α in the Progression of Chronic Heart Failure in Patients with Ischemic Heart Disease and Obesity

One of the widespread and prognostically unfavorable complications of cardiovascular diseases is chronic heart failure, where an important role is given to proinflammatory cytokines in the pathogenesis of the disease. Polymorphic variants of the gene of tumor necrosis factor-α are determinants of increased risk in the development of chronic heart failure in patients with ischemic heart disease. Presence of allelic gene A and genotype A/A of polymorphic locus G-308A, the gene of tumor necrosis factor-α in patients with ischemic heart disease and concomitant obesity was associated with chronic heart failure progressing and development of systolic dysfunction of the left ventricle

FEATURES OF CORONARY ARTERIES CHANGES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION DEPENDING ON THE PRESENCE OR ABSENCE OF CONCOMITANT DIABETES MELLITUS TYPE 2

The article analyzes the features of coronary arteries changes in patients with acute myocardial infarction (AMI) depending on the presence or absence of concomitant diabetes mellitus (DM) type 2. 60 patients with AMI and concomitant DM type 2 who were treated at the infarctional department of Kharkiv City Clinical Hospital No. 27 (Kharkiv, Ukraine) and cardiology department of the Kharkiv Clinical Hospital on Railway Transport №1 (Kharkiv, Ukraine) were investigated. In order to assess the status of the coronary flow, all patients in both groups underwent coronary angiography. The proportion of cases with multi-vessel lesions of coronary arteries exceeded the proportion of cases with one and twovessel lesions of coronary arteries in patients with acute myocardial infarction and type 2 diabetes.The article analyzes the features of coronary arteries changes in patients with acute myocardial infarction (AMI) depending on the presence or absence of concomitant diabetes mellitus (DM) type 2. 60 patients with AMI and concomitant DM type 2 who were treated at the infarctional department of Kharkiv City Clinical Hospital No. 27 (Kharkiv, Ukraine) and cardiology department of the Kharkiv Clinical Hospital on Railway Transport №1 (Kharkiv, Ukraine) were investigated. In order to assess the status of the coronary flow, all patients in both groups underwent coronary angiography. The proportion of cases with multi-vessel lesions of coronary arteries exceeded the proportion of cases with one and twovessel lesions of coronary arteries in patients with acute myocardial infarction and type 2 diabetes

The assessment of the depressive states severity and their relationship with concomitant type 2 diabetes and obesity in patients with chronic heart failure of ischemic origin

The aim is to assess the prevalence and expressiveness of depressive disorders in patients with chronic heart failure (CHF) of the ischemic origin, depending on the presence of concomitant type 2 diabetes mellitus (T2DM), obesity and their combined course, as well as to assess the influence of existing metabolic disorders on the development of depression in individuals of this cohort. Materials and methods. The study included 154 patients with CHF of ischemic origin. Group 1 included patients with CHF with coronary heart disease (CHD), T2DM and obesity (n = 42). The second group consisted of patients with CHF on the background of CHD with concomitant T2DM (n = 46), and the third group – with concomitant obesity (n = 36). The comparison group was formed from patients who had signs of CHF of ischemic origin without metabolic disorders (n = 30). The Beck Depression Inventory (BDI) was used to assess the presence and nature of depressive disorders. Results. In patients with isolated CHF of ischemic origin, depression was found in 60 % of cases, according to BDI. In the second group depression was manifested in 80.6 % of cases, and in the third group – in 91.3 % of cases. 95.2 % of patients of the first group had depressive disorders. The average value of scores in patients of the first group significantly exceeded that of the patients of the fourth group by almost two times. Comparing the scores of patients of the second and third groups with the fourth group determined their increase by 57 % and 36 %, respectively. It was established that in patients with CHF of ischemic origin against the background of the combined course of T2DM, mild depression was found in 1/3 of patients, a quarter of patients had manifestations of moderate depression, 9.5 % of patients had severe depression and 4.8 % of people in this group had symptoms of mild depression. Conclusions. The presence of type 2 diabetes mellitus is associated with the development of depression in patients with chronic heart failure of ischemic origin. The combined course of type 2 diabetes mellitus and obesity is a risk factor for the development of depression and its progression to a marked/severe form

Galectin-3 and its relationship with the state of coronary arteries in patients with acute myocardial infarction and concomitant obesity

The aim of the study - to evaluate the condition of the coronary arteries according to quartile of galectin-3 serum level in patients with acute myocardial infarction and obesity. Materials and methods. A total of 31 patients with acute myocardial infarction and I and II degree of obesity were examined. A coronaroventriculography was performed with stenting of the infarct-dependent coronary artery within 12 hours from the pain syndrome onset. Galectin-3 was determined using a Human Galectin-3 ELISA kit (China). The degree of coronary atherosclerosis severity was assessed by coronaroventriculography (CVG) using the Gensini score. Results. The most common atherosclerotic lesion was found in the right interventricular artery – 89 % of cases followed by the right coronary artery (59.3 %), about half of patients (48.1 %) had a lesion of the circumflex artery. The greatest vulnerability of the right interventricular artery was accompanied by the highest mean stenosis values – 77.3 % followed by the right coronary artery, the mean stenosis value of which was 68.2 %. The development of acute myocardial infarction predominantly (57.1 %) was due to occlusion of the right interventricular artery. The increase in the level of galectin-3 to 23.48–41.42 ng/ml, which corresponds to 3–4 quartiles of galectin-3 level, was associated with an increase in the number of affected vessels and segments with high Gensini scores. Conclusions. The right interventricular and right coronary arteries are the most vulnerable according to the angiographic findings, both in terms of frequency and degree of lesion, and frequency of hemodynamically significant stenoses in patients with acute myocardial infarction and obesity. An increase in galectin-3 level up to 3 and 4 quartiles is accompanied by a parallel increase in parameters characterizing the progression of atherosclerotic lesion of the coronary arteries. Galectin-3 can be considered as a marker of atherosclerotic process in patients with acute myocardial infarction and obesity due to the association between galectin-3 level and the degree of coronary artery lesion severity

Revealing weak A and B antigens in patients with knee and hip joint arthroplasty

АНТИГЕНЫКРОВЬАНТИТЕЛА АНТИИДИОТИПИЧЕСКИЕАНТИ-АНТИТЕЛААНТИГАММА-ГЛОБУЛИНОВЫЕ АНТИТЕЛААНТИГЛОБУЛИНЫАНТИИДИОТИПНЫЕ АНТИТЕЛАКОМПЛЕМЕНТКОМПЛЕМЕНТБЕЛКИ КОМПЛЕМЕНТАРНЫЕКОМПЛЕМЕНТА БЕЛКИЭРИТРОЦИТЫЦель. Провести анализ методов выявления слабых А и В антигенов на эритроцитах в системе АВ0. Материал и методы. Проведено обследование пациентов с эндопротезированием коленного и тазобедренного суставов с целью определения группоспецифической принадлежности с выявлением слабых А и В антигенов на эритроцитах. Использованы методы абсорбции, реакция агглютинации, агглютинация в присутствии комплемента и антиглобулиновый тест. Результаты. Антиглобулиновый тест с использованием как поликлональной сыворотки, так и сыворотки, содержащей только IgG антитела, позволил выявить слабые A и B подгруппы на эритроцитах при 37{o}С. В реакции абсорбции с анти-А, анти-В поликлональными сыворотками у некоторых пациентов на эритроцитах выявлены А и В антигены, также проявившиеся в реакции агглютинации при 37{o}С, но не обнаруженные при инкубации при комнатной температуре. Агглютинационный тест с использованием комплемента и сыворотки с IgG антителами также способствовал проявлению слабых антигенов. Присутствие IgG антител было определено после обработки сыворотки унитиолом в антиглобулиновом тесте. Наличие в сыворотке только IgG антител, соответствующих антигенам, при участии комплемента приводило к более выраженным изменениям эритроцитов по сравнению с присутствием обоих классов антител – IgM и IgG. Появление гемолиза ассоциировалось с увеличением размеров эритроцитов и гипохромией. Присутствие слабых подгрупп в большинстве случаев было ассоциировано с гемолизирующими, а не агглютинирующими свойствами сыворотки пациента, а также наличием комплементсвязывающих IgG антител. Заключение. Применение абсорбции, агглютинация при 37{o}С, антиглобулиновый тест при 37{o}С с сывороткой, как подвергшейся, так и не подвергшейся обработке унитиолом, а также реакция агглютинации с использованием комплемента способствовали определению слабых антигенов в системе АВ0.Objective. To analyze the methods of revealing weak A and B antigens on the erythrocytes in AB0 system. Methods. Patients after knee and joint arthroplasty were examined on group-specific characteristics with revealing weak A and B antigens on the erythrocytes. Methods of absorption, agglutination, agglutination with complement and antiglobulin test were used. Results. Antiglobulin test with the use of polyclonal serum as well as serum containing the only IgG allowed revealing weak A and B subgroups on erythrocytes at 37{o}С. In some patients A and B antigens on erythrocytes were found while absorption with anti-A, anti-B polyclonal sera and also revealed in agglutination at 37{o}С, but were not revealed while incubation at the room temperature. Agglutination test with the use of complement and IgG was also helpful in determining the weak antigens. Presence of IgG antibodies was revealed by the treatment of the serum with unithiol in antiglobulin test. Presence of complement and only IgG antibodies corresponding to the antigens led to the more expressed changes of erythrocytes as compared to the presence of both types of antibodies – IgM and IgG. Appearance of hemolysis was associated with the increased sizes of erythrocytes and hypochromia. Presence of weak subgroups was mostly associated with hemolytic rather than agglutinating abilities of the patient’s serum, as well as with the presence of complement binding IgG antibodies. Conclusions. Absorption, agglutination at 37{o}С, antiglobulin test at 37{o}C with serum both treated and non-treated with unithiol and agglutination with use of the complement helped to define weak antigens in AB0 system

Specific heat and heat conductivity of the BaTiO3 polycrystalline films with the thickness in the range 20 - 1100 nm

Thermal properties - specific heat and heat conductivity coefficient - of polycrystalline BaTiO3 films on massive substrates were studied as a function of the temperature and the film thickness by ac-hot probe method. The anomalies of specific heat with decreasing of the film thickness from 1100 to 20 nm revealed the reducing of critical temperature (Tc) and excess entropy of the ferroelectric phase transition, which becomes diffused. The critical thickness of the film at which Tc = 0 estimated as 2.5 nm.Comment: 12 pages, 7 figures, 2 tables, 450kb; submitted to J.Phys.:Cond.Mat

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049