Associations of ECG Signs of Ischemic and Non-Specific Signs of Metabolic Changes in the Myocardium With Unfavorable Cardiovascular Prognosis in a 7-Year Prospective Follow-Up of Young People Under 45 Years.

AIM: To study ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium and to determine their relationship with unfavorable cardiovascular prognosis in a 7-year prospective observation of young people under 45 years of age. MATERIAL AND METHODS: A cross-sectional population survey of a random sample aged 25-44 years (n=1363) was conducted in Novosibirsk. The survey program used the standardized epidemiological Rose questionnaire. Biochemical tests were used to measure blood concentrations of total cholesterol (C), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and fasting blood plasma glucose. Systolic and diastolic BP (SBP, DBP), the presence of arterial hypertension (AH), body mass index (BMI), waist circumference (WC), and smoking status were assessed. ECG was recorded at rest in 12 standard leads followed by interpretation according to the Minnesota Code. The presence of ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium was determined. Subjects with ECG signs of ischemic changes in the myocardium were selected for long-term follow-up and additional examination by cardiologists. Then the whole cohort was monitored for 7 years, and cardiovascular events were recorded, including using data from the WHO Myocardial Infarction Registry in Novosibirsk. For statistical analysis of the results, cardiovascular events were combined into a composite endpoint. RESULTS: During 7 years, 40 people (27 men and 13 women) had an unfavorable cardiovascular prognosis. Multivariate regression analysis showed that a 7-year unfavorable cardiovascular prognosis in people younger than 45 years was associated with signs of ischemic myocardial alterations identified on the background ECG (OR 5.319, 95% CI: 1.543-18.342, p=0.008) and nonspecific ECG signs of metabolic changes in the myocardium (OR 2.978, 95% CI: 1.216-7.216, p=0.017) regardless of age, gender, the presence of arterial hypertension (AH) and type 2 diabetes mellitus (DM2). CONCLUSION: In young people under 45 years of age, not only ECG signs of ischemic changes in the myocardium, but also nonspecific ECG signs of metabolic changes in the myocardium are associated with an unfavorable cardiovascular prognosis, directly and independently on age and gender, in a long-term, 7-year period.

Cytokine Profile and Concentrations of Metabolic Hormones in the Blood of Overweight Men with Coronary Arteriosclerosis.

Plasma concentrations of cytokines and metabolic hormones and their association with vulnerable atherosclerotic plaques were studied in 36 overweight men (age 40-77 years; BMI 25.0-29.9 kg/m2) with coronary atherosclerosis who underwent coronary endarterectomy. According to histological analysis, the patients were divided into two groups: with stable (17 (47.2%) men) and vulnerable (19 (52.8%) men) plaques in the coronary arteries. The plasma levels of cytokines and metabolic hormones were measured by multiplex analysis: C-peptide, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, IL-6, insulin, leptin, monocyte chemoattractant protein-1, and TNFα. In overweight patients with vulnerable plaques, the level of glucagon was lower by 4.17 times, GIP - by 2.47 times, and insulin - by 2.1 times. At the same time, the risk of occurrence of a vulnerable plaque increases by 5.4% with a decrease in GIP concentration by 1 pg/ml irrespectively of age, as well as by 3.1% with an increase in insulin concentration by 10 pg/ml, without achieving statistical significance when included in the age model. Overweight men with coronary atherosclerosis and vulnerable plaques have lower levels of insulin, glucagon, and GIP. The levels of GIP and insulin are inversely associated with the risk of having vulnerable atherosclerotic plaque.

Adipokines and adipocytokines in men with coronary atherosclerosis and overweight.

Aim    To study concentrations of adipokines and their associations with proinflammatory cytokines in overweight men with coronary atherosclerosis. Material and methods    This study included 79 men aged 45-60 years with atherosclerosis who had undergone coronary endarterectomy during a coronary bypass surgery, and were overweight (body weight index (BWI), 25.0-29.9 kg /m2). Based on a histological analysis of plaques, the patients were divided into two subgroups: 43 men with stable atherosclerotic plaques and 36 men with unstable plaques in coronary arteries. The control group consisted of 40 age- and BWI-matched men without clinical manifestations of IHD. Blood concentrations of adipokines, including adiponectin, adipsin, lipocalin-2, resistin, and plasminogen 1 activator inhibitor were measured by a multiplex analysis with a MILLIPLEX MAP Human Adipokine Panel 1. Concentrations of proinflammatory cytokines, including tumor necrosis factor α (TNF- α), interleukin (IL)-1ß, IL-6, and C-reactive protein (CRP) were measured by enzyme immunoassay. Results    The blood concentration of lipocalin -2 was higher in patients with coronary atherosclerosis and stable or unstable atherosclerotic plaques than in the control group (p<0.01). Both subgroups of men with coronary atherosclerosis were characterized by significant differences from the control group in concentrations of TNF-α (p<0.05), CRP, and IL-6 (p<0.01). The most significant direct correlations were found between adipokines and TNF-α, IL-6, and CRP (p<0.01). Results of a logistic regression analysis showed that relative odds for the presence of significant coronary stenoses increased with increasing blood concentrations of lipocalin-2 (OR=1.005, 95 % CI: 1.002-1.008, р=0.011) and IL-6 (OR=1.582 , 95 % CI: 1.241-2.017, р=0.001).Conclusion    The changes in blood concentrations of adipokines associated with higher levels of proinflammatory cytokines may represent a factor that increases the probability of clinically significant coronary stenosis in overweight men with coronary atherosclerosis.

Associations of adipokines and metabolic hormones with low-density lipoprotein hypercholesterolemia in men and women under 45 years of age.

Aim    To study the adipokine profile in young people with hypercholesterolemia and low-density lipoproteins (LDL) and to evaluate the relationship between concentrations of LDL cholesterol (LDL-C) and metabolic hormones in men and women younger than 45 years. Material and methods    This study included 304 subjects (group 1, 56 men with LDL-C concentration <2.1 mmol/l; group 2, 87 men with LDL-C concentration ≥4.2 mmol/l; group 3, 90 women with LDL-C concentration <2.1 mmol/l; and group 4, 71 women with LDL-C concentration ≥4.2 mmol/l). Serum concentrations of total cholesterol (C), triglycerides (TG), high-density lipoprotein C, and glucose were measured by an enzymatic assay with ThermoFisher Scientific kits and a KonelabPrime 30i biochemical analyzer. LDL-C was calculated using the Friedewald's formula. Concentrations of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, interleukin 6, insulin, leptin, monocyte chemotactic protein 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor 1 (PAI-1), and resistin were measured by multiplex analysis (Human Metabolic Hormone V3 and Human Adipokine Panel 1 panels).Results    The groups differed in traditional cardiometabolic risk factors. In the male and female patient groups with LDL-C ≥4.2 mmol/l, the prevalence of impaired fasting glucose, incidence of insulin resistance, TG, and TC were higher than in subjects with LDL-C <2.1 mmol/l. The odds for the presence of LDL hypercholesterolemia (LDL-C ≥4.2 mmol/l) were significantly associated with increased concentrations of C-peptide and lipocalin-2 in men and with increased concentrations of lipocalin-2 and decreased concentrations of GLP-1 in women (р<0.05).Conclusion    Increased concentrations of LDL-C in young people were associated with changes in the adipokine profile and with the presence of metabolic syndrome components. These results were confirmed by changes in blood concentrations of metabolic markers that characterize disorders of metabolic processes.

[The Study of Biochemical Factors of Calcification of Stable and Unstable Plaques in the Coronary Arteries of Man].

OBJECTIVE: The aim of the study was to study biochemical factors of calcification in stable and unstable plaques of coronary arteries and in the blood of patients with severe coronary atherosclerosis, to find associations of biochemical factors of calcification with the development of unstable atherosclerotic plaque. MATERIALS AND METHODS: The study included 25 men aged 60,4±6,8 years who received coronary bypass surgery. In the course of the operation intraoperative indications in men were from coronary endarteriectomy (s) artery (a - d) and histological and biochemical analyses of the samples of the intima / media. Out of 85 fragments of intima / media of coronary arteries, 15 fragments of unchanged intima / media, 39 fragments of stable atheromatous plaque and 31 fragments of unstable plaque were determined. In homogenates of samples of intima / media (after measurement of protein by the method of Lowry) and in blood by ELISA were determined by biochemical factors of calcification: osteoprotegerin, osteocalcin, an osteopontin, osteonectin, as well as inflammatory factors (cytokines, chemokines). RESULTS: A significant direct correlation (Spearman coefficient =0.607, p<0.01) between the stages of atherosclerotic focus development to unstable plaque and the degree of calcification of atherosclerotic focus development samples was found. There was an increased content of osteocalcin in stable and unstable plaques by 3.3 times in comparison with the unchanged tissue of intima / media of coronary arteries, as well as in samples with small and dust-like, with coarse-grained calcifications in comparison with samples without calcifications by 2.8 and 2.1 times, respectively. According to multivariate logistic regression analysis, the relative risk of unstable atherosclerotic plaque in the coronary artery is associated with a reduced content of osteocalcin (OR=0.988, 95 % CI 0.978-0.999, p=0.028). Also, the relative risk of calcifications in the atherosclerotic plaque in the coronary artery is associated with an increased content of osteocalcin (OR=1,008, 95 % CI 1,001-1,015, p=0,035). In men with severe coronary atherosclerosis, a significant inverse correlation was found (Spearman coefficient -0.386, p=0.022) between the content of osteoprotegerin in the vascular wall and in the blood.

Association of Level of Proprotein Convertase Subtilisin/Kexin Type 9 with Intima-Media Thickness in Patients with Familial Hypercholesterolemia.

We studied association of PCSK9 protein with the carotid artery intima-media thickness in patients with familial hypercholesterolemia (N=53; age 49.9±6.9 years) treated with statins. Blood level of PCSK9 protein was measured by ELISA; ultrasonography of the carotid arteries with measurement of the thickness of the intima-media complex of the common carotid arteries in the distal segment for 10 mm from the bifurcation on the far wall of the vessel was performed in on-line mode. The mean values were calculated for both sides, the maximum mean value was included in the analysis. It was shown that PCSK9 levels positively correlate with carotid artery intima-media thickness in patients with familial hypercholesterolemia.

Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation Biomarkers in Atherosclerotic Plaques of Coronary Arteries.

We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1ß). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

[Association of decreased external pulmonary function with cognitive impairments].

AIM: To examine the association between the basic indicators of external respiratory function (ERF) and cognitive impairments (CIs). MATERIALS AND METHODS: The materials of a population-based cross-sectional study were used in the investigation; a representative sample consisted of 3818 men and women aged 45-69 years. Forced expiratory volume in the first second (FEV1), the ratio of FEV1 to forced vital capacity (FVC) were determined to assess ERF. CIs were evaluated using the 10-word test described by A.R. Luria, Cog-sum indices (the sum of correctly reproduced words with 3 attempts), and Cog-mean=Cog-sum/3. RESULTS: In patients with an FEV1/FVC <70%, the probability of a Cog-sum of <20 scores was twice higher than in those with an FEV1/FVC ≥70%; in patients with an FEV1 <80%, the probability of a Cog-sum of <20 scores was also 2 times higher than in those with an FEV1 ≥80%. Multiple regression analysis revealed no significant associations between Cog-sum index and smoking index, body mass index, and blood pressure. Cog-sum was inversely related to age and directly related to FEV1 and female sex. Binary logistic regression analysis showed that gender, age, and FEV1 were statistically significant variables. The relative risk of a Cog-sum of <20 that was 1.7 times higher in the men than in the women, 1.8 times higher in the patients with an FEV1 <80% than in those with an FEV1 ≥80% (model 1), 1.7 times higher in the patients with an FEV1/FVC <70% than in those with FEV1/FVC ≥70% (model 2) increased with age. CONCLUSION: The decrease in the basic indicators of ERF (FEV1, FEV1/FVC) is an independent predictor of CIs.

PREVALENCE AND PECULIARITY OF CORPUS ATROPHIC GASTRITIS IN POPULATION WITH HIGH LEVEL OF HELICOBACTER PYLORI INFECTION.

BACKGROUND: Corpus atrophic gastritis (CAG) maybe the outcome of Helicobocterpylori (U pylon) - infection or autoimmune damage of the parietal system, affecting the risk of gastric cancer and requiring different approaches in the treatment and observation. AIM: To study the prevalence and peculiarity of CAG in population with, high prevalence of H.pylori infection. MATERIALS AND METHODS: Prevalence of CAG was studied in the representative group of Novosibirsk citizens (246 subjects aged 45-69,117 males and 129 females) using serology for noninvasive testing of gastritis phenotype Gastro-Panel. Pepsinogen I (Pgl) level < 30 pg/I and/or Pgl/Pgil ratio c 3.0 were interpreted as sever atrophy. In addition, a clinical group with serologically proven corpus atrophy was studied: 39 females and 8 males aged 38-79. Upper endoscopy and morpholojical examination was performed in 38 patients. As a pilot project, in 19 patients with suspicion on autoimmune gastritis (AIG) (low Pgl + high Gastrin-17) parietal cells antibodies (PCA) and vitamin B12 level were determined. CONCLUSION: In Novosibirsk population prevalence of both H.pylori infection and CAG (10.2%) is high. AIG is often associated with H.pylori infection (in 47.4% of cases); however, its role demands a further evaluation. Autoimmune phenotype of gastritis which was found using noninvasive diagnostic was confIrmed with the presence of PCA. In all cases ofAIG atrophy was confirmed morphologically with the presence of intestinal metaplasia in 52.6% and ~ysplasia in 10.5% of cases.

[Association of Some Homozygous Genotypes of Genes Regulating Inflammation, Destruction and Angiogenesis With Laboratory Markers of Atherosclerosis Course in Men With Stable Effort Angina].

Great number of factors stimulating or inhibiting production of proteins in inflammatory process influence serum levels of markers of inflammation. A number of homozygous genotypes of inflammation, destruction, and angiogenesis genes have been found to be associated with basic clinical-laboratory indices of inflammation and atherosclerotic process. The revealed genetic markers can be used as complimentary markers of prognosis of the disease course.

[NONINVASIVE DIAGNOSTICS OF THE PHENOTYPE OF GASTRITIS: ANALISIS OF THE FIRST THOUSAND OF CASES].

The analysis of noninvasive diagnostics of a phenotype of gastritis among 1050 people aged from 18 till 80 years which consistently addressed to policlinic is presented in the article. The instrument of diagnostics was a <>, including a complex of biomarkers - so-called <> (pepsinogen I, pepsinogen II, gastrin-17 and IgG- antibodies to Helicobacter Pylori). High frequency of different variants of atrophic gastritis (25%) with a gastric cancer risk and conditions with a risk of erosive and ulcer damages of the stomach mucous (26 %) was shown. Clinical and economical expediency of noninvasive screening of a phenotype of gastritis is postulated.

Relationship of blood levels of inflammatory and destructive biomarkers in coronary atherosclerosis with long-term results of surgical revascularization.

The relationships between blood levels of inflammatory and destructive biomarkers (TNF-α, IL-1ß, IL-6, IL-8, soluble CD40 ligand, high-sensitivity C-reactive protein, endothelial adhesion molecules, matrix metalloproteinase 3 and 9 and their tissue inhibitor type 1) were studied in men with coronary atherosclerosis before and 5 years after coronary artery bypass surgery. In men with unfavorable course of coronary atherosclerosis in the delayed period, the initial blood levels of C-reactive protein and TNF-α by 1.7 and 3.0 times surpassed those in patients with favorable course of the disease. Associations were revealed between elevated blood content of high-sensitivity C-reactive protein (p=0.01, odds ratio of 1.33) and IL-8 (p=0.02, odds ratio of 1.02) and deaths in the delayed period; IL-6 (p=0.01, odds ratio of 1.02) and cases of myocardial infarction; C-reactive protein (p=0.02, odds ratio of 1.24) and unfavorable course of the delayed period in general (death, myocardial infarction, worsening of angina pectoris functional class).

Activity of the inflammatory process in different types of unstable atherosclerotic plaques.

Inflammatory biomarkers and chemoattractants characteristic and important for different types (lipid; inflammatory erosive; degenerative necrotic) of unstable plaques in coronary arteries were identified and studied in male patients with coronary atherosclerosis without acute coronary syndrome we studied. Among the three types of unstable plaques, elevated concentrations of IL-1ß, IL-6, IL-8, IL-18 and monocyte chemotactic protein-1 were characteristic of not only inflammatory erosive type, but also lipid type compared with degenerative necrotic type. Thus, intensification of the inflammatory process plays an important role in the development of not only inflammatory and destructive, but also of lipid type of unstable atherosclerotic plaques.

Apolipoprotein E gene polymorphism in men with coronary atherosclerosis in Siberia.

Polymorphism of coding fragment of APOE gene was analyzed in two groups of men. The main group consisted of 77 residents of the West Siberian region aged 45-65 years with coronary atherosclerosis (documented by coronary angiography) without acute coronary syndrome with stable effort angina, functional class II-IV. The reference group consisted of 350 residents of Novosibirsk, aged 45-69 years. Statistically significant associations between genotypes of APOE gene coding part polymorphism and some key lipid risk factors (blood total and LDL cholesterol, atherogenic index, etc.) for coronary atherosclerosis were found in male residents of the West Siberian region. Elevated total mean level of cholesterol was detected in male residents of Novosibirsk with the APOE genotypes containing ε4 allele.

Blood level of osteonectin in stenosing atherosclerosis and calcinosis of coronary arteries.

Blood levels of stem cell marker proteins CD34 and osteonectin were studied in male patients with coronary atherosclerosis by direct biomagnetic separation of proteins with magnetic microspheres using the PureProteome Protein A and Protein G Magnetic Beads proteomic technology. High concentration of osteonectin in the blood was detected, particularly in men with stenosing atherosclerosis and coronary artery calcinosis. Blood osteonectin concentration correlated significantly with some key biomarkers of atherosclerosis and with stenosing atherosclerosis and calcinosis of coronary arteries. The results indicate that osteonectin as a marker of stromal stem cells with osteogenic potential presumably plays an important role in atherogenesis and can serve as a new biomarker of stenosing atherosclerosis and calcinosis of coronary arteries.

Antioxidant and endothelium-stabilizing effects of simvaglyzin on rabbits with experimental hypercholesterolemia.

Simvaglyzin, a complex compound of simvastatin and glycyrrhizic acid, administered to rabbits with experimental hypercholesterolemiain in doses equivalent to 66.6 and 40 microg/kg simvastatin exhibited antioxidant capacity (decreased the content of lipid peroxidation products in the blood by 27-41%) and endothelium-normalizing effect (decreased the level of von Willebrand factor and endothelin-1 by 26-58 and 21-29%, respectively, compared to 200 microg/kg simvastatin, p<0.05).