Metabolic Blood Hormones in Young People With Electrocardiographic Signs of Ischemic Myocardial Changes.

Aim    To study changes in blood concentrations of metabolic hormones and adipocytokines in people aged 25-44 years with electrocardiographic (ECG) signs of ischemic changes in the myocardium.Material and methods This study was a part of a cross-sectional survey of a random sample of Novosibirsk population aged 25-44 years. The study included 1363 people divided into two groups: group 1, subjects with ECG signs of ischemic changes in the myocardium and group 2, subjects without ECG changes. Blood serum concentrations of adipocytokines and metabolic hormones were measured by multiplex assay on a Luminex MAGPIX flow-through fluorometer.Results    The group with ECG signs of myocardial ischemia had higher blood concentrations of adiponectin, resistin, glucagon, and interleukin 6 (IL-6) than in the comparison group. A multivariate logistic regression analysis showed that the glucagon concentration was associated with the presence of ECG signs of myocardial ischemia (OR, 1.019; CI, 1.018-1.034; p=0.017).Conclusion    In young people aged 25-44 years, higher blood concentrations of glucagon are associated with the presence of ECG signs of myocardial ischemia.

Associations of Fatty Acid Profile with Abdominal Obesity in Men.

The content of individual unsaturated fatty acids in blood plasma (measured by HPLC) and their association with abdominal obesity in a group of men (mean age 52.2 years) was analyzed. The abdominal obesity was diagnosed according to the criteria of the All-Russian Scientific Society of Cardiology (waist circumference >94 cm). Men with abdominal obesity had higher levels of ω-6 γ-linolenic and dihomo-γ-linolenic acids, as well as ω-3 eicosapentaenoic and docosahexaenoic acids. They also had significantly elevated plasma levels of triglycerides and glucose and lower levels of HDL. Using single-factor ROC analysis we determined optimal cut-off thresholds for fatty acid levels indicating the presence of abdominal obesity. The results of regression analysis showed that the level of γ-linolenic acid is directly associated with the chance of abdominal obesity.s.

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.

Blood Adipokins in Young People with Early Ischemic Heart Disease on the Background of Abdominal Obesity.

Aim      To study blood adipokines spectrum in people aged 25-44 years with early ischemic heart disease (IHD), including that associated with abdominal obesity (AO).Material and methods  A cross-sectional study was performed on a random sample of the population aged 25-44 years in Novosibirsk. 1457 subjects (653 men, 804 women) were evaluated. This study included 123 people divided into four study subgroups: subgroup 1, with IHD associated with AO (n=24); subgroup 2, with IHD and without AO (n=25); subgroup 3, without IHD and with AO (n=44); and subgroup 4, without either IHD or AO (n=30). Concentrations of serum adipokines were measured simultaneously by multiplex assay with a Luminex MAGPIX flow fluorometer and by immune enzyme assay with a MULTISCAN analyzer.Results Subjects with early IHD had lower blood concentrations of adipsin and visfatin than subjects without IHD. Subjects with early IHD associated with AO had higher blood concentrations of adipsin, plasminogen activator inhibitor-1, and leptin and lower concentrations of monocyte chemoattractant protein-1 (MCP-1) and visfatin compared to subjects with early IHD and without AO. The multivariate logistic regression analysis showed that lower blood concentrations of MCP-1 were associated with a likelihood of early IHD.Conclusion      In young people aged 25-44 years, lower blood concentrations of MCP-1 were associated with a likelihood of early IHD, including that associated with AO.

[Calcification and atherosclerosis of the coronary arteries].

Calcification is a very common phenomenon in the coronary arteries, which is part of the atherosclerotic process, and the degree of calcification can predict clinical outcomes in patients at high risk of coronary events. Both the degree of calcification and the patterns of its distribution are of prognostic importance, but the relationship of coronary artery calcification with atherosclerotic plaque instability is extremely complex and not fully understood. This article is devoted to the study of calcification markers and their influence on the development of atherosclerotic foci.

[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.

[Detection of kidney dysfunction potential biomarkers with hypertension in the persons of 25-45 years].

AIM: To assess the significance of symmetrical dimethylarginine (SDMA), uromodulin, retinol-binding protein 4 (RSB-4), transforming growth factorb1 (TGF-b1), plasminogen activator inhibitor 1 (PAI-1) as kidney dysfunction potential biomarkers persons with hypertension in persons 2545 years old. MATERIALS AND METHODS: The study included 147 people. Hypertension was recorded with blood pressure (BP)140/90 mm Hg, renal dysfunction with GFRCKD-EPI90 ml/min/1.73 cm2. Four groups were formed: 1 individuals with hypertension and GFR90 ml/min/1.73 cm2; 2 with hypertension and GFR90 ml/min/1.73 cm2; 3 with BP140/90 mm Hg and GFR90 ml/min/1.73 cm2; 4 with BP140/90 mm Hg and GFR90 ml/min/1.73 cm2. The groups were comparable by gender, age, and number of respondents. Creatinine, SDMA, uromodulin, RSB-4, TGF-b1, PAI-1 levels were examined in all individuals in the serum. RESULTS: The maximum values of SDMA were determined in the 1st and 3rd groups (1.30 and 1.36 mol/l). In the 1st group, an association was found between SDMA and GFR (r=-0.324;p=0.048). In the 1st group, the minimum values of uromodulin were recorded, in the 4th group the maximum values (164.86 and 188.90 ng/ml; at the same timeр=0.921). The level of RSB-4 was the highest in the 1st group, the lowest in the 4th group (88.64 and 80.05 g/ml;p=0.011). The association of RSB-4 with SDMA in the 3rd group (r=0.400;p=0.017), the 4th group (r=0.403;p=0.018) was detected. The level of TGF-b1 was 1.5 times higher in the 1st group than in the 3rd (23.16 and 15.99 g/ml;p=0.026), the association of TGF-b1 with GFR in the 1st group had the opposite direction (r=-0.452;p=0.005). The study of similar indicators of PAI-1 did not reveal its relationship with renal dysfunction in hypertension. CONCLUSION: The results of the study made it possible to consider SDMA, RSB-4, TGF-b1 as potential biomarkers of renal dysfunction in hypertension in persons 2545 years old.

Association of some hemostasis and endothelial dysfunction factors with probability of presence of vulnerable atherosclerotic plaques in patients with coronary atherosclerosis.

OBJECTIVE: The study was dedicated to investigation of some hemostasis and endothelial dysfunction factors association with probability of presence of vulnerable atherosclerotic plaques in coronary arteries in men with atherosclerosis. RESULTS: The blood levels of factor VII, factor XII and MCP-1 were higher, and concentration of sVCAM-1 lower in men with vulnerable atherosclerotic plaques in the coronary arteries, compared to men who had stable plaques. Have been revealed correlation links between the blood levels of factor II, factor XII, MCP-1 and the presence of vulnerable atherosclerotic plaques in the coronary arteries. Results of logistic regression analysis showed that the relative risk of present of vulnerable atherosclerotic plaques in the coronary arteries is associated with an elevated blood level of factor XII and MCP-1.

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.

[The incidence of respiratory symptoms and their associations with serum cotinine levels as a marker of tobacco smoking in 25-45-year-old Novosibirsk dwellers].

AIM: To study the incidence of respiratory symptoms and to reveal their associations with serum cotinine levels (SCL) in 25-45-year-old Novosibirsk dwellers. SUBJECTS AND METHODS: The WHO respiratory symptom questionnaire and the ECRHS screening questionnaire were used for a population-based survey conducted in Novosibirsk to identify respiratory symptoms; 545 people replied to the questions available in the questionnaires. SCL was determined by enzyme immunoassay on a random subsample of 182 examinees. RESULTS: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers: cough (27.7%), more than 3-month cough per year (22%), sputum discharge (25%), forced respiration/wheezing in the past year (22.6%), suffocation fits in the past year (5.3%), and cough/forced respiration/stertor bouts by breathing cold air (14.9%) or contacting animals, plants, or chemical agents (16.5%). There was a significant positive correlation between SCL and the presence of cough, more than 3-month cough per year, sputum discharge, forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The median SCL proved to be significantly higher in the people who complained of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The people who had a SCL of more than 3 ng/ml were ascertained to be at higher risk of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year than those who had a SCL of less than 3 ng/ml. CONCLUSION: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers; SCL was found to be associated with the symptoms characteristic of bronchial obstructive diseases; the expediency of using the SCL threshold of 3 ng/ml as a marker of tobacco smoking was confirmed.

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).

Oxidation and endothelial dysfunction biomarkers of atherosclerotic plaque instability. Studies of the vascular wall and blood.

The concentrations of LPO products (including those present in LDL), oxidative modification of proteins, paraoxonase activity, concentrations of antioxidants, lipid values and biomarkers of endothelial dysfunction were studied in the blood and coronary artery intima/media of male patients with coronary atherosclerosis without acute coronary syndrome. Blood levels of LDL oxidized apolipoproteins and lipoprotein (a) were higher, while the content of NO metabolites, sVCAM endothelial adhesion molecules, and LDL oxidation resistance were lower in men with mainly unstable atherosclerotic plaques in the coronary arteries in comparison with men with mainly stable plaques in the coronary arteries. Of these blood biomarkers, only NO metabolites, oxidized proteins, and sVCAM correlated with the presence of unstable atherosclerotic plaques. A significant correlation between the levels of biomarkers in the vascular wall and blood was detected only for LPO parameters.

[Inflammatory-destructive biomarkers of atherosclerotic plaques instability. Study of arterial wall and blood].

Concentrations of tumor necrosis factor, interleukin 1- and its receptor antagonist, IL-6, IL-8, IL-18, IL-2, ligand of CD40 receptor (CD40L), high sensitive C-reactive protein (hsCRP), monocyte chemotactic protein -1, endothelial monocyte activating protein II, adhesive molecules (sICAM-1 and sVCAM-1), matrix metalloproteinase (MMP-3, MMP-7, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) and endothelin-1 were studied in blood and in coronary artery intima/media of men with coronary atherosclerosis without acute coronary syndrome. Blood levels of hsCRP, IL-8, IL-6 and CD40L were higher, while blood levels of sVCAM and TIMP-1 were lower in men with prevalence of unstable atherosclerotic plaques compared to men with prevalence of stable atherosclerotic plaques in coronary arteries. Blood levels of hsCRP, IL-6 and IL-8 correlated with characteristics of coronary artery atherosclerotic plaques instability. Correlation between hsCRP blood level and hsCRP concentration in coronary artery intima/media material was also revealed.

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.

[Dynamics of changes of blood inflammatory-oxidative biomarkers in acute coronary syndrome].

Some inflammatory cytokines and parameters of low density lipoproteins (LDL) oxidative modification were studied in blood of 250 acute coronary syndrome (ACS) patients--Siberian inhabitants, men and women with myocardial infarction (MI) or unstable angina on first, tenth and thirtieth days of disease. The inflammatory biomarkers in men and women with MI are: increased concentrations of interleukin (IL)-6, IL-8 and C-reactive protein (CRP), especially on the first day of disease. The most significant inflammatory biomarker of ACS is increased CRP level, especially in women. Oxidative biomarkers in men with ACS are increased basal level of LDL lipid peroxidation (LPO) products and decreased LDL resistance to oxidation. Inflammatory-oxidative biomarkers IL-6, IL-8, CRP and basal level of LDL LPO products are correlated and independently associated with MI.

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.

Blood levels of inflammatory and destructive biomarkers in coronary atherosclerosis of different severity.

In male patients with coronary atherosclerosis without acute coronary syndrome, the levels of inflammatory-destructive biomarkers of atherosclerotic plaque instability depended on the severity and dissemination of coronary atherosclerosis. The highest levels of C-reactive protein and matrix metalloproteinase 3 were found in men with atherosclerotic involvement of all three main coronary arteries, primarily their middle and distal segments, and in men with predominance of low-grade stenoses (<50%) of coronary arteries in areas of atherosclerotic plaques.

[Atherogenic oxidative and structural modification of low density lipoproteins in men with coronary atherosclerosis].

We studied parameters of structural and oxidative modification of low density lipoproteins (LDL) in 80 men aged 35 - 65 years with coronary atherosclerosis verified at coronary angiography in comparison with 80 men of the same age without ischemic heart disease. Biochemical studies included determination of parameters of lipid blood composition by enzymatic methods, subfractional LDL profile by electrophoresis in 2 - 16% gradient polyacrylamide gel, degree of oxidative modification of lipid (lipid peroxidation products) and apoprotein (carbonyl groups) components of LDL by fluorometric and spectrophotometric methods. In men with coronary atherosclerosis we revealed elevated level of small dense LDL and substantially oxidized lipid and apoprotein components of these particles. Independent association of structural and oxidative modification was shown.