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.

[Blood Levels of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Men from Different Population Groups and Its Relation to Unfavorable Long-Term Prognosis].

AIM: of the study was to investigate blood levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in men from different population subgroups, their associations with cardiovascular risk factors and with unfavorable 7-years long-term prognosis. MATERIAL AND METHODS: The study included three subgroups of men from a population sample of residents of Novosibirsk, 44-73 years old, not receiving lipid-lowering drugs: subgroup of population proper (183 men), subgroup with hypercholesterolemia (46 men), and subgroup with hypocholesterolemia (18 men). Blood level of PCSK9 was determined by ELISA using the test-systems "Human Proprotein Convertase 9/PCSK9 Immunoassay". Study endpoints (myocardial infarction, cardiovascular death) were registered during 7 years after baseline examination of subgroups using the data of the Registers of myocardial infarction and cardiovascular mortality. RESULTS: Distribution of PCSK9 protein in subgroups with hyper- and hypocholesterolemia was normal. In the subgroup of population proper it was abnormal with leftward shift. PCSK9 protein concentration in the subgroup with hypercholesterolemia was 1.2 times higher than in the population subgroup. PCSK9 protein level correlated significantly with blood levels of total cholesterol (CH), low density lipoprotein (LDL) CH, and glucose. Only 15% of PCSK9 variability was due to the influence of other factors (R Square=0.155, p<0.001). Factors with significant influence on blood level of PCSK9 protein were levels of high density lipoprotein CH (=0.238, p=0.023), triglycerides (=0.253, p=0.049) and LDL CH (=0.751, p=0.009). Multivariate regression analysis revealed significant independent association of PCSK9 protein levels with cardiovascular death during period of registration (7-years) (p=0.048, OR=1.01). This result indicates that in men increase of blood level of PCSK9 protein by 1ng/ml independently of other parameters increases relative risk of cardiovascular death during following 7 years by 1%.

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.

Proteomic Study of Blood Serum in Coronary Atherosclerosis.

Changes in the blood serum proteins were assessed in men with coronary atherosclerosis and without coronary heart disease. Proteins were separated by 2D-electrophoresis, protein fractions were identified by their peptide fingerprint by MALDI method; fractions with more than twofold increase in protein level were determined. In blood serum of patients with coronary atherosclerosis, the content of C4 complement protein increased and ceruloplasmin level decreased, which is typical of heart failure and coronary heart disease.

Effects of simvaglyzin and atorvaglyzin on the expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase in rat liver.

Activity and levels of protein and mRNA of 3-hydroxy-3-methyl-glutaryl-CoA reductase were estimated in rat liver after the administration of atorvastatin and simvastatin and their complexes with glycyrrhizic acid (atorvaglyzin and simvaglyzin). The amount of 3-hydroxy-3-methyl-glutaryl-CoA reductase protein in rats decreased by 13 and 25% (p<0.05) 24 h after treatment with atorvaglyzin and simvaglyzin, respectively. Activity of this enzyme decreased by 46% in rats treated with atorvaglyzin. The amount of messenger RNA in these groups significantly increased as compared to control group (untreated animals).

Study of cholesterol-lowering effect and safety of simvaglisin on rabbit model of hypercholesterolemia.

Using rabbit model of experimental hypercholesterolemia we showed that the hypocholesterolemic effect of simvaglisin, a complex preparation containing simvastatin and glycyrrhizic acid, in doses corresponding to 40, 66.5, and 100 mg/kg/day simvastatin is equal to the hypocholesterolemic effect of 200 mg/kg/day simvastatin alone. The total blood cholesterol decreased by 39, 36, 47, and 38% (p < 0.05), respectively, after 20-day course of the preparation. Myotoxicity of simvaglisin evaluated by serum creatine phosphokinase was lower than that of simvastatin. After 30-day treatment, this parameter was lower by 26, 24, and 29% (p < 0.05) than the corresponding parameter for simvastatin.

[Cholesterol lowering properties of a complex compound simvastatin with glycyrrhizic acid (simvaglyzin) in experimental models].

A molecular complex of simvastatin (SV) and glycyrrhyzic acid (GA) (at the ratio of 1 : 4), has been synthesized. The complex named "simvaglyzin" (SVG) was stable in aqeous and aqua-alcohol solutions at GA concentrations exceeding 0.2 mM. In vitro SVG acted as uncompetitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (Ki = 94 nM). Appearance of this inhibitory activity is associated with the cytochrome P450-dependent conversion of SVG. The addition of 1 mM methyrapone into incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV and SVG (used at 300 nM concentration) inhibited mevalonate synthesis rate by 39.15+/-8.27% and 38.85+/-3.04%, respectively. In vivo SVG showed dose-dependent cholesterol-lowering effect. In rats the cholesterol-lowering effect of SVG used at daily doses corresponding to 66 and 100 mg/kg of SV was equal to the effect of the daily dose 200 mg/kg of SV. The decreases of total cholesterol level in blood serum were 7%, 9% and 8%, respectively. Myotoxicity of those SVG doses estimated by creatine phosphokinase (CPK) activity in blood serum was lower than that of SV. In rats treated with SV the activity of CPK increased by 79% (p<0.01), while in SVG treated rats by 30% and 36% (p<0.05). Any increase of hepatotoxicity markers alanine aminotransferse or aspartate aminotransferase in blood serum was not observed. The data suggest pharmacological synergism attributed to the SV-GA complex formation and elevated safety of the resultant complex compared with the parent compound.

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).