Associations of Adipocytokines with The Development of Cardiovascular Events in Young People.

The research was aimed to study the associations of adipocytokines with the risk of cardiovascular events and to determine the threshold values of adipocytes for the prognosis of cardiovascular events in a young population. MATERIALS AND METHODS: The study is an epidemiological cohort study. The analysis included 1240 people aged 25-44 years. The endpoint was combined and included: death from cardiovascular disease, myocardial infarction, probable myocardial infarction, acute cerebrovascular accident, hospitalization for cardiovascular disease, and revascularization. Adipocytokines were determined with a MILLIPLEX panel. RESULTS: In the examined population, 1.7% of cases of cardiovascular events were detected during cohort observation, of which 28.6% were fatal events. In men, cardiovascular endpoints were recorded 4.3 times more often than in women (17 (81%) vs. 4 (19%), p = 0.003). In individuals with cardiovascular events, arterial hypertension (2.6 times), diabetes mellitus (8.6 times), and overweight/obesity (1.5 times) were more often recorded compared to individuals without cardiovascular events. For tumor necrosis factor-alpha (TNFa), the threshold value was 2.5 pg/mL, with sensitivity assessment (Se) at 85.7% and specificity (Sp) at 83.3%. For amylin, the threshold value was 10.5 pg/mL, with Se at 73.7% and Sp at 67.0%. For pancreatic polypeptide (PP), the threshold value was 43.7 pg/mL, with Se at 85.7% and Sp at 56.7%. CONCLUSION: A method for assessing the risk of cardiovascular events in young people includes determining the levels of amylin, PP, and TNFa in blood serum. The cut-off points for predicting cardiovascular events were levels of amylin above 10.5 pg/mL, PP above 43.7 pg/mL, or a decrease in TNFa below 3.8 pg/mL.

Triglycerides, Obesity and Education Status Are Associated with the Risk of Developing Type 2 Diabetes in Young Adults, Cohort Study.

BACKGROUND: It is important to determine the influence of traditional risk factors on the development of type 2 diabetes mellitus (T2DM) in young adults. Goal of the research: To study the incidence of T2DM and factors that increase the risk of its occurrence during the observation of a cohort of young adults. MATERIALS AND METHODS: 1341 people aged 25-44 were included in the study from 2013 to 2017, of whom 622 were men (46.4%). The examination included anamnesis, anthropometric data, and a blood test. Cases of developed T2DM were identified by comparing the Diabetes Mellitus Register, medical records of patients, and the database of examined individuals from 2019 to 2023. T2DM Results: In the examined population, 11 participants (0.82%) developed T2DM. The prevalence of T2DM was 0.96% in men and 0.69% in women. Patients with T2DM had a higher waist circumference, BMI, SBP, TG, and lower HDL than patients without T2DM, and were also less likely to have a higher education. The risk of developing T2DM increases 6.5 times at a BMI of ≥30 kg/m2, and 5.2 times at a TG level of ≥1.7 mmol/L, regardless of other risk factors. In the absence of a higher education, the risk of developing T2DM is increased by 5.6 times. CONCLUSION: In young people, high triglyceride levels, obesity, and a low level of education are associated with the risk of developing type 2 diabetes, regardless of other factors.

Associations of Adipocytokines and Early Renal Dysfunction in Young People on the Background of Dyslipidemia.

BACKGROUND: There are data supporting the idea that atherogenic dyslipidemia is a risk factor for CKD and reduced GFR. The aim was to evaluate the associations between adipocytokines and early renal dysfunction in young people with dyslipidemia. MATERIALS AND METHODS: A population study was conducted in IIPM-Branch of IC&G SB RAS, in 2013-2017. Furthermore, 1033 people were included in the study (469 men (45.4%) and 564 women (54.6%)). The study included blood sampling, anthropometric data, and adipokines by multiplex analysis. RESULTS: Among people with reduced kidney function and DLP, men were 3.1 times more common than without DLP, women smoked 2 times less often, arterial hypertension was 7.8 times more common, and abdominal obesity was 2.7 times more common (and women with DLP were 3 times more likely than those without DLP). An increase in the level of resistin by 1 mcg/mL was associated with an increased chance of having renal dysfunction by 0.2%. An increase in the level of GIP was associated with an increased chance of having renal dysfunction by 1.1%. CONCLUSIONS: In young people with dyslipidemia, regardless of the presence of abdominal obesity, resistin and GIP are associated with the presence of renal dysfunction.

Blood Adipokines/Cytokines in Young People with Chronic Bronchitis and Abdominal Obesity.

The pathogenesis of the development of chronic lung diseases assumes the participation of systemic inflammation factors, as well as hormone-like substances produced by adipose tissue. The aim of this study was to evaluate the associations of certain adipokines/cytokines and chronic bronchitis against the background of abdominal obesity in young people. The study included 1415 people aged 25-44. In total, 115 people were selected by the random numbers method, who were divided into two subgroups: those with chronic bronchitis and abdominal obesity and those with chronic bronchitis without abdominal obesity. A control group of patients with comparable gender and age was also selected. In the group of patients with chronic bronchitis, adiponectin, TNFa and GIP levels were 1.4 times higher. The levels of C-peptide, MCP-1 and PP in the group of chronic bronchitis were 1.3 times higher compared to the control. Adipsin, lipocalin-2, IL-6 and resistin were significantly higher in the group with chronic bronchitis. Glucagon, amylin and ghrelin were 2.2, 2.3 and 3.2 times lower, respectively, in the group of patients with chronic bronchitis. Against the background of abdominal obesity, the probability of having chronic bronchitis increased with an increase in the level of lipocalin-2 and GIP and TNFa.

Adipokine Levels in Men with Coronary Atherosclerosis on the Background of Abdominal Obesity.

Background. Obesity is associated with dyslipidemia, and excess body fat is associated with unfavorable levels of adipokines and markers of inflammation. The goal of research. To study the level of adipokines and markers of inflammation, their associations with unstable atherosclerotic plaques in men with coronary atherosclerosis on the background of abdominal obesity. Materials and methods. The study involved 82 men aged 40-77 years with coronary atherosclerosis after endarterectomy from the coronary arteries. We divided all men into two groups: 37 men (45.1%) with unstable atherosclerotic plaques, and 45 men (54.9%) who had stable plaques. Obesity was established at a BMI of ≥30 kg/m2. The levels of adipokines and markers of inflammation in the blood were determined by multiplex analysis. Results. In patients with obesity and unstable plaques, the levels of C-peptide, TNFa and IL-6 were 1.8, 1.6, and 2.8 times higher, respectively, than in patients with obesity and stable plaques. The chance of having an unstable plaque increases with an increase in TNFa by 49% in obese patients and decreases with an increase in insulin by 3% in non-obese patients. Conclusions. In men with coronary atherosclerosis and obesity, unstable atherosclerotic plaques in the coronary arteries are directly associated with the level of TNF-α.

Blood Levels of Indicators of Lower Respiratory Tract Damage in Chronic Bronchitis in Patients with Abdominal Obesity.

OBJECTIVE: to study biomolecules associated with pathology in the respiratory system, in particular, with the development of chronic bronchitis in patients with abdominal obesity. MATERIALS AND METHODS: This is a pilot study. The main group consisted of 158 people with chronic bronchitis, divided into two subgroups: one with abdominal obesity, and the other without it. The control group consisted of 68 people without chronic bronchitis. We determined the blood levels of SP-A, SP-D, α1-antitrypsin, CC16, PARC, and RELM-ß. RESULTS: In the first subgroup, patients significantly more often complained of coughing, experienced shortness of breath 1.5 times more often with light physical exertion and 2.7 times more often with moderate physical exertion. In these patients, a Tiffeneau-Pinelli index (FEV1/FVC) below 70% was 1.8 times more common, more patients had FEV1 and FVC of less than 80%, and presented a statistically significant decrease in SP-A, α1-antitrypsin, CC16 levels and an increase in PARC levels than in the second subgroup. CONCLUSION: In patients with chronic bronchitis and abdominal obesity, there is a decrease in the levels of SP-A, α1-antitrypsin, CC16 and an increase in the level of PARC compared with patients without abdominal obesity, which is probably due to the presence of an additional source of chronic inflammation associated with adipose tissue.

Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population.

This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P<0.01). In contrast, serum triglyceride (TG) values increased over time in younger age groups, reached a plateau and decreased in older age groups (> 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements.

Proteomic Studies of Blood and Vascular Wall in Atherosclerosis.

The review is devoted to the analysis of literature data related to the role of proteomic studies in the study of atherosclerotic cardiovascular diseases. Diagnosis of patients with atherosclerotic plaques before clinical manifestations is an arduous task. The review presents the results of research on the new proteomic potential biomarkers of coronary heart disease, coronary atherosclerosis, acute coronary syndrome, myocardial infarction, carotid artery atherosclerosis. Also, the analysis of literature data on proteomic studies of the vascular wall was carried out. To assess the involvement of proteins in the pathological process of atherosclerosis, it is important to investigate the specific relationships between proteins in the arteries, expression and concentration of proteins. The development of proteomic technologies has made it possible to analyse the number of proteins associated with the development of the disease. Analysis of the proteomic profile of the vascular wall in atherosclerosis can help to detect possible diagnostically significant protein structures or potential biomarkers of the disease and develop novel approaches to the diagnosis of atherosclerosis and its complications.

Association of Matrix Metalloproteinases with Coronary Artery Calcification in Patients with CHD.

This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.

Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region.

The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A (r = 0.159, p = 0.001), m.12315G>A (r = 0.119; p = 0.011), m.5178C>A (r = 0.114, p = 0.014), and m.3256C>T (r = 0.130, p = 0.011); a negative correlation with mtDNA mutations m.14846G>A (r = -0.111, p = 0.042) and m.13513G>A (r = -0.133, p = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy.

The Blood Cytokine Profile of Young People with Early Ischemic Heart Disease Comorbid with Abdominal Obesity.

OBJECTIVE: The aim was to study the blood cytokine/chemokine profile of 25-44-year-old people with early ischemic heart disease (IHD) comorbid with abdominal obesity (AO). METHODS: A cross-sectional medical examination of subjects in Novosibirsk, Russia, was conducted after random sampling of the above age group. A total of 1457 subjects, 804 females and 653 males, were analyzed. The epidemiological diagnosis of IHD was made in accordance with 17 validated and functional criteria, employing exercise ECG for confirmation. Simultaneous quantitative analyses of 41 cytokines/chemokines in blood serum were performed by a multiplex assay using the HCYTMAG-60K-PX41 panel (MILLIPLEX MAP) on a Luminex 20 MAGPIX flow cytometer, with additional ELISA testing. RESULTS: Flt3 ligand, GM-CSF, and MCP-1 were significantly associated with the relative risk of early IHD. In the presence of AO, GM-CSF, MCP-1 and IL-4 also significantly correlated with the relative risk of early IHD. By univariate regression analysis, the relative risk of early IHD was associated with lowered blood concentrations of Flt3 ligand, whereas the relative risk of early IHD in the presence of AO was associated with lowered blood concentrations of GM-CSF. Employing multivariable regression analysis, only lower blood levels of Flt3 ligand were associated with a relative risk of early IHD, whereas the relative risk of early IHD in the presence of AO was limited to lower levels of IL-4. CONCLUSION: Findings related to Flt3 ligand, GM-CSF, and IL-4 are consistent with the international literature. Results from the present study are partly confirmative and partly hypothesis generating.

Why does Russia have such high cardiovascular mortality rates? Comparisons of blood-based biomarkers with Norway implicate non-ischaemic cardiac damage.

BACKGROUND: Russia has one of the highest rates of mortality from cardiovascular disease (CVD). At age 35-69 years, they are eight times higher than in neighbouring Norway. Comparing profiles of blood-based CVD biomarkers between these two populations can help identify reasons for this substantial difference in risk. METHODS: We compared age-standardised mean levels of CVD biomarkers for men and women aged 40-69 years measured in two cross-sectional population-based studies: Know Your Heart (KYH) (Russia, 2015-2018; n=4046) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015-2018; n=17 646). A laboratory calibration study was performed to account for inter-laboratory differences. RESULTS: Levels of total, low-density lipoprotein-, high-density lipoprotein-cholesterol and triglycerides were comparable in KYH and Tromsø 7 studies. N-terminal pro-b-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hsCRP) were higher in KYH compared with Tromsø 7 (NT-proBNP was higher by 54.1% (95% CI 41.5% to 67.8%) in men and by 30.8% (95% CI 22.9% to 39.2%) in women; hs-cTnT-by 42.4% (95% CI 36.1% to 49.0%) in men and by 68.1% (95% CI 62.4% to 73.9%) in women; hsCRP-by 33.3% (95% CI 26.1% to 40.8%) in men and by 35.6% (95% CI 29.0% to 42.6%) in women). Exclusion of participants with pre-existing coronary heart disease (279 men and 282 women) had no substantive effect. CONCLUSIONS: Differences in cholesterol fractions cannot explain the difference in CVD mortality rate between Russia and Norway. A non-ischemic pathway to the cardiac damage reflected by raised NT-proBNP and hs-cTnT is likely to contribute to high CVD mortality in Russia.

Data on association of mitochondrial heteroplasmy with carotid intima-media thickness in subjects from Russian and Kazakh populations.

The search for variants of mitochondrial genome associated with atherosclerosis, in particular, with carotid intima-media thickness (cIMT), is necessary to understand the role of the damage of mitochondrial genome in the development of atherosclerosis. Such data can be useful to provide novel genetic markers of predisposition to atherosclerosis and molecular targets for further development of technologies aimed to prevent age-related degenerative pathologies. Data presented in this article demonstrate the association of several heteroplasmic variants of mitochondrial DNA (mtDNA) previously described as proatherogenic ones with cIMT in 251 participants (190 participants from Novosibirsk, Russia, and 61 participant from Almaty, Kazakhstan). It was shown that the occurrence of some variants of mitochondrial genome is different in samples derived from Russian and Kazakh populations; the level of mitochondrial heteroplasmy m.13513G > A correlates negatively with mean cIMT in both Russian and Kazakh participants.