58 results on '"Privalova EV"'
Search Results
2. WNT Signaling Cascade Proteins and LRP6 in the Formation of Various Types of Coronary Lesions in Patients With Coronary Artery Disease.
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Belenkov YN, Iusupova AO, Slepova OA, Pakhtusov NN, Popova LV, Lishuta AS, Krivova AV, Khabarova NV, Abidaev MY, and Privalova EV
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- Humans, Male, Female, Middle Aged, Cross-Sectional Studies, Aged, Wnt3A Protein metabolism, Wnt1 Protein metabolism, Coronary Angiography methods, Biomarkers, Low Density Lipoprotein Receptor-Related Protein-6 metabolism, Coronary Artery Disease physiopathology, Wnt Signaling Pathway physiology
- Abstract
Aim: Assessment of WNT1, WNT3a, and LRP6 concentrations in patients with ischemic heart disease (IHD) and obstructive and non-obstructive coronary artery (CA) disease., Material and Methods: This cross-sectional observational study included 50 IHD patients (verified by coronary angiography, CAG), of which 25 (50%) were men, mean age 64.9±8.1 years; 20 patients had non-obstructive CA disease (stenosis <50%), and 30 patients had hemodynamically significant stenosis. Concentrations of WNT1, WNT3a and LRP6 were measured in all patients., Results: The concentrations of WNT1 and WNT3a proteins were significantly higher in patients with IHD and obstructive CA disease (p < 0.001), while the concentration of LRP6 was higher in the group with non-obstructive CA disease (p = 0.016). Data analysis of the group with obstructive CA disease showed a moderate correlation between WNT1 and LRP6 (ρ=0.374; p=0.042). Correlation analysis of all groups of patients with CA disease revealed a moderate association between the concentrations of WNT1 and uric acid (ρ=0.416; p=0.007). Regression analysis showed that risk factors for the development of IHD, such as increased body mass index, age, smoking, dyslipidemia, and hypertension, did not significantly influence the type of CA disease in IHD patients. According to ROC analysis, the obstructive form of IHD was predicted by a WNT3a concentration higher than 0.155 ng/ml and a LRP6 concentration lower than 12.94 ng/ml., Conclusion: IHD patients with non-obstructive CA disease had the greatest increase in LRP6, while patients with obstructive CA disease had significantly higher concentrations of the canonical WNT cascade proteins, WNT1 and WNT3a. According to the ROC analysis, a WNT3a concentration >0.155 ng/ml can serve as a predictor for the presence of hemodynamically significant CA stenosis in IHD patients (sensitivity 96.7%; specificity 70%), whereas a LRP6 concentration >12.94 ng/ml can predict the development of non-obstructive CA disease (sensitivity 76.7%; specificity 65%).
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- 2024
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3. Assessment of the Level of Matrix Metalloproteinases, VEGF and MicroRNA-34a in Patients With Non-obstructive and Obstructive Lesions of the Coronary Arteries.
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Iusupova AO, Slepova OA, Pakhtusov NN, Popova LV, Ageev AA, Lishuta AS, Privalova EV, Khabarova NV, Dadashovа GМ, and Belenkov YN
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- Humans, Male, Middle Aged, Female, Cross-Sectional Studies, Aged, Coronary Artery Disease genetics, Coronary Artery Disease physiopathology, Coronary Artery Disease diagnosis, Matrix Metalloproteinases genetics, Biomarkers, Coronary Stenosis genetics, Coronary Stenosis physiopathology, Coronary Vessels diagnostic imaging, Coronary Vessels physiopathology, Vascular Endothelial Growth Factor A genetics, MicroRNAs genetics, Coronary Angiography
- Abstract
Aim: To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease., Material and Methods: This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients., Results: The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis., Conclusion: IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.
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- 2024
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4. The EXCEL Study: Long-term Observation of the Effectiveness of Drug and Non-drug Rehabilitation in Patients with Ischemic Heart Failure.
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Belenkov YN, Lishuta AS, Slepova OA, Nikolaeva NS, Khabarova NV, Dadashova GM, and Privalova EV
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- Humans, Quality of Life, Ventricular Function, Left, Stroke Volume, Chronic Disease, Natriuretic Peptide, Brain therapeutic use, Heart Failure, Myocardial Ischemia
- Abstract
Aim: To study the long-term effect of enhanced external counterpulsation (EECP) therapy on exercise tolerance, quality of life (QoL), and indicators of the structural and functional state of the cardiovascular system in patients with stable ischemic heart disease (IHD) complicated by chronic heart failure (CHF)., Material and Methods: This open randomized EXCEL study included 120 patients with verified IHD complicated by NYHA II-III functional class CHF with reduced or mid-range left ventricular (LV) ejection fraction. Patients were randomized into group 1 (n=40), optimal drug therapy (ODT) and EECP (35 hours, 2 courses per year); group 2 (n=40), ODT and EECP (35 hours, 1 course per year); and group 3 (control; n=40), ODT and placebo counterpulsation (35 h, 1 course per year). All patients underwent a 6-minute walk test (6MWT), evaluation of clinical status, QoL with the MLHFQ and SF-36 questionnaires, structural and functional state of large blood vessels and microvasculature, measurement of brain natriuretic peptide precursor (NT-proBNP), and echocardiography at baseline and after 12 months., Results: In groups 1 and 2 after 12 months, the 6MWT distance increased statistically significantly (44.5 and 24.9%, respectively) and the following indexes improved: QoL (SF-36, MLHFQ), the condition of large blood vessels (phase shift, radial augmentation index, central aortic systolic pressure (CASP)) and microvasculature (occlusion index, percentage of perfused capillaries, percentage of capillary recovery), and the LV systolic function (from 40.6±7.5 to 47.5±10.2% and from 41.3± 6.8 to 43.9±10.3%, respectively). The proportion of patients with a >20% increase in the 6MWT at 12 months was 97.5, 72.5, and 7.7%, respectively. A statistically significant decrease in NT-proBNP was observed in all groups. In group 3, the incidence of hospitalizations for CHF and the risk of the composite endpoint were significantly higher., Conclusion: For the 12-month study period, the effects of EECP in patients with IHD complicated by CHF included improvements in exercise tolerance, QoL, vascular and cardiac functional parameters, and a decrease in the incidence of adverse outcomes.
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- 2024
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5. MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease.
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Iusupova AO, Pakhtusov NN, Slepova OA, Belenkov YN, Privalova EV, Bure IV, Vetchinkina EA, and Nemtsova MV
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- Female, Humans, Male, Cross-Sectional Studies, Sirtuin 1 metabolism, Wnt Proteins genetics, Wnt Proteins metabolism, Wnt4 Protein genetics, Atherosclerosis, Coronary Artery Disease metabolism, MicroRNAs genetics, MicroRNAs metabolism, Wnt Signaling Pathway genetics
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MicroRNAs and the WNT signaling cascade regulate the pathogenetic mechanisms of atherosclerotic coronary artery disease (CAD) development., Objective: To evaluate the expression of microRNAs (miR-21a, miR-145, and miR-221) and the role of the WNT signaling cascade (WNT1, WNT3a, WNT4, and WNT5a) in obstructive CAD and ischemia with no obstructive coronary arteries (INOCA)., Method: The cross-sectional observational study comprised 94 subjects. The expression of miR-21a, miR-145, miR-221 (RT-PCR) and the protein levels of WNT1, WNT3a, WNT4, WNT5a, LRP6, and SIRT1 (ELISA) were estimated in the plasma of 20 patients with INOCA (66.5 [62.8; 71.2] years; 25% men), 44 patients with obstructive CAD (64.0 [56.5; 71,0] years; 63.6% men), and 30 healthy volunteers without risk factors for cardiovascular diseases (CVD)., Results: Higher levels of WNT1 (0.189 [0.184; 0.193] ng/mL vs. 0.15 [0.15-0.16] ng/mL, p < 0.001) and WNT3a (0.227 [0.181; 0.252] vs. 0.115 [0.07; 0.16] p < 0.001) were found in plasma samples from patients with obstructive CAD, whereas the INOCA group was characterized by higher concentrations of WNT4 (0.345 [0.278; 0.492] ng/mL vs. 0.203 [0.112; 0.378] ng/mL, p = 0.025) and WNT5a (0.17 [0.16; 0.17] ng/mL vs. 0.01 [0.007; 0.018] ng/mL, p < 0.001). MiR-221 expression level was higher in all CAD groups compared to the control group ( p < 0.001), whereas miR-21a was more highly expressed in the control group than in the obstructive ( p = 0.012) and INOCA ( p = 0.003) groups. Correlation analysis revealed associations of miR-21a expression with WNT1 (r = -0.32; p = 0.028) and SIRT1 (r = 0.399; p = 0.005) protein levels in all CAD groups. A positive correlation between miR-145 expression and the WNT4 protein level was observed in patients with obstructive CAD (r = 0.436; p = 0.016). Based on multivariate regression analysis, a mathematical model was constructed that predicts the type of coronary lesion. WNT3a and LRP6 were the independent predictors of INOCA ( p < 0.001 and p = 0.002, respectively)., Conclusions: Activation of the canonical cascade of WNT-β-catenin prevailed in patients with obstructive CAD, whereas in the INOCA and control groups, the activity of the non-canonical pathway was higher. It can be assumed that miR-21a has a negative effect on the formation of atherosclerotic CAD. Alternatively, miR-145 could be involved in the development of coronary artery obstruction, presumably through the regulation of the WNT4 protein. A mathematical model with WNT3a and LRP6 as predictors allows for the prediction of the type of coronary artery lesion.
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- 2023
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6. [Assessment of systemic inflammation activity, myocardial structure and functional features, their relationship in patients with multiple myeloma, receiving bortezomib therapy].
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Fomina EV, Kardanova SA, Bochkarnikova OV, Murtuzaliev SM, Appolonova SA, Markin PA, Privalova EV, Ilgisonis IS, and Belenkov YN
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- Male, Humans, Female, Bortezomib adverse effects, C-Reactive Protein metabolism, Stroke Volume, Prospective Studies, Ventricular Function, Left, Myocardium, Inflammation, Multiple Myeloma complications, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
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Aim: To study the dynamics of calculated indices [neutrophil-lymphocyte ratio (NLR); systemic inflammation index (SIV)] and biomarkers of systemic inflammation [interleukin-1β (IL-1β); high-sensitivity C-reactive protein (hsCRP)], parameters of the structure-and-function state of the myocardium and intracardiac hemodynamics, and their relationship in patients newly diagnosed with multiple myeloma (MM) at the onset of the disease and after 6 courses of chemotherapy (CT) containing the proteasome inhibitor bortezomib., Material and Methods: This prospective study included 30 patients aged 63.8±10.0 years diagnosed with MM; 17 (56.7 %) of them were men. The following tests were performed for all patients: measurement of IL-1β and hsCRP, calculation of the inflammation indexes NLR and SIV, transthoracic echocardiography before and after 6 courses of bortezomib-containing CT. At the time of study completion, 9 patients dropped out due to reasons not related to cardiovascular complications of CT., Results: The antitumor therapy was associated with increases of immune-inflammation indexes: NLR increased from 1.54 [1.02; 1.83] to 2.9 [1.9; 4.35] (p=0.009) and SIV increased from 402.95 [230.5; 534.0] to 1102.2 [453.1; 1307.9] (р=0.014). IL-1β increased from 5.15 [4.05; 5.77] to 6.22 [5.66; 6.52] pg/ml remaining within the reference range (p=0.142) whereas hsCRP decreased from 1.02 [0.02; 2.71] to 0.02 [0.02; 0.82] IU/l (p=0.138). Statistically significant changes in parameters of heart remodeling and clinical picture of cardiovascular complications were not observed. A correlation analysis showed significant inverse correlations of hsCRP with left ventricular ejection fraction (LV EF) (r= -0.557; p=0.003), the number of plasma cells (PC) with LV EF (r= -0.443; p=0.023), and a direct correlation of the number of PC with hsCRP (r=0.433; p=0.022)., Conclusion: During the study, the accepted criteria for cardiotoxicity of bortezomib-containing chemotherapy in patients with MM, were not met. The identified correlations between the level of markers for acute inflammation, indexes of intracardiac hemodynamics, and the immediate MM substrate may indicate the role of chronic low-intensity inflammation in the pathogenesis of myocardial remodeling in patients with MM. This necessitates further studies on larger samples of patients to assess the prognostic significance.
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- 2023
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7. Relationship of Acylcarnitines to Myocardial Ischemic Remodeling and Clinical Manifestations in Chronic Heart Failure.
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Belenkov YN, Ageev AA, Kozhevnikova MV, Khabarova NV, Krivova AV, Korobkova EO, Popova LV, Emelyanov AV, Appolonova SA, Moskaleva NE, Shestakova KM, and Privalova EV
- Abstract
Background: Progressive myocardial remodeling (MR) in chronic heart failure (CHF) leads to aggravation of systolic dysfunction (SD) and clinical manifestations. Identification of metabolomic markers of these processes may help in the search for new therapeutic approaches aimed at achieving reversibility of MR and improving prognosis in patients with CHF., Methods: To determine the relationship between plasma acylcarnitine (ACs) levels, MR parameters and clinical characteristics, in patients with CHF of ischemic etiology (n = 79) and patients with coronary heart disease CHD (n = 19) targeted analysis of 30 ACs was performed by flow injection analysis mass spectrometry., Results: Significant differences between cohorts were found for the levels of 11 ACs. Significant positive correlations (r > 0.3) between the medium- and long-chain ACs (MCACs and LCACs) and symptoms (CHF NYHA functional class (FC); r = 0.31-0.39; p < 0.05); negative correlation (r = -0.31-0.34; p < 0.05) between C5-OH and FC was revealed. Positive correlations of MCACs and LCACs (r = 0.31-0.48; p < 0.05) with the left atrium size and volume, the right atrium volume, right ventricle, and the inferior vena cava sizes, as well as the pulmonary artery systolic pressure level were shown. A negative correlation between C18:1 and left ventricular ejection fraction (r = -0.31; p < 0.05) was found. However, a decrease in levels compared to referent values of ACs with medium and long chain lengths was 50% of the CHF-CHD cohort. Carnitine deficiency was found in 6% and acylcarnitine deficiency in 3% of all patients with chronic heart disease., Conclusions: ACs may be used in assessing the severity of the clinical manifestations and MR. ACs are an important locus to study in terms of altered metabolic pathways in patients with CHF of ischemic etiology and SD. Further larger prospective trials are warranted and needed to determine the potential benefits to treat patients with CV diseases with aberrate AC levels.
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- 2023
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8. The Effect of COVID-19 on Long-Term Cardiac Function in Patients With Chronic Heart Failure.
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Ageev AA, Kozhevnikova MV, Emelyanov AV, Krivova AV, Shumskaya YF, Musaeva LM, Popova LV, Naymann YI, Abdullaeva GB, Privalova EV, and Belenkov YN
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- Male, Female, Humans, Stroke Volume, Chronic Disease, Ventricular Function, Left, COVID-19 complications, Heart Failure diagnosis, Heart Failure epidemiology
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Aim To evaluate functional changes in the heart in the long-term following COVID-19 in patients with chronic heart failure (CHF).Material and methods Case reports of 54 patients aged 69.1±9.7 years who had COVID-19 from January 2021 through January 2022 and had been previously diagnosed with NYHA functional class II-III CHF were studied. Two comparison groups were isolated: HF with LV EF >50 % (n=39) and <50 % (n=15). Echocardiography was used to evaluate changes in LV EF and pulmonary artery systolic pressure (PASP) 5-6 months following COVID-19.Results In all CHF patients after COVID-19 at 5.8 months on average, LV EF decreased (median difference, 2.5 %; 95 % confidence interval (CI): 6.99×10-5- 4.99) and PASP increased (median difference, 8 mm Hg; 95 % CI: 4.5-12.9). In the HF group with LV EF <50 %, the decrease in EF was greater than in the group with LV EF >50 % (6.9 and 0.7 %, respectively; p=0.037); furthermore, the CHF phenotype did not influence the change in PASP (p=0.4). The one-factor regression analysis showed that the dynamics of LV EF decrease was significantly influenced by the baseline decrease in LV EF, whereas the change in PASP was influenced by the dynamics of LV EF decrease, presence of dyslipidemia, and statin treatment. Furthermore, the multifactorial analysis showed that prognostically significant factors for long-term changes in LV EF following COVID-19 were male gender (odds ratio (OR), 5.92; 95 % CI: 1.31-26.75; p=0.014), LV EF at baseline <50 % (OR, 0.88; 95 % CI: 0.8-0.96; p<0.001); changes in PASP depended on the presence of dyslipidemia (OR, 0.08; 95 % CI: 0.01-0.84; p=0.018).Conclusion This study showed that COVID-19 in the long term can influence the course of CHF; in this process, HF patients with EF <50 % have progression of systolic dysfunction and PASP, whereas patients with EF >50 % have an isolated increase in PASP.
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- 2022
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9. Comparative analysis of tryptophan and downstream metabolites of the kynurenine and serotonin pathways in patients with arterial hypertension and coronary artery disease.
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Kozhevnikova MV, Krivova AV, Korobkova EO, Ageev AA, Shestakova KM, Moskaleva NE, Appolonova SA, Privalova EV, and Belenkov YN
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- Humans, Kynurenine metabolism, Tryptophan metabolism, Kynurenic Acid metabolism, Serotonin metabolism, Hydroxyindoleacetic Acid, Quinolinic Acid, Coronary Artery Disease complications, Coronary Artery Disease diagnosis, Hypertension complications, Hypertension diagnosis, Atherosclerosis complications, Atherosclerosis diagnosis
- Abstract
Aim To compare serum concentrations of tryptophane (Trp) and its metabolites in subjects with no cardiovascular disease (CVD) and patients with СVD, including arterial hypertension (AH) and ischemic heart disease (IHD).Material and methods This study included 131 participants; 58 participants (11 of them with documented peripheral atherosclerosis) were included into the AH group, 46 participants were included into the IHD group, and 27 participants with no signs of CVD were included into the control group. Plasma concentrations of Trp and its metabolites were measured by high-performance liquid chromatography in combination with a triple quadrupole analyzer.Results Comparison of the three study groups revealed significant differences in concentrations of Trp (р=0.029), kynurenine (p<0.001), kynurenine/Trp ratio (p<0.001), quinolinic acid (р=0.007), kynurenic acid (р=0.003), serotonin (p<0.001), and 5‑hydroxyindoleacetic acid (5‑HIAA) (р=0.011). When the AH group was subdivided into subgroups without and with documented peripheral atherosclerosis, the intergroup differences remained for concentrations of kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, serotonin, and 5‑HIAA. Also, correlations were found between concentrations of Trp metabolites and laboratory and instrumental data, primarily inflammatory markers. Conclusion Analysis of serum concentrations of Trp and its metabolites in CVD patients showed increases in kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, and 5‑HIAA along with decreases in concentrations of Trp and serotonin in the groups of AH, AH with documented peripheral atherosclerosis, and IHD.
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- 2022
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10. The Prognostic Value of Neuregulin-1β in Heart Failure Patients With Preserved Ejection Fraction.
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Zhbanov KA, Shchendrygina AA, Salakheeva EY, Sokolova IY, Agadzhanyan AA, Zheleznykh EA, Zektser VY, Privalova EV, and Belenkov YN
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- Aged, Biomarkers, Female, Humans, Male, Middle Aged, Natriuretic Peptide, Brain, Neuregulin-1, Peptide Fragments, Prognosis, Prospective Studies, Stroke Volume, Ventricular Function, Left, Heart Failure diagnosis
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Aim To determine the neuregulin-1β concentration in patients with chronic heart failure with preserved ejection fraction (HFpEF) and the association of this biomarker with the functional status of patients, echocardiographic parameters of the structural and functional condition of the heart, and the risk of unfavorable outcome.Material and methods This observational, prospective study included 47 patients with HFpEF; 32 (68%) of them were females. Mean age was 70 [66-77] years, EF was 57 [56; 58] %. The group of healthy volunteers consisted of 40 people; 32 (55 %) of them were females; mean age was 56 [53-61] years. For all patients, the functional status was evaluated (6-min walk test, 6MWT); standard echocardiography (EchoCG) was performed; and concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and neuregulin-1β were measured. The follow-up period was two years. Cases of cardiovascular (CV) death and hospitalizations for decompensated chronic heart failure (CHF) were recorded.Results Median concentration of neuregulin-1β was 0.969 [0.348; 1.932] ng/ml in the HFpEF group, which was significantly higher than 0.379 [0.195; 0.861] ng/ml in the group of healthy volunteers (р=0.003). Significant correlations between the neuregulin-1β concentration and the distance walked in 6MWT or with EchoCG parameters of left ventricular diastolic function were not found. Mean observation time was 456 [244; 730] days. 21 outcomes were observed, including 2 CV deaths and 19 hospitalizations for CHF. Patients with high concentrations of neuregulin-1β (≥Me) had a greater frequency of hospitalizations for CHF (Log-rank, p=0.046) and a higher risk of this outcome (risk ratio, 1.30; 95 % confidence interval, 1.01-1.66; p=0.037).Conclusion Patients with HFpEF had increased concentrations of neuregulin-1β. High levels of neuregulin-1β were associated with a higher risk of hospitalization for decompensated CHF.
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- 2022
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11. Relationship Between Markers of the Acute Phase of Inflammation, Parameters of Blood Lipid Composition and Intracardiac Hemodynamics During Chemotherapy in Patients With Multiple Myeloma.
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Kardanova SA, Kirichenko YY, Bochkarnikova OV, Antyufeeva ON, Kochkareva YB, Vinogradova OY, Privalova EV, Ilgisonis IS, and Belenkov YN
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- Biomarkers, Bortezomib adverse effects, Cardiotoxicity diagnosis, Cardiotoxicity etiology, Cyclophosphamide therapeutic use, Dexamethasone therapeutic use, Hemodynamics, Humans, Inflammation, Lipids, Lipoproteins, LDL, Pilot Projects, Triglycerides therapeutic use, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Multiple Myeloma pathology
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Aim To evaluate in a pilot study time-related changes in the clinical state, indexes of the acute phase of inflammation, parameters of blood lipid profile, intracardiac hemodynamics, and disorders of cardiac rhythm/conduction in patients who are not candidates for autologous hemopoietic stem cell transplantation, during three bortezomib-containing chemotherapy courses (VCD) followed by a correlation analysis.Material and methods This pilot study included 20 patients diagnosed with myeloma, who were not candidates for autologous hemopoietic stem cell transplantation and who had undergone three courses of VCD chemotherapy (bortezomib, cyclophosphamide and dexamethasone). In addition to mandatory examinations, measurement of blood lipid profile, transthoracic echocardiography (EchoCG), and 24-h Holter electrocardiogram (ECG) monitoring were performed for all participants before and after a specific therapy.Results Following three bortezomib-containing courses of chemotherapy, patients of the study group had significant increases in the neutrophil-lymphocyte ratio (NLR) (1.6±0.2 and 2.5±0.4; р=0.05), cholesterol concentration (4.8±1.1 and 5.6±1.1 mmol/l, р=0.05), and low-density lipoprotein concentration (2.8±0.4 and 3.5±0.8 mmol/l, р=0.02). In comparing the changes in parameters of intracardiac hemodynamics, criteria for genuine cardiotoxicity were not met, however, a tendency to emergence/progression of myocardial diastolic dysfunction was noted. No clinically significant disorders of cardiac rhythm/conduction were observed. The correlation analysis performed prior to the start of chemotherapy, showed significant strong, direct correlations between the C-protein concentration and left atrial (LA) volume (r=0.793; p=0.006), right atrial (RA) volume (r=0.857; p=0.002), left ventricular (LV) end-diastolic dimension (EDD) (r=0.589; p=0.043), and LV end-diastolic volume (EDV) (r=0.726; p=0.017). Following the specific treatment, significant, medium-power and strong correlations were found between NLR and EDV (r= -0.673; p=0.033), NLR and end systolic volume (ESV) (r= -0.710; p=0.021), respectively. Significant direct correlations were found between the bortezomib dose per one injection and the serum concentration of triglycerides following the treatment (r=0.78; p=0.05); a single bortezomib dose and parameters of intracardiac hemodynamics: LA (r=0.71; p=0.026), RA (r=0.74; p=0.014), EDD (r=0.837; p=0.003), EDV (r=0.749; p=0.013), ESV (r=0.553; p=0.049).Conclusion For the first time, a comprehensive evaluation was performed in patients with multiple myeloma, including the dynamics of blood lipid profile, intracardiac hemodynamics and disorders of cardiac rhythm/conduction during bortezomib-containing antitumor therapy, with an analysis of correlation with levels of acute inflammation phase markers. Although in the observation window for genuine cardiotoxicity, clinically significant cardiovascular complications were not detected, the found correlations may evidence a potential role of systemic inflammation activity in myocardial remodeling in the studied patient cohort.
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- 2022
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12. Case Report: AL Amyloidosis Severe Restrictive Cardiomyopathy Associated With Multiple Myeloma-Diagnostic Difficulties.
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Kirichenko YY, Ilgisonis IS, Nakhodnova ES, Sokolova IY, Bochkarnikova OV, Kardanova SA, Lyapidevskaya OV, Privalova EV, Ershov VI, and Belenkov YN
- Abstract
Background: Cardiac AL amyloidosis as a complication of multiple myeloma (MM) is a formidable life-threatening condition. The first-line therapy for both MM and systemic AL amyloidosis is proteasome inhibitors (PIs). Unfortunately, the use of PIs may lead to cardiovascular toxicity development, which requires specific cardio-oncology supervision., Case Report: A 57-year-old woman was admitted to a university hospital with clinical manifestation of progressive chronic heart failure. The patient had hypertension and no history of diabetes mellitus, myocardial infarction (MI), stroke, and arrhythmias. After a series of laboratory and instrumental examination methods, MM complicated by cardiac AL amyloidosis was proved. Upon specific cardio-oncology examination (NT-proBNP 4,274 pg/ml), ECHO showed systolic dysfunction, motion abnormalities in LV basal and middle segments, and a typical depositional myocardium pattern ("luminescence"); cardiac MRI revealed restrictive cardiomyopathy and specific hyperenhancement of the ventricles and atria; 24-h ECG showed QS-pattern in leads V1-V3 and unstable ventricular tachycardia (VT) paroxysms. Cardio-oncology consultation showed baseline cardiovascular risk was very high (≥20%), and cardioprotective therapy [iACE/ARBs, beta-blockers (BB), statins] was administered. The patient underwent VCD (bortezomib; cyclophosphamide; dexamethasone) chemotherapy (CMT) program. By the time of publication, the patient had received four CMT courses with a positive oncohematological and cardiovascular effect., Conclusion: In this clinical case, we described a complication of MM, which was rare according to the severity and manifestation with restrictive cardiomyopathy due to secondary cardiac amyloidosis. The case's features were difficulties in verifying the underlying disease and its own complication, and the complexity of patient management according to modern principles of cardio-oncology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kirichenko, Ilgisonis, Nakhodnova, Sokolova, Bochkarnikova, Kardanova, Lyapidevskaya, Privalova, Ershov and Belenkov.)
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- 2022
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13. Characteristic of cardiovascular status and intracardiac hemodynamics in patients with multiple myeloma before the start of antitumor therapy.
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Kardanova SA, Ilgisonis IS, Ershov VI, Privalova EV, and Belenkov YN
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- Heart, Hemodynamics, Humans, Cardiovascular Diseases etiology, Cardiovascular Diseases prevention & control, Cardiovascular System, Multiple Myeloma complications, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
- Abstract
Aim: assessment of risk factors, cardiovascular status and intracardiac hemodynamics in patients with multiple myeloma before the start of specific antitumor therapy. Materials and methods: The study included 2 equal groups of patients: the first group - 25 patients with a newly diagnosed diagnosis of multiple myeloma (MM), the comparison group - 25 patients with proven cardiovascular diseases (CVD) (hypertension (HD) and coronary heart disease (CHD)). All patients included in the study underwent standard laboratory diagnostics, instrumental research methods (ECG, Echo-KG, 24-hour Holter monitoring); proven CVD risk factors were also evaluated. Results: When comparing the two groups, it was reliably shown that the state of CVD in patients with MM is comparable to that in patients with proven CVD. In patients from the main group, were revealed significant positive correlations of average strength between indicators of systemic inflammation, the lipid spectrum and intracardiac hemodynamics: between the levels of CRP and triglycerides (r=0,415, p<0,05); between the values of CRP and LDL (r=0,345, p=0,09); CRP and LA volume (r=0,434, p<0,05); CRP and final diastolic volume (r=0,30, p<0,05). At the beginning, a high risk of developing CV- events in patients with MM may be due to cardiac remodeling associated with the activity of systemic inflammation., Conclusion: in view the use of potentially cardiovasculartoxicity drugs for the treatment of multiple myeloma, the assessment of the CV status and consultation with a cardiologist/cardiologist with the selection of the necessary therapy should be obligatory step before starting specific treatment.
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- 2022
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14. Possible pathway for heart failure with preserved ejection fraction prevention and treatment: the angiotensin-converting enzyme inhibitor effect on endothelial function in comorbid patients.
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Safonova JI, Kozhevnikova MV, Danilogorskaya YA, Zheleznykh EA, Ilgisonis IS, Privalova EV, Khabarova NV, and Belenkov YN
- Subjects
- Angiotensin-Converting Enzyme Inhibitors, Humans, Prognosis, Stroke Volume, Ventricular Function, Left, Heart Failure drug therapy
- Abstract
Aim To evaluate the effect of perindopril on the endothelial function and levels of endothelial dysfunction markers in groups of patients with heart failure with preserved (HFpEF) and mid-range (intermediate) left ventricular ejection fraction (HFmrEF).Material and methods 40 patients with HFpEF (n=20) and HFmrEF (n=20) were evaluated. At baseline, parameters of the morpho-functional state of large blood vessels and of microvessels were evaluated with photoplethysmography, and levels of E-selectin and endothelin-1 (ET-1) were measured. The patients were prescribed perindopril, and after 12 months of treatment, photoplethysmographic parameters and endothelial dysfunction markers were determined again.Results After 12 months of the perindopril treatment, improvements in the endothelial function of both large blood vessels and microvessels were noted. The phase shift increased from 10.1 to 10.9 ms in the HFpEF group (р=0.001) and from 8.35 to 9.65 ms in the HFmrEF group (р=0.002). Furthermore, the occlusion index increased from 1.45 to 1.75 in patients with HFpEF (р=0.004) and from 1.5 to 1.75 in patients with HFmrEF (р=0.010). The Е-selectin concentration decreased in both groups, from 57.25 to 42.4 ng/ml (р=0.00008) and from 40.5 to 35.7 ng/ml (р=0.010) in patients with HFpEF and HFmrEF, respectively. The ET-1 concentration decreased from pg/ml (р=0.010) in patients with HFpEF whereas in patients with HFmrEF, there was no significant change in the ET-1 concentration after 12 months of the perindopril treatment.Conclusion At 12 months, the endothelial function improved and E-selectin and ET-1 levels decreased in patients with HFpEF and HFmrEF.
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- 2022
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15. [Assessment of the structural and functional state of blood vessels in patients with hypertrophic cardiomyopathy].
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Bogatyreva FM, Kaplunova VRY, Kozhevnikova MV, Shakaryants GA, Khabarova NV, Privalova EV, and Belenkov YN
- Subjects
- Adult, Aged, Capillaries, Echocardiography, Electrocardiography, Humans, Male, Microscopic Angioscopy, Middle Aged, Cardiomyopathy, Hypertrophic diagnosis
- Abstract
Aim To evaluate the structural and functional condition of the vasculature using fingertip photoplethysmography and computerized videocapillaroscopy in patients with hypertrophic cardiomyopathy (HCMP).Material and methods The study included patients with HCMP (n=48; 28 (57 %) men; age, 54.3±13.6 years) and healthy volunteers (control group, n=33, 15 (45 %) men; age, 58.2±8.8 years). Standard laboratory and instrumental examination (blood count and biochemistry, electrocardiography, echocardiography, Holter electrocardiogram monitoring) were performed for all HCMP patients. The condition of vascular wall at various levels of the vasculature was evaluated by fingertip photoplethysmography (apparatus Angioscan-01) and computerized nail-fold videocapillaroscopy (apparatus Capillaroscan-01). The photoplethysmography study analyzed structural parameters, including the arterial wall stiffness index (aSI) of large blood vessels and the resistance index (RI) of small muscular arteries. Endothelial dysfunction was evaluated by the occlusion index (OI) and phase shift (PS). The capillaroscopy study assessed structural parameters, including the resting capillary density (rCD) and the capillary density following venous occlusion (voCD), and functional parameters, including the percentage of perfused capillaries (PPC), the percentage of restored capillaries (PRC), and the capillary density after the reactive hyperemia test (rhCD).Results The study showed increases in aSI (8.8 [6.8; 12.2] and RI (32.5 [17.4; 47.9] in the HCMP group. The OI was significantly lower in the HCMP group (1.3 [1.1; 1.5]) than in the control group (1.8 [1.5; 2.7], р<0.001). Also, PS values were significantly decreased in the HCMP group (4.4 [2.3; 8.6]) compared to the control group (8.4 [5.1; 12.1]. p=0.018). Disorders of structural and functional capillary indexes were observed in HCMP patients compared to the control group; rCD and voCD were decreased in the HCMP group (60 [52.6; 68] and 88 [75; 90], respectively) compared to the control group (75.8 [60; 87] and 90 [73; 101]), however, no intergroup difference reached a statistical significance. The rhCD, PPC, and PRC values were decreased in the HCMP group (66.3 [55; 72], 86.7 [70.9; 104.2] and 1.7 [-6.95; 20.3], respectively) compared to the control group (86 [68.6; 100], 103 [96; 114] and 18.4 [8.1; 27.4], respectively); PPC and PRC values were significantly different (р<0.005 and p<0.004, respectively).Conclusion In patients with HCMP, fingertip photoplethysmography and computerized videocapillaroscopy showed increased wall stiffness in both large blood vessels and microvasculature, pronounced endothelial dysfunction, and decreases in capillary density and percentage of restored capillaries following respective tests.
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- 2021
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16. Endothelial dysfunction and inflammation in patients with non-obstructive coronary arteries.
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Pakhtusov NN, Iusupova AO, Privalova EV, Khabarova NV, and Belenkov YN
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- Humans, Inflammation, Coronary Artery Disease, Hyperemia, Myocardial Ischemia
- Abstract
Aim To determine levels of markers for endothelial dysfunction and inflammation, endothelin-1, E-selectin, and tumor necrosis factor α (TNF-α) in patients with ischemic heart disease (IHD) and non-obstructive and obstructive coronary artery (CA) disease.Material and methods This study included 32 patients with verified IHD and non-obstructive (main group, n=19) and obstructive (comparison group, n=13) CA disease. Endothelial dysfunction was diagnosed by photoplethysmography and videocapillaroscopy. Serum concentrations of endothelin-1, E-selectin, and TNF- α were measured in all patients.Results Patients with non-obstructive CA disease showed a tendency towards more pronounced endothelial dysfunction (alternative stiffness index, 7.8 m /s [6.35; 9.08]; reflection index, 36.95 % [23.4; 52.65]; capillary density following reactive hyperemia, 54.33 cap /mm2 [48.92; 75.83]; capillary density following venous occlusion, 74.33 cap /mm2 [67.83; 93.00]) compared to the comparison group (alternative stiffness index, 9.05 m/s [7.08; 10.58]; reflection index, 28.25 % [23.35; 53.75]; capillary density following reactive hyperemia, 66.83 cap /mm2 [50.83; 78.67]; capillary density following venous occlusion, 87.0 cap /mm2 [77.58; 78.67]), although statistically significant differences were not found. Concentration of endothelin-1 was significantly higher in the IHD group with non-obstructive CA disease (0.45 ng/ml [0.28;0.65]) compared to patients with CA atherosclerotic stenosis (0.35 ng/ml [0.25; 0.38], p=0.035). Concentrations of E-selectin did not significantly differ between the groups (main group, 21.1 ng/ml [18.45; 35.03]; comparison group, 28.55 ng/ml [19.08; 35.01], p=0.29). In both groups, concentrations of TNF-α did not exceed the lower threshold of sensitivity (<2.3 pg/ml).Conclusion Endothelial dysfunction and increased endothelin-1 in patients with non-obstructive CA disease along with inflammation may additionally contribute to the pathogenesis of IHD in the absence of hemodynamically significant CA stenoses. Too low level of TNFα in both groups prevented us from using it as a diagnostic marker. Further study is needed that would include a greater number of patients and a search for alternative markers.
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- 2021
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17. [Circulating Neuregulin-1 and Chronic Heart Failure with Preserved Ejection].
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Shchendrigina AA, Zhbanov KA, Privalova EV, Iusupova AO, Bytdaeva AH, Danilogorskaya YA, Zheleznykh EA, Suvorov AY, Zektser VY, Mnatsakanyan MG, Lyapidevskaya OV, Khabarova NV, Naymann YI, Belenkov YN, and Starostina ES
- Subjects
- Humans, Myocardium, Neuregulin-1, Stroke Volume, Ventricular Remodeling, Cardiomyopathies, Heart Failure drug therapy
- Abstract
Chronic heart failure (CHF) with preserved ejection fraction (CHFpEF) is an unsolved, socially relevant challenge since it is associated with a high level of morbidity and mortality. Early markers for this pathology are unavailable, and therapeutic approaches are undeveloped. This necessitates extensive studying the mechanisms of CHFpEF to identify therapeutic targets. According to current notions, systemic inflammation and endothelial dysfunction play an important role in the pathogenesis of CHFpEF. These processes induce the development of myocardial fibrosis and impairment of cardiomyocyte relaxation, thereby resulting in diastolic dysfunction and increased left ventricular (LV) filling pressure. Neuregulin-1 (NRG-1) is a paracrine growth factor and a natural agonist of ErbB receptor family synthesized in the endothelium of coronary microvessels. The NRG-1 / ErbB4 system of the heart is activated at early stages of CHFpEF to enhance the cardiomyocyte resistance to oxidative stress. Preclinical and clinical (phases II and III) studies have shown that the recombinant NRG-1 therapy results in improvement of myocardial contractility and in LV reverse remodeling. Results of recent studies suggest possible anti-inflammatory and antifibrotic effects of NRG-1, which warrants studying the activity of this system in patients with CHFpEF.
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- 2020
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18. Relationship between the plasma acylcarnitine profile and cardiometabolic risk factors in adults diagnosed with cardiovascular diseases.
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Kukharenko A, Brito A, Kozhevnikova MV, Moskaleva N, Markin PA, Bochkareva N, Korobkova EO, Belenkov YN, Privalova EV, Larcova EV, Ariani A, La Frano MR, and Appolonova SA
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- Adult, Aged, Cardiometabolic Risk Factors, Cardiovascular Diseases metabolism, Carnitine blood, Carnitine metabolism, Female, Humans, Male, Middle Aged, Cardiovascular Diseases blood, Cardiovascular Diseases diagnosis, Carnitine analogs & derivatives
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The development of cardiovascular diseases (CVDs) is often asymptomatic. Identification of initial indicators of cardiometabolic disruption may assist in its early detection. The objective was to determine the relationships between plasma acylcarnitines (ACs) and cardiometabolic risk factors in adults with and without CVDs. The AC profile in human plasma of healthy controls [non-CVD group, n = 13)] and individuals diagnosed with CVDs (CVD group, n = 34) were compared. A targeted analysis of 29 ACs was performed using flow injection analysis-tandem mass spectrometry. There were significant direct correlations (p < 0.05) between ACs and cardiometabolic risk factors. Comparing the groups after adjustment for covariates, showed that the ACs that were best differentiated (p < 0.05) between the two groups and that presented "good" diagnostic accuracy were carnitine [30.7 (25.5-37.7) vs. 37.7 (32.3-45.0) µM], the short-chain ACs: acetylcarnitine [8.9 (7.4-10.2) vs. 11.9 (9.2-14.4) µM] and isovalerylcarnitine [0.10 (0.06-0.13) vs. 0.13 (0.10-0.16) µM], and the medium-chain ACs: hexanoylcarnitine [0.04 (0.03-0.05) vs. 0.06 (0.05-0.07) µM] and decenoylcarnitine [0.18 (0.12-0.22) vs. 0.22 (0.17-0.32) µM]. This assessment contributes to the identification of the unique metabolic features exhibited in association with cardiometabolic risk in adults diagnosed with CVD. The altered metabolites have the potential to be used as biomarkers for early detection of CVD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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19. [Vasculotoxicity of Chemotherapy: Assessment оf Endothelial Dysfunction Biomarkers' Levels in Gastric Cancer Patients].
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Kirichenko YY, Belenkov YN, Privalova EV, Naymann YI, Gitel EP, Novikova OV, and Ilgisonis IS
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- Biomarkers, Echocardiography, Humans, Hypertension chemically induced, Stomach Neoplasms drug therapy
- Abstract
Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р<0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р<0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р>0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= -0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.
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- 2020
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20. [E-Selectin as a Marker of Endothelial Dysfunction in Patients with Coronary Artery Disease Including Those with Type 2 Diabetes Mellitus].
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Zhito AV, Iusupova AO, Kozhevnikova MV, Shchendrygina AA, Privalova EV, and Belenkov YN
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- Biomarkers, Humans, Coronary Artery Disease complications, Diabetes Mellitus, Type 2 complications, E-Selectin blood, Myocardial Ischemia
- Abstract
Aim To determine concentration of the endothelial dysfunction (ED) marker, serum E-selectine, in patients with ischemic heart disease (IHD) in combination with type 2 diabetes mellitus (DM) and without DM.Material and methods The study included 60 IHD patients; 31 of them also had type 2 DM. E-selectin was measured in blood of all patients. In addition, a comprehensive evaluation of the morpho-functional condition of large blood vessels and microvasculature (MV) was performed by laser finger plethysmography (LFP) and nailfold computed videocapillaroscopy (CVC).Results Concentration of E-selectin was increased in IHD patients with type 2 DM (35.2 [29.0; 47.35] ng / ml vs. 31.7 [20.85; 36.68] ng / ml for IHD patients; p=0.028). A significant (p=0.018 and 0.016, respectively) decrease in the phase shift was observed in IHD patients with type 2 DM ( - 4.4 [ - 8.7; - 2.45] ms) compared to IHD patients ( - 1.9 [ - 3.95; - 0.38] ms). The capillary density evaluated in the venous occlusion test was reduced in IHD patients with type 2 DM (67.70 [57.83; 80.69]) compared to IHD patients (80.80 [69.05; 99.08]).Conclusion The signs of ED observed in patients of both groups were more pronounced in IHD patients with type 2 DM.
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- 2020
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21. [Focus on the Myocardial Hypertrophy from the Perspective of Transcriptomics and Metabolomics].
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Shakaryants GA, Kozhevnikova MV, Kaplunova VY, Privalova EV, Lishuta AS, Korobkova EO, and Belenkov YN
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- Humans, Metabolomics, Transcriptome, Cardiovascular Diseases, Hypertrophy
- Abstract
This review presents major directions in studies of myocardial hypertrophy from the aspect of transcriptomics and metabolomics. Understanding of trigger mechanisms of myocardial hypertrophy will permit transition from basic studies to individualized clinical application of innovative technologies in the treatment of heart diseases, such as targeted therapy. At the present time, methods have been developed for diagnostics and prediction of cardiovascular diseases based on the metabolomic profiling and the evaluation of microRNA expression. Progress in studying molecular and genetic processes underlying the development of cardiovascular diseases may provide invaluable information for clinical cardiology.
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- 2020
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22. [The effect of chemotherapy on endothelial function and microcirculation in patients with gastric cancer].
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Kirichenko YY, Ilgisonis IS, Belenkov YN, Privalova EV, Naymann YI, Lyamin AM, Kozhevnikova MV, Korobkova EO, Khabarova NV, and Ogorodnikov NV
- Subjects
- Capillaries, Humans, Microcirculation, Microscopic Angioscopy, Stomach Neoplasms drug therapy, Vascular Stiffness
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Objective: To evaluate and study the dynamics of endothelial dysfunction instrumental indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer (adenocarcinoma) before and after chemotherapy; compare it with the results obtained from healthy volunteers and patients with cardio-vascular diseases., Materials and Methods: The study included 65 people: 25 healthy volunteers, 15 patients with known cardio-vascular diseases (CVD) and 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage 2-4 who underwent surgical treatment followed by chemotherapy according to the FOLFOX, XELOX, and XP regimes. For non-invasive assessment of the vascular wall's state of large vessels and microcirculation, all patients in the main group underwent computer nailfold capillaroscopy and finger photoplethysmography before chemotherapy and within a month after the completion of the last course. For healthy volunteers and patients with CVD, the above studies were performed once during the examination., Results: The data obtained indicate a significant increase in the reflection index of small muscle arteries (RI) and the stiffness index of large conducting arteries (aSI) during chemotherapy. In cancer patients, even before the treatment, endothelial dysfunction was detected, which significantly worsened after treatment (occlusion index (IO) before and after chemotherapy 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p<0.0002, respectively). Significant differences in the compared indices in cancer patients and CVD group were revealed only after chemotherapy. Significant structural and functional disorders of capillaries were noted in the studied groups, which also worsened during chemotherapy in the main group (density of the capillary network at rest 43.23cap/mm2 vs. 42.19cap/mm2, p <0.01, respectively; density of the capillary network after the reactive hyperemia test 46.77cap/mm2 vs. 44.11cap/mm2, p<0,02, respectively)., Conclusion: In this study, for the first time, the dynamics of endothelial dysfunction indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer were studied, and a reliable increasing of these changes was proved during chemotherapy. The results indicate the need for a further search for accurate and effective methods of identifying early signs of close and distant vasculotoxicity, the development of individual prevention programs in order to significantly reduce the risk of cardiovascular events during and after chemotherapy.
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- 2020
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23. [Comorbidity of Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: Place of Therapy with Modern β-Adrenoblockers].
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Belenkov YN, Tsvetkova OA, Privalova EV, An GV, Ilgisonis IS, and Voronkova OO
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- Adrenergic beta-Antagonists, Comorbidity, Humans, Cardiovascular Diseases epidemiology, Heart Failure, Pulmonary Disease, Chronic Obstructive epidemiology
- Abstract
Chronic obstructive pulmonary disease (COPD) is the fourth largest cause of worldwide mortality. Presence of comorbidities is registered in 96% of COPD patients. The most important of these are cardiovascular diseases (coronary artery disease, arterial hypertension, chronic heart failure), which contribute to COPD patients' mortality in every third case. COPD and cardiovascular diseases have common risk factors and pathogenesis mechanisms. Cardioselective beta-blockers reduce morbidity risk and frequency of COPD exacerbation, are effective and safe in treatment of COPD patients.
- Published
- 2019
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24. [Markers of Vascular Wall Fibrosis Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinases-1 in Patients with Ischemic Heart Disease with and without Concomitant Type-2 Diabetes Mellitus].
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Belenkov YN, Privalova EV, Iusupova AO, and Zhito AV
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- Diabetes Mellitus, Type 2, Humans, Matrix Metalloproteinase 9, Metalloproteases, Tissue Inhibitor of Metalloproteinase-1, Myocardial Ischemia
- Abstract
The prevalence of ischemic heart disease (IHD) and diabetes mellitus type 2 (DM type 2) is permanently increasing both worldwide and in theRussian Federation. That is why studies of mechanisms of pathogenesis of both diseases is continuing for prevention of complications and mortality. DM type 2 contributes a lot to deterioration of IHD. One of pathogenetic features these two pathologies share is pronounced blood vessel wall fibrosis. In this review we present analysis of studies devoted to the determination of the role of metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 indevelopment of vascular wall fibrosis.
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- 2019
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25. Antihypertensive Efficacy of a Triple Fixed-Dose Combination of Perindopril, Indapamide, and Amlodipine: Clinical Effectiveness in Ambulatory Practice (Results of the PETRA Study).
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Privalova EV and Lishuta AS
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- Blood Pressure, Drug Combinations, Female, Humans, Male, Prospective Studies, Treatment Outcome, Amlodipine therapeutic use, Antihypertensive Agents therapeutic use, Hypertension drug therapy, Indapamide therapeutic use, Perindopril therapeutic use
- Abstract
Most patients with arterial hypertension (AH) for successful long-term blood pressure (BP) control require combination of antihypertensive drugs acting on various target organs. Accumulated experience shows that about 30 % of patients require combination therapy with 3 drugs from different pharmacological classes. Efficacy of BP control in real clinical practice with the use of various doses of perindopril, indapamide, and amlodipine as components of taken once-daily triple fixed combination was assessed in the 3-months prospective observational open-label PETRA study. In this study data of office BP measurements and 24-hour ambulatory BP monitoring (ABPM) were obtained from 11209 ambulatory patients (47.6 % women) with AH. Initial mean office BP (BPmoff) was 156.58±16.10 / 91.56±9.33 mm Hg, AH duration - 9.48±7.19 years. After switching to triple fixed dose combination of perindopril, indapamide, and amlodipine BPmoff decreased by 24.81±15.47 / 11.41±9.90 mm Hg (p<0.0001). Doses of perindopril, indapamide, and amlodipine in combination at the final visit were 5 / 1.25 / 5, 10 / 2.5 / 5, and 10 / 2.5 / 10 mg. 24-hour ambulatory BP monitoring (ABPM) was carried out in 76 patients. Mean 24-hour BP lowed from mean 155.51±17.43 / 85.28±11.48 down to 134.63±12.51 / 77.83±8.99 mm Hg (p<0.0001). Clinically relevant improvement of a number of parameters of metabolism occurred after 3 months of the study (in particular, lowering of levels of total and low-density lipoprotein cholesterol [-8.6 and - 11.4 %, respectively], triglycerides [-12,1 %], fasting blood glucose [-6.6 %]). Thus, results of the PETRA study confirmed 24-hour long antihypertensive efficacy of triple fixed dose combination of perindopril, indapamide, and amlodipine. This drug combination can present novel possibility in treatment of patients with AH who have not achieved target BP values on preceding dual combination therapy and fully corresponds with the single pill concept for formation of adherence to therapy.
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- 2018
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26. Combination Antihypertensive Therapy with Perindopril and Indapamide in Patients with Essential Hypertension: Effect on Endothelial and Cognitive Markers of Vascular Improvement.
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Zheleznykh EA, Danilogorskaya YA, Privalova EV, Belenkov YN, Schendrygina AA, Chekneva IS, Pavlov NA, and Tishman MI
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- Aged, Antihypertensive Agents administration & dosage, Antihypertensive Agents pharmacokinetics, Blood Pressure drug effects, Dose-Response Relationship, Drug, Drug Combinations, Female, Humans, Male, Middle Aged, Russia epidemiology, Treatment Outcome, Cognition drug effects, Endothelium, Vascular drug effects, Essential Hypertension diagnosis, Essential Hypertension drug therapy, Essential Hypertension epidemiology, Essential Hypertension psychology, Indapamide administration & dosage, Indapamide pharmacokinetics, Microcirculation drug effects, Perindopril administration & dosage, Perindopril pharmacokinetics
- Abstract
Introduction: The objective of this study was to assess the impact of a single-pill combination (SPC) of perindopril/indapamide (PER/IND) at full doses (10/2.5 mg) on endothelial and cognitive function as a clinical intermediate marker of vascular improvement., Methods: This open-label, uncontrolled, observational study enrolled 30 patients (20 females and 10 males) with grade II-III uncontrolled arterial hypertension (SBP/DBP ≥ 160/100 mmHg) and no evidence of cerebrovascular disease. All patients underwent assessment of macro- and microvascular endothelial function parameters at baseline and after 12 months of treatment with SPC PER/IND using photoplethysmography and video capillaroscopy. Cognitive function was assessed using the Montreal Cognitive Assessment scale (MoCA)., Results: All patients (mean age 60.06 ± 10.19 years) were at high risk for cardiovascular events: mean body mass index (BMI) 31.2 ± 3.9 kg/m
2 , 33% diagnosed with coronary artery disease angina class I, 30% with impaired glucose tolerance, and 7% with type 2 diabetes. Impaired endothelial function was observed at the both micro- and macrovascular levels. Endothelial function parameters improved after 12-month treatment with SPC PER/IND with an increase in occlusion index from 1.4 to 1.8 (P < 0.00005) and phase shift from 5.0 to 10.8 (P < 0.00001); all values achieved levels in the normal range. Resting capillary network density (CND) increased from 44.8 to 52 cap/mm2 (P < 0.00007), and CND after a venous occlusion test increased from 55 to 61 cap/mm2 (P < 0.006). Signs of cognitive impairment were present at baseline with a mean MoCA score of 23 (normal cognitive function score ≥ 26), but improved after 12-month treatment with a mean MoCA score of 27 (P< 0.0001). Treatment was well tolerated., Conclusion: SPC PER/IND at full doses for 12 months improves endothelial function, structural and functional parameters of the microcirculation, as well as cognitive function in patients with arterial hypertension at high cardiovascular risk., Funding: Les Laboratoires Servier.- Published
- 2018
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27. [Metabolomic Profiling of Patients With Cardiovascular Diseases].
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Belenkov YN, Privalova EV, Kozhevnikova MV, Korobkova EO, Ilgisonis IS, Kaplunova VY, SHakaryants GA, Appolonova SA, Kuharenko AV, Larcova EV, and Mesonzhik NV
- Subjects
- Biomarkers blood, Humans, Mass Spectrometry, Cardiovascular Diseases metabolism, Metabolomics
- Abstract
Cardiovascular diseases (CVD) are the main cause of death worldwide. A broad study of the pathogenetic mechanisms of the CVD onset and progression has led to understanding of the importance of endothelial dysfunction (ED) in these processes. During recent years intensive work has been conducted in the direction of searching for markers of ED. Metabolomics is an intensively advancing approach to early diagnostics of diseases. Metabolomic analysis based on mass spectrometry allows to study complete metabolic profiles and their deviations resulting from changes in expression of genes and RNA, protein activity, or environmental factors. Metabolomic analysis has already demonstrated significant results in the solving of different scientific and clinical problems. It appears to be a promising method for detecting early biomarkers of CVD. Various aspects of application of metabolomic profiling in the field of cardiovascular diseases are discussed in this article.
- Published
- 2018
28. [Vascular Complications Of Cancer Chemotherapy].
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Belenkov YN, Privalova EV, Kozhevnikova MV, and Kirichenko YY
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- Antineoplastic Agents therapeutic use, Arrhythmias, Cardiac chemically induced, Heart Failure chemically induced, Humans, Hypertension chemically induced, Incidence, Thrombosis chemically induced, Antineoplastic Agents adverse effects, Cardiovascular Diseases, Cardiovascular System drug effects, Neoplasms drug therapy
- Abstract
Development and use of new anticancer drugs has resulted in the improving of 5‑year survival rates in patients with cancer. However, many of the modern chemotherapies are associated with cardiovascular toxicities that increases cardiovascular risk in cancer patients, including hypertension, heart failure, thrombosis and thromboembolism, cardiomyopathy, and arrhythmias. These side effects limitation restrict treatment options and farther perspectives. With increasing use of modern chemotherapies and prolongation of the cancer patients survival, the incidence of cardiovascular disease in this patient population will continue to increase. Accordingly, careful assessment and management of cardiovascular risk factors in cancer patients by oncologists and cardiologists working together is essential for optimal care.
- Published
- 2018
29. [Hypertrophic Cardiomyopathy and Ischemic Heart Disease. Variants of Combination Pathology].
- Author
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Kaplunova VY, SHakaryants GA, Kozhevnikova MV, Ilgisonis IS, Privalova EV, Khabarova NV, Naymann YI, Belenkov YN, and Shakaryants VA
- Subjects
- Genetic Markers, Heart, Humans, Prognosis, Cardiomyopathy, Hypertrophic, Myocardial Ischemia
- Abstract
The issues of epidemiology and pathophysiology of hypertrophic cardiomyopathy (HCMP), as well as the search for its additional clinical-instrumental and genetic markers, environmental factors capable to influence the formation of its clinical variant and prognosis are subjects of great interest to the modern scientific community. Besides genetic markers of main neurohumoral systems, and morphofunctional parameters of intracardiac hemodynamics clinical course of the disease is influenced by a complex of concomitant pathology including ischemic heart disease (IHD), joining of which is possible in 10% of cases. IHD substantially aggravates course of HCMP and hampers selection of medical therapy. It should be noted that prognosis of primary hypertrophies is affected by episodes of ischemia of complex genesis and addition of IHD significantly increases risk of sudden death in these patients.
- Published
- 2017
30. [Effect of Combined Antihypertensive Therapy With Perindopril and Indapamide on Morpho-Functional Parameters of The Heart, Blood Vessels of Small and Medium Caliber in Patients With Essential Hypertension].
- Author
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Zheleznyh EA, Danilogorskaya YA, Privalova EV, Belenkov YN, Schendrygina AA, Pavlov NA, and Tishman MI
- Subjects
- Aged, Drug Therapy, Combination, Echocardiography, Essential Hypertension pathology, Essential Hypertension physiopathology, Female, Humans, Male, Microcirculation, Middle Aged, Antihypertensive Agents therapeutic use, Essential Hypertension drug therapy, Indapamide therapeutic use, Perindopril therapeutic use
- Abstract
Aim: to study effect of therapy with fixed combination of angiotensin-converting enzyme infibitor and diuretic on structural-functional parameters of the heart and vessels and cognitive function., Material and Methods: We included into this study 30 patients (20 women) with mean age 60.06+/-10.19 years, duration of hypertensive disease 14.7 (3; 32) years, body mass index 31.19+/-3.93 kg/m2, and without history of cerebrovascular diseases. Methods of investigation included clinical examination, measurement of parameters of hemodynamics, electro- and echocardiography. Vascular endothelial function and structural - functional state of finger skin capillary network was studied by photopletismography and video capillaroscopy, respectively. The state of cognitive sphere was evaluated with the help of the Montreal Cognitive Assessment (MoCA) test., Results: We noted improvement of endothelial function of middle caliber arteries and microcirculatory vascular bed (MCVB) (increase of occlusion index at the level of MCVB from 1.4 to 1.8, p<0.00005; increase of density of skin capillary network at rest from 45 to 52 kap/2, p<0.00007); improvement of cognitive function according to changes of MoCA test results (from 23 to 27, p<0,0001). There were no changes of lipid and carbohydrate metabolism, and electrolyte balance. Conclision. The use of fixed of perindopril+indopamide is combination characterized by good tolerability and high results.
- Published
- 2016
- Full Text
- View/download PDF
31. [Microvascular angina. Modern aspects of pathogenesis, diagnostics and treatment].
- Author
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Yusupova AO, Shendrygina AA, Privalova EV, and Belenkov YN
- Subjects
- Disease Management, Humans, Microvascular Angina diagnosis, Microvascular Angina etiology, Microvascular Angina physiopathology, Microvascular Angina therapy
- Abstract
Microvascular angina was included in the European guidelines on the management of patients with stable coronary artery disease in 2013. Topical aspects of etiology, pathogenesis, clinical course, diagnosis, and treatment of microvascular angina are discussed in this review.
- Published
- 2016
32. [Modern approaches to the problem of hypertrophic cardiomyopathy].
- Author
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Kaplunova VY, Shakar'yants GA, Kozhevnikova MV, Khabarova NV, Privalova EV, and Belenkov YN
- Subjects
- Disease Management, Humans, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic etiology, Cardiomyopathy, Hypertrophic physiopathology, Cardiomyopathy, Hypertrophic therapy
- Abstract
This review presents modern data about a hereditary disease of myocardium - hypertrophic cardiomyopathy. The main features of its epidemiology, pathophysiological changes in intracardiac hemodynamics, formation of main clinical symptoms of the disease and variants of its clinical course are considered in terms of modern concepts. Much attention is given to characteristics of the variants of the disease and understanding of the formation of its clinical picture of each of them for the choice of the strategy for the management of these patients.
- Published
- 2016
33. [Effect of 12-Months Therapy With Perindopril A on Structural-Functional State of the Microcirculatory Vascular Bed in Patients With Chronic Heart Failure].
- Author
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Belenkov YN, Privalova EV, Danilogorodskaya YA, Zheleznykh EA, Shchendrygina AA, Tishman MI, and Chekneva IS
- Subjects
- Aged, Chronic Disease, Female, Heart Failure physiopathology, Humans, Male, Middle Aged, Severity of Illness Index, Vasodilation drug effects, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Heart Failure drug therapy, Microcirculation drug effects, Perindopril therapeutic use
- Abstract
Background: Experimental and clinical data confirm that endothelial dysfunction (ED) of microvessels is one of mechanisms of progression of chronic heart failure (CHF)., Purpose: To assess the impact of 12-month treatment with perindopril A (5-10 mg/day) on structural and functional state of microcirculatory vascular bed in patients with CHF., Material and Methods: We included into this study 30 patients aged 45-70 years with NYHA class II-III CHF. All patients received perindopril A 5-10 mg/day for 12 months. For assessment of endothelial function we used test with reactive hyperemia. During this test we evaluated flow dependent vasodilation by photoplethysmography, and registered the state of skin capillary network by computer videocapillaroscopy. We also measured level of proinflammatory cytokines - von Willebrand factor, and -tumor necrosis factor (-TNF)., Results: After treatment with perindopril A 5 we observed improvement of microvascular endothelial function (occlusion index rose from 1.5 [1.2; 2.9] to 2.0 [1.7; 2.4], p=0.03), and of functional state of the finger skin capillary network (percentage of perfused capillaries rose from 88 [77; 95] to 95 [87; 97], p=0.05, percentage of recovered capillaries rose from 8 [4.5; 12.1] to 14.2 [9.3; 17.1], p=0.04). These effects were associated with significant lowering of (-TNF) level (from 6.58 [3.72, 10.3] to 3.35 [0.15; 6.33] g/L, p<0.01).
- Published
- 2015
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- View/download PDF
34. [Matrix metalloproteinases and hypertrophic cardiomyopathy].
- Author
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Privalova EV, Kaplunova VIu, Kozhevnikova MV, Khabarova NV, Shakar'iants GA, and Belenkov IuN
- Subjects
- Adult, Biomarkers metabolism, Female, Heart Ventricles metabolism, Heart Ventricles pathology, Heart Ventricles physiopathology, Humans, Male, Middle Aged, Polymorphism, Genetic, Prognosis, Statistics as Topic, Atrial Fibrillation etiology, Atrial Fibrillation genetics, Atrial Fibrillation physiopathology, Cardiomyopathy, Hypertrophic complications, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic genetics, Cardiomyopathy, Hypertrophic physiopathology, Matrix Metalloproteinase 3 genetics, Ventricular Remodeling genetics
- Abstract
Prognosis of patients with hypertrophic cardiomyopathy (HCMP) to a great extent is determined by clinical variant of the disease. As the system of matrix metalloproteinases (MMPs) plays an important role in development and progression of the processes of fibroformation and tissue remodeling polymorphisms of modifier genes regulating its components can influence clinical course of HCMP. Among possible markers of prognostication of the course of cardiovascular diseases the role of MMPs and their tissue inhibitors has been discussed. With the aim of studying effects of MMPs on the course of HCMP we conducted this investigation in which we included 58 patients and a group of healthy volunteers (control group) with comparable sex and age. In all participants (n=112) we determined polymorphism of MMP-3 - rs3025058 and markers of fibroformation (MMP-3, TIMP-1, TIMP-2, and collagen IV). We found that unfavorable allele variant MMP-3 1171 was associated with hypertrophy of interventricular septum. We also established that levels of TIMP-1 in the group of patients with HCMP were significantly lowered in comparison with those in control group. Concentration of marker MMP-3 was elevated in the group of patients with variant "atrial fibrillation" compared with groups of stable course and progressing course. We revealed medium degree reverse correlation between MMP-3 marker and thickness of left ventricular posterior wall and direct correlation of this parameter with coefficient of asymmetry. Polymorphism MMP-3 - 1171 produced an impact on the level of TIMP-1 marker. The data obtained by us confirm effect of the system of MMPs on formation of hypertrophic remodeling of the heart in HCMP.
- Published
- 2014
- Full Text
- View/download PDF
35. [Effect of 6-month therapy with perindopril A on structural-functional state of arterial vascular bed in patients with chronic heart failure].
- Author
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Belenkov IuN, Privalova EV, Danilogorskaia IuA, Zheleznykh EF, and Shchendrygina AA
- Subjects
- Aged, Brachial Artery drug effects, Brachial Artery physiopathology, Chronic Disease, Endothelium, Vascular physiopathology, Female, Heart Failure physiopathology, Humans, Hyperemia physiopathology, Male, Middle Aged, Vasodilation, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Endothelium, Vascular drug effects, Heart Failure drug therapy, Perindopril therapeutic use
- Abstract
Unlabelled: In patients with chronic heart failure (CHF) endothelial dysfunction of large vessels is an independent predictor of repeated hospitalizations because of CHF aggravation and cardiac death., Objective: To evaluate the effect of perindopril A (5-10 mg/day) on endothelial function of large vessels in patients with CHF., Material and Methods: The study included 30 patients with NYHA class II-III CHF aged 45-70 years. Patients took perindopril A 5-10 mg for 6 months. Patients underwent 24-h BP monitoring, assessment of endothelium vasodilation., Results: In the end of period of treatment hypotensive effect and improvement of endothelial function of large vessels were achieved. We observed increase of flow-mediated vasodilation (FMD) measured by high-frequency ultrasound of brachial artery after reactive hyperemia: FMD1 4.25 (3.9; 4.8) vs FMD2 6.8 (5.1; 7.4), p = 0.003) and enhancement of pulse wave amplitude estimated by photoplethysmography (shear phase - SF): SF1 6.62 (2.4; 8.7) vs SF2 7.36 (3.8; 10.2) (p = 0.003).
- Published
- 2014
- Full Text
- View/download PDF
36. [Renin-angiotensin-aldosterone system in hypertrophic cardiomyopathy].
- Author
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Kozhevnikova MV, Kaplunova VIu, Privalova EV, Khabarova NV, and Belenkov IuN
- Subjects
- Adult, Biomarkers blood, Female, Genes, Modifier, Genome-Wide Association Study, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Genetic, Prognosis, Severity of Illness Index, Angina Pectoris diagnosis, Angina Pectoris etiology, Angina Pectoris genetics, Angiotensin II blood, Cardiomyopathy, Hypertrophic, Familial complications, Cardiomyopathy, Hypertrophic, Familial diagnosis, Cardiomyopathy, Hypertrophic, Familial genetics, Cardiomyopathy, Hypertrophic, Familial metabolism, Cardiomyopathy, Hypertrophic, Familial physiopathology, Chymases genetics, Peptidyl-Dipeptidase A blood, Renin-Angiotensin System genetics, Ventricular Premature Complexes diagnosis, Ventricular Premature Complexes etiology, Ventricular Premature Complexes genetics
- Abstract
Keeping in mind an important role of renin-angiotensin aldosterone system (RAS) in developing of cardiac remodeling and fibrosis, genetic polymorphisms coding its components could have influence with clinical variants of the course. Biomarkers could appear predictors of adverse. To examine the contribution of the RAS to developing of different hypertrophic cardiomyopathy (HCM) clinical variants of the course we studied 58 patients with HCM and controls comparable by age and gender. All patients were genotyped of gene polymorphisms CMA1 A(-1903)G rs1800875, AGTM235T rs699, AGTR1 A1166C rs5186, CYP11B2-344 T/C rs1799998. Angiotensin-converting enzyme (ACE) and angiotensin II (AII) levels were measured in 40 patients with HCM and 39 controls. We found out that AII were significantly decreased in patients with HCM than in healthy controls. The positive correlation between AII and left ventricle posterior wall (LVPW) were detected. Severity of heart hypertrophy were associated with pejorative genotype of AGT M235T polymorphism and CMA1 A(-1903) polymorphism. Significant association between the AG genotype of CMA1 A(-1903) polymorphism and angina class II-III and ventricular extrasystole of high gradation was observed. Our data not only support the hypothesis that RAAS polymorphisms may influence phenotype, but also allow for create new approaches to possible predicting adverse outcomes.
- Published
- 2014
- Full Text
- View/download PDF
37. [Microvascular angina].
- Author
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Iusupova AO, Shchendrygina AA, Privalova EV, and Belenkov IuN
- Subjects
- Coronary Vessels drug effects, Coronary Vessels physiopathology, Diagnostic Techniques, Cardiovascular, Disease Management, Humans, Microcirculation, Prognosis, Cardiovascular Agents therapeutic use, Microvascular Angina diagnosis, Microvascular Angina etiology, Microvascular Angina physiopathology, Microvascular Angina therapy
- Abstract
Microvascular angina is a rather widely spread disease which is associated with high rate of unfavorable outcomes and substantial economical cost of examination and treatment. However problems of noninvasive diagnostics of the disease have not been entirely solved as well as clear-cut algorithm of management has not been elaborated. We present in this paper consideration of contemporary aspects of etiology, pathogenesis, clinical course, diagnosis, and treatment of microvascular angina in accordance with European recommendations on management of patients with stable ischemic heart disease.
- Published
- 2014
- Full Text
- View/download PDF
38. [Hypertrophic cardiomyopathy -- modern state of the problem. Issues of epidemiology and nomenclature, genetics and pathophysiology, variants of course and differential diagnosis].
- Author
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Belenkov IuN, Privalova EV, Kaplunova VIu, Khabarova NV, and Shakar'iants GA
- Subjects
- Diagnosis, Differential, Global Health, Humans, Morbidity, Risk Factors, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic epidemiology, Cardiomyopathy, Hypertrophic genetics, Diagnostic Techniques, Cardiovascular, Genetic Predisposition to Disease, Terminology as Topic
- Abstract
The problem of the study of hypertrophic cardiomyopathy (HCM) has preserved its actuality because of high prevalence (1:500), risk of sudden cardiac death (SCD) in individuals of young able-bodied age. Subject of great interest appear problems of search for additional clinical, instrumental and genetic markers, environmental factors which are capable to influence formation of a clinical variant of HCM course, risk of SCD, and prognosis of HCM. Important problem requiring further study appears to be molecular genetic characteristic of the disease. Integrated nomenclature of various forms and variants of course of HCM is essential for elaboration of tactics of management of patients and assessment of results of multicenter trials.
- Published
- 2013
39. [Contemporary trends of genetic analysis in hypertrophic cardiomyopathy].
- Author
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Belenkov IuN, Privalova EV, Kaplunova VIu, Khabarova NV, and Shakar'iants GA
- Subjects
- Blood Coagulation genetics, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic physiopathology, Echocardiography, Gene-Environment Interaction, Genes, Modifier, Genetic Predisposition to Disease, Genetic Testing, Humans, Multifactorial Inheritance, Myocardium metabolism, Myocardium pathology, Nitric Oxide Synthase Type III genetics, Renin-Angiotensin System genetics, Cardiomyopathy, Hypertrophic genetics, Mutation, Polymorphism, Genetic, Sarcomeres genetics
- Abstract
Subject of great interest of contemporary scientific community is a search for additional genetic and environmental factors which are capable to influence formation of a clinical variant of the course of hypertrophic cardiomyopathy (HCMP). It has been shown by many works that besides mutations in genes of sarcomere proteins clinical course of HCMP is also affected by modifier genes of the cardiovascular system such as association of polymorphisms RAAS, sympathoadrenal system, NO-synthase, endothelin system, and system of blood coagulation. Attempts have been made to study effects of these polymorphisms on formation of clinical variant of HCMP course and to search for associations with development of unfavorable variants.
- Published
- 2012
40. [Remodeling of vascular bed in patients with arterial hypertension: possibilities of diagnostics and correction].
- Author
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Belenkov IuN, Privalova EV, Danilogorskaia IuA, Zheleznykh EA, and Shchendrygina AA
- Subjects
- Aged, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Angiotensin-Converting Enzyme Inhibitors pharmacokinetics, Biological Availability, Calcium Channel Blockers administration & dosage, Calcium Channel Blockers pharmacokinetics, Drug Combinations, Drug Synergism, Humans, Male, Secondary Prevention, Treatment Outcome, Amlodipine administration & dosage, Amlodipine pharmacokinetics, Blood Vessels drug effects, Blood Vessels pathology, Blood Vessels physiopathology, Hypertension diagnosis, Hypertension drug therapy, Hypertension physiopathology, Microcirculation drug effects, Perindopril administration & dosage, Perindopril pharmacokinetics
- Abstract
Arterial hypertension determines the remodeling of the vascular bed at all levels, resulting in a high risk of developing cardiovascular complications. Recent studies performed on the basis of evidence-based medicine, demonstrated the high efficiency of the combination drug therapy with perindopril and amlodipine in preventing such complications. This may be due to the positive influence of a fixed combination of these drugs on the parameters of the state of the microcirculatory level of the vascular bed.
- Published
- 2012
41. [Comparative analysis of antioxidant activity of nebivolol in patients with chronic heart failure with and without concomitant type 2 diabetes].
- Author
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Belenkov IuN, Privalova EV, Chekneva IS, Zheleznych EA, Khiazeva LV, Azizova OA, Aseĭchev AV, Baranova OA, and Shvachko AG
- Subjects
- Adrenergic beta-1 Receptor Antagonists administration & dosage, Adrenergic beta-1 Receptor Antagonists adverse effects, Adrenergic beta-1 Receptor Antagonists pharmacokinetics, Aged, Antioxidants administration & dosage, Antioxidants adverse effects, Antioxidants pharmacokinetics, Blood Glucose metabolism, Chronic Disease, Drug Monitoring, Endothelium, Vascular metabolism, Female, Humans, Male, Middle Aged, Monitoring, Physiologic, Nebivolol, Severity of Illness Index, Treatment Outcome, Benzopyrans administration & dosage, Benzopyrans adverse effects, Benzopyrans pharmacokinetics, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Diabetes Mellitus, Type 2 physiopathology, Endothelium, Vascular drug effects, Ethanolamines administration & dosage, Ethanolamines adverse effects, Ethanolamines pharmacokinetics, Heart Failure complications, Heart Failure diagnosis, Heart Failure drug therapy, Heart Failure metabolism, Heart Failure pathology, Heart Failure physiopathology, Oxidative Stress drug effects
- Abstract
Unlabelled: Consistent neurohormonal activation of sympatho-adrenal system in patients with chronic heart failure (CHF) and hyperglycemia contributes to development of oxidative stress--one of the most important pathogenetic mechanisms of endothelial dysfunction., Purpose: To study the impact of nebivolol concerning modification of clinical and hemodynamic indicators and parameters of oxidative stress in patients with CHF and with or without concomitant diabetes mellitus type 2 (DM2)., Material: Nebivolol was used in complex therapy of CHF in 82 patients, suffering from NYHA class I - III CHF (EF < 50%) of ischemic genesis with or without comorbid DM2, average age 63.2 +/- 8.2 years., Results: After 8 months of therapy significant improvement of clinical status was observed in both groups, tolerance to physical activity increased (significant reduction of average class of CHF in the group with DM2 from 2.5 +/- 0.58 to 2.125 +/- 0.71, p = 0.001, and in the second group from 2.3 +/- 0.5 to 1.9 +/- 0.4, p = 0.01). We also noted in both groups increase of plasma oxidative resistance (reduction of intensity of fast flash in lipid peroxidation h from 7 to 6 mm, p = 0.016, and from 8 to 6 mm, p = 0.03, respectively) and increase of antioxidant plasma protection (increase of SH-groups from 154.19 to 182.4 mmol/1, p = 0.00035, and from 176 to 205, p = 0.004, respectively)., Conclusion: Nebivolol is a modern neurohormonal modulator, which contributes to reverse evolution of oxidative changes in patients with CHF and hyperglycemia.
- Published
- 2011
42. [Analysis of morpho-functional parameters of the heart and polymorphisms of Renin-Angiotensin-aldosterone system genes in patients with different variants of the course of hypertrophic cardiomyopathy].
- Author
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Belenkov YN, Privalova EV, Kaplunova VY, Stambol'skiĭ DV, and Fomin AA
- Subjects
- Adult, Alleles, Angiotensinogen genetics, Cardiomyopathy, Hypertrophic, Familial diagnosis, Cardiomyopathy, Hypertrophic, Familial diagnostic imaging, Cardiomyopathy, Hypertrophic, Familial metabolism, Chymases genetics, Cytochrome P-450 CYP11B2 genetics, Disease Progression, Electrocardiography, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Heart physiopathology, Humans, Male, Middle Aged, Molecular Diagnostic Techniques, Myocardium metabolism, Myocardium pathology, Radiography, Receptor, Angiotensin, Type 1 genetics, Ultrasonography, Cardiomyopathy, Hypertrophic, Familial genetics, Cardiomyopathy, Hypertrophic, Familial physiopathology, Polymorphism, Genetic, Renin-Angiotensin System genetics
- Abstract
Background: Clinical course and prognosis of a hereditary myocardial disease hypertrophic cardiomyopathy (HCMP) is determined by multiple factors most of which have genetic nature., Aim: To study morpho functional parameters of the heart and polymorphisms of renin angiotensin aldosterone system genes in patients with various variants of the course of HCMP: stable variant (18%), atrial fibrillation (20%), progressing variant (51%), sudden cardiac death (9%) and "terminal stage" of disease (2%). Control group comprised 55 healthy people (mean age 44.6 +/- 10.3 years, =0.43). All patients went through examination which included molecular genetic and instrumental methods of investigation., Results: In the group of patients with progressing course we observed most frequent development of ECG changes characteristic of HCMP as well as asymmetrical myocardial hypertrophy caused by obstruction of LVOT. In the group of patients with variant "atrial fibrillation" we revealed increase of duration of P wave on ECG, development of more pronounced left atrial dilation and diastolic dysfunction. We established that presence of HCMP was associated with I/D polymorphism of gene and 1166/ polymorphism of AGTR1 gene. Unfavorable combination of allele variants of polymorphisms of RAAS genes exerts cumulative effect on phenotype of the disease and is associated with development of pronounced hypertrophy of the myocardium. The structure of hereditary susceptibility to development of stable variant of the disease course in patients with HCMP includes allele variants of -344 / polymorphism of CYP11B2 gene and 235 polymorphism of AGT gene. Development of the variant with atrial fibrillation is associated with allele variants of 1166/ polymorphism of AGTR1 gene and of the variant with progressing course - with I/D polymorphism of gene and -1903 A/G polymorphism of CMA1 gene.
- Published
- 2010
43. [Brain natriuretic peptide - contemporary marker of chronic heart failure].
- Author
-
Belenkov IuN, Privalova EV, and Chekneva IS
- Subjects
- Biomarkers blood, Chronic Disease, Humans, Severity of Illness Index, Heart Failure blood, Natriuretic Peptide, Brain blood
- Published
- 2008
44. [Hypertrophic cardiomyopathy: course characteristics in long-term follow-up].
- Author
-
Belenkov IuN, Privalova EV, Kaplunova VIu, and Fomin AA
- Subjects
- Adult, Cardiomyopathy, Hypertrophic diagnosis, Coronary Angiography, Disease Progression, Echocardiography, Doppler, Electrocardiography, Ambulatory, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Severity of Illness Index, Time Factors, Cardiomyopathy, Hypertrophic physiopathology, Stroke Volume physiology, Ventricular Function, Left physiology, Ventricular Remodeling physiology
- Abstract
Aim: To detect relations between intracardiac hemodynamics and clinicoanamnestic features of patients with hypertrophic cardiomyopathy (HCMP)., Material and Methods: We observed 84 patients with different clinical variants of a HCMP course. Of them, 15 patients were treated surgically. The patients were followed up from 3 to 24 years (mean 8.4 +/- 1.1 years). All the patients have undergone standard ECG, transthoracic echocardiography with doppler echocardiography, 24-h ECG monitoring, part of them--stress echocardiography (exercise and/or dobutamine), MRT of the heart, coronaroangiography and probing of the heart., Results: The analysis of cardiac remodeling parameters in HCMP patients showed significance of diastolic disorders in development of basic clinical symptoms of the disease. A rise of atrial-ventricular index (AVI) reflects severity of a HCMP course. Patients with the most severe course of the disease had AVI equal or higher than 1.1. In obstructive and non-obstructive variants of HCMP time of the first symptoms onset did not differ significantly. In the disease onset the patients had asthenic syndrome, cardialgia, dyspnea. The disease ends with heart failure., Conclusion: Long-term follow-up of HCMP patients and comparison of clinico-morphological parameters revealed the role of diastolic dysfunction in formation of clinical symptoms.
- Published
- 2008
45. [Markers of thrombophilia in pulmonary fibrosis complicated by pulmonary hypertension].
- Author
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Arkhipova DV, Privalova EV, Kozlovskaia LV, Kornev BM, Popova EN, Kraeva VV, Osipenko VI, and Bitsadze VO
- Subjects
- Adult, Aged, Biomarkers blood, Blood Circulation physiology, Blood Coagulation physiology, Female, Humans, Hypertension, Pulmonary complications, Hypertension, Pulmonary physiopathology, Male, Middle Aged, Pulmonary Fibrosis complications, Pulmonary Fibrosis physiopathology, Thrombophilia etiology, Thrombophilia physiopathology, Blood Coagulation Factors analysis, Hypertension, Pulmonary blood, Pulmonary Fibrosis blood, Thrombophilia blood
- Abstract
Aim: To determine the role of enhanced blood coagulation in pathogenesis of pulmonary hypertension (PH) at an early stage of fibrosing alveolitis (FA)., Material and Methods: Clinical, functional, roentgenological, coagulation and immunological examinations were performed in 17 patients with idiopathic FA (IFA), in 6 patients with exogenic allergic alveolitis (EAA), in 15 FA patients with diffuse diseases of the connective tissue (FA-DDCT). The diagnosis was verified with high resolution computed tomography (HRCT). Lesser circulation was assessed by Doppler echocardiography. Morphological impairment of the lungs was specified in all the patients using analysis of the bronchoalveolar lavage. In 9 FA patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy volunteers. Thrombin-antithrombin complex (TAT) and thrombocytic factor 4 (TF-4) were estimated with ELISA as stable, highly sensitive markers of thrombophilia., Results: The TF-4 level was elevated in all IPD patients (p < 0.05), the elevation being highest in FA-DDCT (p < 0.007). With FA progression, TF-4 concentration went down. A weak negative correlation (p < 0.047, r = -0.38) was found with average pressure in the pulmonary artery (PAAP). TAT was higher than control in all the groups (p < 0.05). Maximal TAT values were registered in EAA. If HRCT detected active inflammation and in development of irreversible fibrous changes TAT was higher vs control. A direct correlation between TAT level and PAAP was not found., Conclusion: Disorders in thrombocytic and plasmic links of hemostasis are detectable early in IPD. Stable markers of thrombophilia (TAT and TF-4) reflect activity of inflammation in FA. They can be also used as sensitive diagnostic tests for diagnosis of PH and diagnosis of patients with activated coagulation system in IPD.
- Published
- 2004
46. [Role of endothelial dysfunction and coagulation disorders in the development of pulmonary fibrosis in patients with interstitial lung diseases].
- Author
-
Ppova EN, Arkhipova DV, Kozlovskaia LV, Privalova EV, Bitsadze VO, and Kornev BM
- Subjects
- Endothelium pathology, Endothelium physiopathology, Female, Humans, Lung pathology, Lung Diseases, Interstitial pathology, Male, Middle Aged, Blood Coagulation Disorders complications, Blood Coagulation Disorders physiopathology, Lung physiopathology, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial physiopathology, Pulmonary Fibrosis complications, Pulmonary Fibrosis physiopathology
- Abstract
Thirty-two patients with different forms of interstitial lung diseases (ILD), such as idiopathic fibrosing alveolitis (IFA) (n = 17) and fibrosing alveolitis concurrent with diffuse connective tissue diseases (FA-DCTD), were examined. Clinical, echocardiographic, computed tomographic, coagulative, and immunological studies were performed. Enzyme immunoassay was used to determine the levels of a complex of thrombin and antithrombin III (TAT) and platelet factor IV (PF-IV). There were significant increases in the levels of PF-IV (4.36 +/- 0.25 mg/l) and TAT (10.87 +/- 3.8 mg/l) in patients with ILD as compared to the control (2.75 +/- 0.47 and 1.8 +/- 0.2 mg/l, respectively; p < 0.05). In patients with early FA-DCTD with the predominance of the milk glass syndrome during high-resolution CT (HRCT), the level of PF-IV was greater than the normal levels (p < 0.05) and decreased with the progression of the disease and with the formation of the honeycomb lung. If there were HRCT signs of active inflammation, the level of TAT was higher than that in the control; this was also in the development of irreversible fibrous changes.
- Published
- 2004
47. [Role of certain neurohumoral factors in development of pulmonary hypertonia in patients with interstitial lung diseases].
- Author
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Arkhipova DV, Kornev BM, Popova EN, Kogan EA, Osipenko VI, Privalova EV, Kobylenskiĭ AG, Meshcheriakova SA, and Efremov EE
- Subjects
- Adult, Aged, Case-Control Studies, Humans, Middle Aged, Histamine physiology, Lung Diseases, Interstitial physiopathology, Nitric Oxide physiology, Peptidyl-Dipeptidase A physiology
- Abstract
Aim: To ascertain the role of some neurohumoral factors--nitric oxide (NO), ACE, histamine--in development of pulmonary hypertension (PH) in patients with interstitial lung diseases (ILD)., Material and Methods: A total of 32 ILD patients were examined. Of them 14 had idiopathic fibrosing alveolitis (IFA), 6 had exogenous allergic alveolitis (EAA) and 12 patients had ILD in diffuse disease of the connective tissue (ILD-DDCT). In addition to routine tests, those for NO, ACE, histamine, serotonin in plasma were performed; Doppler echocardiography and high-resolution computed tomography were conducted. In 9 patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy subjects., Results: The highest mean pressure in the pulmonary artery (PmPA) was registered in IFA vs EAA and ILD-DDCT patients (p < 0.001). NO concentration in plasma was higher in ILD-DDCT than in control patients. In IFA and EAA the level of NO was like in controls. Concentration of NO in plasma of IDL patients correlated with high activity of the process. No correlation was found between ACE in plasma and PmPA, ACE levels were much higher in controls than in the ILD patients (p < 0.05). Histamine levels were higher in ILD patients than in controls being the highest in ILD-DDCT. Serotonin was insignificantly higher in ILD patients than in controls., Conclusion: Damage to the endothelium of the pulmonary arteries and imbalance of neurohumoral factors may be considered as a mechanism of development and stabilization of PH in ILD patients.
- Published
- 2003
48. [Pulmonary hypertension in interstitial diseases of the lungs].
- Author
-
Arkhipova DV, Kornev BM, Popova EN, Osipenko VI, Fokina OA, Privalova EV, Kogan EA, and Mukhin NA
- Subjects
- Adult, Aged, Female, Humans, Hypertension, Pulmonary diagnosis, Lung Diseases, Interstitial diagnosis, Male, Middle Aged, Tomography, X-Ray Computed, Hypertension, Pulmonary physiopathology, Lung Diseases, Interstitial physiopathology
- Abstract
Clinical, functional, immunological and x-ray examinations were performed in 32 patients with interstitial pulmonary diseases (14 with idiopathic fibrosing alveolitis, 6 with exogenic allergic alveolitis and 12 with diffuse affection of the connective tissue). The diagnosis was verified using high resolution computed tomography. Lesser circulation was studied with doppler-echocardiography. In 9 patients the diagnosis was verified by thoracoscopic biopsy of the lung. Control group consisted of 16 healthy subjects. The highest pressure in the trunk of the pulmonary artery (31 +/- 4.3 mmHg) was registered in patients with idiopathic fibrosing alveolitis. The severity of pulmonary arterial hypertension correlated with that of respiratory disorders, clinical symptoms and changes in the lungs. Blood pressure in the pulmonary artery trunk tended to elevation with progression of alterations in the lungs registered by computed tomography.
- Published
- 2002
49. [Enalapril treatment of residual pulmonary hypertension in patients operated rheumatic mitral valve defects].
- Author
-
Privalova EV, Ershov VI, Ermakov AI, Ivanov AS, Baloian GM, Kulagina TI, Aksiuk MA, and Dobrovol'skaia TN
- Subjects
- Adult, Female, Heart Valve Diseases complications, Heart Valve Diseases surgery, Humans, Hypertension, Pulmonary etiology, Male, Middle Aged, Pulmonary Wedge Pressure drug effects, Rheumatic Heart Disease complications, Treatment Outcome, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Enalapril therapeutic use, Hypertension, Pulmonary drug therapy, Mitral Valve, Rheumatic Heart Disease surgery
- Abstract
A pilot trial of efficiency of enalapril maleate in the treatment of residual pulmonary hypertension was made in 22 patients operated for rheumatic mitral valve defects. Degree I, II and III of pulmonary hypertension was registered in 5, 13 and 4 patients, respectively. Thus, the patients had NYHA functional classes III and IV (22.7 and 77.3%, respectively. Enalapril given for 6 months in a mean daily dose 12.3 +/- 1.57 mg/m2 (5-30 mg a day) normalized pressure in the pulmonary artery in 18.2% of patients. 50% of patients showed hypertension degree I, only one female retained hypertension degree III. To the end of the treatment the functional classes were the following: II--in 68.2%, III--in 27.3% and IV--in 4.5%.
- Published
- 2000
50. [Program of examination for patients with isolated mitral valve defects to evaluate the degree of pulmonary hypertension].
- Author
-
Cherepenin LP, Privalova EV, Ivanov AS, Ershov VI, Baloian GM, Kulagina TI, Aksiuk MA, Buravikhina TA, and Filimonova MV
- Subjects
- Adult, Echocardiography, Electrocardiography, Evaluation Studies as Topic, Female, Heart Valve Diseases complications, Heart Valve Diseases surgery, Heart Ventricles diagnostic imaging, Heart Ventricles physiopathology, Humans, Hypertension, Pulmonary etiology, Hypertension, Pulmonary physiopathology, Male, Radiography, Thoracic, Reproducibility of Results, Rheumatic Heart Disease complications, Diagnosis, Computer-Assisted methods, Heart Valve Diseases diagnosis, Hemodynamics physiology, Hypertension, Pulmonary diagnosis, Mitral Valve
- Abstract
98 patients with isolated rheumatic mitral valve defects of the heart entered the study. Their central hemodynamics was studied intraoperatively before surgical correction of the defect. The results were compared to those provided by conventional noninvasive methods: chest x-ray, ECG, echo-CG, external respiration function test. Correlation analysis using computer intellect PolyAnalyst v.1.01R helped to design a program and practical nomogram which can quantitatively determine the degree of pulmonary hypertension on the basis of digital values of Rv1 wave amplitude (ECG) and right ventricular cavity size (echoCG).
- Published
- 2000
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