Prognostic value of vascular remodeling parameters in the development of adverse cardiovascular events in patients with gastric cancer

Aim. To determine a possible prognostic marker for adverse cardiovascular events in patients with gastric cancer by studying the early and long-term effects of multiagent chemotherapy (MAC) on the structural and functional vascular wall parameters.Material and methods. The study included 25 patients with newly diagnosed gastric cancer who received courses of chemotherapy with platinum-based agents and fluoropyrimidines. All patients before, immediately after MAC courses and in the long-term period underwent a non-invasive assessment of vascular wall and endothelial function (photoplethysmography (PPG)). In the survivors’ cohort, a correlation analysis was performed to assess the risk of future cardiovascular events depending on changes of PPG parameters.Results. Before the MAC courses, cancer patients had endothelial dysfunction (mean occlusion index, 1,7 (1,4; 1,9), N>1,8) and structural vascular wall disorders (mean stiffness index, 8,9 m/s (7,7; 9,7), N<8 m/s, mean reflection index, 32,4% (27,5; 37,7), N<30%). All indicators significantly worsened after MAC in the form of endothelial dysfunction progression and vascular remodeling: mean occlusion index, 1,3 (1,2; 1,5) (p<0,0002), stiffness index, 10,3 m/s (9,5; 11,2) (p<0,0001), reflection index, 40,2% (35,5; 43,6) (p<0,001). Long-term follow-up averaged 2,9 years (2,3-3,7 years). All-cause and cardiovascular mortality was 32% and 12%, respectively. Nine patients developed a cardiovascular events (CVEs) (de novo, progression of prior CVD). Significant changes of vascular indicators in the long-term period was not revealed. A trend towards association between increased reflection index and a higher probability of cardiovascular pathology was revealed (OR 1,20, 95% CI 1,01-1,55, p=0,081).Conclusion. In this study, for the first time, a comprehensive assessment of the effect of MAC on endothelial dysfunction and vascular stiffness, including, in the long-term follow-up period, was carried out in patients with gastric cancer. A significant aggravation of all parameters of vascular remodeling immediately after treatment in the absence of their significant dynamics in the future has been proven. A possible prognostic marker, namely the reflection index, of an unfavorable cardiac outcome in patients with gastric cancer has been identified, which requires further study

The Effect of Enhanced External Counterpulsation on the Vascular State, Indicators of Glycemic Control and Quality of Life in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus

Aim. To study the effect of enhanced external counterpulsation (EECP) on the functional status, quality of life, structural and functional state of the vascular bed, and markers of glycemic control in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM).Material and methods. A pilot prospective randomized study included 30 patients with CAD and DM. Using a random number generator, patients were randomized into 2 groups: EECP (n=15) and a comparison group (n=15). All patients (n=30) received optimal medical therapy (OMT) during 3 months of follow-up. Patients in the EECP group underwent a course of EECP (35 hours, cuff pressure: 220-280 mmHg) during the first 7 weeks of the study. At baseline and after 3 months of follow-up, patients in both groups underwent an assessment of clinical status, quality of life (based on the SF-36 questionnaire), as well as a 6-minute walk test to assess exercise tolerance. The dynamics of fasting glucose, postprandial glucose, insulin resistance index (HOMA-IR) and glycated hemoglobin were assessed. Photoplethysmography and applanation tonometry were performed to assess the state of the vascular bed.Results. In the EECP group, after 3 months, there was a decrease in the frequency of angina attacks and an improvement in the functional class of angina according to the Canadian Cardiovascular Society (CCS) classification. A significant improvement in exercise tolerance was revealed [an increase in the 6-minute walking distance by 51 (35; 65) m, p<0.05], as well as an improvement in the physical and mental components of health according to the SF-36 questionnaire. A positive dynamics was shown in relation to the indicators of the state of both large vessels and the microvasculature (p>0.05), with the exception of the reflection index and the stiffness index (p<0.05). There was also a significant decrease in the HOMA-IR [-9.9% (-26.5; -4.0) vs 7.7% (-7.9; 13.8), p=0.004], as well as in the levels of fasting glucose [-10.5% (-15.8; -4.0) vs -2.7 (-8.3; 5.9), p=0.012] in the EECP group, compared with the OMT group.Conclusion. EECP course therapy in addition to OMT has a positive effect on the functional status and quality of life of patients with CAD and DM. After 3 months of observation, there was noted a positive dynamics of the vascular state, as well as markers of glycemic control, and these changes were more pronounced in the EECP group. The results obtained may indicate the effectiveness of EECP as an add-on treatment for this group of patients

Inflammatory Activity in Patients with Obstructive and Non-obstructive Coronary Artery Disease

Aim. To study the levels of pro-inflammatory biomarkers  in patients with obstructive  and non-obstructive coronary  artery disease (CAD), to identify possible differences  for diagnosing the degree of coronary  obstruction.Material and methods. The observational  study included two groups of patients: with non-obstructive (main group,  coronary artery stenosis <50%; n=30) and obstructive  (comparison group,  hemodynamically significant  coronary  artery stenosis according to the results of coronary  angiography; n=30) CAD.  The levels of interleukin-1β (IL-1β) and interleukin 6 (IL-6) were measured in plasma using enzyme  immunoassay.Results. IL-6  levels were significantly higher in patients with obstructive  CAD  (p=0.006) than in patients with non-obstructive CAD.  There were no significant  differences  in the level of IL-1β in both groups  (p=0.482). When  constructing the ROC  curve,  the threshold  value of IL-6  was  26.060 pg/ml. At the level of IL-6  less than this value, CAD  was diagnosed with hemodynamically insignificant stenoses of the coronary  arteries.Conclusion. The results of this study confirm that in patients with different types of coronary  artery lesions, there are differences  in the activity of the inflammation process in the arterial wall. IL-6  was higher in the obstructive  lesion group,  and IL-1β levels did not differ between groups.  Thus, it can be assumed  that hemodynamically significant  obstruction  of the coronary  arteries develops  as a result of highly  active inflammation of the vascular wall. Given the presence of a proven biological  basis and the available data on the effectiveness of monoclonal antibodies to IL-1β, one cannot exclude their possible benefit in a cohort of patients with CAD  and hemodynamically insignificant stenoses

Evaluation of Fibrosis Markers as a Potential Method for Diagnosing Non-Obstructive Coronary Artery Disease in Patients with Stable Coronary Artery Disease

Aim. To study the levels of fibrosis markers in patients with stable coronary artery disease (CAD) and various types of coronary artery (CA) lesions (obstructive and non-obstructive), to identify possible differences for diagnosing the types of coronary obstruction.Material and methods. The observational study included three groups of patients: with non-obstructive (main group, coronary artery stenosis <50%; n=20) and obstructive (comparison group, hemodynamically significant coronary artery stenosis according to the results of coronary angiography; n=20) CAD and healthy volunteers (control group; n=40). Transforming growth factor beta 1 (TGF-β1) and matrix metalloproteinase 9 (MMP-9) levels were measured in plasma by enzyme immunoassay. According to the results of echocardiography, all patients included in the study were divided into four groups depending on the type of myocardial remodeling.Results. TGF-β1 levels were significantly higher in patients with obstructive CAD (p=0.008) than in patients with non-obstructive CAD and healthy volunteers (p <0.001). There were no significant differences between the main and control groups (p>0.05). There were no statistically significant differences in TGF-β1 levels depending on the type of left ventricular remodeling (p=0.139). The maximum level of MMP-9 was in the group with obstructive coronary disease and significantly differed from the main group (p <0.001) and the control group (p=0.04).Conclusio. The maximum levels of TGF-β1 and MMP-9 were found in the group with obstructive coronary artery disease. The levels of these biomarkers in the main group were statistically different from the values obtained in the control group. Thus, considering the pathogenesis of the development of non-obstructive CAD, the use of fibrosis markers TGF-β1 and MMP-9 may be promising for diagnosing the severity of CA obstruction

Neuregulin-1β, Biomarkers of Inflammation and Myocardial Fibrosis in Heart Failure Patients

Neuregulin-1β (NRG-1) is an emerging biomarker of heart failure (HF). The mechanisms of its action in HF patients are yet  to be investigated. Cardioprotective and anti-inflammatory  effects of NRG-1 have been reported.Aim. To assess NRG-1 levels in HF patients and investigate the association between NRG-1 and biomarkers of inflammation and myocardial fibrosis.Material and Methods. NRG-1, biomarkers of inflammation and fibrosis (hsCRP, IL-6, sVCAM-1, MMP-9, Galectin-3, ST2, TGF-β) were assessed in 47 patients with HF and preserved ejection fraction (HFpEF); 39 patients with HF and reduced ejection  (HFrEF) and 40 healthy participants. The associations between  NRG-1 and biomarkers of inflammation and fibrosis, as well as  the composite outcomes of cardiovascular death and HF  hospitalisations were assessed.Results. Median NRG-1 levels in HFpEF were 0.969 (0.348; 1.932) ng/ml, in HFrEF – 0.63 (0.348; 1.932), in healthy participants 0.379 (0.195; 0.861) ng/ml, and was significantly higher in HFpEF compared to healthy volunteers (р=0.004). There was no  difference in NRG-1 concentration between HFpEF and HFrEF. In  HF patients, all biomarkers of inflammation and fibrosis were  higher than in controls. ST2, IL-6 and TGF-β were significantly higher in HFrEF compared to HFpEF patients, while hsCRP,  sVCAM-1, MMP-9, and Galectin-3 levels were comparable. In  HFpEF, NRG-1 was associated with hsCRP (rs=0.378, p=0.023) and IL-6 (rs=0.378, p=0.014). Median follow-up time in patients with HFpEF and in patients was 312 (236; 388) days, in HFrEF – 147 (98; 237) days. In HFpEF, 2 patients died and 19 were  hospitalized due to HF. In HFrEF, 10 deaths and 19  hospitalizations were registered. Kaplan-Mayer analysis showed that HFpEF patients with increased NRG-1 and IL-6 had higher  levels of HF hospitalisation (log rank test, р=0.046 and р=0.012, respectively). In a multivariable cox proportional hazard model,  the association between the NRG-1 and outcomes remained significant after adjustment for age, gender and NTproBNP but diminished when hsCRP and IL-6 were included in the model.Conclusion. NGR-1 level significantly higher in HFpEF compared to healthy participants, and comparable with NRG-1 concentrations in HFrEF. In HFpEF, NRG-1 was associated with biomarkers of inflammation and fibrosis. The prognostic value of NRG-1 in HF requires further investigations

Plasma Level’s of Neuregulin-1 in Healthy People

Aim. To determine the median levels of neuregulin-1 (NRG-1; endothelium-derived growth factor and the natural agonist of the ERBB3 and ERBB4 receptors) NRG-1 in healthy volunteers and to study the associations of NRG-1 levels with gender and age.Material and Methods. Ninety seven healthy participants were enrolled (median age of 44 [32-54], men 45 men [46.4%]). The following age groups were identified: 20-29 y.о. (n=20, men – 50.0%),  30-39  y.о.  (n=21,  men  –  52.4%),  40-49  y.о.  (n=22,  men  –  45.5%),  50-59  y.о. (n=22, men – 36.4%); 60-69 y.о. (n=12, men – 50.0%). Peripheral blood samples were collected at the time of enrolment, standard laboratory tests were performed, and NRG-1 levels were determined in the plasma samples by ELISA.Results. In the cohort of 97 healthy participants the median value of NRG-1 was 0.3 [0.121-2.24] ng/ml. NRG-1 levels did not differ significantly between men and women (p=0.145), indicating that NRG-1 levels are not influenced by gender. The levels of NRG-1 were similar in the different age groups: age 20-29 years=0.26 [0.17-0.37] ng/ml; age 30-39=0.24 [0.1-0.39] ng/ml; age 40-49=0.31 [0.19-1.15] ng/ml; age 50-59=0.37  [0.19-1.0] ng/ml; age 60-69=0.4 [0.13-0.81] ng/ml. Correlation analysis between NRG-1 levels and route blood measurements (haemoglobin, lipids, glucose, creatinine, and uretic acid) did not show significant associations.Conclusions. In this study, the median value of NRG-1 plasma levels were determined. The results of the study show that age and gender had no influence on NRG-1 values

Aromatic Amino Acids: Phenylalanine and Tyrosine in Patients with Hypertension and Coronary Artery Disease

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p<0,05) and Tyr (r=-0,583, p<0,05), as well as the level of Phe with total cholesterol (r=-0,461, p<0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p<0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p<0,05), and the level of Tyr with LDL (r=0,349, p<0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target

Diagnosis and Treatment of Elderly and Senile Chronic Constipation: an Expert Consensus

Aim. An appraisal of practitioners with chronic constipation management details in older and senile adults.Key points. Chronic constipation is a common issue in geriatrics. Aside to age-related physiological bowel disfunction, a higher constipation incidence is conditioned by declined physical activity and frailty, polypharmacy and a series of secondary constipation-developing chronic states and diseases. Chronic constipation is associated with a higher risk of cardiovascular disease and complications, impaired general perception of health and pain, growing alarm and depression, and reduced quality of life. The treatment tactics in chronic constipation is cause-conditioned and should account for the patient’s history and therapy line, overall clinical condition, cognitive status and functional activity level. An essential baseline aspect of constipation management is apprising the patient and his family of the underlying factors and methods for non-drug and drug correction. An higher-fibre diet is recommended as first measure, with osmotic laxatives added and titrated to clinical response if none observed towards the non-drug and high-fibre regimens. Stimulant laxatives and prokinetics should be recommended in patients reluctant to fibre supplements and osmotic laxatives. Subsidiary correction includes biofeedback, transanal irrigation, acupuncture, foot reflexology and percutaneous tibial nerve stimulation.Conclusion. Elderly and senile chronic constipation is a prevalent multifactorial state requiring an efficient management via assessment and correction of total risk factors and consistent use of non-medication and drug therapies

Left Atrium Involvement in Lymphoma Patients: Single Center Observational Study

Aim. To assess the structure and performance of left atrium (LA) before and after 3 cycles of anticancer treatment in lymphoma patients, as well as the incidences of supraventricular arrhythmia (SVA) and the levels of biomarkers of inflammation.Material and Methods. This is a prospective observational study of patients with confirmed diagnosis of lymphoma [n=23; 57% men; median age 52 (34;64) years], who had no prior polychemotherapy. The comparison group included persons without lymphoma [n=18; 50% men; median age 43 (37; 54) years] comparable with the main group in terms of sex, age and risk factors for cardiovascular diseases. Patients with lymphoma underwent 24h-ECG monitoring and advanced transthoracic echocardiography at baseline and after 3 cycles (within 3 months) of anticancer treatment. Biomarkers of inflammation were measured. The results were compared with the data of the comparison group.Results. In lymphoma patients, LA reservoir, conduit, and booster function were found to be impaired at baseline but were comparable with these in matched controls. After 3 cycles of anticancer treatment, a trend to reduction of LA booster and conduit strain was found. The proportion of those with SVA was significantly higher in lymphoma patients before chemotherapy compared to those after anti-cancer treatment or controls: 57% vs 10% and 33% respectively (p<0.05). Lymphoma patients had a higher number of premature ventricular beats at baseline than after treatment or in control [183 (14;841) vs 38 (14;94) and 9 (4;38) respectively]. There were no associations found between the parameters of LA structure and function and SVA. Moderate positive correlation between ESR and supraventricular premature complexes was found (rS=0.44; p<0.05). A positive correlation between LA contractile function and inflammatory biomarkers were revealed: LA active ejection fraction (LA EFact) and ESR (rS=0.42, p<0.05); LA volume index and β-globulin (rS=0.43, p<0.05); LA EFact and neuregulin-1β (rS=0.42, p<0.05); LA expansion index and neuregulin-1β (rS=0.55, p<0.05).Conclusions. In lymphoma patients, LA phasic strain parameters were impaired regardless of anticancer treatment. The associations between inflammatory biomarkers with SVA and parameters of LA performance were found

Соотношение изменений гемодинамики малого круга кровообращения и сократимости желудочков сердца у больных с дилатационной кардиомиопатией

In 32 patients with acute dilatational cardiomyopathy (ACMP) the relation between left and right section of lesser circulation with and without high pulmonary hypertension (PH) was studied. In the patients with the low stroke volume of the right ventricle it was not found significant differences in PH level in comparison with the subgroup with the more higher stroke volume. This fact testifies that in patients with ACMP the level of PH depends in general on the relationship between impairments of left and right ventricles.У 32 больных острой дилатационной кардиомиопатией (ОКМП) изучено соотношение нарушений гемодинамики левых и правых отделов сердца малого круга кровообращения с высокой легочной артериальной гипертензией (ЛАГ) и без нее. У больных ОКМП с низкой фракцией выброса правого желудочка не было получено достоверных отличий в величине ЛАГ по сравнению с подгруппой с более высокой фракцией выброса правого желудочка. Это свидетельствует о том, что у больных ОКМП ЛАГ в основном зависит от соотношения левого и правого желудочковых нарушений