Correlation of intracardiac hemodynamics indicators with von Willebrand factor – Marker of endothelial dysfunction in patients with coronary artery disease combined with coronavirus disease (COVID-19)

The research relevance is predefined by the need to establish the relationship and identify new markers and potential contributions to clinical practice and scientific progress. This opens up new opportunities for further development in the field of cardiology and infectious diseases, which is of great importance for improving diagnosis and treatment. The research aims to establish the relationship between indicators and the role of endothelial dysfunction in the pathogenesis of various conditions. The clinical observation method was used, and data such as symptoms, medical history, and laboratory and instrumental studies were collected. The conclusions of the study are based on the analysis of the collected data and indicate the existence of a relationship between the indicators. The study revealed an increased activity of von Willebrand factor in the majority of patients. When comparing groups of patients depending on the presence of concomitant coronavirus disease, it was found that the highest level of von Willebrand factor was observed in patients with coronary heart disease in combination with coronavirus disease, a lower level in patients with coronavirus disease alone, and the lowest level in patients with chronic coronary heart disease. This indicates a correlation between the level of von Willebrand factor and the presence of concomitant coronavirus disease, which emphasises the importance of vascular endothelial dysfunction in the pathogenesis of coronary heart disease. It was found that the value of the von Willebrand factor correlates with the left ventricular end-diastolic size in both patients with coronary heart disease and patients with coronary heart disease in combination with coronavirus disease. This demonstrates that there is a strong association between von Willebrand factor and the clinical manifestation of coronary heart disease in combination with coronavirus disease, which may indicate a dysfunction of the vascular endothelium in these patients

Hypercoagulability in patients with atrial fibrillation and associated obesity: a way to hemorrhage or thromboembolia?

Despite the increased hypercoagulability of the blood plasma in patients with AF, the study of the processes of plasma hemostasis has still received insufficient attention, especially in patients with comorbid obesity or with excessive body weight. Purpose of the study. To establish the specific features of the effect of concomitant obesity on the indices of plasma hemostasis in patients with AF, on the basis of which to identify prognostically significant risk factors for adverse arrhythmia. Materials and methods. 75 patients with permanent AF were examined. For deducing prognostically significant risk factors, we conducted a retrospective analysis of the case histories of 421 inpatients. Results. The presence of concomitant obesity in patients with AF is accompanied by an acceleration of the prothrombinase-forming stage both in the internal and external hemocoagulation pathways. At the same time, the increase in procoagulant properties of blood is associated with a significant increase in fibrinogen and soluble fibrin-monomer complexes against the background of depletion of fibrinolytic and anticoagulant blood activity, which is a reflection of changes at the level of all links of hemocoagulation. Most diagnostically significant coagulation factors in the risk of thrombotic complications in patients with atrial fibrillation and concomitant obesity can be considered a measure of INR 30 minutes. Prognostically significant risk factors for small bleeding in patients with AF and associated obesity when taking warfarin are a BMI> 40kg/m2, level of AT III ≥40 % and ≥130 %, and in patients with AF and normal body weight, the amount of small bleeding increases if variability of INR beyond 2.0–3.0 and levels of AT III ≥130 %, as well as in the spring period of the year. Conclusions. Patients with AF are characterized by a moderate increase in the thrombogenic potential of the blood, which is accompanied by a significant inhibition of anticoagulant activity, while an increase in BMI leads to further deterioration of hemostasis equilibrium with an increase in procoagulant properties, depletion of fibrinolytic and anticoagulant blood activity

KIDNEY ULTRASOUND PARAMETERS AND RENAL BLOOD BIOCHEMISTRY MARKERS IN POST-HEMORRHAGIC STROKE HYPERTENSIVE SURVIVORS

Introduction. Hemorrhagic stroke is a serious and devastating complication of arterial hypertension, which leads to increased mortality in survivors even after the early recovery period. Being other target organs for arterial hypertension, kidneys take part in blood pressure regulation. Investigation of their peculiarities in such patients may provide valuable data on possible reasons of poor long-term prognosis in this category of patients. The aim of the study: to compare kidney ultrasound parameters and renal blood biochemistry tests between the post-hemorrhagic stroke hypertensive subjects in a stable phase of recovery period and the patients with arterial hypertension who had no cerebrovascular and cardiovascular events. Materials and methods. There were 100 subjects enrolled into the study. They formed two investigatory groups: the main (n=64; age – 52,2±8,41 years, M±SD years) and the control (n=36; age – 51,8±5,92 years) one. Hypertensive patients of the main group developed hemorrhagic stroke – subarachnoid hemorrhage (SAH) (n=42) or intracerebral hemorrhage (ICH) (n=22) – ≥6 months prior to the examination conducted at this study. The control group consisted of patients with non-complicated arterial hypertension. In both groups of patients, the kidney ultrasound parameters and blood plasma urea, creatinine and uric acid concentration levels were determined. Estimated glomerular filtration rate (eGFR) was calculated. Results. The indices of kidney ultrasound parameters in the main group and the control group were the following ones, respectively: the pole-to-pole size of the right kidney was 9,96±1,05 and 11,63±1,26 cm, the same size of the left kidney – 10,39±0,93 and 11,95±1,23 cm, p<0,01 for both pairs. Among the biochemistry blood plasma indices, uric acid concentration reached significant difference as well – 411,21±60,36 and 360,91±75,3 µmol/L in the relevant groups, respectively (p=0,04). On the other hand, eGFR did not show the difference between the study groups. The main group was characterized by a higher prevalence of kidney stone formation – OR 5,00 (95% CI, 1,83-13,65). The statistically significant higher incidence rate of calculus development was identified in two subgroups of the main group as well: for SAH – OR 3,08 (95% CI, 1,05-9,02), for ICH – OR 13,33 (95% CI, 3,69-48,15). When comparing to the control group, kidney cyst identification rate in the SAH subgroup referred to OR 3,08 (95% CI, 1,05-9,02), while kidney pelvis/calyces enlargement incidence rate was higher in the ICH subgroup OR 9,17 (95% CI, 2,15-39,06). Conclusions. The obtained data indicate the smaller pole-to-pole dimension of both kidneys in hypertensive subjects who suffered hemorrhagic stroke, accompanying higher incidence rate of kidney calculus formation in view of the increased blood plasma uric acid concentration. The same is typical for the SAH individuals subgroup but with the addition of prevalence of kidney cysts incidence rate. As for the ICH subgroup, in addition to the main group findings, pelvis/calyces enlargement is observed more frequently when comparing to the hypertensive only subjects

Effect of type 2 diabetes mellitus and mutations of the cyp2c19 gene on the platelets functional activity of patients with ischemic heart heart disease

Abstract Goal To establish sensitivity to clopidogrel in carriers of various G681A alleles of the CYP2C19 gene on the basis of a comprehensive assessment of platelet hemostasis. Materials and methods We examined 120 patients with various forms of coronary heart disease (CHD), including: 60 patients with acute coronary syndrome (ACS), 60 patients with chronic coronary syndrome (CCS). All patients were treated with clopidogrel. Results Genotyping of patients revealed that 73.3% of the examined cohorts of patients with ACS and 86.4% of patients with CCS were dominated by the native genotype G/G. In the cohort of patients with ACS, the degree of spontaneous platelet aggregation (SPA) among patients with G/A-A/A genotype exceeded the control values by 4.6 times (p&amp;lt;0.001). When compared with the corresponding indicator in patients with G/G genotype, it was found that the presence of a mutated A-allele had no significant effect on the increase in SPA (OR=2,450; 95% CI: 0.462–12.982; p=0.480). The degree and rate of arachidonic acid (AA)-induced platelet aggregation was significantly lower than the control values in all subgroups, but did not differ between subgroups of patients with different polymorphisms (OR=0.625; 95% CI: 0.065–6.090; p=0.912). Studying the degree and rate of ADP-induced platelet aggregation did not reveal statistically significant changes either in comparison with the control group or in the intergroup analysis. There was also no significant association between CYP2C19 gene polymorphisms and the degree of ADP aggregation (OR=0.795; 95% CI: 0.216–2.928; p=0.983). In patients with stable CHD, despite the use of clopidogrel in all patients, the level of SPA was significantly higher than the control values and depended on the polymorphism of the CYP2C19 gene. To evaluate the effect of diabetes on the effectiveness of inhibition of platelet functional activity by clopidogrel in carriers of different allelic variants of the CYP2C19 gene, we compared the G/G and G/A-A/A genotypes. The group of isolated coronary heart disease consisted of 48 patients with G/G genotype (80%) and 12 patients with mutated A-allele (20%). Patients with pathology of carbohydrate metabolism were distributed as follows: 47 patients had G/G genotype (78%), and 13 - G/A-A/A (22%). It was found that when carrying the G/A-A/A genotype, the intergroup difference was 72.6% (57.65 [49.34; 67.8] vs. 33.4 [32.47; 37.99], p&amp;lt;0.01). The chance of encountering a high degree of ADP-induced aggregation among carriers of the A-allele of the CYP2C19 gene with diabetes was almost 17 times significantly higher than the group of patients with isolated coronary heart disease (OR=16,667 (2,273–122,218), p=0.009). Conclusion The data obtained in our study showed that the patients with CHD and concomitant diabetes mellitus who had a mutated A-allele CYP2C19 gene was less sensitive to clopidogrel, which was manifested in a higher degree of ADP-induced platelet aggregation. Funding Acknowledgement Type of funding sources: None. </jats:sec

State of platelet-plasma hemostasis in patients with hypertension and non-alcoholic fatty liver disease in condition of hypercholesterolemia

Abstract   Non-alcoholic fatty liver disease (NAFLD) is a marker of metabolic and dyslipidemic disorders. Given the prevalence of atherogenic dyslipidemias and their proven effect on the development of thrombotic cardiovascular complications in patients with NAFLD, it is important to understand the role of hemostatic blood activity. Aim of the study To increase the effectiveness of early diagnosis of thrombophilic blood changes in patients with hypertension (HT) combined with non-alcoholic fatty liver disease by determining the state of plasma hemostasis in conditions of hypercholesterolemia and concomitant statin therapy. Materials and methods 152 patients were examined. Groups of patients: I – 46 patients with stage II GC, II – 54 patients with NAFLD without GC, group III – 52 patients with stage II GC with concomitant NAFLD. The analysis of spontaneous and induced platelet aggregation, indicators of coagulation, anticoagulant and fibrinolytic hemostasis. Results The degree of spontaneous aggregation was significantly higher in patients with hypercholesterolemia – by 32.4% (p&amp;lt;0.05). The level of fibrinogen was higher by 13.5% (p&amp;lt;0.05) due to hypercholesterolemia, at the same time there was a decrease in antithrombin (AT) III by 8.7% (p&amp;lt;0.05) in patients with high cholesterol. Patients with comorbid HT and NAFLD on statin therapy had a 16.5% (p&amp;lt;0.05) lower degree of spontaneous aggregation than patients who did not receive this treatment. In the NAFLD group, patients receiving statins had a significantly lower degree of arachidonic acid-induced aggregation against patients without lipid-lowering therapy (by 54.0%, p&amp;lt;0.001). However, the analysis of the general population of the examined revealed a decrease in the degree of collagen-induced aggregation by 38.7% (p&amp;lt;0.05) in a subgroup of patients receiving treatment. We observed a 23.4% (p&amp;lt;0.001) shortening of prothrombin time in the NAFLD group and a 16.0% (p&amp;lt;0.05) shortening in the combined course of HT and NAFLD. In the absence of statin therapy in the NAFLD group, there was a significant decrease in INR – by 9.7% (p&amp;lt;0.05) – compared with patients receiving lipid-lowering therapy. A decrease in thrombin time by 12.2% (p&amp;lt;0.05) was observed in the subgroup receiving statins among patients with NAFLD. In the general cohort, the use of statins increased the activity of AT III by 10.7% (p&amp;lt;0.01), but in the NAFLD group this difference was more significant – by 14.3% (p&amp;lt;0.001) AT III was more active in patients who received lipid-lowering therapy. Conclusion The results of the analysis showed that patients with hypercholesterolemia have procoagulant and prothrombogenic activity of blood. But statin treatment decrease platelet aggregation, blood coagulation potential and increased activity of anticoagulant hemostasis, which complements the mechanism of prophylactic effect of HMG CoA reductase inhibitor (statin). Funding Acknowledgement Type of funding sources: None. </jats:sec

Hypercholesterolemia as a factor in the risk stratification of patients with hypertension depending on the ITGA2 gene polymorphism

Abstract   Mutation C807 in the ITGA2 gene is associated with the risk of early myocardial infarction, ischemic stroke, embolism, thrombosis after angioplasty and stenting of coronary arteries. Aim To study the relationship between ITGA2 gene polymorphism and increased risk of CAD in patients with hypertension and hypercholesterolemia Materials and methods 72 patients were included. Study involved patients with ACS, which developed on the background of hypertension, 32 patients also had coronary angiography and stenting. We used analysis of spontaneous and induced platelet aggregation, polymorphism of C807T of the ITGA2 gene was determined by polymerase chain reaction. Results At 82.5% of patients with ACS genotype ITGA 2 C/T was prevalent – 40.3%, T/T – 31.9%. Aggregation capability research in the studied groups has shown that patients of all groups had their degree of spontaneous aggregation significantly exceeding limits of control. Wherein, the highest indices were recorded in the T/T genotype group, which exceeded reference values by 3,02 times. AA-induced aggregation in the group of patients with T/T genotype exceeded indexes of the C/C group by 17.3%, while C/T group's rates-by 16.5% (p&amp;lt;0.05 in both cases). Studying the degree of collagen-induced aggregation, it was noted that the highest rates were recorded in T/T genotype group – 1.68 times higher than control group. Conclusion It is found that T allele of ITGA2 carrier is typical for 72.1% of patients with acute coronary syndrome and combined with spontaneous acceleration of platelet aggregation and increases sensitivity of platelets to ADP and collagen. Results allow us to consider the carrier of the T-allele as a marker of predisposition to thrombophilia. Funding Acknowledgement Type of funding sources: None. </jats:sec

The state of platelets and their functional activity in patients with arterial hypertension in combination with non-alcoholic fatty liver disease

Abstract Background According to modern concepts of hypertension (HT) and obesity, the hemostatic system in these diseases is characterized by prothrombogenic changes. Since the liver is the site of the formation of many factors of hemostasis, the concomitant non-alcoholic fatty liver disease (NAFLD), which often accompanies the course of both of these diseases, is an actual problem. Purpose To improve the efficiency of early diagnosis of thrombophilic blood changes in hypertensive patients with concomitant obesity and NAFLD by determining the state of platelets and their functional activity. Materials and methods We examined 167 patients (80 men and 87 women). The average patient age 55.5 [47.0; 61.0] years. Patients were divided into three groups: I - 46 patients with hypertension without NAFLD, II - 54 patients with NAFLD without hypertension, III group - 52 hypertensive patients with NAFLD. The control group consisted of 15 healthy subjects matched for age and sex. Platelet count and mean platelet volume (MPV) was performed on an automated analyzer, spontaneous and induced platelet aggregation was evaluated by laser aggregometer. Results A significant increase in the degree of spontaneous aggregation of platelet has been found in patients in all groups compared to the control group: I group - 2.2-fold increasing in aggregation (p&amp;lt;0.05), II group to 4.2-fold (p&amp;lt;0.05), III group had increasing by 4.1-fold (p&amp;lt;0.05). ADP-induced platelet aggregation was the same in I group and control, but it was 39% higher (p&amp;lt;0.001) in II cohort and by 22.6% (p&amp;lt;0.01) in III group. Adrenalin-induced platelet activity increased in all groups versus control: I group – 2.1-fold (p&amp;lt;0.001), II group – 2.3-fold (p&amp;lt;0.001), III group – 1.6-fold (p&amp;lt;0.01) elevation. Arachidonic acid-induced aggregation elevated by 64,2% (p&amp;lt;0.001) in I group and decreased by 56.3% (p&amp;lt;0.01) in II and by 43% (p&amp;lt;0.05) III cohorts. Collagen-induced activity had not significant difference between groups. MPV was increased in both groups with NAFLD by 5.9, but in II group significance level was higher - p&amp;lt;0.01 than in group III - p&amp;lt;0.001. MPV had not significant changes in I group versus control. Conclusion Spontaneous platelet aggregation is increased in hypertensive patients and it is significantly enhanced in combination with NAFLD. Thus in patients with isolated NAFLD also observed a statistically significant increase in spontaneous aggregation of platelets. That is possibly explained by an increase in MPV which can be considered as one of the NAFLD risk factors thrombophilic changes in primary hemostasis. An analysis of induced platelet aggregation showed that patients with NAFLD may have a lower sensitivity to acetylsalicylic acid therapy. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Bogomolets National Medical University </jats:sec

Hemodynamic Load on the Intracranial Arterial System in Subjects Who Have Suffered A Hemorrhagic Stroke as A Complication of Essential Arterial Hypertension

The aim of the investigation was to compare a hemodynamic load on the intracranial arterial system, assessed by the indices of 24-hours ambulatory blood pressure monitoring and ultrasonography of the large cervical arteries between the group of patients with essential arterial hypertension in ≥6 months after a hemorrhagic stroke and a group of patients with essential arterial hypertension without complications. The first one was the main group (n=94; age – 54.4±0.9 years), М±m), the second one – the comparison group (n=104; age – 53.7±0.9 years). The indices of 24-hours ambulatory blood pressure monitoring in the main group and the comparison group were the following: the mean daytime systolic blood pressure was 109.6±1.6 and 121.1±1.1 mm Hg, the minimal one was 74.4±2.0 mm Hg and 82.3±12.5 mm Hg, and the maximal one was 168.2±1.9 and 161.9±1.7 mm Hg, p&lt;0.05. The daytime systolic blood pressure sigma (17.9±0.6) and the average real variability of systolic blood pressure (11.31±2.52 mm Hg) were bigger in the main group (p&lt;0.01). The daytime index of hyperbaric load of systolic blood pressure was bigger in the main group: it was 403.6±25.9 against 231.7±12.1 mm Hg × h in the comparison group (p&lt;0.01). The maximal pulse pressure for a 24-hours interval was 74.2±2.0 and 66.4±0.9 mm Hg, respectively (p&lt;0.01). The indices of ultrasonography of the large cervical arteries in the right and left vessels of the main group were the following: the Gosling's pulsatility index was 1.578±0.059 and 1.552±0.042 for the common carotid artery, 1.210±0.044 and 1.102±0.037 for the internal carotid artery, 1.191±0.030 and 1.150±0.023 for the vertebral artery. The above-mentioned indices were bigger in the main group than in the comparison one (p&lt;0.01). The diameters of all the large cervical arteries were bigger in the main group (p&lt;0.01). Therefore, according to the above-mentioned indices which are associated with a bigger risk of cerebrovascular events, a bigger hemodynamic load on the intracranial arterial system was found in the main group than in the comparison one, despite the smaller mean systolic blood pressure indices