WNT Signaling Cascade Proteins and LRP6 in the Formation of Various Types of Coronary Lesions in Patients With Coronary Artery Disease.

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%).

Assessment of the Level of Matrix Metalloproteinases, VEGF and MicroRNA-34a in Patients With Non-obstructive and Obstructive Lesions of the Coronary Arteries.

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.

The Effect of COVID-19 on Long-Term Cardiac Function in Patients With Chronic Heart Failure.

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.

[Management of patients with atrial fibrillation and minor bleeding during therapy with direct oral anti-coagulants].

The recommended tactics for prevention of thromboembolic complications of atrial fibrillation (AF) is the oral anticoagulant (OAC) treatment. The drugs of choice for preventing stroke for most patients with AF, excluding some valvular defects, are direct OACs (DOACS). Regardless of the drug class, all anticoagulants, even at appropriate doses, increase the risk of bleeding. However, the development of minor bleedings is not an absolute indication for DOAC withdrawal. This review presents a tactics for management of patients with minor bleeding associated with the DOAC treatment.

[Recommendations on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (Based on 2018 European Heart Rhythm Association Practical Guide)].

Non-vitamin K antagonist oral anticoagulants (NOACs) - direct oral anticoagulants - are getting the ever-broadening use in clinical practice. However, many problems related to optimal use of NOACs in specific clinical situations remain unresolved. European Heart Rhythm Association in April 2018 issued the renovated recommendations on the use of NOACs in patients with atrial fibrillation. The authors of recommendations presented some specific clinical variants for which they formulated practical advices based on the evidence obtained in randomized clinical trials. They also outlined the indications for use of NOACs, formulated practical start-program and scheme of subsequent follow-up management of patients taking NOACs. Recommendations contain information on pharmacokinetics of NOACs and their interactions with other drugs, consideration of feasibility of NOACs use in patients with chronic renal insufficiency or advanced liver disease. Many other practical problems are covered as well.

[Non-vitamin K antagonist oral anticoagulants for heart diseases]. / Peroral'nye antikoagulianty - antagonisty vitamina K pri zabolevaniiakh serdtsa.

Non-vitamin K antagonist oral anticoagulants (NОАСs) are highly effective drugs that prevent venous thrombosis and stroke in atrial fibrillation. Their use has difficulties that are associated with the need for laboratory control and with the influence of many factors on the activity of these medications. The emerged direct oral anticoagulants have some advantages over NOACs. Nevertheless, there are a number of pathological conditions, in which NOACs remain first-line drugs. These include prosthetic mechanical heart valves, a glomerular filtration rate less than 60 mL/min/1.73 m2, and left atrial thrombus.

[Antiplatelet therapy in cardiology].

Platelets are important components of hemostasis and play a key role in the formation of atherothrombosis. Rupture or erosion of atherosclerotic plaque gives rise to a thrombus with the involvement of platelets. Antiplatelet agents are instrumental in preventing the development of atherothrombosis of different localization, including coronary arteries.

[Intensity of intravascular microcoagulation in chronic obstructive pulmonary disease with atherotrombosis and thrombophilia].

The growing occurrence of thrombophilic conditions in recent years, the discovery of new forms of thrombophilia, the involvement of intravascular microcoagulation in the development of many diseases make their study of primary importance especially in patients with chronic obstructive pulmonary disease and atherothrombosis. Such investigations would facilitate a deeper understanding of the detailed mechanisms of thrombosis in these patients and thereby contribute to the optimization of their treatment and prevention.

[What are thrombophilias to-day?].

Modern concepts of thrombophilia, its role in pathogenesis of arterial and venous thrombosis are discussed. The author's view of further development of this issue is expounded.

[Stroke in the clinical practice of a therapist].

The stroke resulting in serious neurologic deficit is the third most frequent cause of death and loss of working ability. In 60-65% of the cases, it is provoked by atherothrombosis located in aortic arch, common and internal carotid arteries. Thromboembolism of cerebral vessels originating in heart cavities is responsible for 15-18% of the cases. Stroke prevention is an interdisciplinary problem encountered not only by neurologists but also by many other physicians. A major preventive tool for the stroke is healthy lifestyle while therapy with antithrombotic drugs (antiaggregants, oral anticoagulants) is the main component of secondary prevention. The choice of therapy depends on the cause and degree of stroke.

[Atherothrombosis: state-of-the-art review and approaches to the problem].

Acute ischemia resulting from arterial lesions poses a real threat to mankind. The concept of atherothrombosis aims to unite doctors of different specialities to combat this pathology; it suggests active exchange of experience in the management of aherothrombosis between representatives of different medical disciplines. The concept is expected to promote treatment of the patients. The common pathogenetic mechanism of ischemic disorders of the heart, brain, and lower extremities provides a basis for the recommendation of active antithrombotic therapy for their prevention. The current approach to the management of atherothrombosis is prone to further improvement despite certain reports of successful inpatient treatment of acute myocardial infarction. Prevention of blood clot formation, i.e. prophylaxis of atherosclerosis, remains a challenging problem. Statins may prove of great help in this respect. Studies of the effect of infectious factors on the integrity of the fibrous envelope of an atherosclerotic plaque are currently underway.

[The features of myocardial infarction clinical course at gene of endothelial NO-synthase polymorphisms].

81 patients were included in the research into study of acute myocardial infarction (AMI) clinical course features in patients with various polymorphism of gene. These patients besides traditional examination, received genetic examination for determination of of NO-synthase gene in intron 4 (eNOS 4a/4b polymorphism) and mutation in position 298 of protein sequence leading to replacement of rest of glutamine acid by asparaginic acid (Glu298Asp). Patients with allele 4a polymorphism of endothelial NO-synthase gene in intron 4 (genotypes 4a/4a and 4a/4b) had low level of high-density lipoprotein cholesterol (HDLC) in comparison with 4b homozygote patients. Inverse association of 4a allele with HDLC did not depend on the AMI therapy character. Besides, it was detected that AMI patients with 4a/4a polymorphism had bronchial asthma and chronic hepatitis more frequently than patients with 4b/4b genotype. AMI patients with 4a allele had early postinfarction angina and gastroesophagoreflux disease. The relation of allele 4a carriage with development of early postinfarction angina depended on presence of bronchial asthma in AMI patients. AMI patients with Glu298Asp polymorphism Asp/Asp genotype did not have significant differences in AMI and concomitant pathology course in comparison with Glu/Glu genotype patients.

[Susceptibility to endothelium-dependent vasoactive agents in patients with coronary artery calcinosis].

Coronary artery calcinosis was measured with ECG-gated multislice spiral CT in 68 patients, mean age 57.54+/-1.04 (M+/-m), including 47 men (69.1%) and 21 women (30.9%). Vascular reactivity of microcirculatory bed was assessed with laser Doppler flowmetry after acetylcholine and histamine administration. Coronary artery calcinosis correlated negatively with vascular susceptibility to acetylcholine (r=-0.380, p=0.002). This correlation did not depend on sex, age and concomitant drug therapy. Smoking was shown to affect significantly microvascular reactivity to histamine in persons free from coronary atherosclerosis. History of smoking determined the disturbances of vascular reactivity to histamine in patients with coronary artery calcinosis.

[Present-day problems of venous thromboses].

Venous thrombosis (VT) is a frequent pathology associated with a high mortality. A high risk of VT is associated with a variety of diseases, syndromes, and situations, connected with a congenital predisposition (thrombophilia) or not. Clinical and instrumental data in VT are non-specific. The diagnosis of these conditions is very difficult. Correct and timely treatment decreases mortality associated with pulmonary arterial thromboembolism (PATE). Unfortunately, this index is still very high: a lot of patients die within first minutes and even seconds of the moment of pulmonary arterial obturation with a thrombus. All this suggests that PATE belongs to diseases that are easier to prevent than to treat. In connection with this, a doctor examining a patient must always keep the possibility of VT and PATE in mind and evaluate the risk of their development, thus taking a decision concerning the necessity, duration, and a method of preventive treatment.

[Diagnostic possibilities of ultrasonic scanning of the knee joints in osteoarthrosis].

AIM: To examine diagnostic potential of arthrosonography (ASG) in diagnosis of tendenitis in combination with synovitis in patients with gonarthrosis stage I-III by Kellgren's classification. MATERIAL AND METHODS: A total of 40 patients with gonarthrosis exacerbation were examined with x-ray and ultrasound scanning (80 joints). ASG was made on Aloka-SSD-630 device using two-dimentional scanning in 4 longitudinal and 4 transverse positions. RESULTS: Clinical symptoms of synovitis were predominant in patients with gonarthrosis x-ray stage II (68.3%). In ASG synovitis was detected in 41 (51.25%) of 48 knee joints with clinical picture of synovitis. Ultrasound detected such synovitis signs as increased amount of water in the knee joint cavity and b. suprapatellaris, thickening of the synovial membrane more than 0.3 cm and changes in its structure. Six (7.5%) joints were affected with subclinical synovitis diagnosed only in ASG. Ultrasound visualized Baker's cyst in 5 patients and in 5 knee joints. Periarthritis was detected in 77.5% joints, in 46.25% joints it combined with synovitis, ASG provided differential diagnosis of synovitis with periarthritis. Thinning of the cartilage was detected in most of the joints both in synovitis and in its absence but it was more significant in synovitis (62.5 and 40%, respectively). CONCLUSION: ASG is an informative diagnostic method in periarthritis and synovitis, including subclinical, and give additional information for x-ray diagnosis in gonarthrosis stage I-III.

[Relationship of vascular reactivity to blood lipid spectrum and lipid peroxidation in unstable angina]. / Sootnoshenie sosudistoi reaktivnosti s lipidnym spektrom krovi i sostoianiem perekisnogo okisleniia lipidov pri nestabil'noi stenokardii.

AIM: To examine the relationship between the vascular response of the microcirculatory bed to vasoactive agents and lipid peroxidation (LPO) and antioxidative defense in patients with unstable angina pectoris. MATERIALS AND METHODS: Thirty male patients (mean age 58.0 +/- 2.4 years) were examined. The patients were divided into 2 groups: 1) those with high alpha-cholesterolemia alone and 2) those with high alpha-cholesterolemia concurrent with hyperglyceridemia and elevated total cholesterol levels. Photoplethysmographic determination was used to evaluate vascular responses to norepinephrine (vasopressor function) and histamine (vasodilating function), the blood levels of cortisol, LPO products, antioxidative protection components, histamine, and serotonin. RESULTS: Vascular dilating function was found to be most pronounced in Group 1. Moreover, Group 1 patients had a significant depression of the antioxidative defense system and the highest blood levels of cortisol, and serotonin. The levels of LPO products did not differ significantly in both groups though they were significantly higher than those in healthy individuals. CONCLUSION: Impairment in the antioxidant system and in coordination of vasodilating function to histamine stimulation are typical of patients with unstable angina.

[The mass of the myocardium and tolerance for physical exercise in the postinfarct period in hypertension patients]. / Massa miokarda i perenosimost' fizicheskoi nagruzki v postinfarktnom periode u bol'nykh gipertonicheskoi bolezn'iu.

As many as 56 patients with stage-II hypertensive disease (HD) as per the WHO classification were examined. On day 30 of myocardial infarction (MI) the left ventricular myocardium mass was calculated and six months later exercise tolerance was evaluated using bicycle ergometer. The evaluation done showed that the presence of hypertrophy of the Left ventricle in HD patients by day 30 of MI was a prognostic sign of low exercise tolerance in postinfarction period, which fact permits exercise tolerability to be foreseen, and issues related to the patients' fitness for work to be settled as early as the hospital stage of rehabilitation of MI patients.

[Left ventricular mass of the myocardium and its contractile capacity in hypertensive patients in the postinfarct period]. / Massa miokarda levogo zheludochka i ego sokratitel'naia sposobnost' u bol'nykh gipertonicheskoi bolezn'iu v postinfarktnom periode.

Seventy patients with hypertonic disease (HD) in the IInd stage were examined echocardiographically 30 days and 6 months after macrofocal myocardial infarction with the view to study contractility of myocardium of the left ventricle depending on its mass. Increase of the left ventricle mass (LVM) in patients with HD after infarction was established to be associated with rise of myocardial contractility. Fall of the LVM occurs at the account of thinning of ventricular wall without changes in volumic parameters of the left ventricle.