Atherothrombotic Ischemic Stroke Research Articles

Relationship between biomarkers of autophagy and inflammation in acute period of ischemic stroke

Postischemic neuroinflammation is a critical pathophysiological process within the entire pattern of cerebral ischemia, spanning early injury and tissue repair. According to recent experimental data, autophagy is involved in the regulation of neuroinflammation, influencing the outcome of the acute period of ischemic stroke (IS).Objective. To evaluate the relationship between autophagy biomarkers and inflammation indicators in the dynamics of the acute period of atherothrombotic IS.Materials and methods. 112 patients in the acute period of newly developed atherothrombotic IS and 56 donors (control group) were examined. Patients underwent dynamic clinical and neurological examination on the 1st, 7th and 14th days from the onset of the disease (magnetic resonance imaging, testing using the NIHSS scale, modified Rankin scale). At the same time intervals, blood was drawn for testing. The number of active autophagosomes in peripheral blood was assessed by flow cytometry using a specific Cyto-ID dye. The serum concentrations of proinflammatory cytokines IL‑1β, IL‑8, IL‑18 (interleukins‑1β, -8, -18), TNFα (tumor necrosis factor-α), autophagy biomarkers Beclin‑1, LC 3 and p62 were determined by enzyme-linked immunosorbent assay analysis. C-reactive protein was assessed by a highly sensitive immunoturbidimetric method.Results. A statistically significant increase in the studied parameters was revealed compared to the control group. The maximum increase in inflammation biomarkers was observed on the 1st day, and the maximum increase in key indicators of autophagy (LC 3, Beclin‑1, Cyto-ID) – on the 7th day after the development of ischemia. A direct relationship was established between the level of autophagy and the concentration of inflammatory biomarkers (CRP, IL‑1β, IL‑18, TNF-α) on the 1st and 7th days of acute IS.Conclusions. The identified correlations indicate the participation of activated autophagy in the regulation of post-ischemic neuroinflammation and its involvement in ischemic brain damage in the early stages of the acute period of IS (days 1–7). The results obtained confirm the literature data on the influence of autophagy on the outcome of the acute period of the disease.

Novel Therapeutic Approaches to Prevent Atherothrombotic Ischemic Stroke in Patients with Carotid Atherosclerosis.

Atherothrombotic stroke represents approximately 20% of all ischemic strokes. It is caused by large-artery atherosclerosis, mostly in the internal carotid artery, and it is associated with a high risk of early recurrence. After an ischemic stroke, tissue plasminogen activator is used in clinical practice, although it is not possible in all patients. In severe clinical situations, such as high carotid stenosis (≥70%), revascularization by carotid endarterectomy or by stent placement is carried out to avoid recurrences. In stroke prevention, the pharmacological recommendations are based on antithrombotic, lipid-lowering, and antihypertensive therapy. Inflammation is a promising target in stroke prevention, particularly in ischemic strokes associated with atherosclerosis. However, the use of anti-inflammatory strategies has been scarcely studied. No clinical trials are clearly successful and most preclinical studies are focused on protection after a stroke. The present review describes novel therapies addressed to counteract inflammation in the prevention of the first-ever or recurrent stroke. The putative clinical use of broad-spectrum and specific anti-inflammatory drugs, such as monoclonal antibodies and microRNAs (miRNAs) as regulators of atherosclerosis, will be outlined. Further studies are necessary to ascertain which patients may benefit from anti-inflammatory agents and how.

History of Carotid Artery Reconstruction around the World and in Japan.

Since ancient times, physicians have been aware of correlations between the carotid artery and consciousness; however, carotid stenosis was only recently identified as the cause of atherothrombotic ischemic stroke. In 1658, Wepfer described the first suggestion of a link between symptoms of cerebral arterial insufficiency and carotid pathology. In 1951, Fisher reported details of the symptoms and pathological findings and emphasized that cervical atheromatous lesions induced cerebral infarction with various symptoms. The beginning of carotid artery surgery was ligation of the carotid artery for neck or head injury, but surgeons were aware that this operation induced cerebral symptoms due to lack of blood supply. Carotid endarterectomy (CEA) was first reported by Eastcott et al. in 1954, and in Japan, Kimoto performed a successful CEA in 1962. In 1979, percutaneous transluminal angioplasty (PTA) was performed for patients with fibromuscular dysplasia, and then, carotid artery stenting (CAS) was first performed in 1989 by Mathias. In Japan, Kuwana et al. were the first to perform carotid PTA, in 1981, whereas Yamashita et al. performed the first CAS in 1997. Yoshimura et al. proposed staged carotid stenting to prevent hyperperfusion syndrome. Some issues in carotid reconstruction are still debated today, which include conventional (standard) CEA versus the eversion technique, CEA versus CAS versus medical therapy, and medical economic problems. In the future, we must continue to develop more effective, safer, and less expensive therapeutic methods to prevent carotid stroke, carrying on the efforts of the ancient peoples who pioneered this research.

Identification of the relationship between biomarkers of autophagy, apoptosis and inflammation in the acute period of atherothrombotic ischemic stroke

The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response.

Role of osteoprotegerin rs3102735 gene polymorphism in acute ischemic stroke patients

BackgroundIschemic stroke ranks third among leading causes of death and disability. Both endothelial and vascular smooth muscle cells generate osteoprotegerin (OPG). Ischemic stroke and its severity may be enhanced by the OPG rs3102735 gene polymorphism. Our research aims to investigate OPG rs3102735 gene polymorphism role in ischemic stroke risk and to assess its association with stroke severity at presentation and degree of vascular stenosis and evaluate its potential as a predictor of stroke severity. Fifty people with acute ischemic stroke as well as fifty controls were studied. The NIHSS and ASPECTS were utilized to evaluate stroke severity and the infarction size, respectively. All subjects underwent extracranial carotid duplex study and molecular assessment for genotyping of OPG rs3102735) gene polymorphism.ResultsStroke patients had markedly higher concentrations of OPG in the plasma than controls (311.60 ± 109.48 versus 240.20 ± 75.96 mmol/ml, p = 0.001). The optimal plasma OPG cutoff value for the predicting the occurrence of stroke was determined to be > 250 mmol/ml, the 95% confidence interval (CI) was (0.625–0.843), sensitivity was 68% and specificity was 72%. Ischemic stroke had a significantly different genotype distribution for the OPG rs3102735 gene polymorphism than did controls (36 CC, 13 CT, and 1 TT) versus (28 CC, 15 CT, and 7 TT) respectively. Stroke patients had a significantly greater CC + CT genotype than controls did (P = 0.041), also they had a higher propensity for carrying the C allele than the T allele (P = 0.017). Carotid intima medium thickness and the NIHSS both had positive correlations with OPG serum level (r = 0.39, p = 0.02 and r = 0.4, p = 0.02, respectively), whereas ASPECTS had an inversed correlation (r = − 0.65, p = 0.001).ConclusionsThe current study shows that as an independent risk factor, increased plasma OPG level, may participate in the atherothrombotic ischemic stroke pathophysiology, in addition, genetic variants in the OPG gene (rs3102735) are a separate risk factor for large artery atherosclerosis and plasma OPG level can serve as a biomarker to determine the severity of a stroke.

Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis

Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an 18F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(-)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(-). In a multivariable logistic regression analysis, the levels of LDL(-), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15-25.44, p < 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26-44.83, p < 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21-95.93, p < 0.033), indicating that an increased proportion of LDL(-) is associated with vulnerable atherosclerotic plaque.

ANALYSIS OF THE BLOOD HYPERCOAGULATION RISK IN PATIENTS WITH ISCHEMIC ATHEROTHROMBOTIC STROKE DEPENDING OF THE VDR GENE POLYMORPHISMS.

Aim: of our study was the analysis of the blood hypercoagulation risk in patients with ischemic atherotrombotic stroke depending of the VDR gene polymorphisms. Materials and Methods: Blood of 170 patients with ischemic atherothrombotic stroke (IATS) and 124 healthy individuals (control group) was used for genotyping. Four polymorphisms (FokI, BsmI, ApaI, TaqI) of gene VDR were examined with PCR-RFLP methodology. Statistical analysis was performed by using SPSS-17.0 program. Results: Among patients with IATS who are carriers of the f/f genotype, FokI polymorphism of VDR gene by high thrombin time and a decrease in the rate of spontaneous fibrinolysis was registered. In individuals with the B/B genotype homozygous for the polymorphic variant, BsmI had significantly lower mean values of prothrombin and thrombin time and increased the rate of spontaneous fibrinolysis. The homozygotes for the A-allele ApaI polymorphism have 2.7 times higher risk of developing blood hypercoagulation than homozygotes for the a-allele was found. Conclusions: Biochemical signs of hypercoagulation syndrome among patients with IATS who are carriers of the f/f genotype of the FokI polymorphic variant and among B/B homozygotes of the BsmI polymorphic variant and homozygotes for the A-allele of the AрaI polymorphism of the VDR gene were registered.

Optimization of secondary prevention in patients with high-risk atherothrombotic ischemic stroke or transient ischemic attacks

High and very high risk atherothrombotic ischemic stroke (ATIS) includes patients with severe extracranial atherosclerosis, any intracranial atherosclerosis, and aortic arch atheromatosis. The article discusses the most effective approaches to medical short- and long-term secondary prevention of ATIS, major vascular events and death, based on the results of modern research and current clinical guidelines. Clinical studies of recent years have proven the possibility of individualization and intensification of secondary prevention of ATIS. In the treatment of high-risk patients, it is advisable to use more widely short-term dual antiplatelet therapy (combination of ASA with clopidogrel or ticagrelor), long-term dual antithrombotic therapy (combination of ASA and rivaroxaban at a dose of 2.5 mg twice a day not earlier than 30 days from the development of stroke or TIA) to reduce the risk of recurrent stroke and death, as well as intensive lipid-lowering therapy (including the use of a combination of statins and ezetimibe or PCSK9 inhibitors).

Regional Anesthesia for Carotid Endarterectomy in Patients with Acute Ischemic Stroke (Pilot Study)

Objective. The aim of this study is to assess the safety of the use of regional anesthesia for performing carotid endarterectomy (CEA) in patients in the acute phase of ischemic stroke.Material and methods. The study included 66 patients in the acute phase of ischemic stroke (atherothrom-botic subtype according to the TOAST classification) who underwent carotid endarterectomy. The inclusion criteria for the study were as follows: acute phase of atherothrombotic ischemic stroke (first 28 days), ipsilateral symptomatic ≥ 50% stenosis of the internal carotid artery, 1-4 points neurological deficit according to the modified Rankin Scale (mRS), 1-13 points neurological deficit according to the National Institutes of Health Stroke Scale (NIHSS), size of the cerebral ischemic lesion ≤ 4 cm. This single-center prospective cohort study compared two anesthetic approaches, regional anesthesia (RA, 46 patients) and general anesthesia (GA, 20 patients). The RA techniques included ultrasound-guided superficial and deep cervical plexus blocks on the side of the surgery.Results. The study found no significant differences in the baseline patient characteristics, surgery techniques and clinical outcomes between the groups. There were no neurological or cardiovascular toxic reactions to the local anesthetics. Conversions from RA to GA were not performed. In the RA group, recurrent ipsilateral ischemic strokes, myocardial infarctions, wound hemorrhagic complications and lethal outcomes did not occur.Conclusion. This pilot study has demonstrated the safety of RA for performing CEA in patients in the acute phase of ischemic stroke. RA provides adequate neuromonitoring and timely intraoperative recognition of «new» ischemic complications. To compare the efficacy of RA and GA for performing CEA in patients with acute ischemic stroke, large randomized controlled trials are needed.

Components of a healthy diet and different types of physical activity and risk of atherothrombotic ischemic stroke: A prospective cohort study.

BackgroundDiet and physical activity (PA) are modifiable risk factors thought to influence the risk of ischemic stroke (IS). However, few studies have examined their effect on different subtypes of IS.AimTo examine components of overall diet quality and different types of PA in relation to the risk of atherothrombotic IS (aIS).Materials and methodsThe study population included 23,797 participants (mean age 58 years; 63% women) from the Malmö Diet and Cancer Study cohort. Participants were enrolled between 1991 and 1996 and followed until end of 2016 (median follow-up 21.5 years). Incident aIS events were identified using national registries (total cases 1,937). Measures of PA (total, leisure-time, occupational, and domestic) were assessed using a baseline questionnaire and dietary intakes were estimated using a modified diet history method. Overall diet quality was assessed using a diet quality index. Intake of key food groups and beverages associated with overall diet quality were investigated separately. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression models adjusting for confounders.ResultsA high diet quality with high intake of fruit and vegetables, fish and shellfish and low intake of sugar-sweetened beverages and red and processed meat compared to a low diet quality was associated with lower risk of aIS (HR = 0.82, 95% CI = 0.69–0.97; p = 0.015). Leisure-time PA was associated with reduced risk of aIS (HR = 0.95 per SD increase in MET-hours/week, 95% CI = 0.91–0.99; p = 0.028) with null associations observed for total, occupational and domestic PA level. We observed no significant interaction between diet and PA on the risk of aIS. The standardized 20-year risk of aIS among subjects with low leisure-time PA and low diet quality was 8.1% compared to 6.1% among those with high leisure-time PA and high diet quality.ConclusionSeveral components of a healthy diet and being physically active may reduce the risk of aIS, however, the absolute risk reduction observed was modest. A high diet quality seemed to have a risk reducing effect regardless of level of PA suggesting that individuals with a sedentary lifestyle may still gain some positive health benefits through a healthy diet.

Evaluation of hemostasis clinical and laboratory indicators of patients with stroke and coronavirus infection (COVID-19) on the basis of a multidisciplinary hospital in the period of its conversion to an infectious diseases hospital

Introduction. The COVID-19 impact on hemostasis of stroke survivors with community-acquired pneumonia is an urgent problem. The aim of the study is to analyze the features of clinical and laboratory parameters in cerebral stroke combined with community-acquired pneumonia caused by the SARS-Co-V-2 virus. Materials and methods. The instrumental and laboratory examination results of 88 patients aged 73.0 (12.3) years in the acute period of stroke with community-acquired viral pneumonia symptoms were analyzed. The present study included 39.8 % (n=53) male and 60.2 % female (n=35) with duration of diagnosed infectious disease less than 7 days. The symptoms of cerebral stroke were compared with the results of laboratory testing of the hemostasis system, lipid metabolism, and the activity of the systemic inflammatory response. The severity of lung tissue damage and the outcomes of the diagnosed changes were assessed. Results. All patients had mild or moderate COVID-19. In 87.5 % (n=77) cases unspecified (40.2 %, n=31), cardioembolic (36.4 %, n=28), lacunar (3.9 %, n=3) and atherothrombotic (19.5 %, n=15) ischemic stroke subtype was diagnosed. Focal ischemia lesion in the left middle cerebral artery (LMCA) territory was detected in 45.6 % (n=35), in the right middle cerebral artery (RMCA) territory in 41.6 % (n=32). Manifestations of hemorrhagic stroke were noted in 12.5 % (n=11) with signs of parenchymal hemorrhage in 54.5 % (n=6), ventricular hemorrhage in 27.3 % (n=3), subarachnoid hemorrhages were noted in 18.2 % (n=2). The indicators of the coagulation system in terms of the number of platelets corresponded to 251.3 (90.7); the APTT value was in the range of 29.2 (26.7 33.0) (s); the INR parameter was 1.16 (1.05 1.25); the value of prothrombin ( %) corresponded to the value of 85.9(23.4). Conclusion. We do not observe the great disorders of haemostasis in the most acute period of the stroke. When combined with COVID-19 the most common stroke is ischemic stroke. The stroke survivors with the community-acquired pneumonia caused by SARS-CoV-2 laboratory tests show that increase of inflammatory markers are above the reference range.

The predictive value of carotid artery strain and strain-rate in assessing the 3-year risk for stroke and acute coronary syndrome in patients with metabolic syndrome

Abstract Purpose The goal of this study is to see if carotid strain and strain rate can predict major cardio-vascular events (MACE) in people who have metabolic syndrome (MS) over a 3-year period of time. Methods In this prospective observational research, we enrolled 220 adult MS patients (60.7±7.5 years old, 53% male). Bilateral 2D common carotid carotid artery (CCA) speckle-tracking ultrasound was used to determine the peak circumferential strain (CS) and the peak circumferential strain rate (CSR). Clinical outcomes were assessed throughout a three-year follow-up period. Results After a 3-year follow-up period follow-up, 14 (7%) experienced MACE: Eight (4%) suffered an atherothrombotic ischemic stroke, four (2%) had acute coronary syndrome, and two (1%) were hospitalized for heart failure. Univariate regression analysis of the clinical and echocardiographic features of the MS patients found that age, systemic hypertension, diabetes mellitus, and the CCA circumferential strain and strain rate were significantly associated with the risk of MACE. Multivariate logistic regression identified two independent predictors of MACE in patients with MS, namely the CCA-related CS (%) and CSR (1/s), P&amp;lt;0.01. The ROC curve analyses of these independent predictors of MACE indicated appropriate sensitivities and specificities. CS (AUC = 0.806, sensitivity = 82.6%, specificity = 79.2%, P&amp;lt;0.0001); CSR (AUC = 0.779, sensitivity = 82.6%, specificity = 72.4%, P&amp;lt;0.0001). The cut-off values were ≤2.9% for carotid CS and ≤0.35 s–1 for carotid CSR. Using these cut-off values, we obtained Kaplan-Meier survival curves, and these showed that MACE, ischemic stroke, and ACS-free survival was significantly lower among the MS patients with lower carotid CS and CSR (P&amp;lt;0.0001). Conclusion Carotid CS and CSR were independent predictors of major cardio- and cerebrovascular events in prospectively monitored MS patients without established cardiovascular disease. Carotid deformation could be valuable as an early prognostic indicator for the cardiovascular risk in this population group. Funding Acknowledgement Type of funding sources: None.

Control of dyslipidemia in the prevention of recurrent ischemic cerebrovascular accidents (expert opinion)

On July 6, 2022, an interdisciplinary meeting of the Expert Council was held on the topic "Control of dyslipidemia in the prevention of acute and recurrent ischemic cerebrovascular accidents". The conclusion of the Expert Council was that after verification of a lipid metabolism abnormality, in patients with ischemic stroke (IS) and transient ischemic attack (TIA) it is recommended to start or continue statin therapy as early as possible. For secondary prevention of IS, it is necessary to achieve the target level of low-density lipoprotein cholesterol (LDL-C) set for each category of cardiovascular risk, with consistent administration of the maximum tolerated dose of statins with biochemical monitoring of the effectiveness and safety of therapy in the interval of 4–12 weeks. The insufficient effectiveness of statins requires the inclusion of ezetimibe therapy and the decision to increase the dose of statins; in case of intolerance to statins and / or contraindications to their administration, early administration of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors: evolocumab, alirocumab – or an PCSK9 synthesis inhibitor, inclisiran, should be considered. At a LDL-C level of &gt;5.0 mmol/l in patients of the extreme or very high risk group who have had atherothrombotic IS / TIA, necessary administration of a combination including a statin, ezetimibe and an PCSK9 inhibitor (evolocumab, alirocumab) or a PCSK9 synthesis inhibitor (inclisiran) should be considered as early as possible.

Assessment of the dynamics of autophagy and apoptosis biomarkers in the acute period of ischemic stroke using flow cytometry

The objective was to conduct a comparative analysis of the dynamics of biomarkers of apoptosis and autophagy in the eripheral blood of patients in the acute period of ischemic stroke (IS) and compare it with the dynamics of the severity of neurological deficit according to the NIHSS (National Institutes of Health Stroke Scale) and the volume of the brain lesion according to the results of magnetic resonance imaging (MRI). To assess the role of the studied parameters in the prognosis of the outcome of the acute period of the disease.Methods and material. We examined 56 patients in the acute period of newly developed atherothrombotic IS. The control group consisted of 29 healthy donors. Patients underwent a dynamic clinical and neurological examination on the 1st, 7th and 14th days from the onset of the disease. At the same time intervals, the dynamics of the expression of biomarkers of apoptosis and autophagy in peripheral blood was evaluated by flow cytometry and compared with neurological status indicators on the 1st, 7th, and 14th days, respectively, using correlation analysis.Results. A statistically significant increase in the expression of annexin V and caspase-3 compared with the control group was observed throughout the study in all populations of leukocytes with a maximum increase in the first 24 hours. Increased expression levels of annexin V and caspase-3 positively correlated with the severity of neurological deficit and the amount of brain damage on the 1st and 7th days. A direct correlation was found between increased values of autophagy biomarkers LC3, Cyto-ID, the amount of brain damage, and the severity of neurological deficit on the 7th day.Conclusion. A statistically significant increase in biomarkers of apoptosis and autophagy in the peripheral blood in the acute period of IS correlates with the severity of clinical and neurological parameters. The role of a significant increase in caspase-3 as a predictor of adverse disease outcome requires further study.

The Predictive Value of Carotid Artery Strain and Strain-Rate in Assessing the 3-Year Risk for Stroke and Acute Coronary Syndrome in Patients with Metabolic Syndrome

Purpose: The goal of this study is to see if carotid strain and strain rate can predict major cardio-vascular events (MACE) in people who have metabolic syndrome (MS) over a 3-year period of time. Methods: In this prospective observational research, we enrolled 220 adult MS patients (60.7 ± 7.5 years old, 53% male). Two-dimensional common carotid carotid artery (CCA) speckle-tracking ultrasound was used to determine the peak circumferential strain (CS) and the peak circumferential strain rate (CSR). Clinical outcomes were assessed throughout a three-year follow-up period. Results: After a 3-year follow-up period follow-up, 14 (7%) experienced MACE: Eight (4%) suffered an atherothrombotic ischemic stroke, four (2%) had acute coronary syndrome, and two (1%) were hospitalized for heart failure. Univariate regression analysis of the clinical and echocardiographic features of the MS patients found that age, systemic hypertension, diabetes mellitus, and the CCA circumferential strain and strain rate were significantly associated with the risk of MACE. Multivariate logistic regression identified two independent predictors of MACE in patients with MS, namely the CCA-related CS (%) and CSR (1/s), p &lt; 0.01. The Receiver operating characteristic (ROC) curve analyses of these independent predictors of MACE indicated appropriate sensitivities and specificities. CS (AUC = 0.806, sensitivity = 82.6%, specificity = 79.2%, p &lt; 0.0001) and CSR (AUC = 0.779, sensitivity = 82.6%, specificity = 72.4%, p &lt; 0.0001) with cut-off values of ≤2.9% for carotid CS and ≤0.35 s-1 for carotid CSR. Using these cut-off values, we obtained Kaplan-Meier survival curves, and these showed that MACE, ischemic stroke, and ACS-free survival was significantly lower among the MS patients with lower carotid CS and CSR (p &lt; 0.0001). Conclusions: Carotid CS and CSR were independent predictors of major cardio- and cerebro-vascular events in prospectively monitored MS patients without established cardiovascular disease. Carotid deformation could be valuable as an early prognostic indicator for the cardiovascular risk in this population group.

Дослідження зв’язку поліморфізмів генів ACE, AGT та FGB із ризиком раннього розвитку ішемічного інсульту атеротромботичного підтипу в популяції осіб, які проживають на території України

Актуальність. Атеротромботичний підтип ішемічного інсульту становить 50 % випадків захворювання та є причиною інвалідизації працездатного населення середнього віку. Судинні порушення можуть бути пов’язані зі змінами у структурі генів ангіотензинперетворюючого ферменту (АСЕ), ангіотензиногену (AGT) та бета-фібриногену (FGB). Мета дослідження. Дослідити зв’язок наявності I/D (rs1799752) поліморфізму гена АСЕ, Т174М (rs4762) поліморфізму гена AGT та С-148Т (rs1800787) поліморфізму гена FGB із ризиком раннього розвитку ішемічного інсульту атеротромботичного підтипу в популяції осіб білої раси, які проживають на території України. Матеріали та методи. Генетичний аналіз було проведено 78 хворим (24 жінки, 54 чоловіки), які перенесли ішемічний інсульт, та 55 особам популяційного контролю (20 жінок, 35 чоловіків), які не мали тяжких серцево-судинних захворювань. Середній вік пацієнтів експериментальної групи становив 53,9 ± 9,43 року, групи контролю — 59,8 ± 14,8 року. Поліморфізми генів AGT та FGB досліджували методом полімеразної ланцюгової реакції з подальшою рестрикцією ампліфікованих фрагментів. Генотипування поліморфізму I/D гена АСЕ було проведено методом алель-специфічної полімеразної ланцюгової реакції. Результати. Дослідження ризику розвитку захворювання показало, що носії I/D- та DD-генотипу гена АСЕ мають менший ризик захворіти на ішемічний інсульт атеротромботичного підтипу, ніж носії I/І-генотипу (OR = 0,303, 95% CI 0,134–0,688; р &lt; 0,05, та OR = 0,303, 95% CI 0,134–0,688; р &lt; 0,05 відповідно). Носії поліморфного генотипу -148СТ гена FGB частіше ніж удвічі ризикують захворіти на ішемічний інсульт (OR = 2,452; 95% CI 1,201–5,005; р &lt; 0,05), ніж носії генотипу -148СС. Зв’язок поліморфізму гена AGT T174M із ризиком розвитку ішемічного інсульту був відсутній. Висновки. Поліморфний генотип -148С/Т гена FGB, а також алель І та генотип ІІ гена АСЕ є факторами ризику раннього розвитку ішемічного інсульту атеротромботичного підтипу в популяції осіб, які проживають на території України.

Нейротрофічний фактор мозку як маркер відновлення моторних та когнітивних функцій у гострому періоді кардіоемболічного та атеротромботичного ішемічного інсульту

церебральний ішемічний інсульт - одне з найбільш поширених захворювань, що спричиняють психоемоційні, когнітивні та рухові розлади. Сучасні дослідження спрямовані на пошук біологічних маркерів ураження головного мозку при діагностиці інсультів, зокрема, фізичних, візуалізаційних, електрофізіологічних, гістологічних, генетичних та нейрональних, визначення яких може прискорити диференційну діагностику. Мета дослідження – оцінити рівень нейротрофічного фактору мозку в крові, стан моторних і когнітивних функцій в гострому періоді ішемічного інсульту на 1 та 14 добу, а також можливість використання рівня нейротрофічного фактору мозку крові в якості маркера відновлення рухової та інтелектуально-мнестичної сфери при атеротромботичному та кардіоемболічному підтипах ішемічного інсульту. У дослідження було включено 34 особи з діагнозом гострий ішемічний інсульт. Залежно від результатів клінічного обстеження пацієнтів було розподілено на 2 групи: група 1 – пацієнти, в яких ішемічний інсульт виник внаслідок атеросклеротичного ураження судин каротидної системи з розвитком оклюзії за механізмом атеротромбозу (17 осіб), група 2 – пацієнти, у яких ішемічний інсульт виник внаслідок ураження судин каротидної системи з розвитком оклюзії за кардіоемболічним механізмом (17 осіб). Для порівняння клініко-лабораторних показників додатково було виділено контрольну групу (пацієнти неврологічного відділення, які не мали ураження центральної нервової системи - 11 осіб). Обстеження пацієнтів проведено на 1 та 14 добу захворювання. Моторні функції оцінювали за ступенем повсякденної активності життя, що визначали за індексом Бартел, стан когнітивних функцій - за шкалою Mini-Mental State Examination. Індекс Бартел на 1 добу гострого періоду ішемічного інсульту перебував в межах легкої залежності для кардіоемболічного підтипу та помірної - для атеротромботичного. Протягом 14 днів у досліджуваних пацієнтів обох груп відбувалося зростання індексу до рівня повної незалежності у групі 1 та легкого ступеню залежності у групі 2. У обстежених пацієнтів із ішемічним інсультом було визначено середні значення за шкалою Mini-Mental State Examination на рівні помірного когнітивного дефіциту на 1 добу при обох підтипах ішемічного інсульту. Відновлення когнітивних функцій протягом 14 днів після ішемічного інсульту відбувалося тільки у другій групі до легких когнітивних розладів. Концентрація нейротрофічного фактору мозку на 1 добу ішемічного інсульту різко знижувалася порівняно з контрольною групою. Отримані результати дозволяють розглядати визначення мозкового нейротрофічного фактору об’єктивним біомаркером як тяжкості перебігу кардіоемболічного та атеротромботичного ішемічного інсульту, так і прогнозу відновлення моторних і когнітивних функцій.

Prospective Comparison of Plasma Biomarker and Traditional Risk Factor Profiles for Incident Isolated Atherosclerotic Disease and Incident Isolated Abdominal Aortic Aneurysm.

Background: Traditional risk factors for atherosclerotic disease (AD) are well-known, of which some are relevant also for abdominal aortic aneurysms (AAA). The present study compares the importance of plasma biomarkers and traditional risk factor profiles for incident AD without concomitant AAA (isolated AD) and AAA without concomitant AD (isolated AAA) during long-term follow-up.Methods: In the Malmö Diet and Cancer Study—cardiovascular cohort, 5,381 participants were free from atrial fibrillation or flutter, AD (coronary artery disease, atherothrombotic ischemic stroke, carotid artery disease, or peripheral artery disease), and AAA underwent blood sampling under standardized fasting conditions between 1991 and 1994. Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95% CIs.Results: During a median follow-up of 23.1 years, 1,152 participants developed isolated AD, and 44 developed isolated AAA. Adjusted HR for lipoprotein-associated phospholipase A2 (mass) (HR 1.53, 95% CI 1.14–2.04 vs. HR 1.05, 95% CI.99–1.12) was higher for incident isolated AAA compared to incident isolated AD, respectively. Mid-regional pro-adrenomedullin (MR-proADM) was associated with incident isolated AD (HR 1.17, 95% CI 1.1–1.25) and incident isolated AAA (HR 1.47, 95% CI 1.15–1.88). MR-proADM was correlated (r = 0.32; p < 0.001) to body mass index (BMI), and BMI was associated with increased risk of incident isolated AAA (HR 1.43, 95% CI 1.02–2). No participant with diabetes mellitus (DM) at baseline developed isolated AAA (0/44), whereas DM was associated with an increased risk of isolated AD (HR 2.57, 95% CI 2.08–3.18). Adjusted HR for male sex (HR 4.8, 95% CI 2.42–9.48, vs. HR 1.76, 95% CI 1.56–1.98) and current smoking (HR 4.79, 95% CI 2.42–9.47 vs. HR 1.97, 95% CI 1.73–2.23) were higher in the incident isolated AAA group compared to the incident isolated AD group, respectively.Conclusions: The data supports the view that components of vascular inflammation and cardiovascular stress drives AAA development, whereas glycated cross-links in abdominal aortic wall tissue may have a plausible role in reducing AAA risk in individuals with DM.

Analysis of relationship between rs4102217-MALAT1 gene polymorphism with ischemic atherothrobotic stroke in persons with normal and high blood pressure

Background. Ischemic atherothrombotic stroke (IATS) – multifactorial disease caused by a combination of genetic and environmental factors. Despite numerous studies of the pathogenetic component of ischemic stroke, there are no preclinical biomarkers that could support the study of molecular and physiological processes that lead to stroke. That's why a strategy for studying the pathogenesis of stroke is to start by identifying the genes associated with stroke. In particular, with ischemic stroke, an abnormal expression of MALAT1 plays an important role in such processes as angiogenesis, apoptosis, and inflammation. However, the study of the connection of the SNP variant of the MALAT1 with an IATS is few and not carried out in the Ukrainian population.The aim of this study was to investigate the possible association of rs4102217-polymorphism of the MALAT1 gene with ischemic stroke in individuals with normal and high blood pressure. Materials and methods. Venous blood of 200 patients with IATS was used for the study; the control group consisted of 234 practically healthy donors. To determine the SNP of rs4102217 MALAT1 was used polymerase chain reaction (Real-Time PCR). SPSS program (version 17.0, IBM, USA) was used for most statistical analyses. Results. It was found that the ratio of GG, GC and CC genotypes among the persons of the control group that had an increased AP - 84.9%, 13.7% and 1.4% respectively, and in the subgroup of persons from the main group with high blood pressure - 62,7%, 30.0%, 7.3% respectively. By applying χ2 – Pearson criterion was established a statistically significant difference in the distribution of genotypes between the comparative groups (χ2 - 12,015; P - 0,002). The results of logistic regression analysis showed statistically significant associations of IATS polymorphism in three models. So, the risk of development of IATS increases 2,97 times for patients with arterial hypertension, who are carriers of the C-allele (ORadj = 2,97; 95% CI = 1,286-6,785; Padj = 0,011 - for a dominant model). Conclusions. There is a link between the rs4102217-polymorphism of the MALAT1 gene and the development of IATI in people with normal and high blood pressure.

Cerebrovascular Disease and Statins.

Elevated low-density lipoprotein-cholesterol (LDL-C) is a causal factor for the development of atherosclerotic cardiovascular disease (ASCVD); accordingly, LDL-C lowering is associated with a decreased risk of progression of atherosclerotic plaques and development of complications. Currently, statins play a central role in any ASCVD management and prevention strategies, in relation to their lipid-lowering action and potentially to pleiotropic effects. After coronary artery disease, stroke is the most frequent cause of ASCVD mortality and the leading cause of acquired disability, a major public health problem. There is often a tendency to aggregate all types of stroke (atherothrombotic, cardioembolic, and haemorrhagic), which have, however, different causes and pathophysiology, what may lead to bias when interpreting the results of the studies. Survivors of a first atherothrombotic ischemic stroke are at high risk for coronary events, recurrent stroke, and vascular death. Although epidemiological studies show a weak relationship between cholesterol levels and cerebrovascular disease as a whole compared with other ASCVD types, statin intervention studies have demonstrated a decrease in the risk of stroke in patients with atherosclerosis of other territories and a decrease in all cardiovascular events in patients who have had a stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial demonstrated the benefit of high doses of atorvastatin in the secondary prevention of ischemic stroke. In this review, we discuss the evidence, use and recommendations of statins in the primary and secondary prevention of stroke, and their role in other scenarios such as the acute phase of ischemic stroke, cerebral hemorrhage, cardioembolic stroke, small vessel disease, and cognitive impairment.