Stable Plaque Research Articles

Clinical Significance of Peptidase M20 Domain Containing 1 Ii Patients with Carotid Atherosclerosis.

ResumoFundamento A aterosclerose é a principal causa da maioria das doenças cardiovasculares, e novos biomarcadores para essa condição são sempre necessários. O domínio da peptidase M20 contendo 1 (PM20D1) está associado ao metabolismo lipídico e à obesidade. No entanto, nenhum estudo se concentra no papel do PM20D1 na aterosclerose carotídea.Objetivo O objetivo deste estudo foi investigar o papel do PM20D1 em pacientes com aterosclerose carotídea.Métodos Estudo observacional prospectivo conduzido com um total de 231 pacientes com aterosclerose carotídea que estiveram em nosso departamento entre julho de 2018 e dezembro de 2019. Amostras de sangue e dados médicas foram obtidos de outros 231 indivíduos saudáveis com o mesmo índice de massa corporal (IMC) dos pacientes com aterosclerose carotídea. O PM20D1 sérico foi determinado por ensaio imunossorvente ligado a enzima (ELISA). As características clínicas e demográficas de todos os pacientes foram listadas, incluindo idade, sexo biológico, IMC e histórico médico. Os níveis de proteína C reativa (PCR), fator de necrose tumoral, homocisteína, colesterol total, triglicerídeos, leptina-colesterol de alta densidade e leptina-colesterol de baixa densidade foram registrados. Realizou-se análise estatística no software SPSS, com p<0,05 considerado estatisticamente significante.Resultados Os níveis séricos de PM20D1 foram marcadamente mais baixos em pacientes com aterosclerose carotídea comparados aos controles saudáveis, sendo significativamente mais baixos em pacientes com aterosclerose carotídea grave e pacientes com aterosclerose carotídea/acidente vascular cerebral. Pacientes com placas instáveis apresentaram PM20D1 marcadamente menor quando comparados a pacientes com placas estáveis. Nenhuma diferença significativa foi encontrada entre pacientes com aterosclerose carotídea com diferentes IMC. Pacientes com níveis mais elevados de PM20D1 apresentaram expressão significativamente menor de PCR, fator de necrose tumoral, homocisteína, triglicerídeos, colesterol total e colesterol de baixa densidade. PM20D1 correlacionou-se negativamente com PCR, fator de necrose tumoral, homocisteína, colesterol total e leptina de baixa densidade em pacientes com aterosclerose carotídea, podendo ser usado como biomarcador para pacientes com aterosclerose carotídea grave ou com aterosclerose carotídea e acidente vascular cerebral. Sexo biológico, fator de necrose tumoral, homocisteína e PM20D1 foram considerados fatores de risco para aterosclerose carotídea.Conclusão O PM20D1 estava diminuído em pacientes com aterosclerose carotídea e foi associado com gravidade, estabilidade da placa, níveis de PCR, fator de necrose tumoral, homocisteína, triglicerídeos, colesterol total e colesterol de baixa densidade em pacientes com aterosclerose carotídea.

Coronary Computed Tomography Angiography Analysis of Calcium Content to Identify Non-culprit Vulnerable Plaques in Patients With Acute Coronary Syndrome.

BackgroundAside from the culprit plaque, the presence of vulnerable plaques in patients with acute coronary syndrome (ACS) may be associated with future cardiac events. A link between calcification and plaque rupture has been previously described.AimTo assess whether analysis of the calcium component of coronary plaques using CT angiography, coronary computed tomographic angiography (CCTA) can help to detect additional vulnerable plaques in patients with non-ST elevation myocardial infarction (NSTEMI).Materials And MethodsCross sectional study of consecutive patients referred for NSTEMI from 30 July to 30 August 2018 with CCTA performed before coronary angiography with systematic optical coherence tomography (OCT) analysis of all coronary arteries within 24 h of clinical onset of NSTEMI. Three types of plaques were defined: culprit plaques defined by angiography (vulnerable culprit plaques–VCP) – plaques with a fibrous cap thickness < 65 microns or thrombus in OCT (vulnerable non-culprit plaque–VNCP) – plaques with a fibrous cap thickness ≥ 65 microns in OCT (stable plaque–SP).ResultsA total of 134 calcified plaques were identified in 29 patients (73% male, 59 ± 14 years) with 29(22%) VCP, 28(21%) VNCP and 77(57%) SP. Using CCTA analysis of the calcium component, factors associated with vulnerable plaques were longer calcification length, larger calcification volume, lower calcium mass, higher Agatston score plaque-specific (ASp), presence of spotty calcifications and an intimal position in the wall. In multivariate analysis, ASp, calcification length and spotty calcifications were independently associated to vulnerable plaques. There was no difference between VCP and VNCP.ConclusionsCCTA analysis of calcium component of the plaque could help to identify additional vulnerable plaques in NSTEMI patients.

PCSK9 Inhibitors Safely and Effectively Lower LDL After Heart Transplantation: A Systematic Review and Meta-Analysis

<h3>Purpose</h3> Coronary allograft vasculopathy (CAV) continues to afflict a majority of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT, however data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. <h3>Methods</h3> We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15^th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. <h3>Results</h3> `A total of six studies including 97 patients were evaluated, most of which either had statin intolerance or refractory hyperlipidemia. Over a mean follow up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI -119.15 to -46.07; <i>I²</i>=82%) (<b>Figure 1</b>) from baseline. Serious adverse drug reactions were rarely reported, and none were attributable to the PCSK9i therapy. Three studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. No studies reported on immunologic safety (i.e. development of DSA), hence this endpoint cannot be assessed. <h3>Conclusion</h3> Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.

Relationship of the Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio with a Vulnerable Plaque in Patients with Severe Carotid Artery Stenosis: A Case-Control Study in the Han Chinese Population.

Carotid plaque is often an important factor in ischemic stroke after it changes from stable to vulnerable, and low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) are associated with plaque vulnerability. We aimed to investigate whether the LDL-c/HDL-c ratio, an easily available and novel biomarker, is associated with vulnerable plaques and enhances the warning effect on vulnerability compared to LDL-c or HDL-c alone. We conducted a retrospective study of 187 patients with severe CAS admitted to the Department of Vascular Surgery at the Nanjing Drum Tower Hospital from January 2019 to July 2021. They were divided into a stable plaque group and a vulnerable plaque group according to carotid ultrasonography, carotid angiography (CTA), and plaque pathology. Baseline information was collected and compared between the two groups. Correlation analysis was used to determine the degree of correlation between clinical variables. Univariate and multifactor logistic regression analyses were used to examine independent risk factors for vulnerable plaque in patients with severe CAS. Receiver operating characteristic (ROC) curves were used to assess the capacity of LDL-c/HDL-c to predict the occurrence of vulnerable plaque. The age of the vulnerable plaque group was 68.12 ± 8.90 years, with 85 males (89.91%); the age of the stable plaque group was 68.77 ± 8.43 years, with 70 males (89.74%). Multivariate logistic regression analysis showed that LDL-c/HDL-c, smoking and diabetes were independent risk factors for vulnerable plaque (all P <0.05). The risk of vulnerable plaque was 4.78-fold greater in the highest LDL-c/HDL-c quartile (≥ 2.63) than in the lowest quartile (≤ 1.31) (P-trend <0.001), and the area under the ROC curve for LDL-c/HDL-c (AUC=0.681, P <0.001) was higher than that for LDL-c and HDL-c. LDL-c/HDL-c, smoking and diabetes were independent risk factors for vulnerable plaque in patients with severe CAS, and LDL-c/HDL-c had a higher predictive value for the presence of vulnerable plaque compared with other lipid parameters.

Triglyceride-Glucose Index Is Related to Carotid Plaque and Its Stability in Nondiabetic Adults: A Cross-Sectional Study.

BackgroundCarotid plaque plays an important role in the development of stroke. The triglyceride-glucose (TyG) index is a reliable alternative marker of insulin resistance. However, there are limited data regarding the relationship between TyG index and carotid plaque and its stability in nondiabetic adults.MethodsThis study was carried out on 24,895 urban workers (10,978 men and 13,917 women) aged 20 years or older who participated in a comprehensive health screening between January 2016 and December 2017 at the First Affiliated Hospital of Zhengzhou University, China. Carotid plaque was assessed using ultrasonography. TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL) /2]. Logistic regression models and restricted cubic spline (RCS) models were used to estimate the association of the TyG index with carotid plaque and its stability by odds ratios (ORs) and 95% confidence intervals (CIs).ResultsCarotid plaque was detected in 5,668 (22.8%) respondents, with stable and unstable plaque accounting for 2,511 (10.1%) and 3,158 (12.7%), respectively. There was a significant positive association between the prevalence of carotid plaque and TyG index quartile levels, and the same associations were observed for the prevalence of stable and unstable carotid plaque (P for trend <0.0001). The multivariable-adjusted ORs (95% CIs) for the highest vs. lowest quartile of TyG index were 1.30 (1.15–1.47) for carotid plaque, 1.38 (1.17–1.63) for stable carotid plaque, and 1.24 (1.07–1.43) for unstable carotid plaque. The RCS analysis showed a linear association between TyG index and carotid plaque, and linear associations were also observed between TyG index and both stable carotid plaque and unstable carotid plaque (P for linearity<0.05).ConclusionOur findings suggested that the TyG index was significantly associated with carotid plaque and might be a useful indicator for the early identification of carotid plaque in nondiabetic subjects.

Increased Neutrophil elastase and proteinase 3 are closely associated with occurrence and severity of stroke and acute myocardial infarction in patients with type 2 diabetes mellitus

AimsThe role of Neutrophil elastase (NE) and proteinase 3 (PR3) in the occurrence and severity of stroke and acute myocardial infarction (AMI) have not been explored in type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship and predictive ability of NE and PR3 in the development of stroke and AMI in patients with T2DM, and to explore the pattern of NE and PR3 in atherosclerotic plaques. Methods465 patients with T2DM (stroke or AMI, n = 234; non stroke or AMI, n = 231) were recruited. Clinical characteristics, and NE and PR3 concentration were measured in all subjects. Semi-quantitative analysis of immunohistochemistry staining for NE and PR3 was performed in detached emboli and stable plaques. ResultsPatients with stroke or AMI had a higher level of NE and PR3, with a more pronounced increase in more severe cases (higher mRS score in stroke and Gensini score in AMI) and associated with clinical markers. An increase in NE and PR3 was an independent risk factor for stroke (OR = 4.318, P = 0.017; OR = 2.979, P = 0.048, respectively) and AMI (OR = 8.385, P = 0.015; OR = 5.540, P = 0.047). Finally, immunohistochemistry staining revealed that the NE and PR3 positive area increased significantly in detached emboli compared with stable plaques. ConclusionIncreased NE and PR3 was associated with occurrence and severity of stroke and AMI in patients with T2DM. Enriched NE and PR3 in detached emboli may be associated with plaque vulnerability.

Preliminary study on the differentiation of vulnerable carotid plaques via analysis of calcium content and spectral curve slope by using gemstone spectral imaging.

Growing evidence indicates that vulnerable carotid plaque rupture is an important cause of stroke. However, the role of novel gemstone spectral imaging (GSI) in the assessment of vulnerable carotid plaques has remained to be sufficiently explored. Therefore, the aim of the present study was to provide a comprehensive evaluation of carotid atherosclerotic plaques using both GSI imaging biomarkers and serological biomarkers, and further explore their possible roles in the atherogenic process. The present study analyzed GSI data, including calcium content of carotid atherosclerotic plaques and spectral curve slope, as well as serum high-sensitivity C-reactive protein (Hs-CRP) and monocyte chemotactic protein-1 (MCP-1) levels in patients with a carotid atherosclerotic plaque using GSI-computed tomographic angiography and immunoturbidimetry. Patients with unstable plaque exhibited a significantly lower calcium content and higher spectral curve slope than those of the stable plaque group. In addition, patients with unstable plaque exhibited an increase in Hs-CRP and MCP-1 levels compared with those of the stable plaque and normal control groups. The alteration in GSI calcium content and spectral curve slope reflects a close link between calcification and plaque instability, while aberrant Hs-CRP and MCP-1 expression are involved in the formation or development of vulnerable plaques. Taken together, the present results strongly support the feasibility of using these serological and newly identified imaging parameters as multiple potential biomarkers relevant to plaque vulnerability or stroke progression.

Relationship between subclasses low-density lipoprotein and carotid plaque.

BackgoundLow-density lipoprotein (LDL) cholesterol can lead to the occurrence of atherosclerotic plaques, but patients with normal LDL still have atherosclerotic plaques in clinical practice. With the proposal of LDL subclass, this experiment investigated the relationship between the LDL content of different subclasses and the stability of carotid plaques.MethodsPlaque stability was suggested by carotid ultrasound results. 37 patients with stable plaques were classified into one group and 41 patients with unstable plaques were classified into another group. The data of age, glycosylated hemoglobin (Ghb), and homocysteine (Hcy) were collected. The contents of LDL subclasses were measured by LIPOPRINT system. The data of total cholesterol (TC), LDL cholesterol, and triglyceride (TG) were collected. The plaque stability was assessed by carotid artery color Doppler ultrasound and the intima-media thickness (IMT) was measured.ResultsThe levels of LDL-1 subclass 19.00 (13.00, 27.50) and LDL-2 subclass (21.62 ± 7.24) in the stable plaque group were higher than those in the unstable plaque group (p < 0.05). The levels of LDL-3 subclass (12.24 ± 4.58), LDL-4 subclass 5.00 (2.00, 9.00), and sd-LDL 0 (0.00, 3.00) in the unstable plaque group were higher than those in the stable plaque group (p < 0.05). LDL-1 subclass (adjusted OR = 0.923 and p < 0.05), and LDL-3 subclass (adjusted OR = 1.176 and p < 0.05) were independent risk factors for plaque stability.ConclusionElevated LDL1 is associated with stable plaques whereas LDL3 was found associated with unstable plaques.

Osteomodulin Gene Expression Is Associated With Plaque Calcification, Stability, and Fewer Cardiovascular Events in the CPIP Cohort.

Stable atherosclerotic plaques are characterized by thick fibrous caps of smooth muscle cells, collagen, and macrocalcifications. Identifying factors of plaque stability is necessary to design drugs to prevent plaque rupture and symptoms. Osteomodulin, originally identified in bones, is expressed by bone synthesizing osteoblasts and involved in mineralization. In the present study, we analyzed osteomodulin expression in human carotid plaques, its link with plaque phenotype, calcification, and future cardiovascular events. Osteomodulin gene expression (OMD; n=82) was determined by RNA sequencing and osteomodulin protein levels by immunohistochemistry (n=45) in carotid plaques obtained by endarterectomy from patients with or without cerebrovascular symptoms from the CPIP (Carotid Plaque Imaging Project) cohort, Skåne University Hospital, Sweden. Plaque components were assessed by immunohistochemistry, RNA sequencing, and multiplex analysis. Patients were followed for cardiovascular events or cardiovascular death during a median of 57 or 70 months, respectively, using national registers. OMD levels were increased in plaques from asymptomatic patients compared to symptomatics. High OMD levels were associated with fewer cardiovascular events during follow-up. OMD correlated positively with smooth muscle α-actin (ACTA2; r=0.73, P=10-13) and collagen (COL1A2; r=0.4, P=0.0002), but inversely with CD68 gene expression (r=-0.67, P=10-11), lipids (r=-0.37, P=0.001), intraplaque hemorrhage (r=-0.32, P=0.010), inflammatory cytokine, and matrix metalloproteinase plaque contents. OMD was positively associated with MSX2 (Msh Homeobox 2) (r=0.32, P=0.003), a marker of preosteoblast differentiation, BMP4 (bone morphogenetic protein) (r=0.50, P=0.000002) and BMP6 (r=0.47, P=0.000007), plaque calcification (r=0.35, P=0.016), and was strongly upregulated in osteogenically stimulated smooth muscle cells, which was further increased upon BMP stimulation. Osteomodulin protein was present in calcified regions. Osteomodulin protein levels were associated with plaque calcification (r=0.41, P=0.006) and increased in macrocalcified plaques. These data show that osteomodulin mRNA and protein levels are associated with plaque calcification in human atherosclerosis. Furthermore, osteomodulin mRNA, but not protein levels, is associated with plaque stability.

The Applications of Single-Cell RNA Sequencing in Atherosclerotic Disease.

Atherosclerosis still is the primary cause of death worldwide. Our characterization of the atherosclerotic lesion is mainly rooted in definitions based on pathological descriptions. We often speak in absolutes regarding plaque phenotypes: vulnerable vs. stable plaques or plaque rupture vs. plaque erosion. By focusing on these concepts, we may have oversimplified the atherosclerotic disease and its mechanisms. The widely used definitions of pathology-based plaque phenotypes can be fine-tuned with observations made with various -omics techniques. Recent advancements in single-cell transcriptomics provide the opportunity to characterize the cellular composition of the atherosclerotic plaque. This additional layer of information facilitates the in-depth characterization of the atherosclerotic plaque. In this review, we discuss the impact that single-cell transcriptomics may exert on our current understanding of atherosclerosis.

Pharmacological Inhibition of Factor XIIa Attenuates Abdominal Aortic Aneurysm, Reduces Atherosclerosis, and Stabilizes Atherosclerotic Plaques.

Background 3F7 is a monoclonal antibody targeting the enzymatic pocket of activated factor XII (FXIIa), thereby inhibiting its catalytic activity. Given the emerging role of FXIIa in promoting thromboinflammation, along with its apparent redundancy for hemostasis, the selective inhibition of FXIIa represents a novel and highly attractive approach targeting pathogenic processes that cause thromboinflammation-driven cardiovascular diseases. Methods The effects of FXIIa inhibition were investigated using three distinct mouse models of cardiovascular disease—angiotensin II-induced abdominal aortic aneurysm (AAA), an ApoE −/− model of atherosclerosis, and a tandem stenosis model of atherosclerotic plaque instability. 3F7 or its isotype control, BM4, was administered to mice (10 mg/kg) on alternate days for 4 to 8 weeks, depending on the experimental model. Mice were examined for the development and size of AAAs, or the burden and instability of atherosclerosis and associated markers of inflammation. Results Inhibition of FXIIa resulted in a reduced incidence of larger AAAs, with less acute aortic ruptures and an associated fibro-protective phenotype. FXIIa inhibition also decreased stable atherosclerotic plaque burden and achieved plaque stabilization associated with increased deposition of fibrous structures, a >2-fold thicker fibrous cap, increased cap-to-core ratio, and reduction in localized and systemic inflammatory markers. Conclusion Inhibition of FXIIa attenuates disease severity across three mouse models of thromboinflammation-driven cardiovascular diseases. Specifically, the FXIIa-inhibiting monoclonal antibody 3F7 reduces AAA severity, inhibits the development of atherosclerosis, and stabilizes vulnerable plaques. Ultimately, clinical trials in patients with cardiovascular diseases such as AAA and atherosclerosis are warranted to demonstrate the therapeutic potential of FXIIa inhibition.

Optical Coherence Tomography Based Biomechanical Fluid-Structure Interaction Analysis of Coronary Atherosclerosis Progression.

In this paper, we present a complete workflow for the biomechanical analysis of atherosclerotic plaque in the coronary vasculature. With atherosclerosis as one of the leading causes of global death, morbidity and economic burden, novel ways of analyzing and predicting its progression are needed. One such computational method is the use of fluid-structure interaction (FSI) to analyze the interaction between the blood flow and artery/plaque domains. Coupled with in vivo imaging, this approach could be tailored to each patient, assisting in differentiating between stable and unstable plaques. We outline the three-dimensional reconstruction process, making use of intravascular Optical Coherence Tomography (OCT) and invasive coronary angiography (ICA). The extraction of boundary conditions for the simulation, including replicating the three-dimensional motion of the artery, is discussed before the setup and analysis is conducted in a commercial finite element solver. The procedure for describing the highly nonlinear hyperelastic properties of the artery wall and the pulsatile blood velocity/pressure is outlined along with setting up the system coupling between the two domains. We demonstrate the procedure by analyzing a non-culprit, mildly stenotic, lipid-rich plaque in a patient following myocardial infarction. Established and emerging markers related to atherosclerotic plaque progression, such as wall shear stress and local normalized helicity, respectively, are discussed and related to the structural response in the artery wall and plaque. Finally, we translate the results to potential clinical relevance, discuss limitations, and outline areas for further development. The method described in this paper shows promise for aiding in the determination of sites at risk of atherosclerotic progression and, hence, could assist in managing the significant death, morbidity, and economic burden of atherosclerosis.

Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Aim. The goal of the study was to analyze the differential expression of lipid metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis.Material and Methods. The study was performed on the specimens of atherosclerotic plaques in 45–65-year-old patients with coronary atherosclerosis with stable exertional angina functional class II-IV without acute coronary syndrome. Coronary atherosclerosis was verified by coronary angiography. Atherosclerotic plaque tissue was sampled intraoperatively when indicated. Whole-genome sequencing of ribonucleic acid (RNA) was performed using the TruSeq RNA Sample Preparation Kit (Illumina, USA).Results. We analyzed the differences in the expression of 12 genes including LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, ABCA1, APOA1, APOE, LPL, SCARB1, and SREBF2 depending on the type of atherosclerotic plaques. The expression level of APOE gene was eight times higher in unstable atherosclerotic plaques of dystrophic-necrotic type (p &lt; 0.0001). The expression levels of LDLR and APOB genes were eight times higher in stable atherosclerotic plaques (p &lt; 0.0001). We did not find differences in the expression levels of the ABCG5, ABCG8, APOC3, CETP, CLPS, CYP7A1, and PNPLA5 genes.Conclusion. The study showed the differences in the activity of individual metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis. Obtained data may become the basis for the development of test systems aimed at predicting the development of atherosclerotic process and its complications.

The Role of Hematological Indices in Patients with Acute Coronary Syndrome

Background: Acute coronary syndrome (ACS) including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina - is an umbrella term for life-threatening situations that occur when the blood supply to the heart is altered due to destabilization of a previously stable atherosclerotic plaque. This alteration hinders the heart muscle from functioning properly and even could lead to death. This study aimed to identify the role of hematological indices in patients with acute coronary syndrome.&#x0D; Methods: This prospective cohort study was carried out on 75 patients; they were divided into 3 groups each of them included 25 patients. Group I represent patients with myocardial infarction (MI), group II represents patients with unstable angina (UA) and control group included 25 subjects. All patients were subjected to complete history taking, clinical examination and routine laboratory investigation. Patients also were subjected to electrocardiography, transthoracic echo Doppler and coronary angiography.&#x0D; Results: Regarding hematological indices for prediction of MI, the ROC revealed: NLR ≥ 4.45 with sensitivity 96%, specificity 92%, Area under the curve 0. 99 and accuracy 94%. RDW ≥ 14.15 with sensitivity 96% specificity 72%, Area under the curve 0.973 and accuracy 84%. PLR ≥ 88.8 with sensitivity 96%, specificity 96%, Area under the curve 0.994 and accuracy 96%. MPV ≥ 9.65 with sensitivity 68%, specificity 52%, Area under the curve 0.646 and accuracy 60%. PDW ≥ 15.15 with sensitivity 96%, specificity 96%, Area under the curve 0.998 and accuracy 96%.&#x0D; Conclusions: There is a high demand for a reliable, accessible, noninvasive, and hematological prognostic marker in ACS, which would identify patients of high cardiovascular risk in secondary prevention and tailor the therapy to their needs. The inflammatory processes play a key role in the development of atherosclerosis, destabilization of atherosclerotic plaques and formation of clots on the plaque surface. There is a significance role of NLR, PLR, PDW, MPV, and RDW in the prognosis of ACS.

Белок S100A8 в атеросклеротических поражениях у человека

Introduction. In the pathogenesis of atherosclerosis, a change in the content of different proteins in S100 protein family may play an important role in the formation of atherosclerotic lesions in the vascular wall. The aim was to study the content of mononuclear cells expressing protein S100A8 in different types of atherosclerotic lesions secondary to the development of the inflammatory process in the vascular wall during atherogenesis in humans. Materials and methods. Immunohistochemical and morphometric studies were performed on autopsy material (18 cases) obtained from patients who died from acute cardiovascular insufficiency of atherosclerotic etiology. We detected the expression of S100A8 protein in the aortic segments (from the arc, thoracic and abdominal regions), coronary arteries, and arteries of the circle of Willis (40 tissue samples) using a highly sensitive two-stage streptavidin-biotin method. Comparative analysis was subjected to normal areas of arteries, lipid stain, and unstable and stable atherosclerotic plaques. We performed a statistical analysis with the computer program Statistica Version 10. The significance of the differences between the samples studied was determined by the Student’s T-criterion. Results. Intracellular localization of S100A8 protein was found in the intima of unstable atherosclerotic lesions. Its expression was mainly concentrated in the cytoplasm of macrophages. Intracellular production of S100A8 was minimal or absent in normal areas of aorta intima, coronary arteries, a. basilaris, and in the cap of stable atherosclerotic plaques. We detected numerous inflammatory mononuclear cell infiltrates in the areas of the vascular wall with S100A8 expression. According to the morphometry, their content in the intima of unstable plaques significantly exceeded the similar rate in the intima of normal areas of arteries and stable lesions. Conclusion. We hypothesize that protein S100A8 may contribute to the activation of immune-inflammatory reactions in the vascular wall, which are the basis for the formation of unstable progressive atherosclerotic lesions leading to the development of acute coronary syndrome. Further research may provide more evidence to support that S100A8 proteins are a promising drug target in the prevention and therapy of atherosclerosis. Keywords: atherogenesis, S100A8 protein, unstable atherosclerotic plaque

Predictive values of carotid high-resolution magnetic resonance imaging for large embolus shedding in carotid artery stenting.

Embolus shedding is one of the important complications in carotid artery stenting (CAS). Carotid high-resolution magnetic resonance imaging (HR-MRI) is often used to directly reflect important biological characteristics, such as plaque size and composition, as well as the structure of the carotid artery wall. The aim of this study was to investigate the predictive values of carotid HR-MRI for large embolus shedding in CAS. In total, 195 patients with carotid stenosis were enrolled. Preoperative carotid HR-MRI was performed to define the nature of the carotid plaques. CAS was performed in all patients, and intraoperative embolic protection devices were used to collect the shed emboli. According to the diameter and number of shed emboli, the patients were divided into the small-embolus group (group X) and largeembolus group (group Y). Logistic regression analysis was used to analyze the risk factors of large embolus shedding. Group Y included 58 patients, and group X included 137 patients. Age, stenosis length, smoking, and ≥3 transient cerebral ischemic attacks were risk factors for large embolusshedding. Two cases of shed large emboli developed from stable plaques, and 56 cases of large emboli developed from vulnerable plaques. When vulnerable plaques were associated with more risk factors, the incidences of large embolus shedding in cases with vulnerable plaques combined with 0, 1, 2, 3, and 4 risk factors were 44 % (4/9), 68.1% (15/22), 72.2% (13/18), 76.5% (13/17), and 84.6% (11/13), respectively. Carotid HR-MRI can predict the incidence of large embolus shedding in CAS.

Atherogenic index of plasma: A valuable novel index to distinguish patients with unstable atherogenic plaques.

Background:Plaque instability is a leading cause of morbidity and mortality in coronary artery disease (CAD) patients. Numerous efforts have been made to figure out and manage unstable plaques prior to major cardiovascular events incidence. The current study aims to assess the values of the atherogenic index of plasma (AIP) to detect unstable plaques.Materials and Methods:The current case-control study was conducted on 435 patients who underwent percutaneous coronary intervention due to chronic stable angina (stable plaques, n = 145) or acute coronary syndrome (unstable plaques, n = 290). The demographic, comorbidities, chronic medications, biochemical and hematological characteristics of the patients were entered into the study checklist. The baseline AIP was measured according to the formula of triglycerides/high-density lipoprotein logarithm. Binary logistic regression was applied to investigate the standalone association of AIP with plaque instability. Receiver operating curve (ROC) was depicted to determine a cut-off, specificity, and sensitivity of AIP in unstable plaques diagnosis.Results:AIP was an independent predictor for atherogenic plaque unstability in both crude (odds ratio [OR]: 3.677, 95% confidence interval [CI]: 1.521–8.890; P = 0.004) and full-adjusted models (OR: 15, 95% CI: 2.77–81.157; P = 0.002). According to ROC curve, at cut-point level of 0.62, AIP had sensitivity and specificity of 89.70% and 34% to detect unstable plaques, respectively (area under the curve: 0.648, 95% CI: 0.601–0.692, P < 0.001).Conclusion:According to this study, at the threshold of 0.62, AIP as an independent biomarker associated with plaque instability can be considered a screening tool for patients at increased risk for adverse events due to unstable atherosclerotic plaques.

Histological Analysis of Carotid Plaques: The Predictors of Stroke Risk

ObjectivesThe morphology and histological structure of the atherosclerotic plaque seem critical to its stability. Our study aimed to identify the epidemiological, morphological and histological parameters associated with stable and unstable plaques. Materials and MethodsThe study included 280 plaques harvested from 269 consecutive patients. Epidemiological and demographic data were recorded as well as the histological features of plaque, i.e. calcifications, myxoid changes, bleeding into plaque, presence of thrombus, inflammation, macrophages, giant cell reaction, siderophages, neovascularization and plaque ossification. All specimens were classified according to the American Heart Association (AHA). ResultsMonofactorial analysis identified three significant histological predictors for the symptomatic plaque: a plaque with a large necrotic core (odds ratio, OR=2.0, p = 0.03), thrombosis (OR=3.7, p = 0.01) and the formation of foamy macrophages (OR=2.0, p = 0.01). Multifactorial logistic regression revealed that the presence of foamy macrophages (OR=1.9, p = 0.03) and thrombosis (OR=3.5, p = 0.02) were significant predictors of symptomatic stenosis. Symptomatic plaques were significantly more frequently classified as AHA type VI than AHA type IV-V compared to asymptomatic ones (OR=1.8, p = 0.03). ConclusionsOur study shows that no single histological feature, except for the presence of foamy macrophages and thrombosis on the plaque, is predictive of plaque instability. Rather, a complex plaque structure (AHA type VI) is predictive of plaque instability. Our findings should be kept in mind during the assessment of non-invasive imaging and stroke risk estimation.

Viral Agents and Systemic Levels of Inflammatory Cytokines in Vulnerable and Stable Atherosclerotic Carotid Plaques

To investigate the presence of genetic material of viral agents and the serum level of inflammatory cytokines in patients submitted to carotid endarterectomy having vulnerable versus stable atherosclerotic plaques. Data of patients consecutively submitted to carotid endarterectomy for a significant stenosis from July 2019 to December 2019 were prospectively collected. The genetic material of Epstein-Barr (EBV), CitoMegalo (CMV), Herpes Simplex (HSV), Varicella-Zoster (VZV) and Influenza (IV) Viruses was searched in the patient's plaques, both in the "mid" of the plaque and in an adjacent lateral portion of no-plaque area. The serum levels of TNF-α, IL-1β, IL-6, IL10 and CCL5 were determined. The obtained results were then correlated to the histologic vulnerability of the removed carotid plaque. P values < 0.05 were considered statistically significant. Data of 50 patients were analyzed. A vulnerable plaque was found in 31 patients (62%). The genome of CMV, HSV, VZV and IV was not found in any of the vascular samples, while the EBV genome was found in the "mid" of 2 vulnerable plaques, but not in their respective control area. Eighty-two percent of patients who did not receive anti-IV vaccination (23/28) had vulnerable carotid plaque, compared with 36% of vaccinated patients (8/22, P=0.001). Serum levels of TNF-α and IL-6 were higher in patients with a vulnerable plaque compared to patients with a stable plaque (73.6 ± 238.2 vs. 3.9 ± 13.1 pg/ml, P= 0.01, and 45.9 ± 103.6 vs. 10.1 ± 25.3 pg/ml, P= 0.01, respectively), independent of comorbidities, viral exposure or flu vaccination. The EBV genome was found in the "core" of 2 vulnerable carotid plaques, but not in their respective adjacent control. Influenza vaccination was associated with a lower incidence of carotid plaque vulnerability. Serum levels of TNF-α and IL-6 were higher in patients with a vulnerable plaque compared to patients with a stable plaque.

Smooth muscle cells affect differential nanoparticle accumulation in disturbed blood flow-induced murine atherosclerosis.

Atherosclerosis is a lipid-driven chronic inflammatory disease that leads to the formation of plaques in the inner lining of arteries. Plaques form over a range of phenotypes, the most severe of which is vulnerable to rupture and causes most of the clinically significant events. In this study, we evaluated the efficacy of nanoparticles (NPs) to differentiate between two plaque phenotypes based on accumulation kinetics in a mouse model of atherosclerosis. This model uses a perivascular cuff to induce two regions of disturbed wall shear stress (WSS) on the inner lining of the instrumented artery, low (upstream) and multidirectional (downstream), which, in turn, cause the development of an unstable and stable plaque phenotype, respectively. To evaluate the influence of each WSS condition, in addition to the final plaque phenotype, in determining NP uptake, mice were injected with NPs at intermediate and fully developed stages of plaque growth. The kinetics of artery wall uptake were assessed in vivo using dynamic contrast-enhanced magnetic resonance imaging. At the intermediate stage, there was no difference in NP uptake between the two WSS conditions, although both were different from the control arteries. At the fully-developed stage, however, NP uptake was reduced in plaques induced by low WSS, but not multidirectional WSS. Histological evaluation of plaques induced by low WSS revealed a significant inverse correlation between the presence of smooth muscle cells and NP accumulation, particularly at the plaque-lumen interface, which did not exist with other constituents (lipid and collagen) and was not present in plaques induced by multidirectional WSS. These findings demonstrate that NP accumulation can be used to differentiate between unstable and stable murine atherosclerosis, but accumulation kinetics are not directly influenced by the WSS condition. This tool could be used as a diagnostic to evaluate the efficacy of experimental therapeutics for atherosclerosis.