High-risk Atherosclerotic Plaques Research Articles

Computed Tomography Angiography Identified High-Risk Coronary Plaques: From Diagnosis to Prognosis and Future Management.

CT angiography has become, in recent years, a main evaluating modality for patients with coronary artery disease (CAD). Recent advancements in the field have allowed us to identity not only the presence of obstructive disease but also the characteristics of identified lesions. High-risk coronary atherosclerotic plaques are identified in CT angiographies via a number of specific characteristics and may provide prognostic and therapeutic implications, aiming to prevent future ischemic events via optimizing medical treatment or providing coronary interventions. In light of new evidence evaluating the safety and efficacy of intervening in high-risk plaques, even in non-flow-limiting disease, we aim to provide a comprehensive review of the diagnostic algorithms and implications of plaque vulnerability in CT angiography, identify any differences with invasive imaging, analyze prognostic factors and potential future therapeutic options in such patients, as well as discuss new frontiers, including intervening in non-flow-limiting stenoses and the role of CT angiography in patient stratification.

Management of Coronary VulnerablePlaque With Medical Therapyor LocalPreventive Percutaneous CoronaryIntervention.

Acute coronary syndromes (ACS) often result from the rupture or erosion of high-risk coronary atherosclerotic plaques (ie, vulnerable plaques). Advances in intracoronary imaging such as intravascular ultrasound, optical coherence tomography, or near-infrared spectroscopy have improved the identification of vulnerable plaques, characterized by large plaque burden, small minimal luminal area, thin fibrous cap, and large lipid content. Although pharmacology, including lipid-lowering agents, and intensive risk-factor control are pivotal for management of vulnerable plaques and secondary prevention, recurrent events tend to accrue despite intensive pharmacotherapy. Therefore, it has been hypothesized that local preventive percutaneous coronary intervention may passivate these vulnerable plaques, preventing the occurrence of plaque-related ACS. However, solid evidence is lacking on its use for treatment of non-flow-limiting vulnerable plaques. As such, the optimal management of vulnerable plaques has not been established. Herein, we have reviewed the diagnosis and management of vulnerable plaques, focusing on systematic pharmacology and focal treatments.

What Is the Added Value of Carotid CEUS in the Characterization of Atherosclerotic Plaque?

Background and Objectives: Unstable atherosclerotic plaque in the arteries is one of the main risk factors for cerebral ischemia. Duplex ultrasound is a frequently used diagnostic method, but it has some limitations for microvascularization and neovascularization evaluation. The aim of this review was to evaluate the role of the new multiparametric US method-contrast-enhanced ultrasound (CEUS)-in atherosclerotic plaque instability verification. Materials and Methods: Original studies, reviews, and meta-analyses were included in this article. A total of 53 studies were retrieved; 29 were included in this study. Results: Carotid artery CEUS as a part of the multiparametric ultrasound method shows promising results and provides additional characteristics of soft- and high-risk atherosclerotic plaques; it can be advised in clinical practice for patients with carotid artery soft- and high-risk plaques. However, there are some limitations, such as extensive calcinosis with important acoustic shadows in carotid atherosclerotic plaque neovascularization diagnostics by CEUS. The added value of CEUS in the characterization of atherosclerotic plaque is that it indicates regions with high neovascularization and visualizes ulcerations on plaque surfaces, suggestive of increased instability risk.

CT Coronary Angiography: Technical Approach and Atherosclerotic Plaque Characterization.

Coronary computed tomography angiography (CCTA) currently represents a robust imaging technique for the detection, quantification and characterization of coronary atherosclerosis. However, CCTA remains a challenging task requiring both high spatial and temporal resolution to provide motion-free images of the coronary arteries. Several CCTA features, such as low attenuation, positive remodeling, spotty calcification, napkin-ring and high pericoronary fat attenuation index have been proved as associated to high-risk plaques. This review aims to explore the role of CCTA in the characterization of high-risk atherosclerotic plaque and the recent advancements in CCTA technologies with a focus on radiomics plaque analysis.

Biomarkers for identification of high-risk coronary plaques in patients with suspected coronary artery disease

Abstract Background Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether elevated levels of biomarkers of ischemia e.g. TnI and inflammation e.g. high sensitive C-reactive protein (hsCRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) evaluated on coronary computed tomography angiography (CCTA) is not well described. Objectives To assess the association between 1) TnI and 2) hsCRP and quantified coronary plaque burden, luminal diameter stenosis and HRP in symptomatic patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred to CCTA evaluation. Methods On enrolled patients (n=1,615), CCTA were analysed using a semiautomatic software for coronary artery plaque characterization. Patients with high (>6 ng/L) and low (<3 ng/L) TnI as well as high (>2 mg/L) and low (<1 mg/L) hsCRP were identified. Associations of high levels of TnI and hsCRP compared to low levels were investigated for the following: high plaque burden (defined as having total plaque volume above the 75th percentile on CCTA), presence of significant stenosis (defined as ≥50% luminal diameter stenosis on CCTA), and presence of HRP (defined as having a plaque with at least two risk features on CCTA). Results TnI and hsCRP were both positively correlated with total plaque burden (TnI rs=0.14, p<0.001; hsCRP rs=0.08, p<0.001). In multivariate logistic regression analyses, high TnI was when compared to low TnI associated with presence of stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p=0.034), the presence of HRP (OR 1.79, 95% CI: 1.17– 2.74, p=0.008) and further the subtypes of HRP including low attenuation plaque (OR 1.93, 95% CI: 1.24–3.00, p=0.003) and positive remodelling (OR 1.51, 95% CI: 1.07–2.13, p=0.018). For high hsCRP levels, only the presence of stenosis and the HRP-subtype napkin ring sign correlated significantly. Conclusion In patients with suspected CAD TnI and hsCRP are associated with the presence of HRP features. These findings suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and potentially also affect patient management.

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study

Background and AimsEpidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden.MethodsThis study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk.ResultsA total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001) .ConclusionElevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.What is already known on this topic?Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear.What this study adds?Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.How this study might affect research, practice or policy?Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions: A Systematic Review and Meta-Analysis

BackgroundThe clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non–flow-limiting lesions remains uncertain. ObjectivesThe authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE). MethodsThirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling. ResultsCPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the MACE rate was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes. ConclusionsCharacterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810)

Roadmap on the use of artificial intelligence for imaging of vulnerable atherosclerotic plaque in coronary arteries.

Artificial intelligence (AI) is likely to revolutionize the way medical images are analysed and has the potential to improve the identification andanalysis of vulnerable or high-risk atherosclerotic plaques in coronary arteries, leading to advances in the treatment of coronary artery disease. However, coronary plaque analysis is challenging owing to cardiac and respiratory motion, as well as the small size of cardiovascular structures. Moreover, the analysis of coronary imaging data is time-consuming, can be performed only by clinicians with dedicated cardiovascular imaging training, and is subject to considerable interreader and intrareader variability. AI has the potential to improve the assessment of images of vulnerable plaque in coronary arteries, but requires robust development, testing and validation. Combining human expertise with AI might facilitate the reliable and valid interpretation of images obtained using CT, MRI, PET, intravascular ultrasonography and optical coherence tomography. In this Roadmap, we review existing evidence on the application of AI to the imaging of vulnerable plaque in coronary arteries and provide consensus recommendations developed by an interdisciplinary group of experts on AI and non-invasive and invasive coronary imaging. We also outline future requirements of AI technology to address bias, uncertainty, explainability and generalizability, which are all essential for the acceptance of AI and its clinical utility in handling the anticipated growing volume of coronary imaging procedures.

Atherosclerotic plaque classification in carotid ultrasound images using machine learning and explainable deep learning

ObjectiveThe incidence of cardiovascular diseases (CVD) is rising rapidly worldwide. Some forms of CVD, such as stroke and heart attack, are more common among patients with certain conditions. Atherosclerosis development is a major factor underlying cardiovascular events, such as heart attack and stroke, and its early detection may prevent such events. Ultrasound imaging of carotid arteries is a useful method for diagnosis of atherosclerotic plaques; however, an automated method to classify atherosclerotic plaques for evaluation of early-stage CVD is needed. Here, we propose an automated method for classification of high-risk atherosclerotic plaque ultrasound images. MethodsFive deep learning (DL) models (VGG16, ResNet-50, GoogLeNet, XceptionNet, and SqueezeNet) were used for automated classification and the results compared with those of a machine learning (ML)-based technique, involving extraction of 23 texture features from ultrasound images and classification using a Support Vector Machine classifier. To enhance model interpretability, output gradient-weighted convolutional activation maps (GradCAMs) were generated and overlayed on original images. ResultsA series of indices, including accuracy, sensitivity, specificity, F1-score, Cohen-kappa index, and area under the curve values, were calculated to evaluate model performance. GradCAM output images allowed visualization of the most significant ultrasound image regions. The GoogLeNet model yielded the highest accuracy (98.20%). ConclusionML models may be also suitable for applications requiring low computational resource. Further, DL models could be more completely automated than ML models.

Intravascular Imaging of Atherosclerosis by Using Engineered Nanoparticles.

Atherosclerosis is a leading cause of morbidity and mortality, and high-risk atherosclerotic plaques can result in myocardial infarction, stroke, and/or sudden death. Various imaging and sensing techniques (e.g., ultrasound, optical coherence tomography, fluorescence, photoacoustic) have been developed for scanning inside blood vessels to provide accurate detection of high-risk atherosclerotic plaques. Nanoparticles have been utilized in intravascular imaging to enable targeted detection of high-risk plaques, to enhance image contrast, and in some applications to also provide therapeutic functions of atherosclerosis. In this paper, we review the recent progress on developing nanoparticles for intravascular imaging of atherosclerosis. We discuss the basic nanoparticle design principles, imaging modalities and instrumentations, and common targets for atherosclerosis. The review is concluded and highlighted with discussions on challenges and opportunities for bringing nanoparticles into in vivo (pre)clinical intravascular applications.

Hepatic fat as a novel marker for high-risk coronary atherosclerotic plaque features in familial hypercholesterolaemia

Background & aimsHepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography. MethodsWe conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles. ResultsOf 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09–2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18–1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mm3 vs Q1: 414 mm3, p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03). No differences in pericoronary adipose tissue attenuation were observed. ConclusionsHepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis.Clinical trial number: N/A.

Therapeutic inhibition of MPO stabilizes pre-existing high risk atherosclerotic plaque

Currently there are no established therapies to treat high-risk patients with unstable atherosclerotic lesions that are prone to rupture and can result in thrombosis, abrupt arterial occlusion, and a precipitous infarction. Rather than being stenotic, rupture-prone non-occlusive plaques are commonly enriched with inflammatory cells and have a thin fibrous cap. We reported previously that inhibition of the pro-inflammatory enzyme myeloperoxidase (MPO) with the suicide inhibitor AZM198 prevents formation of unstable plaque in the Tandem Stenosis (TS) mouse model of plaque instability. However, in our previous study AZM198 was administered to animals before unstable plaque was present and hence it did not test the significant unmet clinical need present in high-risk patients with vulnerable atherosclerosis. In the present study we therefore asked whether pharmacological inhibition of MPO with AZM198 can stabilize pre-existing unstable lesions in an interventional setting using the mouse model of plaque instability. In vivo molecular magnetic resonance imaging of arterial MPO activity using bis-5-hydroxytryptamide-DTPA-Gd and histological analyses revealed that arterial MPO activity was elevated one week after TS surgery, prior to the presence of unstable lesions observed two weeks after TS surgery. Animals with pre-existing unstable plaque were treated with AZM198 for one or five weeks. Both short- and long-term intervention effectively inhibited arterial MPO activity and increased fibrous cap thickness, indicative of a more stable plaque phenotype. Plaque stabilization was observed without AZM198 affecting the arterial content of Ly6B.2+- and CD68+-cells and MPO protein. These findings demonstrate that inhibition of arterial MPO activity converts unstable into stable atherosclerotic lesions in a preclinical model of plaque instability and highlight the potential therapeutic potency of MPO inhibition for the management of high-risk patients and the development of novel protective strategies against cardiovascular diseases.

Coronary plaque characteristics associated with major adverse cardiovascular events in atherosclerotic patients and lesions – a systematic review and meta-analysis

Abstract Background The clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non-flow-limiting lesion remains uncertain. Purpose We performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE). Methods We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for studies evaluating the association of CPC with patient-level and lesion-level MACE. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low attenuation plaque, spotty calcification, napkin ring sign, or positive remodelling. Results Thirty studies (21 retrospective, 9 prospective) with 30,369 patients were included. CPCs were evaluated by invasive intravascular techniques in 9 studies (optical coherence tomography=4, intravascular ultrasound imaging=3, near-infrared spectroscopy intravascular ultrasound imaging=2) and by coronary computed tomography angiography (CCTA) in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For each CPC, the risks were higher for lesion-level (HR range 3.2–16.8) as compared with patient-level MACE (HR range 1.8–4.1). Accuracy was modest to good for most CPCs at the patient-level (AUC for MACE ranging between 0.53 and 0.84) and moderate to good for most CPCs at the lesion-level (AUC for MACE ranging between 0.71 and 0.83). Plaques with more than one CPC had the highest accuracy for lesion-level MACE (AUC 0.87, 95% CI 0.84–0.90). The pooled sensitivities of CPCs for lesion-level MACE ranged between 40% and 63% and specificities between 73% and 98%. As the pooled prevalence of CPCs among plaques was low (3% to 28%), the estimated positive predictive values for lesion-level MACE were modest (range 1% to 26%). Conclusions CCTA and intravascular imaging characterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (PROSPERO identifier: CRD42021251810). Funding Acknowledgement Type of funding sources: None.

Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice.

High-risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self-gated, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe-/- atherosclerotic mice during natural disease progression. Twenty-four, 8-week-old, female Apoe-/- mice were divided into four groups (n = 6 each) and imaged with self-gated DCE-MRI at 4, 8, 12, and 16 weeks after high-fatdiet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high-fat diet and imaged longitudinally at the same time points. Aortic-root pseudo-concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash-in and washout slopes (b1 and b2 ) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b2 , indicating contrast agent washout, was significantly higher in mice kept on an high-fat diet for longer periods of time (p= 0.03). Group comparison revealed significant differences between mice on a high-fat diet for 4 versus 16 weeks (p= 0.03). Macrophage density also significantly increased with diet duration (p= 0.009). Spearman correlation between b2 from DCE-MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p= 0.20). Validated piecewise linear modeling of the DCE-MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single-slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.

Neutrophil membrane camouflaged nanoprobes for NIR-II fluorescence imaging of inflamed, high-risk atherosclerotic plaques in mouse and rabbit models

Atherosclerosis is the leading cause of vascular death worldwide, and inflammation plays a crucial role in atherosclerotic plaque progression and rupture. Fluorescent nanoprobes that can detect inflamed, high-risk atherosclerotic plaques and evaluate the therapeutic efficacy at the animal level in vivo are particularly meaningful. Herein, we developed a kind of neutrophil membrane-camouflaged nanoprobe in the second near-infrared spectral region (NIR-II) for the imaging of inflamed, high-risk atherosclerotic plaques in both mouse and rabbit models. Compared with free indocyanine green (ICG), the NIR-II fluorescence intensity of neutrophil biomimetic nanoparticles (Neu-NPs) was increased by 276% and had good stability in serum. Neu-NPs could specifically target inflamed, high-risk atherosclerotic plaques through the interaction of the chemokine receptor LFA-1with ICAM-1, which are highly expressed in inflamed sites. In the ApoE−/− mouse model, the signal-to background (S/B) ratio of the Neu-NP-treated mice was 1.67-fold higher than that of NP-treated mice. Even in large animals, such as the New Zealand white rabbit atherosclerosis model, Neu-NPs exhibited excellent targeting to high-risk atherosclerotic plaques. Moreover, the Neu-NPs could be used to reflect the reduction in plaque inflammation after the treatment and could thus be used for therapeutic evaluation and drug screening. Therefore, this highly biocompatible neutrophil membrane-camouflaged nanoprobe may be a new nanocarrier for the treatment of chronic inflammatory diseases such as atherosclerosis. Moreover, the use of NIR-II fluorescence imaging in mice and rabbits with atherosclerosis extends the scope of this emerging imaging technology.

Impact of PCSK9 Inhibition on Proinflammatory Cytokines and Matrix Metalloproteinases Release in Patients with Mixed Hyperlipidemia and Vulnerable Atherosclerotic Plaque.

Atherosclerosis is a disorder in which, in addition to high cholesterol levels, several plasma factors play a significant role in its development. Among these cytokines and molecules are interleukin 6 (IL-6), interleukin 18 (IL-18), tumor necrosis factor α (TNF-α), metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9), all of which may contribute to the stabilization of atherosclerotic plaque. The purpose of this study was to determine the effect of advanced lipid-lowering therapy on the levels of these determinants by utilizing proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in patients with verified high-risk atherosclerotic plaque. Methods: The study involved patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography and who were eligible to begin alirocumab treatment. The levels of IL-6, IL, 18, TNF-α, and MMPs were determined in this group before and after three months of therapy. After treatment, a statistically significant decrease in concentrations of Il-18, Il-6, TNF-α (p < 0.001) and MMP-2 (p < 0.05) was observed. Additionally, we observed that the concentrations of these markers were significantly higher in the group of patients prior to initiating therapy than in the control group. Our study’s results suggest that PCSK-9 inhibitor therapy significantly reduces the concentration of factors influencing the stability of atherosclerotic plaque, which may explain their essential importance in reducing cardiovascular risk in patients receiving this treatment.

Plasma Concentrations of Cytokines in Patients with Combined Hyperlipidemia and Atherosclerotic Plaque before Treatment Initiation-A Pilot Study.

Background and Objectives: The formation and destabilization of atherosclerotic plaques is a complex process involving several proteins and cytokines. Interleukin 6 (IL-6), interleukin 18 (IL-18), and tumor necrosis factor (TNF-α) are examples of such cytokines. The goal of our research is to compare the concentrations of the above-mentioned indicators in the plasma of patients with verified high-risk atherosclerotic plaque to the plasma levels of healthy people before lipid lowering therapy. Materials and Methods: Patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography were included in the study. The concentrations of IL-6, IL-18 and TNF-α in the plasma of these people were determined and compared with the concentrations of these cytokines in the plasma of the control group. Results: Levels of lipid panel, IL-6 and IL-18 were significantly lower in the group of healthy people than in the study group. Conclusions: The concentrations of IL-6 and IL-18 in the plasma of patients with ruptured plaque are higher than in the plasma of healthy people, suggesting that these cytokines as a panel might be used as new indicators of the presence of unstable atherosclerotic plaque.

Significance of Insignificant Left Main Disease

Significance of Insignificant Left Main Disease

Plaque Characteristics in Young Adults With Symptomatic Intracranial Atherosclerotic Stenosis: A Preliminary Study.

PurposeTo determine how intracranial vascular wall and atherosclerosis plaque characteristics differ between young and old adults with sICAS.MethodsEighty-four consecutive patients with sICAS who underwent high-resolution magnetic resonance imaging (HRMRI) from December 2017 to July 2020 were retrospectively collected. These participants were divided into young adult group (18–50 years, n = 28) and old adult group (>50 years, n = 56). Reviewers were blinded to any clinical information and HRMRI scans were analyzed for qualitative and quantitative indicators of vascular walls and plaque at the maximal lumen narrowing site using the independent-sample t-test, Mann–Whitney U-test, chi-square test or Fisher exact test, and logistic regression analysis.ResultsYoung patients with sICAS had significantly smaller maximum wall thickness (1.45 ± 0.38 vs.1.75 ± 0.51 mm2, P = 0.003), higher prevalence of positive remodeling (53.57 vs. 21.43%, P = 0.003), and lower prevalence of diabetes mellitus (14.29 vs. 35.71%, P = 0.04) than old patients. Plaque burden and other plaque features were comparable between young and old patients.ConclusionYoung patients with sICAS have smaller maximum wall thickness and greater ability to reconstruct, and are more likely to show positive remodeling, which may lead to some atherosclerotic lesions being missed. Young patients with evidence of vessel narrowing should be carefully examined for presence of high-risk atherosclerotic plaque.

ZEB2 Shapes the Epigenetic Landscape of Atherosclerosis.

Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, and make up the majority of cells in the atherosclerotic plaque. To better understand the epigenetic and transcriptional mechanisms that mediate these cell state changes, and how they relate to risk for coronary artery disease (CAD), we have investigated the causality and function of transcription factors at genome-wide associated loci. We used CRISPR-Cas 9 genome and epigenome editing to identify the causal gene and cells for a complex CAD genome-wide association study signal at 2q22.3. Single-cell epigenetic and transcriptomic profiling in murine models and human coronary artery smooth muscle cells were used to understand the cellular and molecular mechanism by which this CAD risk gene exerts its function. CRISPR-Cas 9 genome and epigenome editing showed that the complex CAD genetic signals within a genomic region at 2q22.3 lie within smooth muscle long-distance enhancers for ZEB2, a transcription factor extensively studied in the context of epithelial mesenchymal transition in development of cancer. Zeb2 regulates SMC phenotypic transition through chromatin remodeling that obviates accessibility and disrupts both Notch and transforming growth factor β signaling, thus altering the epigenetic trajectory of SMC transitions. SMC-specific loss of Zeb2 resulted in an inability of transitioning SMCs to turn off contractile programing and take on a fibroblast-like phenotype, but accelerated the formation of chondromyocytes, mirroring features of high-risk atherosclerotic plaques in human coronary arteries. These studies identify ZEB2 as a new CAD genome-wide association study gene that affects features of plaque vulnerability through direct effects on the epigenome, providing a new therapeutic approach to target vascular disease.