Risk Of Plaque Rupture Research Articles

Teriparatide administration is osteoanabolic but does not impact atherosclerotic plaque calcification and progression in a mouse model of menopause

Menopause exacerbates osteoporosis and increases the risk of atherosclerotic plaque rupture, leading to cardiovascular mortality. Osteoporotic women are increasingly treated with teriparatide (TPTD, 1–34 parathyroid hormone), one of the few treatments that stimulate bone formation. Despite the fact that atherosclerotic plaque calcification is a hallmark of plaque development, the impact of TPTD administration on plaque calcification remain unclear. In this context, we sought to determine the effects of TPTD administration on atherosclerosis in ovariectomized (OVX) apolipoprotein E deficient mice (ApoE−/−), as a model of postmenopausal osteoporosis. OVX ApoE−/− mice, fed a high fat, high cholesterol diet to induce atherosclerosis, received either vehicle or TPTD daily injections (40 μg/kg/d) for 4 or 10 weeks, at which points plaques are respectively weakly and heavily calcified. After sacrifice, bone remodeling was evaluated by serum markers and bone histomorphometry. Bone architectural parameters were measured by μCT. Aortic plaques were analyzed histologically, and their calcification with von Kossa staining and the calcium tracer Osteosense. Plaque inflammation and calcification markers were measured by RT-qPCR. Intermittent TPTD increased bone volume in OVX mice, due to a higher stimulation of bone formation relatively to bone resorption. These effects were not accompanied by changes in serum levels of cholesterol, triglycerides, glucose or insulin. TPTD neither significantly affected aortic plaque size, inflammation, and calcification, even if it slightly increased vascular smooth muscle cell transdifferentiation into calcifying cells. In conclusion, TPTD exhibits osteoanabolic effects in OVX ApoE−/− mice, without significantly influencing atherosclerotic plaque progression or calcification in the short term.

The relationship between atherogenic index of plasma and plaque vulnerabilities: an optical coherence tomography study

Abstract Background Atherogenic index of plasma (AIP) has been recommended as a marker of plasma atherogenicity. The impact of AIP on plaque characteristics is not fully understood. Purpose The study investigates the relationship between AIP and coronary plaque features in patients with acute coronary syndrome (ACS). Methods From January 2015 to June 2017 pre-intervention optical coherence tomography (OCT) was performed in 522 ACS patients. AIP was defined as the base 10 logarithm of the ratio of the concentrations of triglyceride to high-density lipoprotein cholesterol. Patients were divided into four groups according to AIP quartiles. Results A total of 332 patients were included for the analysis. The incidence of thin-cap fibroatheroma (TCFA) (group I [lowest] 9.09% vs group II 16.5% vs group III 44.7% vs group IV [highest] 52.9%), macrophage accumulation (group I 18.2% vs group II 22.4% vs group III 31.8% vs group IV 47.1%), plaque rupture (group I 10.4% vs group II 14.1% vs group III 17.6% vs group IV 34.1%) and plaque erosion (group I 2.6% vs group II 2.4% vs group III 14.1% vs group IV 12.9%) were significantly different among AIP quartiles. Multivariate logistic regression revealed the risk of TCFA (odds ratio 11.938, 95% confidence interval 4.723-30.174, p<0.001) and plaque rupture (OR 4.976, 95% CI 1.993-12.424, p<0.001) increased in group IV compared to group I. Receiver operating characteristics curve showed the predictive value of AIP for TCFA and plaque rupture were 0.720 and 0.669 respectively. Conclusions AIP is an independent predictor for vulnerable plaques beyond traditional factors. It can be integrated in clinical practice for risk stratification of ACS patients.Multivariate logistic analysisROC curves

Automated Classification of Coronary Plaque on Intravascular Ultrasound by Deep Classifier Cascades.

Intravascular ultrasound (IVUS) is the gold standard modality for in vivo visualization of coronary arteries and atherosclerotic plaques. Classification of coronary plaques helps to characterize heterogeneous components and evaluate the risk of plaque rupture. Manual classification is time-consuming and labor-intensive. Several machine learning-based classification approaches have been proposed and evaluated in recent years. In the current study, we develop a novel pipeline composed of serial classifiers for distinguishing IVUS images into five categories: normal, calcified plaque, attenuated plaque, fibrous plaque, and echolucent plaque. The cascades comprise densely connected classification models and machine learning classifiers at different stages. Over 100,000 IVUS frames of five different lesion types were collected and labeled from 471 patients for model training and evaluation. The overall accuracy of the proposed classifier is 0.877, indicating that the proposed framework has the capacity to identify the nature and category of coronary plaques in IVUS images. Further, it may provide real-time assistance on plaque identification and facilitate clinical decision-making in routine practice.

Biomechanics cerebral and carotid arteries: aneurysm development and atherosclerotic plaque detachment in the presence of combined pathologies

Today, the main cause of mortality in the world remains cardiovascular diseases. In this case, the combined pathology of the neck and head arteries, in which atherosclerosis affects the carotid arteries and there is a change in blood flow in the vertebral arteries or in the circle of Willis due to aplasia of the communicating artery, significantly increases the risk of aneurysms formation and their subsequent rupture. Assessing the risk of complications in this type of pathological condition may allow the physician to initiate timely preventive measures in specific clinical cases. The paper presents the results of modelling various variants of combined pathologies in the arteries of the neck and head. The segment under consideration includes sections of the common carotid, external and internal carotid arteries, as well as vessels of the circle of Willis and the basilar artery. The main idea of the study was to create a prognostic model to assess the risks of aneurysm formation in the circle of Willis and atherosclerotic plaque rupture in the carotid arteries. Such a system may be useful for physicians in routine practice when planning treatment tactics in patients with combined pathologies of the arterial channel. Based on the literature analysis, a number of pathologies of the cerebral and carotid arteries, most frequently occurring in various combinations, were identified: stenoses of the ICA (30 % and 70 %) and aplasia (absence) of one of the connecting arteries were considered from the point of view of geometrical features. In addition, the character of blood flow in the basilar artery, which can change its direction in steal-syndrome, was taken into account. Based on the analysis of blood flow and wall shear stress, two degrees of risk of aneurysm formation were distinguished. High risk corresponds to cases for which both of these values were statistically significantly different from the norm. Medium risk corresponds to cases for which only one of the values was statistically significantly different from the norm. For models containing atherosclerotic plaques, data on shear and normal stresses on the surfaces of atherosclerotic plaques were tabulated. The risk of plaque rupture on each side was determined for each case by analysing the result sets 11 combinations of pathological conditions with increased risk were indicated.

HUC-MSCs mitigate atherosclerosis induced by a high-fat diet in ApoE−/− mice by regulating the intestinal microbiota

BackgroundThe mechanism underlying human umbilical cord mesenchymal stem cells (hUC-MSCs) regulating the stability of atherosclerotic plaque was explored by establishing mice models of atherosclerosis induced by a high-fat diet and hUC-MSCs intervention. MethodsThe ApoE−/− mice atherosclerosis model was constructed using a high-fat diet, and mice were divided into a normal diet group (ND), high-fat diet group (HFD), hUC-MSCs treatment group (HFDM), while the blank control (BC) consisted of C57BL/6J mice. After successful establishment of the model, the feces, hearts, and aorta of mice were collected. Morphological features were detected using HE, oil red O, and Masson staining. Afterward, 16s rRNA gene sequences was used to detect the species and abundance of the intestinal flora in mice, and an atomic force microscope (AFM) was used to detect the Young's modulus of the fibrous cap of atherosclerotic plaques. Lastly, the expression level of the inflammatory factors NLRP3, IL-1β, and IL-18 were detected via immunohistochemistry and immunofluorescence assays. ResultsIn terms of morphological characteristics, the expression level of NLRP3, Young's modulus of the fibrous cap, and plaque stability were significantly reduced in HFD, whereas the ratio of Firmicutes to Bacteroidetes (F/B) was significantly increased. Interestingly, hUC-MSCs treatment reversed the above indices, thus enhancing plaque stability. ConclusionHFD led to dysregulation of intestinal flora homeostasis and induced aberrant expression levels of NLRP3, resulting in a decrease in the Young's modulus of plaques. However, hUC-MSCs treatment improved the biomechanical properties of plaque by modulating the intestinal flora and NLRP3, thereby elevating plaque stability and minimizing the risk of plaque rupture.

Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody: Rationale and design of the randomized FITTER trial

Non-culprit coronary artery lesions are commonly present in patients presenting with an acute coronary syndrome (ACS). Additional stenting of non-culprit lesions in addition to the culprit lesion intends to prevent secondary events caused by these lesions. At the same time, multiple trials have demonstrated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in reducing plaque size and changing plaque composition of non-culprit lesions. Whether intensive low-density lipoprotein cholesterol (LDL-C) reduction with PCSK9 inhibitor evolocumab improves non-culprit vessel hemodynamics, reduces the risk of plaque rupture of important non-culprit lesions, and might obviate the need for additional stenting has not been investigated. The “Functional Improvement of non‐infarcT related coronary artery stenosis by Extensive LDL‐C Reduction with a PCSK9 Antibody” (FITTER) trial is a multi-center, randomized, double-blind, placebo-controlled clinical trial for patients presenting with ACS and multivessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) is performed in non-culprit vessels amenable for percutaneous coronary intervention (PCI). Coronary intervention in patients with hemodynamically important non-critical lesions (FFR: 0.67–0.85) is staged after baseline imaging using near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). Eligible patients are randomized and treated for 12 weeks with either evolocumab or placebo, in addition to high-intensity statin therapy. Follow-up angiography with repeat FFR and IVUS-NIRS is scheduled at 12 weeks. Staged PCI is performed at the operator's discretion.The FITTER trial is the first study to evaluate the effect of maximal LDL-C reduction by the PCSK9 inhibitor evolocumab on invasively measured FFR, plaque size, and plaque composition in hemodynamically important non-culprit lesions, during a treatment period of just 12 weeks after an ACS. Currently, all patients have been included (August 2023) and data analysis is ongoing. Trial registration numberclinicaltrials.gov NCT04141579.

Machine learning based analysis of entropy production and wall shear stress in blood flow through stenosed artery

The building up of cholesterol and various substances on the inner boundary of arterial walls forms a plaque (stenosis), which results in the narrowing of walls of arteries, and this exerts additional stress on the walls. Shear stress at the wall of arteries may cause the formation of plaque, plaque growth, and expansive arterial remodeling, and it may also result in an increased risk of plaque rupture. The purpose of this research work is to use machine learning approaches to analyze the wall shear stress and entropy generation through irreversible processes of blood flow in a porous stenosed artery within the context of magnetohydrodynamic consideration. As a way of illustrating blood’s non-Newtonian behavior, the Casson fluid model is used. A blood flow model in the context of mild stenosis has been developed, and it has subsequently been computationally addressed using an explicit finite difference method. The velocity, temperature, entropy generation, Bejan number, and wall shear stress are visualized for different values of pertinent variables. The result reflects the increased velocity in the stenosed region. A hybrid machine learning method using artificial neural network and particle swarm optimization is implemented to optimize the entropy generation and wall shear stress. The network is trained using Stochastic gradient–descent training procedure as well as Levenberg–Marquardt training procedure, and the outcomes of both training procedures are compared. Using this machine learning process, the minimum entropy production has been found for specific values of the Hartmann number, dimensionless temperature difference, and pulsatile component of pressure gradient. This machine learning-based optimization approach enhances the ability to forecast quantitative changes in affecting parameters, which will contribute to minimized damage to the arterial wall, improved blood flow efficiency and the delivery of necessary components to tissues.

Pathological Intraplaque Hemorrhage as the Gold Standard to Assess the Efficacy of Ultrasound in Predicting Vulnerable Carotid Plaque Rupture.

To assess the clinical utility of ultrasound in predicting the risk of carotid vulnerable plaque rupture using pathological intraplaque hemorrhage as the gold standard. A total of 118 patients who underwent endarterectomy due to symptomatic carotid artery stenosis were enrolled. Conventional ultrasound assessed the plaque thickness, area stenosis rate, echo, and surface morphology. Neovascularization were assessed by contrast-enhanced ultrasound (CEUS) and tracing intraplaque nonenhanced areas. According to neovascularization grade (0-4), plaques were classified as low-, intermediate-, and high risk. Fresh intraplaque hemorrhage within the pathology was adopted as the gold standard for diagnosing plaque rupture risk. Thus, we divided patients into ruptured risk and nonruptured risk groups to assess the value of crucial factors for plaque rupture risk using ultrasound. Of the 118 patients, hypertension accounted for 71.2%, hyperlipidemia 68.6%, diabetes 52.5%, and statin history 64.4%. In the rupture risk group, diabetes, smoking, and stenosis rate were significantly higher than the nonrupture risk group (P < .001); plaque thickness ≥4 mm (P > .05); and mainly hypoechoic with irregular surface morphology (P < .001), nonenhanced areas in the plaques (P < .001), and neovascularization >grade 2 (P < .001). Compared with the low-risk group, plaque rupture risk was 7.219 times higher in the medium-risk group and 18.333 times higher in the high-risk group. The kappa value of the interobserver consistency of crucial ultrasound parameters was >0.75, and the intraclass correlation coefficient was 0.919 (P < .01). Both conventional ultrasound and CEUS have significant clinical importance in the prediction of rupture risk in vulnerable carotid plaques, thereby enabling stroke risk stratification and the assessment of plaque rupture risk.

Effect of variability of mechanical properties on the predictive capabilities of vulnerable coronary plaques

Background and Objective:Coronary plaque rupture is a precipitating event responsible for two thirds of myocardial infarctions. Currently, the risk of plaque rupture is computed based on demographic, clinical, and image-based adverse features. However, using these features the absolute event rate per single higher-risk lesion remains low. This work studies the power of a novel framework based on biomechanical markers accounting for material uncertainty to stratify vulnerable and non-vulnerable coronary plaques. Methods:Virtual histology intravascular ultrasounds from 55 patients, 29 affected by acute coronary syndrome and 26 affected by stable angina pectoris, were included in this study. Two-dimensional vessel cross-sections for finite element modeling (10 sections per plaque) incorporating plaque structure (medial tissue, loose matrix, lipid core and calcification) were reconstructed. A Montecarlo finite element analysis was performed on each section to account for material variability on three biomechanical markers: peak plaque structural stress at diastolic and systolic pressure, and peak plaque stress difference between systolic and diastolic pressures, together with the luminal pressure. Machine learning decision tree classifiers were trained on 75% of the dataset and tested on the remaining 25% with a combination of feature selection techniques. Performance against classification trees based on geometric markers (i.e., luminal, external elastic membrane and plaque areas) was also performed. Results:Our results indicate that the plaque structural stress outperforms the classification capacity of the combined geometric markers only (0.82 vs 0.51 area under curve) when accounting for uncertainty in material parameters. Furthermore, the results suggest that the combination of the peak plaque structural stress at diastolic and systolic pressures with the maximum plaque structural stress difference between systolic and diastolic pressures together with the systolic pressure and the diastolic to systolic pressure gradient is a robust classifier for coronary plaques when the intrinsic variability in material parameters is considered (area under curve equal to [0.91–0.93]). Conclusion:In summary, our results emphasize that peak plaque structural stress in combination with the patient’s luminal pressure is a potential classifier of plaque vulnerability as it independently considers stress in all directions and incorporates total geometric and compositional features of atherosclerotic plaques.

Navigating Choices: A Questionnaire-based Study on Usage of Antiplatelet Therapies in Management of Acute Coronary Syndrome in India

Percutaneous coronary intervention (PCI) is a common invasive cardiac procedure used to treat acute coronarysyndrome (ACS). The main objective of anticoagulant therapy in PCI is to minimize the risk of plaque rupture and decreasethe formation of blood clots. Understanding clinicians' prescription patterns is crucial for optimizing treatment strategiesfor patients with ACS who have undergone PCI. Methods: It was a cross-sectional, questionnaire-based, noninterventionalstudy which included questionnaire responses from 136 cardiologists, regarding usage of antiplatelets in ACS management.Results: Ticagrelor and aspirin dual antiplatelet therapy (DAPT) is favored by 54% cardiologists in managing ACS patientswho have undergone PCI, regardless of the presence or absence of type 2 diabetes mellitus (T2DM). Further, 78% of theparticipants preferred long-term DAPT over short-term and medium-term alternatives. Forty percent respondents preferreda 1-month triple antithrombotic therapy (TAT) for PCI patients with atrial fibrillation. Additionally, the study emphasizedthe importance of considering factors like age, bleeding history, hemoglobin, and creatinine clearance in determining theoptimal antithrombotic strategy. Conclusion: This study contributes valuable insights into the real-world practices of healthcare practitioners, paving the way for more informed and personalized ACS management strategies in Indian patients.

Association of angiogenesis-associated genes with atherosclerotic plaque progression, intraplaque hemorrhage, and immune infiltration

Mounting evidence suggests that intraplaque angiogenesis is associated with the progression of atherosclerotic plaques and the development of intraplaque hemorrhage. The specificity of intraplaque immune cell infiltration may be associated with abnormalities in the structure and function of the nascent capillaries. Here, we analyzed expression levels of angiogenesis-associated genes in early and advanced carotid atheromatous plaque tissues as well as in stable and intraplaque hemorrhage plaques. Expression profiles of advanced arterial plaques based on angiogenesis-associated genes were classified into subtypes by performing a consensus clustering analysis. The correlation between the immune microenvironment of plaques and expression of angiogenesis-associated genes was also explored using the single sample gene set enrichment analysis method and the CIBERSORT algorithm. We identified hub angiogenesis-associated genes showing similar expression patterns throughout plaque adverse progression, and constructed a prediction model using the random forest algorithm. Receiver operating curves were constructed to evaluate efficacy in identification of intraplaque hemorrhage in a plaque. Our results suggest that heterogeneity of angiogenesis-related genes may promote the malignant development of plaques and cause plaque rupture. In conclusion, we propose a model based on expression of angiogenesis-related genes to predict the risk of plaque rupture.

Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis.

The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can contribute to the development of chronic inflammatory diseases. Important among these diseases is atherosclerosis, which refers to focal lesions in the arterial intima driven by elevated apolipoprotein B-containing lipoproteins, notably low-density lipoprotein (LDL), and characterized by the formation of a plaque composed of inflammatory immune cells, a collection of dead cells and lipids called the necrotic core, and a fibrous cap. As the disease progresses, the necrotic core expands, and the fibrous cap becomes thin, which increases the risk of plaque rupture or erosion. Plaque rupture leads to a rapid thrombotic response that can give rise to heart attack, stroke, or sudden death. With marked lowering of circulating LDL, however, plaques become more stable and cardiac risk is lowered-a process known as atherosclerosis regression. A critical aspect of both atherosclerosis progression and regression is the crosstalk between innate (myeloid cells) and adaptive (T-lymphocytes) immune cells. Myeloid cells are specialized at clearing apoptotic cells by a process called efferocytosis, which is necessary for inflammation resolution. In advanced disease, efferocytosis is impaired, leading to secondary necrosis of apoptotic cells, inflammation, and, most importantly, defective tissue resolution. In regression, efferocytosis is reawakened aiding in inflammation resolution and plaque stabilization. Here, we will explore how efferocytosing myeloid cells could affect T-cell function and vice versa through antigen presentation, secreted factors, and cell-cell contacts and how this cellular crosstalk may contribute to the progression or regression of atherosclerosis.

Impact of residual stress on coronary plaque stress/strain calculations using optical coherence tomography image-based multi-layer models.

Mechanical stress and strain conditions play an important role in atherosclerosis plaque progression, remodeling and potential rupture and may be used in plaque vulnerability assessment for better clinical diagnosis and treatment decisions. Single layer plaque models without residual stress have been widely used due to unavailability of multi-layer image segmentation method and residual stress data. However, vessel layered structure and residual stress have large impact on stress/strain calculations and should be included in the models. In this study, intravascular optical coherence tomography (OCT) data of coronary plaques from 10 patients were acquired and segmented to obtain the three-layer vessel structure using an in-house automatic segmentation algorithm. Multi- and single-layer 3D thin-slice biomechanical plaque models with and without residual stress were constructed to assess the impact of residual stress on stress/strain calculations. Our results showed that residual stress led to a more uniform stress distribution across the vessel wall, with considerable plaque stress/strain decrease on inner wall and increase on vessel out-wall. Multi-layer model with residual stress inclusion reduced inner wall maximum and mean plaque stresses by 38.57% and 59.70%, and increased out-wall maximum and mean plaque stresses by 572.84% and 432.03%. These findings demonstrated the importance of multi-layer modeling with residual stress for more accurate plaque stress/strain calculations, which will have great impact in plaque cap stress calculation and plaque rupture risk assessment. Further large-scale studies are needed to validate our findings.

Computational Investigation of Vessel Injury Due to Catheter Tracking During Transcatheter Aortic Valve Replacement.

Catheter reaction forces during transcatheter valve replacement (TAVR) may result in injury to the vessel or plaque rupture, triggering distal embolization or thrombosis. In vitro test methods represent the arterial wall using synthetic proxies to determine catheter reaction forces during tracking, but whether they can account for reaction forces within the compliant aortic wall tissue in vivo is unknown. Moreover, the role of plaque inclusions is not well understood. Computational approaches have predicted the impact of TAVR positioning, migration, and leaflet distortion, but have not yet been applied to investigate aortic wall reaction forces and stresses during catheter tracking. In this study, we investigate the role that catheter design and aorta and plaque mechanical properties have on the risk of plaque rupture during TAVR catheter delivery. We report that, for trackability testing, a rigid test model provides a reasonable estimation of the peak reaction forces experienced during catheter tracking within compliant vessels. We investigated the risk of rupture of both the aortic tissue and calcified plaques. We report that there was no risk of diseased aortic tissue rupture based on an accepted aortic tissue stress threshold (4.2MPa). However, we report that both the aortic and plaque tissue exceed a rupture stress threshold (300kPa) with and without the presence of stiff and soft plaque inclusions. We also highlight the potential risks associated with shorter catheter tips during catheter tracking and demonstrate that increasing the contact surface will reduce peak contact pressures experienced in the tissue.

Thin-cap fibroatheroma in acute coronary syndrome: Implication for intravascular imaging assessment

Acute coronary syndrome (ACS), a significant cardiovascular disease threat, has garnered increased focus concerning its etiological mechanisms. Thin-cap fibroatheroma (TCFA) are central to ACS pathogenesis, characterized by lipid-rich plaques, profuse foam cells, cholesterol crystals, and fragile fibrous caps predisposed to rupture. While TCFAs may be latent and asymptomatic, their pivotal role in ACS risk is undeniable. High-resolution imaging techniques like Optical coherence tomography (OCT) and Intravascular ultrasound (IVUS) are instrumental for effective TCFA detection. Therapeutic strategies encompass pharmacological and interventional measures, including antiplatelet agents, statins, and Percutaneous Coronary Intervention (PCI), aiding in plaque stabilization, inflammation reduction, and rupture risk mitigation. Despite the strong correlation between TCFAs and adverse prognoses in ACS patients, early detection and rigorous treatment significantly enhance patient prognosis and diminish cardiovascular events. This review aims to encapsulate recent advancements in TCFA research within ACS, covering formation mechanisms, clinical manifestations, and prognostic implications.

In Situ Imaging of GGT and HOBr-Triggered Atherosclerotic Plaque Rupture via Activating the RunX2/Col IV Signaling Pathway.

Calcification and abnormal collagen deposition within blood vessels constitute causative factors for atherosclerotic plaque rupture, and their occurrence is intimately linked with γ-glutamyltranspeptidase (GGT) and hypobromous acid (HOBr). However, the underlying regulatory mechanisms of GGT and HOBr in plaque rupture remain unclear. Hence, we developed a dual-responsive near-infrared (NIR) fluorescent probe (BOC-H) that effectively avoids spectral crosstalk for the in situ visualization of the fluctuations in GGT and HOBr levels during atherosclerotic plaque rupture. We found that both GGT and HOBr contents increase significantly in the calcification models of cells and animals. The overexpressed GGT participated in intracellular oxygen-promoting behavior, which obviously upregulated the expression of RunX2 and Col IV by facilitating H2O2 and HOBr secretion. This process triggered calcification and abnormal collagen deposition within the plaque, which raised the risk of plaque rupture. PM2.5-induced arteriosclerotic calcification models further verified the results that GGT and HOBr accelerate plaque rupture via activation of the RunX2/Col IV signaling pathway. Moreover, the assessment of GGT and HOBr in serum samples from patients with acute myocardial infarction further confirmed the co-regulation of GGT and HOBr in the plaque rupture. Together, our studies highlight the involvement of GGT and HOBr in driving plaque rupture and offer new targets for the prevention and treatment of acute cardiovascular disease.

Association of Lipoprotein-associated phospholipase A2 With Carotid Intima-Media Thickness in Acute Cerebral Infarction Patients.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory marker associated with atherosclerotic and cardiovascular diseases. This study aimed to explore the association of Lp-PLA2 with carotid intima-media thickness (cIMT) in patients with acute ischemic stroke (AIS) and explore a threshold level to predict the risk of vulnerable plaques. This retrospective observational study included patients with AIS in the Neurology Department of our Hospital between January 2018 and December 2019. The study included 293 patients aged 65.29 ± 12.11years, including 212 males, of whom 124 had carotid intima-media thickening (42.32%). Multivariable logistic regression showed that Lp-PLA2 level was an independent risk factor for cIMT (odds ratio [OR] = 1.004, 95% confidence interval [95% CI] 1.001-1.008, P = .008). Threshold effect analysis showed that the risk of vulnerable carotid plaque occurrence increased by 2% for every 1ng/mL increase in Lp-PLA2 level with serum Lp-PLA2 levels between 157 and 279ng/mL; this increase was statistically significant (OR = 1.02, 95% CI 1.01-1.03, P < .001). Serum Lp-PLA2 is an independent risk factor for increased cIMT in patients with AIS, and a threshold Lp-PLA2 level between 157 and 279ng/mL showed a higher risk of carotid plaque rupture.

On the Impact of Residual Strains in the Stress Analysis of Patient-Specific Atherosclerotic Carotid Vessels: Predictions Based on the Homogenous Stress Hypothesis

The identification of carotid atherosclerotic lesion at risk for plaque rupture, eventually resulting in cerebral embolism and stroke, is of paramount clinical importance. High stress in the fibrous plaque cap has been proposed as risk factor. However, among others, residual strains influence said stress predictions, but quantitative and qualitative implications of residual strains in this context are not well explored. We therefore propose a multiplicative kinematics-based Growth and Remodeling (G&R) framework to predict residual strains from homogenizing tissue stress and then investigate its implication on plaque stress. Carotid vessel morphology of four patients was reconstructed from clinical Computed Tomography-Angiography (CT-A) images and equipped with heterogeneous tissue constitutive properties assigned through a histology-based artificial intelligence image segmentation tool. As compared to a purely elastic analysis and depending on patient-specific morphology and tissue distributions, the incorporation of residual strains reduced the maximum wall stress by up to 30%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$30\\%$$\\end{document} and resulted in a fundamentally different distribution of stress across the atherosclerotic wall. Regardless residual strains homogenized tissue stresses, the fibrous plaque cap may persistently be exposed to spots of high stress. In conclusion, the incorporation of residual strains in biomechanical studies of atherosclerotic carotids may be important for a reliable assessment of fibrous plaque cap stress.

Atherosclerotic plaque features relevant to rupture-risk detected by clinical photon-counting CT ex vivo: a proof-of-concept study

BackgroundTo identify subjects with rupture-prone atherosclerotic plaques before thrombotic events occur is an unmet clinical need. Thus, this proof-of-concept study aims to determine which rupture-prone plaque features can be detected using clinically available photon-counting computed tomography (PCCT).MethodsIn this retrospective study, advanced atherosclerotic plaques (ex vivo, paraffin-embedded) from the Carotid Plaque Imaging Project were scanned by PCCT with reconstructed energy levels (45, 70, 120, 190 keV). Density in HU was measured in 97 regions of interest (ROIs) representing rupture-prone plaque features as demonstrated by histopathology (thrombus, lipid core, necrosis, fibrosis, intraplaque haemorrhage, calcium). The relationship between HU and energy was then assessed using a mixed-effects model for each plaque feature.ResultsPlaques from five men (age 79 ± 8 [mean ± standard deviation]) were included in the study. Comparing differences in coefficients (b1diff) of matched ROIs on plaque images obtained by PCCT and histology confirmed that calcium was distinguishable from all other analysed features. Of greater novelty, additional rupture-prone plaque features proved discernible from each other, particularly when comparing haemorrhage with fibrous cap (p = 0.017), lipids (p = 0.003) and necrosis (p = 0.004) and thrombus compared to fibrosis (p = 0.048), fibrous cap (p = 0.028), lipids (p = 0.015) and necrosis (p = 0.017).ConclusionsClinically available PCCT detects not only calcification, but also other rupture-prone features of human carotid plaques ex vivo.Relevance statementImproved atherosclerotic plaque characterisation by photon-counting CT provides the ability to distinguish not only calcium, but also rupture-prone plaque features such as haemorrhage and thrombus. This may potentially improve monitoring and risk stratification of atherosclerotic patients in order to prevent strokes.Key points• CT of atherosclerotic plaques mainly detects calcium.• Many components, such as intra-plaque haemorrhage and lipids, determine increased plaque rupture risk.• Ex vivo carotid plaque photon-counting CT distinguishes haemorrhage and thrombus.• Improved plaque photon-counting CT evaluation may refine risk stratification accuracy to prevent strokes.Graphical

Effects of hematocrit levels on flow structures and stress levels in the healthy and diseased carotid arteries

Flow structures and wall shear stress (WSS) distribution in human arteries depend strongly on blood rheology. Blood viscosity undergoes significant alterations due to varying hematocrit (Hct) levels. Hematocrit levels can change from the normal level (45%) due to numerous disorders such as leukemia, lymphoma, and congenital heart disease. However, the effects of Hct levels on the flow features and WSS levels in large stenotic arteries are not well reported in literature. The present study computationally assesses the variation in flow features in healthy and stenosed carotid arteries due to changes in blood Hct levels. We have reported variations in axial and secondary flow characteristics, vortex structures, and WSS-based parameters for different Hct levels. Specifically, we consider high (65%) and low (25%) Hct levels in addition to a normal Hct level. Our results reveal that both high and low Hct levels have adverse effects on the hemodynamic features inside a healthy carotid artery model. The low Hct level displays a much more widespread low time-averaged WSS (TAWSS) area, while the high Hct shows an increased oscillatory shear index (OSI) zone at the carotid sinus wall. In stenotic arteries, low Hct enhances the spread of the low TAWSS zone in the post-stenotic carotid sinus, whereas high Hct increases the risk of plaque rupture. The high Hct level also increases the spread of high OSI zone at the inner wall of internal carotid artery for the moderately stenosed artery.