Search Results (44)

Coronary artery disease (CAD) is the main cause of morbidity and death worldwide, and atherosclerosis represents the leading pathophysiological pathway responsible for CAD. Atherosclerotic process is a complex interplay of mechanisms and mediators resulting in plaque formation, progression and destabilization, the latter being the most frequent cause of acute cardiovascular events. Considering the systemic nature of atherosclerosis, polyvascular disease involvement is possible and has been described since 1960s. Accordingly, epidemiologic studies reported that concomitant CAD and atherosclerosis in other arterial beds like carotid arteries, lower limb arteries, mesenteric and renal circulation, and aorta, is frequent and related to increased chance of future cardiovascular events. Although risk factors, atherosclerotic plaque features and mechanisms of plaque destabilization are largely shared across different sites, many studies have reported some disparities among districts. Moreover, simultaneous polyvascular disease has been associated with increased likelihood of having particular plaque characteristics depending on the affected arterial level. In this comprehensive narrative review, we aim to discuss about epidemiology of concomitant CAD and atherosclerosis in other arterial beds, and to examine differences in risk factors, plaque features and mechanisms of plaque instability between CAD and other atherosclerotic locations. Finally, we review the studies observing differences on plaque features according to involved atherosclerotic sites, focusing on CAD. Full article

Carotid stenosis is a common pathology in clinical practice and unfortunately carries a high risk of serious cerebrovascular events. The early recognition of carotid plaque and, consequently, a careful analysis by means of multimodal imaging are the necessary steps to undertake a correct management pathway, aimed at preventing or, if not possible, reducing the risk of atherogenic phenomena responsible for cerebral infarction. In particular, the presence or absence of clinical symptoms, understood as the occurrence of events such as TIAs in the last 6 months, non-disabling strokes or repeated episodes of amaurosis fugax, and the degree of carotid stenosis, are certainly the most studied parameters, and as reported by several international guidelines, can lead to the best therapeutic strategy: whether to rely on conservative medical therapy or to resort to mechanical revascularization of the carotid stenosis. According to the recommendations of the European Society of Vascular Surgery, mechanical revascularization is recommended for stenosis > 50% in symptomatic patients and stenosis > 60% in asymptomatic patients. In contrast, the latest findings on plaque vulnerability have focused attention on individual patient characteristics and clinical comorbidities that may be responsible for plaque inflammation and should therefore be taken into consideration to decide if revascularization treatment is needed even in those subjects who present stenosis with less degree than reported as critical value. Moreover, further radiological investigations are fundamental to finding the presence of entities such as plaque ulceration, plaque neo-vascularization, fibrous caps, and intraplaque lipid core that are responsible for increased vulnerability. Medical therapy involves interventions aimed at eliminating cardiovascular risk factors by administering drugs that control the comorbidities responsible for worsening carotid stenosis. Recent studies are also evaluating the effectiveness of new plaque-modifying drugs or targeted anti-inflammatory agents in reducing the risk of plaque development and complications. Revascularization therapies, on the other hand, include surgery (CEA), the endovascular technique (CAS), and a new hybrid technique (TCAR): they are all valid alternatives for the treatment of carotid stenosis, each with specific technical difficulties, but on the whole with comparable safety profiles and risk rates of postoperative complications, although some recent emergencies have focused attention on possible short- and long-term gender-dependent outcome differences. The aim of this manuscript is to present the state of the art in the management of patients with carotid stenosis and to take a closer look at revascularization options. In our opinion, the choice of one strategy over another should therefore depend on gender, anatomical features of the patient, preoperative comorbidities, and last but not least, the experience of the center and the multidisciplinary team involved in the management of the patient. Full article

Background/Objectives: Common carotid artery dissection (CCAD) can result in severe neurological sequelae; however, its diagnosis may be challenging due to consciousness disturbance and aphasia. The objective of this article is to propose a new imaging feature to assist in the identification of CCAD. Methods: This retrospective case series enrolled 139 patients with discharge diagnoses of aortic dissection who underwent carotid ultrasound during admission over a period of three years. Results: Among these patients, 23 had type A aortic dissection, and 113 had type B aortic dissection or related conditions. Notably, among the 23 patients with type A aortic dissection, eight had associated common carotid artery dissection (CCAD), and a total of nine CCAD events were identified. Meanwhile, a B-mode ultrasound revealed six double lumens with intimal flaps and three intramural thrombi. The ‘train-line’ pattern in ultrasonography was discerned by detecting a hypoechoic thickened wall, which was characterized by a margin formed by two parallel linear reflections in close proximity. This distinctive “train-line” pattern was identified in three intimal flaps and two intramural thrombi. Conclusions: While double lumens and intramural thrombus are prevalent findings, the latter may be misinterpreted as atherosclerotic plaque. The “train-line” pattern may aid in distinguishing intramural thrombus from atheromatous plaque, offering an additional diagnostic tool alongside the identification of double lumens with intimal flaps. Full article

Background and Objectives: Atherosclerosis is a chronic inflammatory disease significantly contributing to cardiovascular morbidity and mortality. This study primarily aims to evaluate the role of baseline blood glucose levels and inflammatory markers in the histopathological features of atherosclerotic plaques in the carotid and femoro-popliteal arteries. Materials and Methods: In this retrospective, observational, and monocentric study, 165 patients diagnosed with infrainguinal peripheral arterial disease or carotid artery disease hospitalized in the Vascular Surgery Clinic, between January 2019 and December 2023, were included. From the electronic database of the hospital, we documented demographic data, cardiovascular comorbidities, including hypertension, atrial fibrillation, ischemic heart disease, and chronic heart failure, as well as chronic kidney disease, diabetes, and prevalent risk factors such as active smoking, dyslipidemia, and obesity. Additionally, we recorded the arterial site from which the atherosclerotic plaque was obtained, along with laboratory data obtained at the time of admission prior to the surgery. The patients were divided into “Carotid Artery” and “Femoro-Popliteal Axis” based on anatomical location. Results: A greater prevalence of male patients (p = 0.008) and dyslipidemia (p = 0.002) was found in the group with atherosclerotic plaques from the femoro-popliteal axis. Laboratory data also showed increased lymphocyte (p = 0.020) and PLT (p = 0.028) levels in this group. There was no significant difference in the types of atherosclerotic plaques between the two patient groups. However, those in the Carotid Artery group showed a higher rate of antiaggregant treatment and a reduced incidence of dual therapy (p < 0.001). The Spearman correlation analysis revealed a positive correlation between baseline glucose levels and NLR (r = 0.402, p < 0.001), MLR (r = 0.217, p = 0.005), PLR (r = 0.306, p < 0.001), and LGI (r = 0.693, p < 0.001). Furthermore, the predictive roles of glucose, NLR, MLR, and LGI were assessed through multivariate analysis. Consequently, elevated baseline values of the parameters above were associated with unstable atherosclerotic plaques, independent of demo-graphic data, standard cardiovascular risk factors, site of artery harvest, and chronic vascular treatments at the time of admission (for all p < 0.05). Conclusions: This study highlights the significant relationships between glucose levels and various inflammatory markers in patients with different histopathological diagnoses of atherosclerotic plaques. Additionally, elevated glycemic and systemic inflammation biomarkers were associated with unstable atherosclerotic plaque, independent of demographic data, comorbidities, cardiovascular risk factors, anatomical artery harvest, and vascular chronic medication at the time of admission. Full article

Background/Objectives: Carotid artery disease is a condition affecting 3% of the general population which significantly contributes to the development of cerebrovascular events. Fibroblast Growth Factor-23 (FGF-23) is a hormone that has been linked to atherosclerosis and increased cardiovascular risk, including stroke and myocardial infarction. This review explores the association of FGF-23 with carotid artery disease progression in an endarterectomy clinical context. Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a search was performed relying on MEDLINE, Scopus and Web of Science, identifying publications focused on the correlation between serum FGF-23 and carotid artery disease. Assessment of study quality was made using National Heart, Lung and Blood Institute Study Quality Assessment Tool (NHLBI). Results: Three observational studies, comprising 1039 participants, were included. There was considerable heterogeneity among the populations from the different studies. Elevated FGF-23 levels were consistently associated with unstable plaque features, including intraplaque neovascularization, as identified through Superb Microvascular Imaging (SMI). Plasma levels of inflammatory mediators, such as Interleukin-6 (Il-6), Monocyte Chemoattractant Protein-1 (MCP-1), and Osteoprotegerin (OPG), positively correlated with carotid artery disease, but their link to unstable plaques is conflicting. None of the studies investigated clinical complications following carotid endarterectomy. Conclusions: FGF-23 is a potential biomarker for plaque vulnerability in carotid disease. Despite promising findings, limitations such as small sample sizes and lack of longitudinal data suggest the need for larger and more diverse studies to improve risk stratification and inform personalized treatment strategies for carotid atherosclerosis. Full article

Atherosclerosis involves an inflammatory response due to plaque formation within the arteries, which can lead to ischemic stroke and heart disease. It is one of the leading causes of death worldwide, with various contributing factors such as hyperlipidemia, hypertension, obesity, diabetes, and smoking. Wall shear stress (WSS) is also known as a contributing factor of the formation of atherosclerotic plaques. Since the causes of atherosclerosis cannot be attributed to a single factor, clearly understanding the mechanisms and causes of its occurrence is crucial for preventing the disease and developing effective treatment strategies. To better understand atherosclerosis and define the correlation between various contributing factors, computational fluid dynamics (CFD) analysis is primarily used. CFD simulates WSS, the frictional force caused by blood flow on the vessel wall with various hemodynamic changes. Using apolipoprotein E knockout (ApoE-KO) mice subjected to partial ligation and a high-fat diet at 1-week, 2-week, and 4-week intervals as an atherosclerosis model, CFD analysis was conducted along with the reconstruction of carotid artery blood flow via magnetic resonance imaging (MRI) and compared to the inflammatory factors and pathological staining. In this experiment, a comparative analysis of the effects of high WSS and low WSS was conducted by comparing the standard deviation of time-averaged wall shear stress (TAWSS) at each point within the vessel wall. As a novel approach, the standard deviation of TAWSS within the vessel was analyzed with the staining results and pathological features. Since the onset of atherosclerosis cannot be explained by a single factor, the aim was to find the correlation between the thickness of atherosclerotic plaques and inflammatory factors through standard deviation analysis. As a result, the gap between low WSS and high WSS widened as the interval between weeks in the atherosclerosis mouse model increased. This finding not only linked the occurrence of atherosclerosis to WSS differences but also provided a connection to the causes of vulnerable plaques. Full article

Background and Objectives: Acute ischemic stroke (AIS) is a leading cause of death and disability with poor long-term outcomes. Creating a predictive score for long-term mortality in AIS might be important for optimizing treatment strategies. The aim of this study is to develop and validate a predictive score for three-year mortality in patients with AIS using several demographic, clinical, laboratory and imaging parameters. Materials and Methods: This study included 244 AIS patients admitted to a tertiary center and followed up for three years. The patients’ data included demographics, clinical features, laboratory tests (including resistin and leptin levels) and imaging parameters. The patients were randomly divided into a predictive group (n = 164) and a validation group (n = 80). Results: Advanced age, a high NIHSS score, low levels of hemoglobin, elevated resistin levels and the presence of carotid plaques were independently associated with three-year mortality. The predictive model incorporated these variables, and it was validated in a separate cohort. Leptin levels did not significantly predict mortality. Conclusions: This study developed and validated a promising predictive score for three-year mortality in patients with AIS. Advanced age, high NIHSS scores, low hemoglobin levels, elevated resistin levels and the presence of carotid plaques were the independent predictors of long-term mortality. Full article

Background: The risk of cardiovascular disease (CVD) has traditionally been predicted via the assessment of carotid plaques. In the proposed study, AtheroEdge™ 3.0_HDL (AtheroPoint™, Roseville, CA, USA) was designed to demonstrate how well the features obtained from carotid plaques determine the risk of CVD. We hypothesize that hybrid deep learning (HDL) will outperform unidirectional deep learning, bidirectional deep learning, and machine learning (ML) paradigms. Methodology: 500 people who had undergone targeted carotid B-mode ultrasonography and coronary angiography were included in the proposed study. ML feature selection was carried out using three different methods, namely principal component analysis (PCA) pooling, the chi-square test (CST), and the random forest regression (RFR) test. The unidirectional and bidirectional deep learning models were trained, and then six types of novel HDL-based models were designed for CVD risk stratification. The AtheroEdge™ 3.0_HDL was scientifically validated using seen and unseen datasets while the reliability and statistical tests were conducted using CST along with p-value significance. The performance of AtheroEdge™ 3.0_HDL was evaluated by measuring the p-value and area-under-the-curve for both seen and unseen data. Results: The HDL system showed an improvement of 30.20% (0.954 vs. 0.702) over the ML system using the seen datasets. The ML feature extraction analysis showed 70% of common features among all three methods. The generalization of AtheroEdge™ 3.0_HDL showed less than 1% (p-value < 0.001) difference between seen and unseen data, complying with regulatory standards. Conclusions: The hypothesis for AtheroEdge™ 3.0_HDL was scientifically validated, and the model was tested for reliability and stability and is further adaptable clinically. Full article

Stroke is the second leading cause of death and a major cause of disability around the world, and the development of atherosclerotic plaques in the carotid arteries is generally considered the leading cause of severe cerebrovascular events. In recent years, new reports have reinforced the role of an accurate histopathological analysis of carotid plaques to perform the stratification of affected patients and proceed to the correct prevention of complications. This work proposes applying an unsupervised learning approach to analyze complex whole-slide images (WSIs) of atherosclerotic carotid plaques to allow a simple and fast examination of their most relevant features. All the code developed for the present analysis is freely available. The proposed method offers qualitative and quantitative tools to assist pathologists in examining the complexity of whole-slide images of carotid atherosclerotic plaques more effectively. Nevertheless, future studies using supervised methods should provide evidence of the correspondence between the clusters estimated using the proposed textural-based approach and the regions manually annotated by expert pathologists. Full article

The rupture of unstable plaques is a major cause of acute cardiovascular events. The early assessment of carotid plaques can significantly reduce the cardiovascular risks, so developing evaluation models suitable for data from different centers is of great clinical importance. This study leverages plaque datasets from multiple centers to develop a Weighted multi-source carotid artery plaque Unsupervised Classification Framework (WUCF). The multi-source domain adaptation module of the WUCF focuses on maintaining feature consistency between each independent source and target center, while also integrating a specialized domain discriminator expert. This ensures that the knowledge from each source center is effectively learned and combined for accurate predictions in the target domain. The experimental evaluation of WUCF, using datasets from three centers, has demonstrated the method’s superiority and robustness. Full article

Background: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. Methods: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent ¹⁸F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUV_max) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. Results: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. ¹⁸F-FDG PET/MRI was performed a mean of 38 days (range 1–90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. Conclusions: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk. Full article

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of ischemic stroke secondary to large-artery atherosclerosis. In macroscopic evaluation, vulnerable plaques are characterized by one or more of the following features: microcalcification; neovascularization; lipid-rich necrotic cores (LRNCs); intraplaque hemorrhage (IPH); thin fibrous caps; plaque surface ulceration; huge dimensions, suggesting stenosis; and plaque rupture. Recognizing these macroscopic characteristics is crucial for estimating the risk of cerebrovascular events, also in the case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that are scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talk governing plaque inflammation, rupture potential, and thrombogenicity. The current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehensive analysis of the current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional attributes that characterize vulnerable plaques. Full article

(1) Background: Non-stenotic complicated plaques are a neglected cause of stroke, in particular in young patients. Atherosclerosis has some preferential sites in extracranial arteries and the prepetrous segment of the internal carotid artery has been rarely described as site of atheroma in general and of complicated atheroma in stroke patients. The aim of this study is to describe the rate of the prepetrous internal carotid artery’s (ICA) involvement in a single-center case series of young stroke patients. (2) Methods: All patients < 50 years old with acute ischemic stroke admitted to a single-center Stroke Unit during two time periods (the first one from 1 January 2018 to 31 December 2019, and the second one from 1 January 2021 to 30 June 2022), were prospectively investigated as part of a screening protocol of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study [ClinicalTrials.gov ID NCT01934725], including extracranial vascular examination by using computed tomography (CT) or magnetic resonance imaging (MRI). (3) Results: Two out of ninety-three consecutive patients (2.15%) had a complicated atheroma in the prepetrous ICA as the cause of stroke and both CT angiography and high-resolution vessel wall MRI were applied to document the main features of positive remodeling, cap rupture, ulceration, intraplaque hemorrhage, and a transient thrombus superimposed on the atheroma. The two patients had a different evolution of healing in the first case and a persisting ulceration at 12 months in the second case. (4) Conclusions: The prepetrous ICA is a rarely described location of complicated atheroma in stroke patients at all ages and it represents roughly 2% of causes of acute stroke in this single-center case series in young people. Full article

Vulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of these asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT), is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. Overall, 177 patients were subjected to carotid Doppler ultrasound at the study admission. The following data were collected: EMT, intima-media thickness (IMT), the presence of carotid plaques, the area of the highest plaque, the presence of “acute culprit” carotid stenosis, and the grade of internal carotid stenosis. “Acute culprit” carotid stenosis was defined as a significant atherosclerotic plaque that leads to a neurologic event within 15 days. From each carotid bifurcation, a right and a left EMT were determined. We analyzed both the mean EMTs (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT [Median = 1.14; IQR = 0.66 versus Median = 0.97; IQR = 0.40; p = 0.001]. A positive correlation was found between the mean EMT and IMT (right: ρ = 0.20; p = 0.010; left: ρ = 0.21; p = 0.007) and between the mean EMT and the area of the largest carotid plaque (right: ρ = 0.17; p = 0.036; left: ρ = 0.22; p = 0.004). Left carotid stenosis ≥ 70% was associated with higher ipsilateral EMT [Median = 1.56; IQR = 0.70 versus Median = 0.94; IQR = 0.42; p = 0.009]. Patients with “acute culprit” carotid stenosis had a higher ipsilateral EMT [left ipsilateral EMT: Median = 1.46; IQR = 0.63; “non-acute”: Median = 0.94; IQR = 0.43; p = 0.009; right ipsilateral EMT: Median = 2.25; IQR = 0.62; “non-acute”: Median = 1.00; IQR = 0.51; p = 0.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an “acute culprit” carotid stenosis decreased (p = 0.036). The amount of peri-carotid adipose tissue, estimated with EMT, was associated with atherosclerosis at the carotid arteries. The mean EMT was associated with the features of chronic atherosclerosis lesions: the presence of carotid plaques, IMT, and the area of the highest plaque. Ipsilateral EMT was linked with “acute culprit” atherosclerotic plaque. Full article

Carotid artery disease has traditionally been assessed based on the degree of luminal narrowing. However, this approach, which solely relies on carotid stenosis, is currently being questioned with regard to modern risk stratification approaches. Recent guidelines have introduced the concept of the “vulnerable plaque,” emphasizing specific features such as thin fibrous caps, large lipid cores, intraplaque hemorrhage, plaque rupture, macrophage infiltration, and neovascularization. In this context, imaging-based biomarkers have emerged as valuable tools for identifying higher-risk patients. Non-invasive imaging modalities and intravascular techniques, including ultrasound, computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have played pivotal roles in characterizing and detecting unstable carotid plaques. The aim of this review is to provide an overview of the evolving understanding of carotid artery disease and highlight the significance of imaging techniques in assessing plaque vulnerability and informing clinical decision-making. Full article