Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking. METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs. RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 µg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 µg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001). CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis.

BACKGROUND: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited. METHODS: To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology. RESULTS: We identified 25 cell populations, each with a unique multiomic signature, including macrophages, T cells, NK (natural killer) cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL-1B (interleukin-1B) or C1Q expression, 2 TREM2-positive foam cells (1 expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing cellular indexing of transcriptomes and epitopes by sequencing data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic versus asymptomatic patients. CONCLUSIONS: Our multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types and the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.

Atherosclerotic Plaque Epigenetic Age Acceleration Predicts a Poor Prognosis and Is Associated With Endothelial-to-Mesenchymal Transition in Humans.

BACKGROUND: Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques is predictive for the risk of cardiovascular events. METHODS: Whole-genome DNA methylation of human carotid atherosclerotic plaques (n=485) and of blood (n=93) from the Athero-Express endarterectomy cohort was used to calculate epigenetic age acceleration (EAA). EAA was linked to clinical characteristics, plaque histology, and future cardiovascular events (n=136). We studied whole-genome DNA methylation and bulk and single-cell transcriptomics to uncover molecular mechanisms of plaque EAA. We experimentally confirmed our in silico findings using in vitro experiments in primary human coronary endothelial cells. RESULTS: Male and female patients with severe atherosclerosis had a median chronological age of 69 years. The median epigenetic age was 65 years in females (median EAA, -2.2 [interquartile range, -4.3 to 2.2] years) and 68 years in males (median EAA, -0.3 [interquartile range, -2.9 to 3.8] years). Patients with diabetes and a high body mass index had higher plaque EAA. Increased EAA of plaque predicted future events in a 3-year follow-up in a Cox regression model (univariate hazard ratio, 1.7; P=0.0034) and adjusted multivariate model (hazard ratio, 1.56; P=0.02). Plaque EAA predicted outcome independent of blood EAA (hazard ratio, 1.3; P=0.018) and of plaque hemorrhage (hazard ratio, 1.7; P=0.02). Single-cell RNA sequencing in plaque samples from 46 patients in the same cohort revealed smooth muscle and endothelial cells as important cell types in plaque EAA. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally confirmed by TGFß-triggered endothelial-to-mesenchymal transition inducing rapid epigenetic aging in coronary endothelial cells. CONCLUSIONS: Plaque EAA is a strong and independent marker of poor outcome in patients with severe atherosclerosis. Plaque EAA was linked to mesenchymal endothelial and smooth muscle cells. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally validated. Epigenetic aging mechanisms may provide new targets for treatments that reduce atherosclerosis complications.

Virus-Associated CD8+ T-Cells Are Not Activated Through Antigen-Mediated Interaction Inside Atherosclerotic Lesions.

INTRODUCTION: Viral infections have been associated with the progression of atherosclerosis and CD8+ T-cells directed against common viruses, such as influenza, Epstein-Barr virus, and cytomegalovirus, have been detected inside human atherosclerotic lesions. These virus-specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis; however, whether they affect disease progression directly remains unclear. In this study, we aimed to characterize the activation status of virus-specific CD8+ T-cells in the atherosclerotic lesion. METHODS: The presence, clonality, tissue enrichment, and phenotype of virus-associated CD8+ T-cells in atherosclerotic lesions were assessed by exploiting bulk T-cell receptor-ß sequencing and single-cell T-cell receptor (α and ß) sequencing datasets on human endarterectomy samples and patient-matched blood samples. To investigate if virus-specific CD8+ T-cells can be activated through T-cell receptor stimulation in the atherosclerotic lesion, the immunopeptidome of human plaques was determined. RESULTS: Virus-associated CD8+ T-cells accumulated more in the atherosclerotic lesion (mean=2.0%), compared with patient-matched blood samples (mean=1.4%; P=0.05), and were more clonally expanded and tissue enriched in the atherosclerotic lesion in comparison with nonassociated CD8+ T-cells from the lesion. Single-cell T-cell receptor sequencing and flow cytometry revealed that these virus-associated CD8+ T-cells were phenotypically highly similar to other CD8+ T-cells in the lesion and that both exhibited a more activated phenotype compared with circulating T-cells. Interestingly, virus-associated CD8+ T-cells are unlikely to be activated through antigen-specific interactions in the atherosclerotic lesion, as no virus-derived peptides were detected on HLA-I in the lesion. CONCLUSIONS: This study suggests that virus-specific CD8+ T-cells are tissue enriched in atherosclerotic lesions; however, their potential contribution to inflammation may involve antigen-independent mechanisms.

Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability.

BACKGROUND: Metabolism is increasingly recognized as a key regulator of the function and phenotype of the primary cellular constituents of the atherosclerotic vascular wall, including endothelial cells, smooth muscle cells, and inflammatory cells. However, a comprehensive analysis of metabolic changes associated with the transition of plaque from a stable to a hemorrhaged phenotype is lacking. METHODS: In this study, we integrated two large mRNA expression and protein abundance datasets (BIKE, n = 126; MaasHPS, n = 43) from human atherosclerotic carotid artery plaque to reconstruct a genome-scale metabolic network (GEM). Next, the GEM findings were linked to metabolomics data from MaasHPS, providing a comprehensive overview of metabolic changes in human plaque. RESULTS: Our study identified significant changes in lipid, cholesterol, and inositol metabolism, along with altered lysosomal lytic activity and increased inflammatory activity, in unstable plaques with intraplaque hemorrhage (IPH+) compared to non-hemorrhaged (IPH-) plaques. Moreover, topological analysis of this network model revealed that the conversion of glutamine to glutamate and their flux between the cytoplasm and mitochondria were notably compromised in hemorrhaged plaques, with a significant reduction in overall glutamate levels in IPH+ plaques. Additionally, reduced glutamate availability was associated with an increased presence of macrophages and a pro-inflammatory phenotype in IPH+ plaques, suggesting an inflammation-prone microenvironment. CONCLUSIONS: This study is the first to establish a robust and comprehensive GEM for atherosclerotic plaque, providing a valuable resource for understanding plaque metabolism. The utility of this GEM was illustrated by its ability to reliably predict dysregulation in the cholesterol hydroxylation, inositol metabolism, and the glutamine/glutamate pathway in rupture-prone hemorrhaged plaques, a finding that may pave the way to new diagnostic or therapeutic measures.

Assessment for Carotid Atherosclerotic Plaque Using Vessel Wall Magnetic Resonance Imaging: A Multireader ROC Study to Determine Optimal Sequence for Detecting Vessel Wall Calcification.

INTRODUCTION: We aimed to compare conventional vessel wall MR imaging techniques and quantitative susceptibility mapping (QSM) to determine the optimal sequence for detecting carotid artery calcification. METHODS: Twenty-two patients who underwent carotid vessel wall MR imaging and neck CT were enrolled. Four slices of 6-mm sections from the bilateral internal carotid bifurcation were subdivided into 4 segments according to clock position (0-3, 3-6, 6-9, and 9-12) and assessed for calcification. Two blinded radiologists independently reviewed a total of 704 segments and scored the likelihood of calcification using a 5-point scale on spin-echo imaging, FLASH, and QSM. The observer performance for detecting calcification was evaluated by a multireader, multiple-case receiver operating characteristic study. Weighted κ statistics were calculated to assess interobserver agreement. RESULTS: QSM had a mean area under the receiver operating characteristic curve of 0.85, which was significantly higher than that of any other sequence (p < 0.01) and showed substantial interreader agreement (κ = 0.68). A segment with a score of 3-5 was defined as positive, and a segment with a score of 1-2 was defined as negative; the sensitivity and specificity of QSM were 0.75 and 0.87, respectively. CONCLUSION: QSM was the most reliable MR sequence for the detection of plaque calcification.

Sex-related differences in coronary and carotid vessel geometry, plaque composition and shear stress obtained from imaging.

Atherosclerosis manifests itself differently in men and women with respect to plaque initiation, progression and plaque composition. The observed delay in plaque progression in women is thought to be related to the hormonal status of women. Also features associated with the vulnerability of plaques to rupture seem to be less frequently present in women compared to men. Current invasive and non-invasive imaging modalities allow for visualization of plaque size, composition and high risk vulnerable plaque features. Moreover, image based modeling gives access to local shear stress and shear stress-related plaque growth. In this review, current knowledge on sex-related differences in plaque size, composition, high risk plaque features and shear stress related plaque growth in carotid and coronary arteries obtained from imaging are summarized.

Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition.

Circulating amyloid-beta 1-40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD (n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment (p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.

Potential protective role of let-7d-5p in atherosclerosis progression reducing the inflammatory pathway regulated by NF-κB and vascular smooth muscle cells proliferation.

The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs. Our aim was to demonstrate that let-7d-5p unbalance could contribute to the pathophysiology of atherosclerosis and serve as a potential diagnostic biomarker. We evaluated let-7d-5p levels in vascular biopsies and exosome-enriched extracellular vesicles (EVs) from patients with carotid atherosclerosis and healthy donors. Moreover, we overexpressed let-7d-5p in vitro in vascular smooth muscle cells (VSMCs) to decipher the targets and the underlying mechanisms regulated by let-7d-5p in atherosclerosis. Our results demonstrate that let-7d-5p was significantly upregulated in carotid plaques from overweight patients with carotid atherosclerosis. Moreover, in EVs isolated from plasma, we found that let-7d-5p levels were increased in carotid atherosclerosis patients compared to control subjects specially in overweight patients. Receiver Operating Characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker for atherosclerosis. In VSMCs, we demonstrated that increased let-7d-5p levels impairs cell proliferation and could serve as a protective mechanism against inflammation by impairing NF-κB pathway without affecting insulin resistance. In summary, our results highlight the role of let-7d-5p as a potential therapeutic target for atherosclerosis since its overexpression induce a decrease in inflammation and VSMCs proliferation, and also, as a novel non-invasive diagnostic biomarker for atherosclerosis in overweight patients.

Carotid intima-media thickness and plaques in internal carotid artery as surrogate markers of lower limb arterial lesions in Chinese patients with diabetic foot

Peripheral arterial disease (PAD) can impair healing of diabetic foot (DF) in patients with diabetes mellitus. To determine whether carotid intima-media thickness (CIMT) can predict lower limb arterial lesions in patients with DF, this cross-sectional study enrolled patients with DF at West China Hospital (China) between January 2012 and December 2015. Ultrasonography was used to measure CIMT, assess the internal carotid arteries (ICA) for plaques, and evaluate lower limb segmental arteries for stenosis. The optimal CIMT cutoff for detecting lower limb PAD was determined by receiver operating characteristic (ROC) curve analysis. Factors associated with PAD were identified by logistic regression analyses. A total of 167 patients (mean age: 69.7±10.3 years; 102 men) were included. Patients with PAD were older and had higher levels of total cholesterol and low-density lipoprotein than patients without PAD (P<0.05). The area under the ROC curve was 0.747 (P<0.001). At the optimal CIMT cutoff of 0.71 mm, the sensitivity, specificity, positive predictive value, and negative predictive value were 79.65, 61.11, 81.08, and 58.93%, respectively. Compared with those without PAD, more patients with PAD had CIMT ≥0.71 mm (79.65 vs 38.89%; P<0.001) and ICA plaques (66.37vs 11.11%; P<0.001). Multivariate logistic regression revealed that age (odds ratio [OR]: 1.118; 95% confidence interval [95%CI]: 1.056-1.183; P<0.001), ICA plaques (OR: 13.452; 95%CI: 4.450-40.662; P<0.001), and CIMT ≥0.71 mm (OR: 2.802; 95%CI: 1.092-7.188; P=0.032) were associated with PAD.CIMT may be a surrogate marker of PAD in patients with DF.

Internal carotid artery aneurysm mimicking normal-tension glaucoma / Aneurisma de carótida interna simulando glaucoma de pressão normal

ABSTRACT Differentiating glaucomatous from nonglaucomatous optic disc cupping remains challenging. We present a case of a 48-year-old woman with an internal carotid aneurysm of approximately 3.5 mm × 6.5 mm that mimicked normal-tension glaucoma. The patient had a 2-year history of low vision acuity in her left eye and frontal oppressive headache. Owing to the carotid aneurysm, she developed an asymmetric vertical cup-to-disc ratio above 0.2, and marked inferotemporal neuronal rim loss and pallor of the residual rim were noted in the left disc. She also developed a visual field defect with an arcuate scotoma in the left eye. The patient was referred to a neurosurgeon and underwent endovascular aneurysm occlusion. This case highlights the diagnostic importance of recognizing that many neurological defects remain underdiagnosed.

RESUMO diferenciação de escavações glaucomatosas e não glaucomatosas ainda permanece um desafio ainda nos dias de hoje. Nos descrevemos um caso de aneurisma de carótida interna medindo 3.5mm x 6.5mm que simulava um glaucoma de pressão normal. O caso é sobre uma paciente feminino de 48 anos com história de 2 anos de baixa acuidade visual no olho esquerdo e cefaléia frontal. Devido ao aneurisma de carótida a paciente desenvolveu uma assimetria de escavação vertical maior que 0.2 no olho esquerdo em relação ao direito com defeito localizado da camada de fibras nervosas temporal inferior. Ela também apresentava um defeito arqueado temporal superior a esquerda, cruzando a linha média vertical consistente. Após o diagnostico confirmado pela ressonância magnética funcional, a paciente foi enviada para o neurocirurgião para realização de uma oclusão endovascular do aneurisma. Esse caso nos alerta da importância de se lembrar que não apenas o glaucoma gera escavações suspeitas no disco óptico e que ainda muitos defeitos por causas neurológicas são subdiagnosticados.

Intima-Media Thickness in the Carotid and Femoral Arteries for Detection of Arteriosclerosis in Human Immunodeficiency Virus-Positive Individuals / Espessamento Mediointimal nas Carótidas e Femorais para Detectar Aterosclerose em Pessoas que Vivem com o Vírus da Imunodeficiência Humana

Abstract Background: The prevalence of atherosclerosis is higher in HIV-positive people, who also experience it earlier than the general population. Objectives: To assess and compare the prevalence of atherosclerosis evaluated by the intima-media thickness of carotid and femoral arteries, and by the ankle-brachial pressure index (ABPI) in HIV patients treated or not treated with protease inhibitors (PIs) and controls. Methods: Eighty HIV+ subjects (40 using PIs and 40 not using PIs) and 65 controls were included in the study. Atherosclerosis was diagnosed by (carotid and femoral) ITM measurement and ABPI. Classical risk factors for atherosclerosis and HIV were compared between the groups by statistical tests. A p ≤ 0.05 was considered significant. Results: An IMT > P75 or the presence of plaque was higher in the HIV+ than in the control group (37.5% vs 19%, p = 0.04). Comparative analysis showed a significant difference (p=0.014) in carotid IMT between HIV+ with PIs (0.71 ± 0.28 mm), without PIs 0.63 ± 0.11 mm and, and controls (0.59 ± 0.11 mm). There was no significant difference in femoral IMT between the groups or in ABPI between HIV+ subjects and controls. However, a significant difference (p=0.015) was found between HIV+ patients not treated with PIs (1.17 [1.08 - 1.23]), and controls 1.08 [1.07 - 1.17]). Conclusion: In HIV patients, atherosclerosis is more prevalent and seems to occur earlier with particular characteristics compared with HIV-negative subjects.

Resumo Fundamento: Pessoas que vivem com o HIV (HIV +) têm maior prevalência de aterosclerose e a desenvolvem mais precocemente do que a população geral. Objetivos: Foi avaliar e comparar as prevalências de aterosclerose avaliada pela medida da espessura mediointimal (EMI) das carótidas comuns e femorais, e do índice tornozelo-braquial (ITB) nos grupos controle e HIV com e sem inibidores de protease (IPs). Métodos: Foram incluídas 80 pessoas com HIV + [40 usavam IPs e 40 não] e 65 controles. O diagnóstico de aterosclerose foi determinado pela medição da EMI (carótidas e femorais) e do ITB. Fatores de risco clássicos para aterosclerose e específicos para o HIV foram comparados entre os grupos, usando testes estatístcos. O valor de p ≤ 0,05 foi cosiderado significativo. Resultados: A EMI > P75 ou presença de placa foi mais elevada no grupo de HIV sem IP que no controle (37,5% vs 19%, p = 0,04). A análise comparativa mostrou diferença significativa (p=0,014) na EMI nas artérias carótidas entre HIV + com IPs (0,71 ± 0,28 mm), sem IPs (0,63 ± 0,11 mm) e controles (0,59 ± 0,11 mm), A EMI na femoral não teve diferença significante entre os grupos. Não houve diferença significante entre os grupos controle e de HIV + quanto ao ITB. No entanto, observou-se uma diferença significativa (p=0,015) no ITB entre os grupos HIV + sem IPs (1,17 [1,08 - 1,23]), e controles [1,08 (1,07 - 1,17)]. Conclusão: Em pacientes com HIV, a aterosclerose é mais prevalente e parece ocorrer mais precocemente, com características distintas, em comparação a indivíduos HIV-negativos.

Hipertensión arterial: el factor de riesgo más importante para grosor íntima-media carotídeo elevado y placa carotídea en adultos de Santiago / Risk factors for a high carotid intima media thickness among healthy adults

Background: Carotid intima media thickness (CIMT) is a marker of cardiovascular damage that can be modified by traditional risk factors. Aim: To determine attributable risk factors for a high CIMT among healthy adults. Material ana Methods: A sample of 1270 individuáis (636 males and 634 femóles) aged 44 ±11 years, was studied. Blood pressure, weight, height, lipidprofile and blood glucose were measured in all. CIMT and thepresence of atheroscleroticplaques were determined by carotid ultrasound. Standard criteria were used to define hypertension, dyslipidemia and diabetes. Results: Mean CIMT in the sample studied was 0.62 ± 0.01 mm and percentile 75 was 0.67. The most important risk factor for a CIMT over percentile 75 and thepresence of atherosclerotic plaques was hypertension with attributable risks of 54 and 57 percent, respectively. Conclusions: In this sample, the main risk factor for a high CIMT was hypertension.

A practical protocol to measure common carotid artery intima-media thickness

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3 percent) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Avaliação da doença aterosclerótica da artéria carótida em pacientes submetidos à cirurgia de revascularização miocárdica por lesão do tronco da artéria coronária esquerda / Evaluation of Carotid Artery Atherosclerotic Disease in Patients Submitted to Myocardial Revascularization Surgery with Left Coronary Artery Lesion

Objetivo: Conhecer a prevalência e severidade da doença aterosclerótica da artéria carótida em pacientes com estenose significativa do tronco da artéria coronária esquerda (TCE) submetidos à cirurgia de revascularização do miocárdio.Métodos: A população estudada consistiu em 18 pacientes submetidos à cirurgia de revascularização do miocárdio no Hospital São José de Criciúma (SC) de fevereiro de 2002 a novembro de 2006 devido à estenose no TCE. A ultra-sonografia (US) foi o exame de eleição para detectar estenose de artérias carótidas, e o cateterismo para detectar estenose do TCE. Resultados: O sexo masculino foi o mais prevalente (77,8%) e a idade média foi de 63,1 anos. O grau de estenose do TCE mais prevalente foi o de 90% em 27,8% dos pacientes. O segmento do TCE predominantemente lesado foi o terço distal em 72,2% dos casos. A US mostrou estenose em 33,3% das carótidas, independente de sua gravidade. Destes, 66,6% tinham, concomitantemente, lesão de carótida direita. Dentre os casos com aterosclerose de carótidas, metade possuía lesão bilateral e significativa (grau de estenose ≥70%). Os segmentos carotídeos mais acometidos foram o bulbo e a carótida interna em 66,6% dos casos. Conclusões: A literatura médica realça uma relação importante da doença aterosclerótica de carótidas com a lesão significativa do TCE. O rastreamento de estenose de carótidas é recomendado a todos os pacientes com aterosclerose de artérias coronárias.

Objectives: Know prevalence and severity of atherosclerotic disease of carotid artery in patients with significative stenosis of left coronary artery (LCA) submitted to myocadial revascularization surgery. Methods: The sample was composed by 18 patients submitted to myocadial evascularization surgery in São José Hospital from Criciúma, South Brazil, between February 2002 to November 2006 due to LCA stenosis. Ultrasonography (US) was the exam of choice to detect stenosis of carotid arteries and the Hearth Catheterization to detect stenosis of LCA. Results: Male sex was the most prevalent (77.8%) and the mean age was 63.1 years old. The LCA stenosis degree most prevalent was of 90% in 27.8% of patients. The LCA segment mainly lesioned was the distal third in 72.2% of the cases. US shows stenosis in 33.3% of carotids, independent of its gravity. Among this patients, 66,6% also had right carotid lesion. Between the cases with carotid atherosclerosis, half had bilateral and significative lesion (stenosis degree ≥70%). The carotid segments most affected was the bulb and internal carotid in 66.6% of the cases.Conclusions: The medical literature enhalces an important relation of carotid atherosclerotic disease with significative lesion of LCA. Screening of carotide stenosis is recommended to all patients with atherosclerosis in coronary arteries.

Ossification of caroticoclinoid ligament and its clinical importance in skull-based surgery

CONTEXT: The medial end of the posterior border of the sphenoid bone presents the anterior clinoid process (ACP), which is usually accessed for operations involving the clinoid space and the cavernous sinus. The ACP is often connected to the middle clinoid process (MCP) by a ligament known as the caroticoclinoid ligament (CCL), which may be ossified, forming the caroticoclinoid foramen (CCF). Variations in the ACP other than ossification are rare. The ossified CCL may have compressive effects on the internal carotid artery. Thus, anatomical and radiological knowledge of the ACP and the clinoid space is also important when operating on the internal carotid artery. Excision of the ACP may be required for many skull-based surgical procedures, and the presence of any anomalies such as ossified CCL may pose a problem for neurosurgeons. CASE REPORT: We observed the presence of ossified CCL in a skull bone. A detailed radiological study of the CCL and the CCF was conducted. Morphometric measurements were recorded and photographs were taken. The ACP was connected to the MCP and was converted into a CCF. Considering the fact that standard anatomy textbooks do not provide morphological descriptions and radiological evaluations of the CCL, the present study may be important for neurosurgeons operating in the region of the ACP.

CONTEXTO Y OBJETIVO: El extremo intermedio de la frontera posterior del hueso del sphenoid presenta el proceso anterior del clinoid (ACP), que está alcanzado generalmente para las operaciones que implican el espacio clinoidal y el sino cavernoso. El ACP es conectado a menudo con el proceso medio del clinoid (MCP) por un ligamento conocido como el ligamento del carotico-clinoid (CCL), que puede ser osificado, formando el agujero del clinoid del carotico (CCF). Las variaciones del ACP con excepción de la osificación, son raras. El CCL osificado puede tener efectos compresivos en la arteria carótida interna. El conocimiento así anatómico y radiológico del ACP y del espacio clinoidal es también importante mientras que funciona en la arteria carótida interna. La supresión del ACP se puede requerir para muchos cirugía basada cráneo y la presencia de cualquier anomalía tal como CCL osificado, puede plantear un problema para el neurocirujano. INFORME DEL CASO: Observamos la presencia de CCL osificado en un hueso del cráneo. Un estudio radiológico detallado del CCL y del CCF fue conducido. Las medidas morphometric fueron registradas y las fotografías fueron tomadas. El ACP fue conectado con el MCP y convertido en un CCF. En vista del hecho, los libros de textos de esa anatomía del estándar no proporcionan la descripción morfológica y la evaluación radiológica de CCL, el actual estudio puede ser importante para los neurocirujanos que funcionan en la región del ACP.

Idiopathic inflammatory pseudotumor of the carotid sheath

We present a biopsy proven case of 47 years-old man with a carotid pseudotumor, clinically presented as carotidynia. CT showed a mass encasing and narrowing the common carotid artery and MRI showed hypointense signal in T2 and intense enhancement after contrast media administration. The patient was suspected to have an inflammatory process and steroids were prescribed. Eight days after the steroid treatment significant radiological and clinical improvement was observed. The patient remains free of symptoms.

Apresentamos um caso comprovado por biópsia de pseudotumor carotídeo em um homem de 47 anos, com apresentação clínica de carotidinia. A TC mostrou massa envolvendo e estenosando a artéria carótida comum direita e a RM apresentava lesão com hipossinal em T2 e importante realce com o uso de meio de contraste paramagnético. O paciente recebeu a hipótese de lesão inflamatória e um tratamento com corticosteróides foi iniciado. Após oito dias de tratamento uma melhora clínica e radiológica significativas foram observadas. O paciente permanece assintomático.

Metaloproteinases de matriz e incorporação de colesterol na lipoproteína de alta densidade(HDL)na doença carotídea / Matrix metalloproteinases and incorporation of cholesterol in high density lipoprotein (HDL) in the carotid artery disease

As doenças cardiovasculares são a maior causa de morbimortalidade nos países emergentes, consistindo em doença arterial central, cerebral e periférica, em especial, a coronária e a carotídea. Dentre os diversos fatores e marcadores de risco que atuam no desenvolvimento e no agravo dessas doenças, encontram-se os relacionados com a aterosclerose. Este estudo avaliou a concentração sérica e a atividade de metaloproteinases de matriz (MMP-1, 2, 8, 9 e 12), a incorporação de colesterol livre na HDL, a atividade da paraoxonase e associação com outros fatores em pacientes com doença carotídea aterosclerótica. Métodos. Este estudo de corte transversal avaliou, em população de 65 indivíduos portadores (32) e não (34) de DCA (doença carotídea aterosclerótica), determinada por ecografia vascular com doppler, ambos os sexos, idade média de 51,1 (± 6,7) anos, a existência de diferenças entre de fatores associados à aterogênese, sua relação com o remodelamento do endotélio vascular e transporte reverso do colesterol. Foram padronizados e utilizados métodos com marcadores isotópicos, ELISA e zimografia por SDS-PAGE para determinação, identificação e verificação da atividade proteolítica. Resultados. Foi constatado que as amostras de soro dos pacientes portadores de DCA incorporaram menos colesterol livre triciado (CL-3H) quando comparados aos pacientes NDCA (não portadores de DCA) e, também, que os índices e demais parâmetros de avaliação do metabolismo lipídico corroboram o fenômeno (HDL-C, r=-0,330; p=0,0606, Pearson), mostrando uma tendência (HDL-C/apoA, r=0,511; p=0,0254) e relação positiva no grupo NDCA. Foram observadas correlações positivas entre MMP-1 e HDL-C (r=0,6175; p=0,002, Pearson) e MMP-1 com MMP-9 (r=0,5109; p=0,0215; Pearson) e MMP-1 com CMV-IgG (r=0,619; p=0,0012; Pearson) e correlação negativa entre MMP-9 e apoB no grupo DCA. Por ELISA foram evidenciadas, no grupo DCA, menores densidades ópticas (DO) de MMP-2 e MMP-9. Contudo, essas mesmas MMP (2 e 9) apresentaram maior atividade proteolítica no zimograma do grupo DCA. Conclusão. A menor incorporação de CL-3H no grupo DCA indica deficiência no transporte reverso do colesterol, essa alteração prejudica os mecanismos de proteção contra a aterogênese. Aliado a isso, observou-se redução das mensurações séricas das MMP no grupo DCA, a qual pressupõe a participação dessas MMP no remodelamento vascular, principalmente, nas placas e/ou lesões ateroscleróticas. As MMP e outros marcadores avaliados nos DCA mostraram que o evento não tem participação somente de moléculas relacionadas ao transporte lipídico, mas também, aquelas relacionadas à infecção por CMV (citomegalovirus), evidenciadas pela presença de correlação positiva entre MMP-1 e CMV-IgG. A menor incorporação de CL-3H, baixa DO de MMP-2 e 9, maior atividade proteolítica no zimograma e a MMP-1 associada à infecção por CMV são fatores a serem avaliados para utilização na predição de risco cardiovascular em pacientes com DCA. As menores DO de MMP-2 e 9 nos DCA em contraposição à maior atividade dessas proteinases suscita a participação de fatores reguladores (e.g. TIMP) da atividade dessas proteinases, atuando de forma distinta daquela dos NDCA.