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.

Loci identified by a genome-wide association study of carotid artery stenosis in the eMERGE network.

Carotid artery atherosclerotic disease (CAAD) is a risk factor for stroke. We used a genome-wide association (GWAS) approach to discover genetic variants associated with CAAD in participants in the electronic Medical Records and Genomics (eMERGE) Network. We identified adult CAAD cases with unilateral or bilateral carotid artery stenosis and controls without evidence of stenosis from electronic health records at eight eMERGE sites. We performed GWAS with a model adjusting for age, sex, study site, and genetic principal components of ancestry. In eMERGE we found 1793 CAAD cases and 17,958 controls. Two loci reached genome-wide significance, on chr6 in LPA (rs10455872, odds ratio [OR] (95% confidence interval [CI]) = 1.50 (1.30-1.73), p = 2.1 × 10-8 ) and on chr7, an intergenic single nucleotide variant (SNV; rs6952610, OR (95% CI) = 1.25 (1.16-1.36), p = 4.3 × 10-8 ). The chr7 association remained significant in the presence of the LPA SNV as a covariate. The LPA SNV was also associated with coronary heart disease (CHD; 4199 cases and 11,679 controls) in this study (OR (95% CI) = 1.27 (1.13-1.43), p = 5 × 10-5 ) but the chr7 SNV was not (OR (95% CI) = 1.03 (0.97-1.09), p = .37). Both variants replicated in UK Biobank. Elevated lipoprotein(a) concentrations ([Lp(a)]) and LPA variants associated with elevated [Lp(a)] have previously been associated with CAAD and CHD, including rs10455872. With electronic health record phenotypes in eMERGE and UKB, we replicated a previously known association and identified a novel locus associated with CAAD.

Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis.

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.

The gut microbiome in subclinical atherosclerosis: a population-based multiphenotype analysis.

OBJECTIVES: An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. METHODS: We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets. RESULTS: By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects. CONCLUSION: Our study revealed a Chinese population-wide phenotype-metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.

[Comparative analysis of safety of carotid endarterectomy performed in acutest and acute periods of ischaemic stroke]. / Sravnitel'nyi analiz bezopasnosti vypolneniia karotidnoi éndarteréktomii v ostreishii i ostryi periody ishemicheskogo insul'ta.

Surgical revascularization of the carotid basin in the acutest period of ischaemic stroke, i.e., within 72 hours, will make it possible to prevent the development of recurrent stroke by removing an embologenically dangerous atherosclerotic plaque of the symptomatic carotid artery and to improve cerebral blood supply, having eliminated haemodynamic stenosis of the carotid artery. However, the problem of safety of carotid endarterectomy in patients during the acutest period of ischaemic stroke still remains debatable. PURPOSE: To comparatively analyse safety of eversion carotid endarterectomy performed in the acutest (0-72 hours) and acute (4-14 days) periods of minor ischaemic stroke. PATIENTS AND METHODS: Between January 2015 and December 2019, specialists of the Department of Vascular Surgery of Municipal Clinical Hospital # 7 of Kazan performed a total of 80 eversion carotid reconstructions in the period of minor ischaemic stroke within 14 days. The patients were divided into 2 groups depending on the terms of performing carotid endarterectomy. The first group comprised 32 (40.0%) patients operated on in the acutest period of ischaemic stroke, i.e., within 72 hours from the onset of first symptoms of neurological deficit. The second group included 48 (60.0%) patients subjected to carotid endarterectomy within 4 to 14 days from the onset of first signs of neurological deficit. RESULTS: According to the obtained findings, haemorrhagic transformation in the early postoperative period occured in 2 Group Two patients, with one lethal outcome on POD 3. Cerebral ischaemia increased in one patient of each group without enlargement of the ischaemic zone according to brain computed tomography, with residual neurological deficit in Group I in remote period (Rankin scale score 1) and complete restoration in Group II (Rankin scale score 0). Recurrent minor ischaemic stroke on POD 1 developed in Group II with formation of a new lacunar region of ischaemia of the brain in the operated carotid basin and was verified by the findings of cerebral MRI with persisting neurological deficit for 6 months (Rankin scale score 2). The comparative assessment of severity of stroke on the day of operation and at discharge, as well as that of neurological symptomatology during the 1st and 6th months of follow up in both groups proved positive. No events of acute coronary syndrome, recurrent strokes or lethal outcomes were observed during the follow-up period. CONCLUSION: According to the findings of our study, patients with acute cerebral circulation impairment caused by embologenically dangerous lesions of internal carotid arteries should be operated on within the first 72 hours, if there are no accompanying changes requiring time for correction thereof.

Carotid artery stenting: Current state of evidence and future directions.

Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomized controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke; however, CEA is more strongly associated with myocardial infarction. Published long-term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in-stent thrombosis, and however, evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarize the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis.

Red blood cell distribution width and carotid intima-media thickness in patients with metabolic syndrome.

BACKGROUND: To evaluate the relationship between red blood cell distribution width (RDW) and carotid intima-media thickness (CIMT) in metabolic syndrome (MetS) patients. METHODS: In this study, we analyzed 803 patients with MetS who underwent carotid ultrasonography examination at Henan Province Hospital of Traditional Chinese Medicine from October 2014 to September 2015. Demographic data were collected using a questionnaire. An automatic biochemistry analyzer measured RDW. Pearson correlation coefficient, multivariate linear and logistic regression was used to evaluate the correlation between RDW and CIMT. RESULTS: Compared with control group, case group had higher RDW level (P < 0.001) and CIMT (P < 0.001). CIMT was positively related to RDW (r = 0.436, P < 0.001). Logistic regression indicated that RDW was a predictor of CIMT ≥ 1 mm. Compared with the first quartile, people with third and fourth quartile level gave obvious higher risk of carotid artery atherosclerotic trend (OR = 1.41, 95% CI:1.01-197; OR = 2.10, 95% CI: 1.30-3.40). Using a cutoff point of 13.9%, RDW predicts elevated CIMT with a sensitivity of 62.1% and a specificity of 70.3%. CONCLUSION: High RDW is related to the increased CIMT in MetS patients, which highlights the role of RDW in the progression of elevated CIMT in MetS patients.

Near-infrared multispectral photoacoustic analysis of lipids and intraplaque hemorrhage in human carotid artery atherosclerosis.

Spectral photoacoustic imaging in combination with unmixing techniques may be applied to retrieve information about high-risk features present in atherosclerotic plaques, possibly providing prognostic insights into future stroke events. We present the photoacoustic spectral contrast found in 12 systematically scanned advanced atherosclerotic plaques in the near-infrared wavelength range (850-1250 nm). The main absorbers are lipid, water, and hemoglobin, with the highest photoacoustic intensities at the lipid's second overtone at 1190 and 1210 nm. Linear unmixing resulted in visualizing regions with high lipid and hemoglobin absorption, corresponding to the histological presence of lipid and intraplaque hemorrhage. A non-negative matrix factorization approach reveals differences in lipid spectral contrast, providing potential insights into the vulnerability of atherosclerotic plaque. These results provide a reference for future, more complex, in vivo photoacoustic imaging of carotid artery atherosclerosis, potentially contributing to assessing the risk of future events and treatment decision.

Relationship between carotid atherosclerosis and lipoprotein (a) in patients with acute ischemic stroke.

Objective: This study aimed to examine the relationship between lipoprotein (a) (Lp[a]) and other blood lipid indexes and carotid artery atherosclerosis in patients with acute ischemic stroke (AIS). Methods: A total of 2,018 patients were selected from the hospital "acute stroke intervention and secondary prevention registration database" by identifying blood fat indexes (cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and Lp[a]). Based on the results of carotid artery ultrasound examinations, the patients were divided into a "no plaque" group, comprising 400 patients, a "plaque and no stenosis" group, comprising 1,122 patients and a "carotid stenosis" group, comprising 496 patients. The relationship between Lp(a) and blood lipid indexes and carotid artery atherosclerosis was then investigated using multi-factor logistics regression analysis. Results: There were 400 patients (19.8%) with no carotid plaque, 1,122 patients (55.6%) with plaque and no carotid stenosis and 496 patients (24.6%) with carotid stenosis. As the degree of carotid artery atherosclerosis increased, the Lp(a) level gradually increased; Lp(a) and cholesterol were identified as independent risk factors for carotid atherosclerosis. Conclusion: Lipoprotein (a) and cholesterol are independent risk factors for patients with AIS with carotid atherosclerosis, and their levels increase with the degree of carotid artery atherosclerosis; therefore, attention should focus on levels of cholesterol and Lp(a) in acute stroke patients to control atherosclerosis effectively.

eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque.

Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2α-dependent manner. Furthermore, the effects of eIF2α on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. Conclusion: Our results indicate that morphological and functional changes in VSMC organelles, especially in ER whorls, can be used as reliable biomarkers for atherosclerotic progression. Moreover, eIF2α plays an important role in integrating multiple stress-signaling pathways to determine the behavior and fate of VSMCs.

Tongmai Zhuke decoction restrains the inflammatory reaction of macrophages for carotid artery atherosclerosis by up-regulating lincRNA-Cox2.

To explore the mechanism of Tongmai Zhuke decoction for promoting blood circulation by taking carotid artery atherosclerosis (CAA) as an example, two sets of in-depth transcriptomic data as well as two sets of single-cell RNA sequencing data related to the macrophages in CAA were included. STAR and DCC software were used to process in-depth transcriptomic data in order to measure the expression level of LncRNAs as well as mRNA according to FPKM analysis. Single-cell RNA sequencing data from Illumina NovaSeq 6000 were further analyzed by CellRanger channel, CellRanger count, Seurat R package, DoubletFinder package, CCA algorithm, LogNormalize, principal-component analysis, t-SNE and ToppGene online tools. Based On unsupervised clustering, a total of four diverse cell populations with distinct transcriptional features were found in human carotid atherosclerotic plaques. The macrophages were further annotated as the "effector cell" in the pathologic process of CAA, based on the expression of CD68+/CD440-. A total of 84 up-regulated genes and 58 down-regulated linc-RNAs were identified in samples with carotid atherosclerotic plaques. Thereinto, lincRNA-Cox2 is the most down-regulated LincRNA. For the macrophages in carotid atherosclerotic plaques, expression level of Il6, Ccl3, Ccl4 Il10 and Tnfa were significantly up-regulated, while Timp1 significantly down-regulated comparing with healthy carotid sample. The expression level of lincRNA-Cox2 was significantly increased in macrophages after treated by Tongmai Zhuke decoction, while Cxcl10, Ccl3, Ccl4, Cxcl2, Ccl5, and Ccl19 were significantly decreased. Collectively, Tongmai Zhuke decoction could restrain the inflammatory reaction of macrophages for carotid artery atherosclerosis by up-regulating lincRNA-Cox2.

Identification of immune cell infiltration and diagnostic biomarkers in unstable atherosclerotic plaques by integrated bioinformatics analysis and machine learning.

Objective: The decreased stability of atherosclerotic plaques increases the risk of ischemic stroke. However, the specific characteristics of dysregulated immune cells and effective diagnostic biomarkers associated with stability in atherosclerotic plaques are poorly characterized. This research aims to investigate the role of immune cells and explore diagnostic biomarkers in the formation of unstable plaques for the sake of gaining new insights into the underlying molecular mechanisms and providing new perspectives for disease detection and therapy. Method: Using the CIBERSORT method, 22 types of immune cells between stable and unstable carotid atherosclerotic plaques from RNA-sequencing and microarray data in the public GEO database were quantitated. Differentially expressed genes (DEGs) were further calculated and were analyzed for enrichment of GO Biological Process and KEGG pathways. Important cell types and hub genes were screened using machine learning methods including least absolute shrinkage and selection operator (LASSO) regression and random forest. Single-cell RNA sequencing and clinical samples were further used to validate critical cell types and hub genes. Finally, the DGIdb database of gene-drug interaction data was utilized to find possible therapeutic medicines and show how pharmaceuticals, genes, and immune cells interacted. Results: A significant difference in immune cell infiltration was observed between unstable and stable plaques. The proportions of M0, M1, and M2 macrophages were significantly higher and that of CD8+ T cells and NK cells were significantly lower in unstable plaques than that in stable plaques. With respect to DEGs, antigen presentation genes (CD74, B2M, and HLA-DRA), inflammation-related genes (MMP9, CTSL, and IFI30), and fatty acid-binding proteins (CD36 and APOE) were elevated in unstable plaques, while the expression of smooth muscle contraction genes (TAGLN, ACAT2, MYH10, and MYH11) was decreased in unstable plaques. M1 macrophages had the highest instability score and contributed to atherosclerotic plaque instability. CD68, PAM, and IGFBP6 genes were identified as the effective diagnostic markers of unstable plaques, which were validated by validation datasets and clinical samples. In addition, insulin, nivolumab, indomethacin, and α-mangostin were predicted to be potential therapeutic agents for unstable plaques. Conclusion: M1 macrophages is an important cause of unstable plaque formation, and CD68, PAM, and IGFBP6 could be used as diagnostic markers to identify unstable plaques effectively.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.

Clinical application of super sensitive microflow ultrasound on the detection of intraplaque neovascularization in patients with atheromatous carotid artery plaque.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a routine technique for detecting intraplaque neovascularization (IPN). However, the invasiveness and complexity of CEUS severely limit its clinical application. This article aims to investigate the application value of AngioPLUS (AP) technique in assessing IPN formation in patients with atheromatous (AS) carotid artery plaque. METHODS: Patients diagnosed with carotid artery atherosclerosis combined plaque formation were recruited and their demographic characteristics including serum fasting blood glucose (FBG), triglyceride (TG), and low-density lipoprotein (LDL) were collected. AP was used to scoring intraplaque microvascular flow (IMVF), measuring the thickness and length of the plaque and determining the number of IPN of the plaque. RESULTS: IMVF score evaluated by AP was positively correlated with plaque length, thickness, IPN number, serum TG, LDL and FBG levels in patients with carotid atherosclerosis with plaque. The evaluation results of CEUS score and IMVF classification detected by AP of plaques were consistent in patients with carotid atherosclerosis. CONCLUSION: IMVF scoring by AP is a promising approach to assess IPN and plaque status in patients with atheromatous carotid artery plaque.

Subclinical Carotid Artery Atherosclerosis and Cognitive Function: A Mini-Review.

Carotid artery atherosclerosis, the result of a multitude of vascular risk factors, is a promising marker for use in risk stratification. Recent evidence suggests that carotid artery atherosclerosis affects cognitive function and is an independent risk factor for the development of cognitive impairment. Both atherosclerosis and cognitive impairment develop over a prolonged period (years), and due to the aging population, markers to identify persons at risk are needed. Carotid artery atherosclerosis can easily be visualized using non-invasive ultrasound, potentially enabling early and intensified risk factor management to preserve cognitive function or delay further decline. However, the burden of atherosclerosis and temporal exposure required to pose a risk of cognitive impairment is unclear. This mini-review aims to explore the available evidence on the association between carotid atherosclerosis and cognition, and furthermore identify the remaining gaps in knowledge.

Proteinuria as a significant predictive factor for the progression of carotid artery atherosclerosis in non-albuminuric type 2 diabetes.

AIMS: This study aimed to evaluate the clinical significance of urine protein to creatinine ratio (uPCR) in relation to the cardiovascular risk associated with carotid artery intima-media thickness (cIMT) progression in subjects with type 2 diabetes (T2D) and normoalbuminuria. METHODS: In this retrospective longitudinal study on T2D, we recruited 927 participants with normoalbuminuria (urine albumin to creatinine ratio [uACR] < 30 mg/g) whose cIMT was measured at baseline and after at least 1 year, and whose initial uPCR and uACR data were available. RESULTS: Higher initial uPCR was positively correlated with a greater increment in maximal cIMT (ß = 0.074, p = 0.028), and this correlation was significant even after adjusting for multiple confounding factors (ß = 0.074, p = 0.046). High baseline uPCR was an independent predictive factor for the increased risk of maximal cIMT progression in a simple logistic regression model (OR, 1.41; 95% CI, [1.08-1.86]; p = 0.013). Even after adjusting for several confounding variables, higher uPCR was significantly associated with a higher risk of cIMT progression (OR, 1.48; 95% CI, [1.08-2.03]; p = 0.014). CONCLUSIONS: These results suggest that high uPCR may be a useful predictive marker for the progression of carotid artery atherosclerosis, even in subjects with T2D and without albuminuria.

Noninvasive prediction of carotid artery atherosclerosis by multiple abdominal fat indices measured via ultrasonography.

PURPOSE: The purpose of this study was to evaluate the efficiency of multiple abdominal fat indices as measured via ultrasonography for predicting the presence and severity of carotid artery atherosclerosis and to compare the predictive capacity of ultrasonographic measurements to that of anthropometric measurements. METHODS: A total of 92 patients were included in this study. All participants underwent clinical and laboratory assessments, and anthropometric measurements were obtained. Ultrasound examinations were performed to measure the values of all abdominal fat indices and the intimamedia thickness, as well as to detect the presence of atherosclerotic plaques. Univariate and multivariate logistic regression analyses were performed. RESULTS: In the multivariate analysis, significant associations were detected between carotid artery atherosclerosis and posterior right perinephric fat thickness (PRPFT) (hazard ratio [HR], 15.23; P<0.001), preperitoneal fat thickness (PPFT) (HR, 4.31; P=0.003), visceral adipose tissue volume (VAT) (HR, 7.61; P<0.001), visceral fat thickness (VFT) (HR, 8.84; P<0.001), the ratio of VFT to subcutaneous fat thickness (VFT/SCFT) (HR, 9.39; P<0.001), and waist-to-height ratio (WHtR) (HR, 2.65; P=0.046). In the multivariate analysis, significant associations were also detected between carotid artery plaque and PRPFT (HR, 7.09; P<0.001), the abdominal wall fat index (AFI) (HR, 3.58; P=0.010), and VFT/SCFT (HR, 4.17; P=0.006). CONCLUSION: Many abdominal fat indices as measured by ultrasound were found to be strong predictors of carotid artery atherosclerosis, including PRPFT, VFT/SCFT, VFT, VAT, PPFT, and WHtR. Moreover, PRPFT, VFT/SCFT, and AFI were identified as strong predictors of the presence of carotid artery plaque.

Vascular events from carotid artery atherosclerosis after radiation therapy for laryngeal and hypopharyngeal cancer: the incidence and risk factors.

In this retrospective cohort study, we evaluated the incidence of vascular events from carotid artery atherosclerosis after radiotherapy indication for laryngeal and hypopharyngeal cancer. From January 2007 to December 2016, we investigated 111 laryngeal/hypopharyngeal cancer patients who underwent curative radiotherapy and were followed up for ≥1 year (median follow-up duration, 60 months). We evaluated the incidence of vascular events from carotid artery atherosclerosis, defined as a transient ischemic attack or an atherothrombotic cerebral infarction, or from undergoing treatment such as carotid artery stenting for carotid artery stenosis. The median radiation dose was 66 Gy (range, 60-74); 48 patients (43.2%) received concurrent chemotherapy. The 5-year overall survival was 86.2%. Six patients required treatment for carotid artery disease. Carotid stenting was performed in three patients with carotid artery stenosis; three patients developed atherosclerotic cerebral infarction and received medical treatment, with a median of 51.7 months (range, 0.3-78.3) after radiotherapy initiation. The vascular event occurrence rate was 5.4% within 5 years and 10.7% within 8 years. In the univariate analysis, dyslipidemia, diabetes mellitus, and carotid calcification were significant factors for event occurrence. Because three out of six cases occurred out of the irradiated field, no carotid artery or carotid bulb dosimetric parameters showed significant correlation. As laryngeal/hypopharyngeal cancer patients, particularly with complications including dyslipidemia and diabetes mellitus, are at a high risk of carotid artery stenosis after radiotherapy, long-term carotid artery evaluation is necessary. Early intervention by stroke specialists can reduce the risk of fatal cerebral infarction.

Associations among Periodontitis, Calcified Carotid Artery Atheromas, and Risk of Myocardial Infarction.

Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area-matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA-particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.

LncRNA ZEB1-AS1 facilitates ox-LDL-induced damage of HCtAEC cells and the oxidative stress and inflammatory events of THP-1 cells via miR-942/HMGB1 signaling.

AIMS: The role of long noncoding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) in carotid artery atherosclerosis remains barely explored. MATERIALS AND METHODS: The viability and apoptosis of HCtAEC cells were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Caspase-3 activity detection assay and flow cytometry. The oxidative stress status and inflammation of THP-1 cells were detected by oxidative stress indicator detection kit and Enzyme-linked immunosorbent assay (ELISA). The abundance of ZEB1-AS1, miR-942 and high-mobility group box 1 (HMGB1) was measured by quantitative real time polymerase chain reaction (qRT-PCR). The targets of ZEB1-AS1 and miR-942 in HCtAEC and THP-1 cells were predicted by DIANA tool, and the combination was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot was conducted to examine the protein expression of HMGB1. KEY FINDINGS: ZEB1-AS1 promoted ox-LDL-mediated injury in HCtAEC and THP-1 cells. MiR-942 was a direct target of ZEB1-AS1, and it was negatively modulated by ZEB1-AS1 in HCtAEC and THP-1 cells. HMGB1 could bind to miR-942, and it was regulated by ZEB1-AS1/miR-942 axis in HCtAEC and THP-1 cells. HMGB1 overexpression or miR-942 depletion reversed the inhibitory effects of ZEB1-AS1 intervention on the injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells. SIGNIFICANCE: LncRNA ZEB1-AS1 contributed to ox-LDL-mediated injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells through up-regulating HMGB1 via sponging miR-942. ZEB1-AS1/miR-942/HMGB1 axis might provide a new direction to treatment carotid artery atherosclerosis.