Carotid Plaque Research Articles

Carotid Plaque Types and Their Correlations with Risk Factors for Myocardial Infarction

Objective: The aim of this study was to investigate different carotid plaque types and their correlations with the risk factors for myocardial infarction (MI) in patients with carotid atherosclerosis (CA). Methods: A total of 557 CA patients were enrolled, and information on general data, carotid artery plaque types, and their combinations, risk factors, and disease diagnoses were retrospectively analyzed. Univariate and multivariate logistic regression analyses were employed to identify the risk factors. Results: Hard plaque was closely related to B-type natriuretic peptide (BNP) and triiodothyronine 3 (FT3); soft plaque to prothrombin time (PT) and PT ratio (PTR); mixed plaque to blood urea nitrogen (BUN), FT3, and cardiac troponin T (cTnT); two coexisting types of plaque (hard plaque and soft plaque, hard plaque and mixed plaque, and soft plaque and mixed plaque) to FT3 and C-reactive protein (CRP); and three coexisting types of plaque (hard plaque, soft plaque, and mixed plaque) to BUN, FT3, BNP, cTnT, D-dimer (D-D), neutrophil count (NEUT), monocyte count (MONO), PT, and PTR. Logistic regression analysis revealed that male sex, soft plaque, and three coexisting types of plaque were possible risk factors for MI. Conclusion: Various risk factors increase when plaque types become complicated. The three coexisting types of plaque were associated with various risk factors (increased BUN, PT, PTR, NEUT, MONO, BNP, cTnT, and D-D, and decreased FT3) for MI. Male sex, soft plaque, and three coexisting types of plaque were possible risk factors for MI, which may be beneficial for early risk stratification and MI prediction.

Cardiovascular Risk in People Living with Human Immunodeficiency (HIV) Viremia Suppression in a Young, Mid-Eastern European Population - Preliminary Study.

People living with HIV are twice as likely to develop cardiovascular diseases (CVDs) and myocardial infarction related to atherosclerosis than the uninfected population. This study aimed to evaluate the prevalence of subclinical atherosclerosis in a young, mid-eastern European population of PLWH receiving ART for undetectable viremia. This was a single-centre study. We included 34 patients below 50 years old, treated in Szczecin, Poland, with confirmed HIV-1 infection, treated with antiretroviral therapy (ART), and undetectable viremia. All patients underwent coronary artery computed tomography (CACT), carotid artery intima-media thickness (IMT) evaluation, and echocardiography. In the primary assessment, only two (5.8%) patients had an increased CVD risk calculated using the Framingham Risk Score (FRS), but we identified coronary or carotid plaques in 26.5% of the patients. Neither traditional risk factors nor those associated with HIV significantly influenced the presence of the plaque. IMT was significantly positively correlated with age and the FRS (R=0.38, p=0.04). Relative wall thickness assessed in echocardiography was higher in those with plaque (0.49 vs 0.44, p=0.04) and significantly correlated with IMT (R=0.38, p=0.04). In our population, more than a quarter of PLWH with undetectable viremia had subclinical atherosclerosis in either the coronary or carotid arteries. The FRS underpredicted atherosclerosis in this population. The role of RWT as a possible early marker of atherosclerosis needs further studies.

Spatial lipidomic profiles of atherosclerotic plaques: A mass spectrometry imaging study

Lipids contribute to atherosclerotic cardiovascular disease but their roles are not fully understood. Spatial lipid composition of atherosclerotic plaques was compared between species focusing on aortic plaques from New Zealand White rabbits and carotid plaques from humans (n = 3), using matrix-assisted laser desorption/ionization mass spectrometry imaging. Histologically discriminant lipids within plaque features (neointima and media in rabbits, and lipid-necrotic core and fibrous cap/tissue in humans) included sphingomyelins, phosphatidylcholines, and cholesteryl esters. There were 67 differential lipids between rabbit plaque features and 199 differential lipids in human, each with variable importance in projection score ≥1.0 and p < 0.05. The lipid profile of plaques in the rabbit model closely mimicked that of human plaques and two key pathways (impact value ≥ 0.1), sphingolipid and glycerophospholipid metabolism, were disrupted by atherosclerosis in both species. Thus, mass spectrometry imaging of spatial biomarkers offers valuable insights into atherosclerosis.

Characterization of carotid plaques using chemical exchange saturation transfer imaging.

The preoperative assessment of carotid plaques is necessary to render revascularization safe and effective. The aim of this study is to evaluate the usefulness of chemical exchange saturation transfer (CEST)-MRI, particularly amide proton transfer (APT) imaging as a preoperative carotid plaque diagnostic tool. We recorded the APT signal intensity on concentration maps of 34 patients scheduled for carotid endarterectomy. Plaques were categorized into group A (APT signal intensity ≥ 1.90 E-04; n = 12) and group B (APT signal intensity < 1.90 E-04; n = 22). Excised plaques were subjected to histopathological assessment and, using the classification promulgated by the American Heart Association, they were classified as intraplaque hemorrhage-positive [type VI-positive (tVI+)] and -negative [no intraplaque hemorrhage (tVI-)]. Of the 34 patients, 22 (64.7%) harbored tVI+- and 12 (35.3%) had tVI- plaques. The median APT signals were significantly higher in tVI+- than tIVI- patients (2.43 E-04 (IQR = 0.98-4.00 E-04) vs 0.54 E-04 (IQR = 0.14-1.09 E-04), p < .001). Histopathologically, the number of patients with tVI+ plaques was significantly greater in group A (100%, n = 12) than group B (45%, n = 22) (p < .01). The number of symptomatic patients or asymptomatic patients with worsening stenosis was also significantly greater in group A than group B (75% vs 36%, p < .01). In unstable plaques with intraplaque hemorrhage and in patients with symptoms or progressive stenosis, the ATP signals were significantly elevated. CEST-MRI studies has the potential for the preoperative assessment of the plaques' characteristics.

Abstract P454: Screening of risk genes for carotid vulnerable plaque based on transcriptomics and experimental verification

Purpose and background: This study aims to conduct an in-depth analysis of human carotid atherosclerotic plaques using transcriptomic data to elucidate the relationship between hypoxia-related genes and the stability of carotid artery plaques and explore their connection with immune infiltration. Methods: Four GEO datasets (GSE21545, GSE24495, GSE159677, and GSE189300) were used. Initially, gene expression data from carotid artery plaque samples in GSE21545 and GSE24495 were analyzed. Hypoxia-related gene sets were obtained from MSigDB, and the "HALLMARK_HYPOXIA" gene set was explicitly selected. GSEA software was used for ultimately selecting CDKN1C and HAS1 as characteristic genes. Subsequently, sample clustering analysis was conducted to determin the optimal number of clusters. Gene set enrichment and differential analysis were performed. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting experiments were conducted for preliminary validation of CDKN1C and HAS1 expression levels in ApoE knockout mice at 16 and 6 weeks. Subsequently, single-cell data from GSE159677 were processed to determine the differential localization of CDKN1C in carotid atherosclerotic plaques, with functional analysis conducted using GSE189300. Results: CDKN1C and HAS1 genes were found to exhibit differential expression in plaques and were correlated with hypoxia and immune scores. Clustering analysis revealed two main clusters, with patients in cluster A showing a higher risk of adverse events and a stronger association with immunity. Genes with a positive effect on atherosclerosis were highly expressed in poorer prognosis cluster A. Validation dataset GSE24495 also confirmed the grouping ability of CDKN1C and HAS1 genes, showing enrichment in atherosclerosis-related pathways. RT-qPCR and protein immunoblotting experiments demonstrated no significant differences in HAS1 expression levels, while CDKN1C showed lower protein expression in 16-week ApoE knockout mice compared to 6 weeks. Single-cell data from GSE159677 localized differential expression of CDKN1C in plaque cells. Finally, immunofluorescence validation confirmed the coexistence of CDKN1C and vascular smooth muscle cells. Conclusion: This study comprehensively analyzed transcriptomics data from carotid atherosclerotic plaques, revealing the significant roles of CDKN1C and HAS1 genes. Immunofluorescence validation further supported the crucial role of these genes in carotid atherosclerosis.

The Association between the Severity of Distal Sensorimotor Polyneuropathy and Increased Carotid Atherosclerosis in Individuals with Type 2 Diabetes.

Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. Individuals with DSPN exhibited lower EDV in the CCA and ICA (p < 0.0001 and p = 0.002), higher PI and RI in both CCA and ICA (all p < 0.0001), and higher CPS (p = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all p < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity.

Development and Validation of a Predictive Score for Three-Year Mortality in Acute Ischemic Stroke Patients.

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.

Hypertension-Mediated Organ Damage in Relation to Severity of Chronic Low Back Pain in Hypertensive Patients.

Chronic pain triggers a stress response, which results in increased blood pressure (BP). We investigated whether chronic low back pain (cLBP) in hypertensive patients is associated with an increased risk of hypertension-related organ damage. We studied 85 consecutive hypertensive patients with a median age of 62 years (55-67), who suffered from cLBP, the severity of which was evaluated according to the Oswestry Disability Index (ODI). Patients underwent transthoracic echocardiography, arterial ultrasonography and vascular tonometry. We assessed carotid artery atherosclerotic plaques, along with carotid-femoral pulse wave velocity (cf-PWV) and left ventricular mass index (LVMI). An equal to or higher than median (16 points) ODI score in 48 subjects (56.5%) was associated with the presence of carotid artery plaques (p = 0.014). In multivariate analysis, after adjusting for covariates, the presence of carotid artery plaques remained independently associated with an ODI score equal to or higher than the median (OR, 3.71; 95% CI, 1.04-13.25; p = 0.044). None of the other analyzed parameters of hypertension-related organ damage demonstrated a significant relationship with the ODI score. We observed that more severe cLBP is associated with a higher prevalence of carotid artery atherosclerotic plaques among hypertensive patients.

Cardiovascular Disease Risk Stratification Using Hybrid Deep Learning Paradigm: First of Its Kind on Canadian Trial Data.

The risk of cardiovascular disease (CVD) has traditionally been predicted via the assessment of carotid plaques. In the proposed study, AtheroEdge™ 3.0HDL (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. 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™ 3.0HDL 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™ 3.0HDL was evaluated by measuring the p-value and area-under-the-curve for both seen and unseen data. 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™ 3.0HDL showed less than 1% (p-value < 0.001) difference between seen and unseen data, complying with regulatory standards. The hypothesis for AtheroEdge™ 3.0HDL was scientifically validated, and the model was tested for reliability and stability and is further adaptable clinically.

Correlation analysis of carotid adipose tissue density and plaque stability in patients with carotid artery stenosis

Objective: To investigate the correlation between perivascular fat density (PFD) and plaque stability in patients with carotid artery stenosis. Methods: Clinical data of 110 patients with carotid artery stenosis treated at Drum Tower Hospital, Nanjing University Medical School from January 2018 to December 2022 were retrospectively collected. Based on pathological results of carotid plaque specimens obtained from carotid endarterectomy (CEA), patients were categorized into stable plaque group (n=51) and vulnerable plaque group (n=59). All patients underwent preoperative carotid CT angiography (CTA) to measure PFD at the narrowest carotid artery. Preoperative levels of interleukin-6 (IL-6) and other hematological parameters were collected. Multivariable logistic regression analysis was used to identify factors associated with plaque stability in carotid artery stenosis patients. Area under the curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive value of PFD for plaque stability. Results: The stable plaque group consisted of 43 males and 8 females with a mean age of (67.6±9.0) years, while the vulnerable plaque group comprised 48 males and 11 females with a mean age of (69.3±9.0) years. The proportions of smokers were 31.4% (16/51) and 50.8% (30/59) in the stable and vulnerable plaque groups, respectively. The proportions of patients with diabetes were 33.3% (17/51) and 52.5% (31/59), respectively. IL-6 levels were 3.46(2.67, 5.34) and 4.51(3.62, 5.51) ng/L in the stable and vulnerable groups, respectively. Mean PFD values were (-69.04±5.35) and (-63.24±6.08) HU, respectively, with maximum PFD values of (-62.90±6.98) and (-56.93±5.90) HU, respectively. The differences were statistically significant (all P<0.05). Multivariable logistic regression analysis showed that increased mean PFD (OR=1.167, 95%CI: 1.029-1.324, P=0.016) and elevated IL-6 levels (OR=1.489, 95%CI: 1.151-1.926, P=0.002) were associated with vulnerability of carotid artery plaques. ROC curve analysis results showed that a cut-off value of -65.5 HU, the AUC for predicting plaque stability based on the mean PFD was 0.756 (95%CI: 0.667-0.844, P<0.001), with sensitivity of 64.4% and specificity of 74.5%. Conclusion: Increased mean PFD at the narrowest carotid artery is associated with vulnerability of plaques in patients with carotid artery stenosis.

Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque.

Cardiovascular risk factors are known to contribute to the formation of atherosclerotic plaques, which can result in carotid stenosis. However, the extent to which these factors are associated with intraplaque neovascularization, a key indicator of plaque vulnerability, remains unclear. To investigate this relationship, a study was conducted utilizing contrast-enhanced ultrasound (CEUS) to assess intraplaque neovascularization in symptomatic patients. A cohort of 157 symptomatic patients underwent evaluation using Contrast-Enhanced Ultrasound (CEUS) imaging to assess carotid intraplaque neovascularization, which was quantified based on the degree of plaque enhancement. The collected data encompassed baseline patient characteristics, results from biochemical examinations, cardiovascular risk factors, and medication usage history. Regression analyses were conducted to elucidate the relationship between carotid plaque neovascularization and various cardiovascular risk factors. Patients with intraplaque neovascularization were more prone to have diabetes mellitus (OR 3.81, 95% CI 1.94-7.46, p < 0.001), dyslipidemia (OR 2.36, 95% CI 1.22-4.55, p = 0.011) and hypertension (OR 2.92, 95% CI 1.50-5.71, p = 0.002). Smoking increased the risk of having intraplaque neovascularization (OR 2.25, 95% CI 1.12-4.54, p = 0.023). Treatment with statins was significantly lower in patients with intraplaque neovascularization (OR 0.37, 95% CI 0.19-0.72, p = 0.003). In the multivariate analysis, diabetes mellitus (OR 3.27, 95% CI 1.10-9.78, p = 0.034) was independently related to the presence of intraplaque neovascularization. Meanwhile, compared to the patients in the first tertile of serum glucose (< 6.20 mmol/L), the patients in the third tertile (> 13.35 mmol/L) had the most significance of intraplaque neovascularization (OR 5.55, 95% CI 1.85-16.66, p = 0.002). The findings indicated that diabetes mellitus is a significant cardiovascular risk factor that is strongly associated with carotid intraplaque neovascularization.

Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis

There is a large body of evidence that cellular metabolism governs inflammation, and that inflammation contributes to the progression of atherosclerosis. However, whether mitochondrial DNA synthesis affects macrophage function and atherosclerosis pathology is not fully understood. Here we show, by transcriptomic analyzes of plaque macrophages, spatial single cell transcriptomics of atherosclerotic plaques, and functional experiments, that mitochondrial DNA (mtDNA) synthesis in atherosclerotic plaque macrophages are triggered by vascular cell adhesion molecule 1 (VCAM-1) under inflammatory conditions in both humans and mice. Mechanistically, VCAM-1 activates C/EBPα, which binds to the promoters of key mitochondrial biogenesis genes - Cmpk2 and Pgc1a. Increased CMPK2 and PGC-1α expression triggers mtDNA synthesis, which activates STING-mediated inflammation. Consistently, atherosclerosis and inflammation are less severe in Apoe−/− mice lacking Vcam1 in macrophages. Downregulation of macrophage-specific VCAM-1 in vivo leads to decreased expression of LYZ1 and FCOR, involved in STING signalling. Finally, VCAM-1 expression in human carotid plaque macrophages correlates with necrotic core area, mitochondrial volume, and oxidative damage to DNA. Collectively, our study highlights the importance of macrophage VCAM-1 in inflammation and atherogenesis pathology and proposes a self-acerbating pathway involving increased mtDNA synthesis.

Geometric changes and clinical risk factors from aortic arch to proximal internal carotid artery between normal subjects and moderate right carotid plaques

The anatomical features spanning from the aortic arch to the proximal carotid artery and the associated cardiovascular risks might significantly influence the development of right carotid plaque. Our research aimed to compare these anatomical and risk factors between individuals with no carotid plaque and those with moderate right-side carotid plaque within a Korean cohort. We conducted a retrospective, cross-sectional analysis involving 413 participants, categorized into a normal group (n = 339) and a right moderate carotid plaque group (defined as > 50% stenosis based on NASCET criteria) (n = 74). We collected data on cardiovascular risk factors and conducted laboratory tests. A 3D model of the carotid artery was constructed using cranio-cervical computed tomography angiography (CTA) data through semi-automated software. Measurements taken on this 3D model included the common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA), and carotid artery bifurcation (CAB) in terms of maximal vascular diameter, sectional area, angles of carotid bifurcation and ICA, and carotid tortuosity. When compared with the normal group, individuals in the right moderate carotid plaque group exhibited smaller angles at the carotid bifurcation, larger CCA diameter and sectional area (p < 0.01), advanced age, and a higher incidence of hypertension, diabetes, and stroke history (p < 0.05), along with reduced glomerular filtration rate (GFR) (p < 0.001). Multivariate analysis revealed that the sectional area of the bifurcation, calcification of the aortic bulb, and GFR were independently associated with the presence of right moderate carotid plaque (p < 0.01). Statistical analyses disclosed significant differences in both clinical risk factors and geometric changes in the region extending from the aortic arch to the proximal carotid artery among subjects with right moderate carotid plaque when compared to those without.

Determinants of vascular impairment in type 1 diabetes–impact of sex and connexin 37 gene polymorphism: A cross-sectional study

BackgroundThe associations of risk factors with vascular impairment in type 1 diabetes patients seem more complex than that in type 2 diabetes patients. Therefore, we analyzed the associations between traditional and novel cardiovascular risk factors and vascular parameters in individuals with T1D and modifications of these associations according to sex and genetic factors.MethodsIn a cross-sectional study, we analyzed the association of risk factors in T1D individuals younger than 65 years using vascular parameters, such as ankle brachial index (ABI) and toe brachial index (TBI), duplex ultrasound, measuring the presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT). We also used photoplethysmography, which measured the interbranch index expressed as the Oliva-Roztocil index (ORI), and analyzed renal parameters, such as urine albumin/creatinine ratio (uACR) and glomerular filtration rate (GFR). We evaluated these associations using multivariate regression analysis, including interactions with sex and the gene for connexin 37 (Cx37) polymorphism (rs1764391).ResultsIn 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years), pulse pressure was strongly associated with unfavorable values of most of the vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI), whereas plasma lipids, represented by remnant cholesterol (cholesterol – LDL-HDL cholesterol), the atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a), were associated primarily with renal impairment (uACR, GFR and lipoprotein (a)). Plasma non-HDL cholesterol was not associated with any vascular parameter under study. In contrast to pulse pressure, the associations of lipid factors with kidney and vascular parameters were modified by sex and the Cx37 gene.ConclusionIn addition to known information, easily obtainable risk factor, such as pulse pressure, should be considered in individuals with T1D irrespective of sex and genetic background. The associations of plasma lipids with kidney function are complex and associated with sex and genetic factors. The decision of whether pulse pressure, remnant lipoproteins, Lp(a) and other determinants of vascular damage should become treatment targets in T1D should be based on the results of future clinical trials.Graphical

Efficacy of acupuncture in patients with carotid atherosclerosis: a randomized controlled clinical trial

BackgroundThe current clinical management of carotid atherosclerosis is based on the control of risk factors and medicine. However, the risk of adverse events associated with the medicine resulting in concerns and low medication compliance makes it necessary to seek a safer alternative therapy. This study assessed the effectiveness and safety of acupuncture as a treatment for carotid atherosclerosis.MethodsIn this randomized controlled trial, patients with carotid atherosclerotic plaques were included and randomly assigned (1:1) to receive real acupuncture or sham acupuncture for 12 weeks. The follow-up period was 12 weeks. The primary outcome included carotid intima-media thickness (cIMT), plaque score (PS), plaque volume (PV) and grey-scale median (GSM). Secondary outcome was pulse wave velocity (PWV). Adverse events results were recorded as safety outcomes.ResultsFrom January 2021 to February 2022, 60 eligible patients were included. 55 patients (91.7%) completed the intervention and the 12-week follow-up and there was no statistical difference in demographics between the groups. At the end of treatment, the real acupuncture group had significantly reduced PS (P = 0.002), PV (P = 0.000), and improved GSM (P = 0.044). There was no significant difference in the reduction in cIMT (Left cIMT: P = 0.338, Right cIMT: P = 0.204) and PWV between the groups (the left BS: P = 0.429; the left ES: P = 0.701; the right BS: P = 0.211; the right ES: P = 0.083). Three mild adverse reactions occurred during the study.ConclusionThis study found that acupuncture had a certain effect on reducing the thickness and volume of carotid plaque and improving the stability of plaque with minor side effects. These findings suggest that acupuncture may be a potential alternative therapy for carotid atherosclerosis.Trial registrationThis trial has been registered at ClinicalTrials.gov (ChiCTR2100041762). Submitted 30 December 2020, Registered 4 January 2021 Prospectively registered.

Treatment with APAC, a dual antiplatelet anticoagulant heparin proteoglycan mimetic, limits early collar-induced carotid atherosclerotic plaque development in Apoe−/− mice

Background and aimsMast cell-derived heparin proteoglycans (HEP-PG) can be mimicked by bioconjugates carrying antithrombotic and anti-inflammatory properties. The dual antiplatelet and anticoagulant (APAC) construct administered, either locally or intravenously (i.v.), targets activated endothelium, its adhesion molecules, and subendothelial matrix proteins, all relevant to atherogenesis. We hypothesized that APAC influences cellular interactions in atherosclerotic lesion development and studied APAC treatment during the initiation and progression of experimental atherosclerosis. MethodsMale western-type diet-fed Apoe−/− mice were equipped with perivascular carotid artery collars to induce local atherosclerosis. In this model, mRNA expression of adhesion molecules including ICAM-1, VCAM-1, P-Selectin, and Platelet Factor 4 (PF4) are upregulated upon lesion development. From day 1 (prevention) or from 2.5 weeks after lesion initiation (treatment), mice were administered 0.2 mg/kg APAC i.v. or control vehicle three times weekly for 2.5 weeks. At week 5 after collar placement, mice were sacrificed, and lesion morphology was microscopically assessed. ResultsAPAC treatment did not affect body weight or plasma total cholesterol levels during the experiments. In the prevention setting, APAC reduced carotid artery plaque size and volume by over 50 %, aligning with decreased plaque macrophage area and collagen content. During the treatment setting, APAC reduced macrophage accumulation and necrotic core content, and improved markers of plaque stability. ConclusionsAPAC effectively reduced early atherosclerotic lesion development and improved markers of plaque inflammation in advanced atherosclerosis. Thus, APAC may have potential to alleviate the progression of atherosclerosis.

Menopausal Vasomotor Symptoms and Subclinical Atherosclerotic Cardiovascular Disease: A Population-Based Study.

Menopausal vasomotor symptoms (VMS) are increasingly emphasized as a potentially important cardiovascular risk factor, but their role is still unclear. We assessed the association between VMS and subclinical atherosclerotic cardiovascular disease in peri- and postmenopausal women. Using a cross-sectional study design, questionnaire data were collected from a population-based sample of women aged 50 to 64. The questionnaire asked whether menopause was/is associated with bothersome VMS. A 4-point severity scale was used: (1) never, (2) mild, (3) moderate, and (4) severe. The VMS duration and time of onset were also assessed. Associations with subclinical atherosclerotic cardiovascular disease, detected via coronary computed tomography angiography, coronary artery calcium score, and carotid ultrasound were assessed using the outcome variables "any coronary atherosclerosis," "segmental involvement score >3," "coronary artery calcium score >100," and "any carotid plaque," using logistic regression. Covariate adjustments included socioeconomic, lifestyle, and clinical factors. Of 2995 women, 14.2% reported ever severe, 18.1% ever moderate, and 67.7% ever mild/never VMS. Using the latter as reference, ever severe VMS were significantly associated with coronary computed tomography angiography-detected coronary atherosclerosis (multivariable adjusted odds ratio, 1.33 [95% CI, 1.02-1.72]). Corresponding results for ever severe VMS persisting >5 years or beginning before the final menstrual period were 1.50 (95% CI, 1.07-2.11) and 1.66 (95% CI, 1.10-2.50), respectively. No significant association was observed with segmental involvement score >3, coronary artery calcium score >100, or with any carotid plaque. Ever occurring severe, but not moderate, VMS were significantly associated with subclinical coronary computed tomography angiography-detected atherosclerosis, independent of a broad range of cardiovascular risk factors and especially in case of long durations or early onset.

Smooth muscle-specific deletion of Ccn2 causes severe aorta malformation and atherosclerosis.

Cellular Communication Network Factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection against atherosclerosis. Global- and SMC-specific Ccn2 knockout mouse models were employed to demonstrate that Ccn2 deficiency leads to SMC de-differentiation, medial thickening, and aorta elongation under normolipidemic conditions. Inducing hyperlipidemia in both models resulted in severe aorta malformation and a 17-fold increase in atherosclerosis formation. Lipid-rich lesions developed at sites of the vasculature typically protected from atherosclerosis-development by laminar blood flow, covering 90% of aortas, and extending to other vessels, including coronary arteries. Evaluation at earlier time points revealed medial lipid accumulation as a lesion-initiating event. Fluorescently labelled LDL injection followed by confocal microscopy showed increased LDL retention in the medial layer of Ccn2 knockout aortas, likely attributed to marked proteoglycan enrichment of the medial extracellular matrix. Analyses leveraging data from the Athero-Express study cohort indicated relevance of CCN2 in established human lesions, as CCN2 correlated with SMC marker transcripts across 654 transcriptomically profiled carotid plaques. These findings were substantiated through in situ hybridization showing CCN2 expression predominantly in the fibrous cap. This study identifies CCN2 as a major constituent of the normal artery wall, critical in regulating SMC differentiation and aorta integrity, and possessing a protective role against atherosclerosis development. These findings underscore the need for further investigation into the potential effects of anti-CCN2-based therapies on the vasculature.

Urinary Phosphate and Subclinical Atherosclerosis: The AWHS Study.

(1) Background: Atherosclerosis is a leading cause of vascular death worldwide. High urinary phosphate has recently been identified as a cardiovascular risk factor, but its role has not been fully established. The aim of this study was to investigate the association between urinary phosphate and subclinical atherosclerosis in the carotid, femoral as well as coronary territories; (2) Methods: We performed a cross-sectional analysis of a sample of 1169 middle-aged men, aged 50.9 years (SD 3.7), without previous cardiovascular disease, belonging to the Aragon Workers Health Study (AWHS). Urinary phosphate was analyzed in urine samples using the Fiske-Subbarow method. The presence of carotid plaque and femoral plaque was assessed by ultrasound and coronary artery calcium score (CACS) by computed tomography. Demographic, anthropometric and clinical data were collected at annual medical examinations. Logistic regression models were used to estimate the prevalence of adjusted atherosclerosis in the different vascular arteries; (3) Results: A significant inverse association was observed between urinary phosphate and subclinical atherosclerosis in the carotid [OR 95% CI 0.69 (0.49-0.99)] and coronary (CACS > 200) [OR 95% CI 0.46 (0.23-0.88)] arteries; however, no statistically significant association was found between urinary phosphate and the presence of atheroma plaques in the femoral territory [OR 1.02 (0.72-1.45)]; (4) Conclusions: In middle-aged men, a higher urinary phosphate concentration is associated with a lower prevalence of subclinical carotid and coronary atherosclerosis compared with those with a lower urinary phosphate concentration.

An Unsupervised Learning Tool for Plaque Tissue Characterization in Histopathological Images.

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.