Carotid Plaque Research Articles

TAT-beclin1 treatment accelerates the development of atherosclerotic lesions in ApoE-deficient mice.

The importance of autophagy in atherosclerosis has garnered significant attention regarding the potential applications of autophagy inducers. However, the impact of TAT-Beclin1, a peptide inducer of autophagy, on the development of atherosclerotic plaques remains unclear. Single-cell omics analysis indicates a notable reduction in GAPR1 levels within fibroblasts, stromal cells, and macrophages during atherosclerosis. Tat-beclin1 (T-B), an autophagy-inducing peptide derived from Beclin1, could selectively bind to GAPR1, relieving its inhibition on Beclin1 and thereby augmenting autophagosome formation. To investigate its impact on atherosclerosic plaque progression, we established the ApoE-/- mouse model of carotid atherosclerotic plaques. Surprisingly, intravenous administration of Tat-beclin1 dramatically accelerated the development of carotid artery plaques. Immunofluorescence analysis suggested that macrophage aggregation and autophagosome formation within atherosclerotic plaques were significantly increased upon T-B treatment. However, immunofluorescence and transmission electron microscopy (TEM) analysis revealed a reduction in autophagy flux through lysosomes. Invitro, the interaction between T-B and GAPR1 was confirmed in RAW264.7 cells, resulting in the increased accumulation of p62/SQSTM1 and LC3-II in the presence of ox-LDL. Additionally, T-B treatment elevated the protein levels of p62/SQSTM1, LC3-II, and cleaved caspase 1, along with the secretion of IL-1β in response to ox-LDL exposure. In summary, our study underscores that T-B treatment amplifies abnormal autophagy and inflammation, consequently exacerbating atherosclerotic plaque development in ApoE-/- mice.

Factors Associated with High-Risk Plaque Characteristics Among Patients with Medium to Severe Carotid Artery Stenosis

ObjectiveThere has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis (CAS). This study aims to identify potential risk factors associated with high-risk carotid plaques. MethodsThis is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, NASCET criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography (MRA) at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (Types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage (IPH) and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated. ResultsA total of 62 patients (mean age: 68.7+/-9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81%±13.53%. In multivariate regression analysis, CRP > 2mg/l was strongly associated with symptomatic stenosis (OR=9.92 [1.12-88.178]; P=0.039), and low HDL levels (<1200mmol/l) were associated with lipidic/necrotic plaque core (OR=16.88 [1.10-259.30]; P=0.043). Low HDL levels (OR=7.22 [1.00-51.95], P=0.049) and HbA1c >7% (OR=0.08 [0.01-0.93], P=0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR=14.26 [1.21-168.34], P=0.035) was associated with Type V plaques. ConclusionsThis preliminary study has revealed some potential risk factors associated with unstable carotid plaques. This data could help the future development of prognostic models in order to early detect patients that could benefit from further intervention.

30-Day Risk Score for Mortality and Stroke in Patients with Carotid Artery Stenosis Using Artificial Intelligence Based Carotid Plaque Morphology

The gold standard for determining carotid artery stenosis intervention is based on a combination of percent stenosis and symptomatic status. Few studies have assessed plaque morphology as an additive tool for stroke prediction. Our goal was to create a predictive model and risk score for 30-day stroke and death inclusive of plaque morphology. Patients with a computed tomographic angiography head/neck between 2010 and 2021 at a single institution and a diagnosis of carotid artery stenosis were included in our analysis. Each computed tomography was used to create a three-dimensional image of carotid plaque based off image recognition software. A stepwise backward regression was used to select variables for inclusion in our prediction models. Model discrimination was assessed with area under the receiver operating characteristic curves (AUCs). Additionally, calibration was performed and the model with the least Akaike Information Criterion (AIC) was selected. The risk score was modeled from the Framingham Study. Primary outcome was mortality/stroke. We created 3 models to predict mortality/stroke from 366 patients: model A using only clinical variables, model B using only plaque morphology and model C using both clinical and plaque morphology variables. Model A used age, sex, peripheral arterial disease, hyperlipidemia, body mass index (BMI), chronic obstructive pulmonary disease (COPD), and history of transient ischemia attack (TIA)/stroke and had an AUC of 0.737 and AIC of 285.4. Model B used perivascular adipose tissue (PVAT) volume, lumen area, calcified volume, and target lesion length and had an AUC of 0.644 and AIC of 304.8. Finally, model C combined both clinical and software variables of age, sex, matrix volume, history of TIA/stroke, BMI, PVAT, lipid rich necrotic core, COPD and hyperlipidemia and had an AUC of 0.759 and an AIC of 277.6. Model C was the most predictive because it had the highest AUC and lowest AIC. Our study demonstrates that combining both clinical factors and plaque morphology creates the best predication of a patient's risk for all-cause mortality or stroke from carotid artery stenosis. Additionally, we found that for patients with even 3 points in our risk score model has a 20% chance of stroke/death. Further prospective studies are needed to validate our findings.

Prevalence of interarm blood pressure difference is notably higher in women; the Viborg population-based screening program (VISP)

BackgroundBilateral blood pressure (BP) measurement is important in cardiovascular prevention for identifying systolic interarm BP difference (IAD) and hypertension. We investigated sex-stratified IAD prevalence and its associations and coexistence with screen-detected peripheral atherosclerosis and hypertension. Furthermore, we determined the proportion misclassified as non-hypertensive when using the lower versus the higher reading arm.MethodsThis sub-study formed part of the Viborg Screening Program (VISP), a cross-sectorial population-based cardiovascular screening programme targeting 67-year-old Danes. VISP includes screening for peripheral atherosclerosis (lower extremity arterial disease and carotid plaque), abdominal aortic aneurysm, hypertension, diabetes mellitus, and cardiac disease. Self-reported comorbidities, risk factors, and medication use were also collected. Among 4,602 attendees, 4,517 (82.1%) had eligible bilateral and repeated BP measurements. IAD was defined as a systolic BP difference ≥ 10 mmHg. IAD-associated factors (screening results and risk factors) were estimated by logistic regression; proportional coexistence was displayed by Venn diagrams (screening results).ResultsWe included 2,220 women (49.2%) and 2,297 men (50.8%). IAD was more predominant in women (26.8%) than men (21.0%) (p < 0.001). This disparity persisted after adjustment [odds ratio (OR) 1.53; 95% confidence interval (CI) 1.32–1.77]. No other association was recorded with the conditions screened for, barring potential hypertension: BP 140–159/90–99 mmHg (OR 1.68, 95% CI 1.44–1.97) and BP ≥ 160/100 mmHg (OR 1.82, 95% CI 1.49–2.23). Overall, IAD and BP ≥ 160/100 mmHg coexistence was 4% in women and 5% in men; for BP ≥ 140/90 mmHg, 13% and 14%, respectively. Among those recording a mean BP ≥ 140/90 mmHg in the higher reading arm, 14.5% of women and 15.3% of men would be misclassified as non-hypertensive compared with the lowest reading arm.ConclusionFemale sex was an independent factor of IAD prevalence but not associated with other arterial lesions. Approximately 15% needed reclassification according to BP ≥ 140/90 mmHg when the lower rather than the higher reading arm was used; verifying bilateral BP measurements improved detection of potential hypertension. In future, the predictive value of sex-stratified IAD should be assessed for cardiovascular events and death to verify its potential as a screening tool in population-based cardiovascular screening.Trial registration for VISPNCT03395509:10/12/2018.

Impact of distribution of carotid intraplaque neovessels on plaque vulnerability

Background and PurposeIntraplaque neovessels (INVs) are considered important contributors to carotid plaque vulnerability. The purpose of this study was to examine whether differences in INV distribution affect plaque vulnerability. MethodsThe study cohort comprised 110 patients with significant stenosis of the carotid artery who had undergone carotid endarterectomy. The distribution of INVs within carotid plaques was assessed by immunohistochemical studies using anti-CD-34 antibody as a marker for endothelial cells. First, we divided the patients into M group and S group depending on the numbers of INVs in middle and shoulder region. Next, we categorized carotid plaques into four categories according to the distributions of INVs: Shoulder, Middle, Mixed, and Scarce. We then compared total area of intraplaque hemorrhage, cholesterol, and calcification, width of thinnest fibrous cap, and number of INVs between the four categories of plaque. ResultsThe area of intraplaque hemorrhage was significantly larger in the M group than in the S group (P = 0.011). Meanwhile, symptomatic carotid stenosis was significantly more frequently associated with the Middle and Mixed than the Shoulder and Scarce categories (P < 0.01). The area of intraplaque hemorrhage was significantly different between the four groups (P = 0.022). Rupture of the fibrous cap was more frequently detected in the Middle and Mixed than the other categories (P = 0.002). ConclusionsINVs in the middle region of carotid plaques are strongly associated with symptomatic carotid stenosis, intraplaque hemorrhage, and rupture of the fibrous cap. Our findings indicate that the distribution of INVs may affect plaque vulnerability.

Unstable plaque is a treatable cause of cognitive decline

While many risk factors are modifiable, there remains a compelling need for novel approaches to prevent cognitive impairment. We propose that unstable carotid plaque causes microemboli that, in turn, cause microinfarcts and other adverse pathophysiological cerebral processes, which individually do not manifest clinically but cumulatively manifest as cognitive decline and ultimately cognitive impairment. Animal models support multiple cerebral microemboli having adverse effects on cognition. By addressing the source for microembolization by endarterectomy or stenting, patients with high-grade atherosclerotic stenosis may have better cognitive outcomes. If our hypothesis is verified, then treatment of carotid plaque at elevated risk of generating cerebral microemboli would be effective in preserving cognition, regardless of whether the stenosis is high-grade or causing cerebral hemispheric hypoperfusion.

Deep Learning-Based Vascular Aging Prediction From Retinal Fundus Images.

The purpose of this study was to establish and validate a deep learning model to screen vascular aging using retinal fundus images. Although vascular aging is considered a novel cardiovascular risk factor, the assessment methods are currently limited and often only available in developed regions. We used 8865 retinal fundus images and clinical parameters of 4376 patients from two independent datasets for training a deep learning algorithm. The gold standard for vascular aging was defined as a pulse wave velocity ≥1400 cm/s. The probability of the presence of vascular aging was defined as deep learning retinal vascular aging score, the Reti-aging score. We compared the performance of the deep learning model and clinical parameters by calculating the area under the receiver operating characteristics curve (AUC). We recruited clinical specialists, including ophthalmologists and geriatricians, to assess vascular aging in patients using retinal fundus images, aiming to compare the diagnostic performance between deep learning models and clinical specialists. Finally, the potential of Reti-aging score for identifying new-onset hypertension (NH) and new-onset carotid artery plaque (NCP) in the subsequent three years was examined. The Reti-aging score model achieved an AUC of 0.826 (95% confidence interval [CI] = 0.793-0.855) and 0.779 (95% CI = 0.765-0.794) in the internal and external dataset. It showed better performance in predicting vascular aging compared with the prediction with clinical parameters. The average accuracy of ophthalmologists (66.3%) was lower than that of the Reti-aging score model, whereas geriatricians were unable to make predictions based on retinal fundus images. The Reti-aging score was associated with the risk of NH and NCP (P < 0.05). The Reti-aging score model might serve as a novel method to predict vascular aging through analysis of retinal fundus images. Reti-aging score provides a novel indicator to predict new-onset cardiovascular diseases. Given the robust performance of our model, it provides a new and reliable method for screening vascular aging, especially in undeveloped areas.

Flow shear force destabilizes carotid plaques by affecting CHOP and GRP78 proteins

BackgroundVarious factors, including blood, inflammatory, infectious, and immune factors, can cause ischemic stroke. However, the primary cause is often the instability of cervical arteriosclerosis plaque. It is estimated that 18-25% of ischemic strokes are caused by the rupture of carotid plaque.1 Plaque stability is crucial in determining patient prognosis. Developing a highly accurate, non-invasive, or minimally invasive technique to assess carotid plaque stability is crucial for diagnosing and treating stroke.Previous research by our group has demonstrated that the expression levels of CHOP (C/EBP homologous protein) and GRP78 (glucose-regulated protein 78) are correlated with the stability of atherosclerotic plaques.2 ObjectThis research assesses changes in GRP78 and CHOP expressions in human umbilical vein endothelial cells(HUVEC) following experiments within the hemodynamic influencing factors test system. Additionally, it includes conducting an empirical study on the impact of blood flow shear force on the stability of human carotid atherosclerotic plaques. The objective is to explore the implications of blood flow shear force on the stability of carotid atherosclerotic plaques. MethodThe hemodynamic influencing factors test bench system was configured with low (Group A, 4 dyns/cm²), medium (Group B, 8 dyns/cm²), and high shear force groups (Group C, 12 dyns/cm²). Relative expression levels of GRP78 and CHOP proteins in human umbilical vein endothelial cells were measured using Western blot analysis, and quantitative analysis of GRP78 and CHOP mRNA was conducted using RT-qPCR. Meanwhile, plaques from 60 carotid artery patients, retrieved via Carotid Endarterectomy (CEA), were classified into stable (S) and unstable (U) groups based on pathological criteria. Shear force at the carotid bifurcation was measured preoperatively using ultrasound. Western blot and RT-qPCR were used to analyze the relative expression levels of GRP78 and CHOP proteins and mRNA, respectively, in the plaque specimens from both groups. ResultExpression levels of GRP78, CHOP proteins, and their mRNAs were assessed in groups A, B, and C via Western blot and RT-qPCR. Results showed that in the low-shear group, all markers were elevated in group A compared to groups B and C. Statistical analysis revealed significantly lower shear forces at the carotid bifurcation in group U compared to group S. In group U plaques, GRP78 and CHOP expressions were significantly higher in group U than in group S. ConclusionBlood flow shear forces variably affect the expression of GRP78 and CHOP proteins, as well as their mRNA levels, in vascular endothelial cells. The lower the shear force and fluid flow rate, the higher the expression of GRP78 and CHOP, potentially leading to endoplasmic reticulum stress(ERS), which may destabilize the plaque.

Diagnostics Accuracy of Magnetic Resonance Imaging in Detection of Atherosclerotic Plaque Characteristics in Carotid Arteries Compared to Histology: A Systematic Review.

Carotid plaque composition represents one of the main risk factors of future ischemic stroke. MRI provides excellent soft tissue contrast that can distinguish plaque characteristics. Our objective was to analyze the diagnostic accuracy of MRI imaging in the detection of carotid plaque characteristics compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis through a systematic review. After prospective registration in PROSPERO (ID CRD42022329690), Medline Ovid, Embase.com, Cochrane Library, and Web of Science Core were searched without any search limitation up to May 27, 2022 to identify eligible articles. Of the 8168 studies, 53 (37 × 1.5 T MRI, 17 × 3 T MRI) evaluated MRI accuracy in the detection of 13 specific carotid plaque characteristics in 169 comparisons. MRI demonstrated high diagnostic accuracy for detection of calcification (3 T MRI: mean sensitivity 92%/mean specificity 90%; 1.5 T MRI: mean sensitivity 81%/mean specificity 91%), fibrous cap (1.5 T: 89%/87%), unstable plaque (1.5 T: 89%/87%), intraplaque hemorrhage (1.5 T: 86%/88%), and lipid-rich necrotic core (1.5 T: 89%/79%). MRI also proved to have a high level of tissue discrimination for the carotid plaque characteristics investigated, allowing potentially for a better risk assessment and follow-up of patients who may benefit from more aggressive treatments. These results emphasize the role of MRI as the first-line imaging modality for comprehensive assessment of carotid plaque morphology, particularly for unstable plaque. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

The Relationship between the complement system and subclinical carotid atherosclerosis in patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) events and CV mortality. Subclinical carotid atherosclerosis is independently associated with rates of incident CV events among patients with RA. The complement system has been related to both the etiopathogenesis of RA and CV disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and carotid intima media thickness and carotid plaque in patients with RA.Methods430 patients with RA were recruited. Functional assays of the three pathways of the complement system, utilizing new-generation techniques, were assessed. Additionally, serum levels of individual components of the complement system belonging to the three pathways were measured: C1q (classical), lectin (lectin), C2, C4, and C4b (classical and lectin), factor D and properdin (alternative), C3 and C3a (common), C5, C5a, and C9 (terminal), as well as regulators factor I and C1-inhibitor. Subclinical carotid atherosclerosis was evaluated by ultrasonography. Multivariable linear regression analysis was conducted to investigate the association between the complement system and carotid intima media thickness and carotid plaque.ResultsAfter multivariable adjustment, which included traditional CV risk factors and disease-related data, C3a and C5a exhibited significant positive correlations with carotid intima media thickness. Additionally, higher values of C1-inhibitor, properdin, C3, C5, and C5a were independently associated with the presence of carotid plaque.ConclusionThe complement system and subclinical carotid atherosclerosis are linked in patients with RA.

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

BackgroundMetabolism 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.MethodsIn 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.ResultsOur 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.ConclusionsThis 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.

Carotid Plaque Score is Associated with 10-year Major Adverse Cardiovascular Events in Low-Intermediate Risk Patients Referred to a General Cardiology Community Clinic.

Atherosclerotic carotid plaque assessments have not been integrated into routine clinical practice due to the time-consuming nature of both imaging and measurements. Plaque score, Rotterdam method, is simple, quick, and only requires 4-6 B-mode ultrasound images. The aim was to assess the benefit of plaque score in a community cardiology clinic to identify patients at risk for major adverse cardiovascular events (MACE). Patients ≥40 years presenting for risk assessment were given a carotid ultrasound. Exclusions included a history of vascular disease or MACE and being >75 years. Kaplan-Meier curves and hazard ratios were performed. The left and right common carotid artery (CCA), bulb, and internal carotid artery (ICA) were given 1 point per segment if plaque present (plaque score 0 to 6). Administrative data holdings at ICES were used for 10-year event follow-up. Of 8,472 patients, 60% were females (n = 5,121). Plaque was more prevalent in males (64% vs 53.9%; P <0.0001). The 10-year MACE cumulative incidence estimate was 6.37% with 276 events (males 6.9 % vs females 6.0%; P = 0.004). Having both maximal CCA IMT <1.00 mm and plaque score = 0, was associated with less events. A plaque score <2 was associated with a low 10-year event rate (4.1%) compared to 2-4 (8.7%) and 5-6 (20%). A plaque score ≥2 can re-stratify low-intermediate risk patients to a higher risk for events. Plaque score may be used as a quick assessment in a cardiology office to guide treatment management of patients.

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

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

Plasma C-reactive protein is associated with a pro-inflammatory and adverse plaque phenotype

Background and aimsSystemic low-grade inflammation, measured by plasma high-sensitivity C-reactive protein (hsCRP) levels, is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). To date, however, it is unknown whether plasma hsCRP is associated with adverse histological plaque features. MethodsPlaques were derived during carotid endarterectomy. Patients with hsCRP levels ≥2 mg/L were evaluated for pro-inflammatory and adverse plaque characteristics, as well as future ASCVD events, and compared with patients with low hsCRP levels. Logistic and linear regression analyses in addition to subdistribution hazard ratios were conducted, adjusted for cardiovascular risk factors. ResultsA total of 1096 patients were included, of which 494 (46.2 %) had hsCRP levels ≥2 mg/L. Elevated hsCRP levels 2 mg/L were independently associated with levels of plaque interleukin 6, beta coefficient of 109.8 (95 % confidence interval (CI): 33.4, 186.5; p = 0.005) pg/L, interleukin 8 levels, 194.8 (110.4, 378.2; p = 0.03) pg/L and adiponectin plaque levels, −16.8 (−30.1, −3.6; p = 0.01) μg/L, compared with plaques from patients with low hsCRP levels. Histological analysis revealed increased vessel density in high hsCRP patients, odds ratio (OR) of 1.57 (1.20, 2.09; p = 0.001), larger lipid core, 1.35 (1.02, 1.73; p = 0.04), and increased macrophage content, 1.32 (1.02, 1.73; p = 0.04). Over a 3-year follow-up period, hsCRP levels ≥2 mg/L were associated with a hazard ratio of 1.81 (1.03, 3.16; p = 0.04) for coronary artery disease event risk. ConclusionsThe distinct inflammatory and histological features observed in carotid plaques among individuals with hsCRP levels ≥2 mg/L underscore the utility of plasma hsCRP as a potent identifier for patients harboring high-risk plaques.

Clinical characteristics of lean metabolic-associated fatty liver disease and the impact of concurrent diabetes mellitus.

Metabolic-associated fatty liver disease (MAFLD) was proposed in 2020 to replace the original term nonalcoholic fatty liver disease (NAFLD) with new diagnostic criteria. The disease risks of lean and overweight/obese MAFLD patients remain controversial. The participants from the Taiwan biobank cohort were included. Advanced liver fibrosis is defined as NAFLD fibrosis score (NFS) >0.675. We use carotid plaques of duplex ultrasounds to diagnose atherosclerosis. A total of 20,058 participants (age 55.67 ± 10.32; males 37.6%) were included in the final analysis. Seven thousand eight hundred and forty-three (39.1%) participants were diagnosed with MAFLD. Of them, 965 (12.3%) were lean MAFLD patients. Among lean MAFLD patients, 25.6% were comorbid with diabetes mellitus (DM). Lean MAFLD patients were older and had higher percentages of females and DM than overweight/obese MAFLD patients. After propensity score matching for age and sex, they had lower levels of NFS but a higher percentage of carotid plaques. Among four subtypes of MAFLD including "lean with DM," "lean without DM," "overweight/obese with DM," and "overweight/obese without DM," logistic regression showed that "lean with DM" subjects had the highest risk of atherosclerosis and "overweight/obese with DM" subjects had the highest risk of advanced liver fibrosis in MAFLD patients. The population-based study revealed that lean MAFLD patients make up 12.3% of all MAFLD patients, and they have a higher proportion of coexisting diabetes. Among lean MAFLD patients concurrent with diabetes, they have the highest risk of atherosclerosis and should receive special attention clinically.

Association between Pericarotid Fat Density and Positive Remodeling in Patients with Carotid Artery Stenosis.

Background/Objectives: The underlying mechanism of the potential involvement of inflammatory crosstalk between pericarotid fat and vascular layers in atherosclerosis pathogenesis is unclear. We investigated the association between pericarotid fat density and positive remodeling and inflammatory markers in carotid stenosis. We hypothesized that pericarotid fat density might serve as a marker of plaque inflammation in a clinical setting. Methods: We evaluated the stenosis degree and pericarotid fat density in 258 patients with carotid plaques. Plaque composition was examined, and the correlation between pericarotid fat density and expansive remodeling was investigated. Pearson's product-moment correlation coefficient was used to examine the relationship between pericarotid fat density and the expansive remodeling ratio. We also evaluated the relationship of pericarotid fat density with plaque composition, degree of stenosis, and macrophage and microvessel counts by. The subgroup analysis compared these factors between symptomatic mild carotid stenosis. Results: The pericarotid fat density was -63.0 ± 11.1 HU. The carotid fat densities were -56.8 ± 10.4 HU in symptomatic and -69.2 ± 11.4 HU in asymptomatic lesions. The pericarotid fat density values in intraplaque hemorrhage, lipid-rich necrotic core, and fibrous plaque were -51.6 ± 10.4, -59.4 ± 12.8, and -74.2 ± 8.4 HU, respectively. Therefore, the expansive remodeling ratio was 1.64 ± 0.4. Carotid fat density and expansive remodeling ratio were correlated. Immunohistochemistry showed high macrophage and microvessel levels (143.5 ± 61.3/field and 121.2 ± 27.7/field, respectively). In symptomatic mild carotid stenosis, pericarotid fat density was correlated with other inflammatory factors. The pericarotid fat density and expansive remodeling ratio (2.08 ± 0.21) were high in mild stenosis (-50.1 ± 8.4 HU). Conclusions: Pericarotid fat and intraplaque components were well correlated. Carotid fat density may be a marker of plaque inflammation in carotid plaques.

The significance of ultrasonographic characteristics in the comprehensive radiological assessment of «high risk» carotid stenoses

Background. The prevalence of asymptomatic carotid stenosis (ACS) requires the existence of an algorythm to identify patients at risk of ischemic stroke. Assessment of carotid atherosclerotic plaque (AP) based on its morphology and composition in addition to the quantitative parameter «stenosis» is possible using a complex of radiological studies including ultrasonographic ones, that can be deepened by new ultrasound techniques. Purpose – define ultrasonographic criteria for vulnerable carotid plaque based on evaluation of plaque characteristics using current ultrasonic techniques. Materials and methods. The study is based on the analysis of data obtained from 105 patients aged 41 to 84, diagnosed with stenosis of the internal carotid artery (ICA) according to ultrasonography (US). Examination methods – clinical, duplex US with the inclusion of shear wave elastography (SWE) and superb microvascular imaging (SMI) techniques to assess plaque stiffness and plaque microvascularisation; brain MRI, MSСT angiography (MSCTA), statistical. Two age-matched group were formed: a group with symptomatic carotid stenosis (SCS), 55 patients, and a group with asymptomatic carotid stenosis (ACS), 50 patients. Results. Statistically significant differences in the groups of patients with and without stroke were determined according to the following parameters of carotid plaques: quantitative criteria – maximum thickness (p = 0,02), with an AP thickness of more than 3.5 mm, the risk of stroke increases 2.2 times (p = 0,03), stenosis degree according to the NASCET protocol (p = 0,01 in the right ICA), plaque stiffness indicator according to SWE data (p = 0,001); qualitative criteria – type of plaque echogenicity according to the Gray-Weale classification (p = 0,001), presence of microvascularization according to SMI data (p = 0,04). Correlation of AP stiffness indicators according to SWE and MSCTA data (ρ = 0,60; р = 0,004) was established, as well as between AP stiffness according to SWE data and echo- type of AP (τ = 0,56; р = 0,006). Conclusions. Determination of plaque thickness greater than 3.5 mm, low plaque stiffness according to SWE data, the presence of microvascularization according to SMI data it is advisable to add to the complex of radiological assessment of carotid stenosis with a high risk of ischemic events, in addition to the standard US criteria of stenosis degree and AP echo-type.

Diagnostic accuracy of carotid plaque instability by noninvasive imaging: a systematic review and meta-analysis.

There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis. Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05). CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment. PROSPERO ID CRD42022329690.

Ultrasound screening for abdominal aortic aneurysm in primary care

IntroductionAbdominal aortic aneurysm (AAA) constitutes a pathology with high mortality. There is currently no screening program implemented in Primary care in Spain. ObjectivesTo evaluate the usefulness of ultrasound in the detection of AAA in the at-risk population in Primary care. Secondarily, to identify subjects whose vascular risk (VR) should be reclassified and to determine whether AAA is associated with the presence of carotid plaque and other risk factors. Material and methodsCross-sectional, descriptive, multicenter, national, descriptive study in Primary care. Subjects: A consecutive selection of hypertensive males aged between 65 and 75 who are either smokers or former smokers, or individuals over the age of 50 of both sexes with a family history of AAA. MeasurementsDiameter of abdominal aorta and iliac arteries; detection of abdominal aortic and carotid atherosclerotic plaque. VR was calculated at the beginning and after testing (SCORE). Results150 patients were analyzed (age: 68.3 ± 5 years; 89.3% male). Baseline RV was high/very high in 55.3%. AAA was detected in 12 patients (8%; 95%CI: 4–12); aortic ectasia in 13 (8.7%); abdominal aortic plaque in 44% and carotid plaque in 62% of the participants. VR was reclassified in 50% of subjects. The detection of AAA or ectasia was associated with the presence of carotid plaque, current smoking and lipoprotein(a), p < 0.01. ConclusionsThe prevalence of AAA in patients with VR is high. Ultrasound in Primary care allows detection of AAA and subclinical atherosclerosis and consequently reclassification of the VR, demonstrating its utility in screening for AAA in the at-risk population.

The hemodynamic and geometric characteristics of carotid artery atherosclerotic plaque formation.

Ischemic stroke, which has a high incidence, disability, and mortality rate, is mainly caused by carotid atherosclerotic plaque. The difference in the geometric structures of the carotid arteries inevitably leads to the variability in the local hemodynamics, which plays a key role in the formation of carotid atherosclerosis. At present, the combined mechanisms of hemodynamic and geometric in the formation of carotid atherosclerotic plaque are not clear. Thus, this study characterized the geometric and hemodynamic characteristics of carotid atherosclerotic plaque formation using four-dimensional (4D) flow magnetic resonance imaging (MRI). Ultimately, 122 carotid arteries from 61 patients were examined in this study. According to the presence of plaques at the bifurcation of the carotid artery on cervical vascular ultrasound (US), carotid arteries were placed into a plaque group (N=69) and nonplaque group (N=53). The ratio of the maximum internal carotid artery (ICA) inner diameter to the maximum common carotid artery (CCA) inner diameter (ICA-CCA diameter ratio), bifurcation angle, and tortuosity were measured using neck three-dimensional time-of-flight magnetic resonance angiography (3D TOF-MRA). Meanwhile, 4D flow MRI was used to obtain the following hemodynamic parameters of the carotid arteries: volume flow rate, velocity, wall shear stress (WSS), and pressure gradient (PG). Independent sample t-tests were used to compare carotid artery geometry and hemodynamic changes between the plaque group and nonplaque group. The ICA-CCA diameter ratio between the plaque group and the nonplaque group was not significantly different (P=0.124), while there were significant differences in the bifurcation angle (P=0.005) and tortuosity (P=0.032). The bifurcation angle of the plaque group was greater than that of the nonplaque group (60.70°±20.75° vs. 49.32°±22.90°), and the tortuosity was smaller than that of the nonplaque group (1.07±0.04 vs. 1.09±0.05). There were no significant differences between the two groups in terms of volume flow rate (P=0.351) and the maximum value of velocity (velocitymax) (P=0.388), but the axial, circumferential, and 3D WSS values were all significantly different, including their mean values (all P values <0.001) and the maximum value of 3D WSS (P<0.001), with the mean axial, circumferential, 3D WSS values, along with the maximum 3D WSS value, being lower in the plaque group. The two groups also differed significantly in terms of maximum PG value (P=0.030) and mean PG value (P=0.026), with these values being greater in the nonplaque group than in the plaque group. A large bifurcation angle and a low tortuosity of the carotid artery are geometric risk factors for plaque formation in this area. Low WSS and low PG values are associated with carotid atherosclerotic plaque formation.