Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry.

BACKGROUND: Currently, noninvasive imaging techniques and circulating biomarkers are still insufficient to accurately assess carotid plaque stability, and an in-depth understanding of the molecular mechanisms that contribute to plaque instability is still lacking. METHODS: We established a clinical study cohort containing 182 patients with carotid artery stenosis. After screening, 39 stable and 49 unstable plaques were included in the discovery group, and quantitative proteomics analysis based on data independent acquisition was performed for these plaque samples. Additionally, 35 plaques were included in the validation group to validate the proteomics results by immunohistochemistry analysis. RESULTS: A total of 397 differentially expressed proteins were identified in stable and unstable plaques. These proteins are primarily involved in ferroptosis and lipid metabolism-related functions and pathways. Plaque validation results showed that ferroptosis- and lipid metabolism-related proteins had different expression trends in stable plaques versus unstable fibrous cap regions and lipid core regions. Ferroptosis- and lipid metabolism-related mechanisms in plaque stability were discussed. CONCLUSIONS: Our results may provide a valuable strategy for revealing the mechanisms affecting plaque stability and will facilitate the discovery of specific biomarkers to broaden the therapeutic scope.

Long-term outcomes of carotid endarterectomy vs transfemoral carotid stenting in a Medicare-matched database.

BACKGROUND: Carotid endarterectomy (CEA) is associated with lower risk of perioperative stroke compared with transfemoral carotid artery stenting (TFCAS) in the treatment of carotid artery stenosis. However, there is discrepancy in data regarding long-term outcomes. We aimed to compare long-term outcomes of CEA vs TFCAS using the Medicare-matched Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network database. METHODS: We assessed patients undergoing first-time CEA or TFCAS in Vascular Quality Initiative Vascular-Vascular Implant Surveillance and Interventional Outcomes Network from January 2003 to December 2018. Patients with prior history of carotid revascularization, nontransfemoral stenting, stenting performed without distal embolic protection, multiple or nonatherosclerotic lesions, or concomitant procedures were excluded. The primary outcome of interest was all-cause mortality, any stroke, and a combined end point of death or stroke. We additionally performed propensity score matching and stratification based on symptomatic status. RESULTS: A total of 80,146 carotid revascularizations were performed, of which 72,615 were CEA and 7531 were TFCAS. CEA was associated with significantly lower risk of death (57.8% vs 70.4%, adjusted hazard ratio [aHR], 0.46; 95% confidence interval [CI], 0.41-0.52; P < .001), stroke (21.3% vs 26.6%; aHR, 0.63; 95% CI, 0.57-0.69; P < .001) and combined end point of death and stroke (65.3% vs 76.5%; HR, 0.49; 95% CI, 0.44-0.55; P < .001) at 10 years. These findings were reflected in the propensity-matched cohort (combined end point: 34.6% vs 46.8%; HR, 0.53; 95% CI, 0.46-0.62) at 4 years, as well as stratified analyses of combined end point by symptomatic status (asymptomatic: 63.2% vs 74.9%; HR, 0.49; 95% CI, 0.43-0.58; P < .001; symptomatic: 69.9% vs 78.3%; HR, 0.51; 95% CI, 0.45-0.59; P < .001) at 10 years. CONCLUSIONS: In this analysis of North American real-world data, CEA was associated with greater long-term survival and fewer strokes compared with TFCAS. These findings support the continued use of CEA as the first-line revascularization procedure.

Natural history of internal carotid artery stenosis progression.

OBJECTIVE: The aim of this study was to investigate the natural history of internal carotid artery (ICA) stenosis progression. METHODS: This single-institution retrospective cohort study analyzed patients diagnosed with ICA stenosis of 50% or greater on duplex ultrasound from 2015 to 2022. Subjects were drawn from our institutional Intersocietal Accreditation Commission-accredited noninterventional vascular laboratory database. Primary outcomes were incidences of disease progression, and stroke or revascularization after index study. Progression was defined as an increase in stenosis classification category. Imaging, demographic, and clinical data was obtained from our institutional electronic medical record via a database mining query. Cases were analyzed at the patient and artery levels, with severity corresponding to the greatest degree of ICA stenosis on index and follow-up studies. RESULTS: Of 577 arteries in 467 patients, mean cohort age was 73.5 ± 8.9 years at the time of the index study, and 45.0% (n = 210) were female. Patients were followed with duplex ultrasound for a mean of 42.2 ± 22.7 months. Of 577 arteries, 65.5% (n = 378) at the index imaging study had moderate (50%-69%) stenosis, 23.7% (n = 137) had severe (70%-99%) stenosis, and 10.7% (n = 62) were occluded. These three groups had significant differences in age, hypertension, hyperlipidemia prevalence, and proportion on best medical therapy. Of the 467-patient cohort, 56.5% (n = 264) were on best medical therapy, defined as smoking cessation, treatment with an antiplatelet agent, statin, and antihypertensive and glycemic agents as indicated. Mean time to progression for affected arteries was 28.0 ± 20.5 months. Of those arteries with nonocclusive disease at diagnosis, 21.3% (n = 123) progressed in their level of stenosis. Older age, diabetes, and a history of vasculitis were associated with stenosis progression, whereas antiplatelet agent use trended towards decreased progression rates. Of the 467 patients, 5.6% (n = 26) developed symptoms; of those, 38.5% (n = 10) had ischemic strokes, 26.9% (n = 7) had hemispheric transient ischemic attacks, 11.5% (n = 3) had amaurosis fugax, and 23.1% (n = 6) had other symptoms. A history of head and neck cancer was positively associated with symptom development. Of 577 affected arteries, 16.6% (n = 96) underwent intervention; 81% (n = 78) of interventions were for asymptomatic disease and 19% (n = 18) were for symptomatic disease. No patient-level factors were associated with risk of intervention. CONCLUSIONS: A significant number of carotid stenosis patients experience progression of disease. Physicians should consider long-term surveillance on all patients with carotid disease, with increased attention paid to those with risk factors for progression, particularly those with diabetes and a history of vasculitis.

Implications of the Centers for Medicare and Medicaid Services (CMS) decision to expand indications for carotid artery stenting.

OBJECTIVE: On October 11, 2023, the Centers for Medicare and Medicaid Services (CMS) expanded the indications for carotid artery stenting (CAS) to include patients with ≥50% symptomatic or ≥70% asymptomatic carotid stenosis. The aim of this article was to investigate the implications of this decision. METHODS: The reasons behind the increased coverage for CAS are analyzed and discussed, as well as the various Societies supporting or opposing the expansion of indications for CAS. RESULTS: The benefits associated with expanding CAS indications include providing an additional therapeutic option to patients and enabling individualization of treatment according to patient-specific characteristics. The drawbacks of expanding CAS indications include a possible bias in decision-making and an increase in inappropriate CAS procedures. CONCLUSIONS: The purpose of the CMS recommendation to expand indications for CAS is to improve the available therapeutic options for patients. Hopefully this decision will not be misinterpreted and will be used to improve patient options and patient outcomes.

Decision aids for patients with carotid stenosis.

BACKGROUND: Shared decision-making tools have been underused by clinicians in real-world practice. Changes to the National Coverage Determination by Medicare for carotid stenting greatly expand the coverage for patients, but simultaneously require a shared decision-making interaction that involves the use of a validated tool. Accordingly, our objective was to evaluate the currently available decision aids for carotid stenosis. METHODS: We conducted a review of the literature for published work on decision aids for the treatment of carotid disease. RESULTS: Four publications met inclusion criteria. We found the format of the decision aid impacted patient comprehension and decision making, although patient characteristics also played a role in the therapeutic decisions made. Notably, none of the available decision aids included the widely adopted transcarotid artery revascularization as an option. CONCLUSIONS: Further work is needed in the development of a widespread validated decision aid instrument for patients with carotid stenosis.

Association of carotid duplex ultrasonography screening with stroke and mortality among patients undergoing coronary artery bypass grafting.

OBJECTIVE: Selection criteria for carotid duplex ultrasonography screening (DUS) before coronary artery bypass grafting (CABG) is primarily based on limited observational analysis, and the risks associated with carotid artery stenosis (CAS) detected by this approach to preoperative DUS are uncertain. This study aimed to determine the association of carotid DUS with stroke and mortality among patients undergoing CABG. METHODS: Adult patients with coronary artery disease who underwent isolated CABG or CABG with concomitant valvular or congenital procedure were identified. CHA2DS2-VASc score was assessed before CABG, and patients were recorded as high risk if they had a score of 3 or higher. The primary outcomes were stroke and all-cause mortality. Secondary outcomes included ischemic stroke, non-ischemic stroke, transient ischemic attack, and cardiovascular mortality. RESULTS: Among 8958 patients who underwent CABG, 70.9% (n = 6347) received carotid DUS preoperatively (low-risk, 57.3%; high-risk, 42.7%). In the low-risk cohort, there was no significant difference in the risk of stroke (20.7 per 1000 patient-years for CAS vs 13.1 per 1000 patient-years for no CAS; adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 0.78-1.68) or mortality (20.5 per 1000 patient-years for CAS vs 16.8 per 1000 patient-years for no CAS; aHR, 1.33; 95% CI, 0.97-1.83) at 15 years. In the high-risk cohort, CAS was associated with significantly higher risks of stroke at 30 days (433.2 vs 279.5 per 1000 patient-years; aHR, 1.92; 95% CI, 1.00-3.70) and mortality at 15 years (38.4 vs 32.7 per 1000 patient-years; aHR, 1.25; 95% CI, 1.01-1.57) compared with no CAS. CONCLUSIONS: CAS did not impact the incidence of stroke or mortality in the low-risk cohort who underwent CABG. However, in the high-risk cohort, CAS was associated with a significant increase in the risks of 30-day stroke and 15-year mortality, indicating selective carotid DUS is necessarily recommended for these patients.

Ulceration location is associated with clinical course in carotid stenosis.

OBJECTIVE: Plaque ulceration in carotid artery stenosis is a risk factor for cerebral ischemic events; however, the characteristics that determine plaque vulnerability are not fully understood. We thus assessed the association between plaque ulceration sites and cerebrovascular ischemic attack. METHODS: We retrospectively collected the clinical data of 72 consecutive patients diagnosed with carotid artery stenosis with plaque ulcers. After excluding patients with pseudo-occlusion, a history of previous carotid endarterectomy or carotid artery stenting before the ulcer was first discovered, follow-up data of less than 1 month, or carotid endarterectomy or carotid artery stenting performed within 1 month after the ulcer was first discovered, 60 patients were ultimately included. Patients were divided into proximal and distal groups based on the ulcer location relative to the most stenotic point. The primary endpoints were ipsilateral cerebrovascular ischemic events ("ischemic events"), such as amaurosis fugax, transient ischemic attack, or ischemic stroke due to carotid artery stenosis with plaque ulceration. The association between ulcer location and ischemic events was also assessed. RESULTS: In the patients with plaque ulcer, more patients had proximal than distal plaque ulcers (39 vs 21; P = .028). The median follow-up duration was 3.8 years (interquartile range, 1.5-6.2 years). Nineteen patients (32%) experienced ischemic event. Ischemic events occurred more frequently in the distal than in the proximal group (18% vs 59%; P = .005). Kaplan-Meier curves demonstrated a significantly shorter event-free time in the distal group (log-rank P = .021). In univariate analysis, distal ulcer location was associated with ischemic events (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.13-7.65; P = .03). Multivariate analysis using two different models also showed that distal ulcer location was independently associated with ischemic events (Model 1: OR, 3.85; 95% CI, 1.26-11.78; P = .03; Model 2: OR, 4.31; 95% CI, 1.49-12.49; P = .009). CONCLUSIONS: Patients with carotid artery stenosis and plaque ulcers located distal to the most stenotic point are more likely to experience cerebrovascular ischemic attacks. Therefore, carotid plaques with ulcers located distal to the most stenotic point may be a potential indication for surgical treatment.

Outcomes following carotid revascularization for stroke stratified by Modified Rankin Scale and time of intervention.

OBJECTIVES: The relationship between baseline Modified Rankin Scale (mRS) in patients with prior stroke and optimal timing of carotid revascularization is unclear. Therefore, we evaluated the timing of transfemoral carotid artery stenting (tfCAS), transcarotid artery revascularization (TCAR), and carotid endarterectomy (CEA) after prior stroke, stratified by preoperative mRS. METHODS: We identified patients with recent stroke who underwent tfCAS, TCAR, or CEA between 2012 and 2021. Patients were stratified by preoperative mRS (0-1, 2, 3-4, or 5) and days from symptom onset to intervention (time to intervention; ≤2 days, 3-14 days, 15-90 days, and 91-180 days). First, we performed univariate analyses comparing in-hospital outcomes between separate mRS or time-to-intervention cohorts for all carotid intervention methods. Afterward, multivariable logistic regression was used to adjust for demographics and comorbidities across groups, and outcomes between the various intervention methods were compared. Primary outcome was the in-hospital stroke/death rate. RESULTS: We identified 4260 patients who underwent tfCAS, 3130 patients who underwent TCAR, and 20,012 patients who underwent CEA. Patients were most likely to have minimal disability (mRS, 0-1 [61%]) and least likely to have severe disability (mRS, 5 [1.5%]). Patients most often underwent revascularization in 3 to 14 days (45%). Across all intervention methods, increasing preoperative mRS was associated with higher procedural in-hospital stroke/death (all P < .03), whereas increasing time to intervention was associated with lower stroke/death rates (all P < .01). After adjustment for demographics and comorbidities, undergoing tfCAS was associated with higher stroke/death compared with undergoing CEA (adjusted odds ratio, 1.6; 95% confidence interval, 1.3-1.9; P < .01) or undergoing TCAR (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.8; P = .03). CONCLUSIONS: In patients with preoperative stroke, optimal timing for carotid revascularization varies with stroke severity. Increasing preoperative mRS was associated with higher procedural in-hospital stroke/death rates, whereas increasing time to-intervention was associated with lower stroke/death rates. Overall, patients undergoing CEA were associated with lower in-hospital stroke/deaths. To determine benefit for delayed intervention, these results should be weighed against the risk of recurrent stroke during the interval before intervention.

The Effects of Carotid Revascularization on 1-Year Cognitive Performance in Patients With Carotid Artery Stenosis.

PURPOSE: The impact of carotid revascularization on cognitive function for patients with severe carotid artery stenosis remains uncertain. This study is aimed to investigate the 1-year neurocognitive outcomes of patients who accept carotid revascularization and identify the risk factors associated with postoperative cognitive decline. METHODS: From April 2019 to April 2021, patients with ≥70% carotid artery stenosis who were treated with carotid endarterectomy (CEA) or carotid artery stenting (CAS) were recruited for this study. The Montreal Cognitive Assessment (MoCA) instrument was used to evaluate cognitive function preoperatively and at 3, 6, and 12 months postoperatively. Logistic regression analysis was built to identify potential risk factors for postoperative long-term cognitive decline. RESULTS: A total of 89 patients who met the criteria were enrolled and completed 1-year follow-up. At 3, 6, and 12 months after carotid revascularization, the total MoCA score, attention, language fluency, and delayed recall score were significantly improved compared with the baseline scores (p<0.05). At 12 months, there was also a significant improvement in cube copying compared with baseline (p=0.034). Logistic regression analysis showed that the advancing age, left side, and symptomatic carotid artery stenosis were independent risk factors for cognitive deterioration at 12 months after surgery. CONCLUSIONS: Overall, carotid revascularization has a beneficial effect on cognition function in patients with severe carotid artery stenosis, while advancing age, left side, and symptomatic carotid artery stenosis were significantly related to a decreased cognitive score after carotid revascularization. CLINICAL IMPACT: This study focused on the changes in cognitive function within 1 year after carotid revascularization in patients with severe carotid stenosis. Of course, carotid revascularization can improve the cognition function in these patients. On the other hand, we found the advancing age, left side and symptomatic carotid artery stenosis were significantly associated with decreased cognitive scores at 1 year after carotid revascularization, which suggests that clinicians may need to be aware of patients with these characteristics.

Effects of Banhabaekchulcheonma-Tang on Brain Injury and Cognitive Function Impairment Caused by Bilateral Common Carotid Artery Stenosis in a Mouse Model.

Vascular dementia (VD) is the second most prevalent dementia type, with no drugs approved for its treatment. Here, the effects of Banhabaekchulcheonma-Tang (BBCT) on ischemic brain injury and cognitive function impairment were investigated in a bilateral carotid artery stenosis (BCAS) mouse model. Mice were divided into sham-operated, BCAS control, L-BBCT (40 ml/kg), and H-BBCT (80 ml/kg) groups. BBCT's effects were characterized using the Y-maze test, novel object recognition test (NORT), immunofluorescence staining, RNA sequencing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses. The NORT revealed cognitive function improvement in the H-BBCT group, while the Y-maze test revealed no significant difference among the four groups. The CD68+ microglia and GFAP+ astrocyte numbers were reduced in the H-BBCT group. Furthermore, H-BBCT treatment restored the dysregulation of gene expression caused by BCAS. The major BBCT targets were predicted to be cell division cycle protein 20 (CDC20), Epidermal growth factor (EGF), and tumor necrosis factor receptor-associated factor 1 (TRAF1). BBCT regulates the neuroactive ligand-receptor interaction and neuropeptide signaling pathways, as predicted by KEGG and GO analyses, respectively. BBCT significantly improved cognitive impairment in a BCAS mouse model by inhibiting microglial and astrocyte activation and regulating the expression of CDC20, EGF, TRAF1, and key proteins in the neuroactive ligand-receptor interaction and neuropeptide signaling pathways.

Systematic review and meta-analysis of the diagnostic value of computed tomography angiography for severe internal carotid artery stenosis.

BACKGROUND: Due to the increasing incidence of ischaemic cerebrovascular diseases, the accurate assessment of internal carotid artery (ICA) stenosis is crucial for the development of treatment plans. This systematic review and meta-analysis aimed to evaluate the diagnostic value of computed tomography angiography (CTA) for severe ICAstenosis, thereby providing support for clinical decision-making and promoting diagnostic updates. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical Literature (CBM) electronic databases were searched from inception to March 21, 2024, to identify publicly available research literature on the use of CTA to diagnose severe ICA stenosis. Literature screening, data extraction, and quality assessment were conducted based on the inclusion and exclusion criteria as well as the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) standards. Data analysis was performed using Stata 17.0 and Meta-Disc 1.4 software. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the included studies were calculated using Stata 17.0 software, and forest plots and summary receiver operating characteristic (SROC) curves were generated. The area under the curve (AUC) was calculated, and funnel plots were constructed to assess publication bias. RESULTS: A total of 16 studies with 2368 vascular segments were included. The meta-analysis revealed that the combined sensitivity and specificity of CTA for severe ICA stenosis were 0.93 (95% CI: 0.88 ~ 0.96) and 0.99 (95% CI: 0.96 ~ 1.00), respectively. The combined positive likelihood ratio and negative likelihood ratio were 92.0 (95% CI: 24.2 ~ 349.6) and 0.07 (95% CI: 0.04 ~ 0.13), respectively. The diagnostic odds ratio was 1302 (95% CI: 257 ~ 6606), and the AUC of the SROC curve was 0.98. The Deeks funnel plot suggested no publication bias among the included studies. CONCLUSION: CTA demonstrated high sensitivity and specificity for diagnosing severe ICA stenosis. Therefore, this study provided important evidence for the accurate diagnosis and treatment of severe ICA stenosis. However, there was considerable heterogeneity among the included studies, thus indicating the need for additional high-quality prospective studies to confirm the clinical applicability of CTA.

Risk factors of internal carotid artery stenosis in patients with proliferative diabetic retinopathy: an analysis using optical coherence tomography and optical coherence tomography angiography.

BACKGROUND: This research investigates the correlation between the severity of internal carotid artery (ICA) stenosis and retinal parameters in patients with proliferative diabetic retinopathy (PDR), aiming to uncover potential risk factors. METHODS: A retrospective analysis of 68 patients (136 eyes) diagnosed with bilateral PDR from January 1, 2017, to December 31, 2021, was conducted. Carotid artery stenosis (CAS) was assessed using neck computed tomography angiography (CTA) and carotid duplex ultrasound (CDUS), with stenosis classified into two groups: normal (group 1) and mild or above (group 2), based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Optical coherence tomography (OCT) and OCT angiography (OCTA) measured several retinal parameters, including sub foveal choroidal thickness (SFCT), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, vessel density (VD), and foveal avascular zone (FAZ) area. Statistical analyses determined correlations between ICA degrees and retinal parameters. RESULTS: This study showed significant differences between groups in total VD, FAZ area, total RNFL thickness, and temporal RNFL thickness, indicating that patients with more severe ICA stenosis had noticeable retinal changes. Other parameters such as hyperlipidemia, total cholesterol levels, and intraocular pressure (IOP) also differed significantly, while no notable differences were observed in SFCT, central VD, average GCIPL, and superior, nasal, and inferior RNFL thickness. CONCLUSION: The study findings highlight retinal changes, such as an increased FAZ area, decreased total VD, and a total and thinner temporal RNFL, which suggest the need for carotid artery evaluation in patients. These findings have important clinical implications for the need for carotid work up in patients with PDR.

Optimal medical therapy is lacking in patients undergoing intervention for symptomatic carotid artery stenosis and protects against larger areas of cerebral infarction.

OBJECTIVES: Carotid interventions are indicated for both patients with symptomatic and a subset of patients with severe asymptomatic carotid artery stenosis (CAS). Symptomatic CAS accounts for up to 12%-25% of overall carotid interventions, but predictors of symptomatic presentation remain poorly defined. The aim of this study was to identify factors associated with symptomatic CAS in our patient population. METHODS: Between January 2015 and February 2022, an institutional retrospective cohort study of prospectively collected data on patients undergoing interventions for CAS was performed. Procedures included carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TF-CAS). Demographic data, comorbidities, procedural details, and anatomic features from various imaging modalities were collected. Comparisons were made between symptomatic (symptoms within the prior 6 months) and asymptomatic patients. RESULTS: During the study period, 279 patients who underwent intervention for symptomatic CAS were paired with a randomly selected cohort of 300 patients who underwent intervention for asymptomatic CAS from a total patient cohort of 1143 patients undergoing interventions for asymptomatic CAS. Demographic data did not differ between groups. Patients with symptomatic CAS more frequently had prior TIA/stroke (>6 months remote to the current event), but less frequently had coronary artery disease or chronic kidney disease and were less likely to receive adequate medical management including antihypertensive agents, lipid-lowering agents, and anti-platelet therapy. On multivariate analysis, remote prior TIA/stroke and lack of anti-platelet therapy remained significant. Among symptomatic patients presenting with stroke, lack of anti-platelet therapy was associated with an overall larger area of parenchymal involvement. No difference was observed with single versus dual anti-platelet therapy. Furthermore, symptomatic patients were more likely to have ulcerated plaques (30.9% vs 18%, p < .001), and symptomatic patients with ulcerated plaques more frequently had less than 50% compared to moderate/severe CAS. Nine patients who presented with symptoms had mild CAS and underwent intervention. CONCLUSIONS: Symptomatic CAS was associated with a history of remote prior symptoms and lack of anti-platelet therapy at time of presentation. Furthermore, symptomatic patients not on anti-platelet agents were more likely to have a greater area of parenchymal involvement when presenting with stroke and symptomatic patients with ulcerated plaques were more likely to have mild CAS, suggesting the role of plaque instability in symptomatic presentation. These findings underscore the importance of appropriate medical management and adherence in all patients with CAS and perhaps a role for more frequent surveillance in those with potentially unstable plaque morphology.

Differential miR-195-5p and its potential role during the development of carotid artery stenosis.

OBJECTIVES: Carotid artery stenosis (CAS) is a leading cause of cerebral ischemic events (CIE). Timely detection and risk assessment can aid in managing CAS patients and improving their prognosis. The aim of the current study is to identify a new biomarker for CAS and to further investigate the impact of miR-195-5p on cellular processes in vascular smooth muscle cells (VSMCs). METHODS: This study involved 112 CAS patients and 65 healthy individuals. Serum miR-195-5p levels were measured using RT-qPCR. The ROC curve was then plotted to evaluate the diagnostic potential of miR-195-5p for CAS. The Kaplan-Meier curve and Cox regression were employed to determine miR-195-5p's prognostic significance. In vitro, the effects of miR-195-5p mimic or inhibitor on VSMC proliferation and migration were assessed using CCK-8 and Transwell assays. RESULTS: In CAS patients, serum miR-195-5p levels were elevated and correlated with the degree of CAS. The ROC curve had an AUC value of 0.897, with sensitivity of 71.4% and specificity of 95.4%. Higher levels of miR-195-5p indicated a higher risk of CIE occurrence and may serve as an independent predictor of CIE. The upregulation of miR-195-5p promoted VSMC proliferation and migration, while downregulation had the opposite effect. CONCLUSIONS: miR-195-5p was demonstrated to have diagnostic and prognostic significance in CAS and may serve as a potential biomarker. It may contribute to the progression of CAS by promoting the proliferation and migration of VSMCs.

International cross-sectional survey on attitudes and practices regarding use of contrast-enhanced ULTRAsound in VASCular surgery: The I-ULTRA-VASC study.

OBJECTIVES: The aim of this cross-sectional survey was to gather attitudes and practices of physicians from different countries regarding the implementation of contrast-enhanced ULTRAsound (CEUS) for vascular diseases in clinical practice as well as in academic research. METHODS: A web-based survey was developed in English, including 35 questions. Two-hundred sixty physicians were invited by email to fill in the survey anonymously on Google Forms using a dedicated link. The survey started on 25th February 2024 and was closed on 13th March 2024 (17 days). A reminder was sent after the first 10 days. In addition to descriptive statistics, sub-analyses of answers according to country of origin (Italy vs other States), years of experience (≤20 years vs > 20 years), and type of institution (Academic/University vs Non-Academic/Private) were also established a priori. RESULTS: A total of 121 practitioners from 20 countries completed our survey (response rate 121/260, 46%). Most responders were males (95/121, 78.5%). Most participants were vascular surgeons (118/121, 97.5%). CEUS was available in 87/121, 70.2% of the centers involved, even though a standardized protocol was present in 54/121, and 44% of surveyed institutions. Italian institutions presented greater CEUS availability (62/72, 86.1% vs 25/49, 51.0%; p = .001) and higher presence of standardized protocols (38/72, 52.8% vs 16/49, 32.6%; p = .022) than foreign institutions. The diagnostic tool was thought to be more useful for carotid artery stenosis in the postoperative phase, while for abdominal aortic aneurysms (AAAs) in the preoperative phase. For diagnosis and/or preoperative management of carotid stenosis 53/121, 44% of physicians believed that CEUS should be performed only in selected cases, while for AAA 42/121, 35% of them believed that it could be useful only for scientific purposes. Similarly, 99/121, 82% of participants answered that CEUS was usually prescribed in 0%-20% of the cases during the preoperative diagnostic pathway of patients with peripheral arterial disease. No differences between country of origin, years of experience, and type of institution were found for the reported items. There was also 106/121, 88% of respondents agreed upon the need for better integration of CEUS in current guidelines and 114/121, 94% of them upon the need for further studies. CONCLUSIONS: This ULTRA-VASC survey has demonstrated that CEUS is still rarely used in current practice for many vascular diseases despite the availability of this tool in most centers Future studies are needed, as well as enhanced guidance on the proper implementation of CEUS from guidelines.

In-stent restenosis estimation following carotid artery stenting: The robust predictive value of atherogenic index of plasma and other non-traditional lipid profiles.

OBJECTIVE: Atherosclerotic carotid artery stenosis is a significant contributor to ischemic strokes, and carotid artery stenting (CAS) has emerged as a pivotal treatment option. However, in-stent restenosis (ISR) remains a concern, impacting the long-term patency of CAS. This study aimed to investigate the predictive value of non-traditional lipid profiles, including the atherogenic index of plasma (AIP), in ISR development. METHODS: This retrospective single-center study involved patients presenting at a tertiary healthcare facility with severe carotid artery disease between 2016 and 2020 who subsequently underwent CAS. A total of 719 patients were included in the study. The study cohort was divided into ISR and non-ISR groups based on restenosis presence, confirmed by angiography following ultrasonographic follow-up assessments. Non-traditional lipid indices, such as AIP, atherogenic index (AI), and lipoprotein combined index (LCI), were evaluated along with traditional risk factors. RESULTS: During a 24-month follow-up, ISR occurred in 4.03% of patients. To determine the predictors of restenosis, three different models were constructed in multivariate analysis for non-traditional lipid indices. Multivariate analysis revealed AIP as a robust independent predictor of ISR (OR: 4.83 (CI 95 % 3.05-6.63, p < .001). Notably, AIP demonstrated superior predictive accuracy compared to AI and LCI, with a higher Area Under the Curve (AUC) of 0.971. CONCLUSION: Non-traditional lipid profiles, especially AIP, were found to be associated with an increased risk of ISR and may serve as predictors of ISR in patients undergoing CAS.

Correlation analysis of serum miR-145 and miR-210 with carotid artery stenosis and their predictive value for cerebral ischemic events.

OBJECTIVE: To analyze the significance of serum miR-145 and miR-210 expression levels in the diagnosis of carotid artery stenosis. METHODS: During the same period, 55 healthy individuals who received physical examination in the same hospital were recruited as controls and assigned to a non-stenosis group. Among the included patients, there were 45 cases of mild stenosis, 14 cases of moderate stenosis, and 6 cases of severe stenosis after carotid color Doppler ultrasonography. The expression levels of miR-145 and miR-210 in serum were measured using real-time fluorescence quantitative polymerase chain reaction (qPCR) technology. RESULTS: The expression levels of serum miR-145 and miR-210 in carotid artery stenosis group were significantly lower than those in non-stenosis group (p < 0.001). Multivariate Logistic regression analysis showed that smoking history, diabetes, hypertension and total cholesterol were positively correlated with the occurrence of carotid artery stenosis (p < 0.05). The expression levels of miR-145 and miR-210 were significantly negatively correlated with carotid artery stenosis (p < 0.001). In addition, patients with carotid artery stenosis and low expression levels of miR-145 and miR-210 had a greater risk of cerebral ischemia (p < 0.05). Cox regression analysis showed that the low expression of miR-145 and miR-210 were independent predictors of cerebral ischemic events. ROC analysis confirmed that miR-145 and miR-210 had good diagnostic efficacy in cerebral ischemia (p < 0.001). CONCLUSION: The decreased expression of miR-145 and miR-210 in serum is closely related to the diagnostic significance of carotid artery stenosis, and may be used to predict the occurrence of cerebral ischemic events.

NO Deficiency Compromises Inter- and Intrahemispheric Blood Flow Adaptation to Unilateral Carotid Artery Occlusion.

Carotid artery stenosis (CAS) affects approximately 5-7.5% of older adults and is recognized as a significant risk factor for vascular cognitive impairment (VCI). The impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral microcirculation. In this study, we aimed to test the hypothesis that the impaired availability of nitric oxide (NO) compromises CBF homeostasis after unilateral carotid artery occlusion (CAO). To investigate this, three mouse models exhibiting compromised production of NO were tested: NOS1 knockout, NOS1/3 double knockout, and mice treated with the NO synthesis inhibitor L-NAME. Regional CBF changes following CAO were evaluated using laser-speckle contrast imaging (LSCI). Our findings demonstrated that NOS1 knockout, NOS1/3 double knockout, and L-NAME-treated mice exhibited impaired CBF adaptation to CAO. Furthermore, genetic deficiency of one or two NO synthase isoforms increased the tortuosity of pial collaterals connecting the frontoparietal and temporal regions. In conclusion, our study highlights the significant contribution of NO production to the functional adaptation of cerebrocortical microcirculation to unilateral CAO. We propose that impaired bioavailability of NO contributes to the impaired CBF homeostasis by altering inter- and intrahemispheric blood flow redistribution after unilateral disruption of carotid artery flow.

The mid-term results of the Carotid Asymptomatic Stenosis (CARAS) observational study.

INTRODUCTION: Carotid endarterectomy (CEA) in patients with asymptomatic carotid stenosis (ACAS) remains a subject of debate. Current recommendations are based on randomized trials conducted over 20 years ago and improvements in medical therapies may have reduced the risk of cerebral ischemic events (CIE). This study presents a mid-term analysis of results from an ongoing prospective observational study of ACAS patients to assess their CIE risk in a real-world setting. METHODS: This is a prospective observational cohort study of patients with ACAS >60 % (NASCET criteria) identified in a single duplex ultrasonography (DUS) vascular laboratory (trial registered: NCT04825080). Patients were not considered for CEA due to their short life expectancy (<3 year) or absence of signs of plaque vulnerability (ulceration, ipoechogenic core). Patient enrollment started in January 2019 and ended in March 2020 with a targeted sample size of 300 patients.A 5-year follow-up was scheduled. Clinical characteristics, risk factors, and medical therapies were documented, and, when necessary, the best medical therapy (BMT), involving antiplatelet agents, blood pressure control, and statins, was recommended during clinical visits. The primary endpoint was to asses CIEs (including strokes, transient ischemic attacks, amaurosis-fugax) ipsilateral to ACAS along with plaque progression rate and patients survival. Follow-up involved annual clinical visit and carotid DUS examination, complemented by telephone interviews at six-month intervals. RESULTS: The study included 307 patients, with an average age of 80 ± 7 years, of whom 55 % were male. Contralateral stenosis exceeding 60 % was present in 61 (20 %) patients. Seventy-seven percent of patients were on BMT. At a mean follow-up of 41±9 months, 7 ispilateral strokes and 9 TIAs occurred, resulting in 14 CIEs (2 patients experienced both TIA and stroke). According to Kaplan-Meier analysis, the 4-year CIE rate was 6±2 %, with an annual CIE rate of 1.5 %. Fifty-eight (19 %) patients had a stenosis progression which was associated with a higher 4-year estimated CIE rate compared to patients with stable plaque (10.3 % vs 3.2 %, P=.01). Similarly, a contralateral carotid stenosis >60 % was associated with a higher 4-year estimated CIE rate: 11.7 % vs 2.9 %, P=.002. These factors were independently associated with high risk for CIE at the multivariate COX analysis: Hazard Ratio (HR): 3.2; 95 % Confidence Interval: 1.1-9.2 and HR: 3.6; 95 % CI: 1.2-10.5. CONCLUSION: The mid-term results of this prospective study suggest that the incidence of CIE in ACAS patients should not be underestimated, with plaque progression and contralateral stenosis serving as primary predictors of CIEs.

The effect of institutional case volume on post-operative outcomes after endarterectomy and stenting for symptomatic carotid stenosis.

OBJECTIVE: To investigate the effects of yearly institutional case volume for carotid endarterectomy (CEA) and stenting (CAS) among symptomatic carotid stenosis patients on the rates of postoperative stroke and inpatient mortality. MATERIALS AND METHODS: Patients with prior stroke ("symptomatic") undergoing CEA or CAS during an inpatient stay were identified from the National Inpatient Sample for years 2012-2015. The primary variable was volume of CEA or CAS performed annually by each institution. The primary outcome was a composite variable for in-hospital death or postoperative stroke. RESULTS: A total of 5,628 patients with symptomatic carotid stenosis underwent CEA, while 245 underwent CAS. In the symptomatic CEA population, 519 (9.2 %) patients experienced postoperative stroke or mortality, and were more likely to be treated at centers with a lower yearly institutional volume (median 10 [IQR 5-15] versus 10 [7-20] cases, p < 0.001). In the symptomatic CAS population, 32 (13.1 %) patients experienced stroke or mortality, and these patients were also more likely to undergo treatment at hospitals with a lower yearly institutional volume (median 5 [IQR 5-7] versus 5 [5-10] cases, p = 0.044). Thresholds for yearly institutional volume found differences in adverse outcome between 0-9, 10-29, and ≥30 cases/year (11.7 % vs 8.4 % vs 6.0 %, p < 0.001) for CEA, and differences in postoperative stroke between 0-9 and ≥10 cases/year for CAS (11.0 % vs 1.4 %, p = 0.028). CONCLUSIONS: Hospitals performing higher volumes of CEA or CAS have fewer postoperative strokes. The threshold reported herein is ≥30 CEA procedures or ≥10 CAS procedures annually for appreciably improved outcomes.