Brain natriuretic peptide is a long-term cardiovascular predictor in carotid endarterectomy.

BACKGROUND: In noncardiac surgery, several biomarkers are known to play a role in predicting long-term complications, such as major adverse cardiovascular events (MACE), myocardial infarction, or death. Carotid endarterectomy (CEA) is considered a low to medium-risk surgery for carotid stenosis aimed at preventing stroke events. Brain natriuretic peptide (BNP) is a biomarker with potential prognostic value regarding MACE. Since its role in patients undergoing CEA is unknown, this study aims to assess the potential role of BNP as a short and long-term predictor of all-cause mortality and MACE in patients undergoing CEA. METHODS: From a prospective database, patients who underwent CEA under regional anesthesia (RA) at a tertiary hospital center were enrolled, and a post hoc analysis was conducted. Patients on which BNP levels were measured up to fifteen days before surgery, and two groups based on the BNP threshold (200 pg/mL) were defined and compared. Kaplan Meier survival curves and adjusted hazard ratios (aHR) were assessed by multivariable Cox regression. The primary outcome was the incidence of long-term MACE and all-cause mortality. Secondary outcomes included the incidence of AMI and AHF. RESULTS: A total of 89 patients were evaluated. The mean age of the cohort was 71.2 ± 8.7 years, with 71 (79.8%) males, and presented a median follow-up of 30 [13.5-46.4] months. BNP > 200 pg/mL has demonstrated positive predictive value for MACE (aHR: 5.569, confidence interval (CI): 2.441-12.7, p < 0.001) and all-cause mortality (aHR: 3.469, CI: 1.315-9.150, p = 0.018). CONCLUSION: BNP has been demonstrated to independently predict long-term all-cause mortality, MACE and AMI following CEA. It serves as a low-cost, ready-to-use biomarker, although further studies are necessary.

Alterations in brain morphology and functional connectivity mediate cognitive decline in carotid atherosclerotic stenosis.

Background: Patients with carotid atherosclerotic stenosis (CAS) often have varying degrees of cognitive decline. However, there is little evidence regarding how brain morphological and functional abnormalities impact the cognitive decline in CAS patients. This study aimed to determine how the brain morphological and functional changes affected the cognitive decline in patients with CAS. Methods: The brain morphological differences were analyzed using surface and voxel-based morphometry, and the seed-based whole-brain functional connectivity (FC) abnormalities were analyzed using resting-state functional magnetic resonance imaging. Further, mediation analyses were performed to determine whether and how morphological and FC changes affect cognition in CAS patients. Results: The CAS-MCI (CAS patients with mild cognitive impairment) group performed worse in working memory, verbal fluency, and executive time. Cortical thickness (CT) of the left postcentral and superiorparietal were significantly reduced in CAS-MCI patients. The gray matter volume (GMV) of the right olfactory, left temporal pole (superior temporal gyrus) (TPOsup.L), left middle temporal gyrus (MTG.L), and left insula (INS.L) were decreased in the CAS-MCI group. Besides, decreased seed-based FC between TPOsup.L and left precuneus, between MTG.L and TPOsup.L, and between INS.L and MTG.L, left middle frontal gyrus, as well as Superior frontal gyrus, were found in CAS-MCI patients. Mediation analyses demonstrated that morphological and functional abnormalities fully mediated the association between the maximum degree of carotid stenosis and cognitive function. Conclusion: Multiple brain regions have decreased GMV and CT in CAS-MCI patients, along with disrupted seed-based FC. These morphological and functional changes play a crucial role in the cognitive impairment in CAS patients.

Determinants of prehospital and in-hospital delay in patients with symptomatic carotid stenosis and their influence on the outcome after elective carotid endarterectomy.

BACKGROUND: This study analyses the determinants of prehospital (index event to admission) and in-hospital delay (admission to carotid endarterectomy (CEA)). In addition, the analysis addresses the association between prehospital or in-hospital delay and outcomes after CEA for symptomatic patients in German hospitals. MATERIALS AND METHODS: This retrospective analysis is based on the nationwide German statutory quality assurance database. 55 437 patients were included in the analysis. Prehospital delay was grouped as follows: 180-15, 14-8, 7-3, 2-0 days or 'in-hospital index event'. In-hospital delay was divided into: 0-1, 2-3 and >3 days. The primary outcome event (POE) was in-hospital stroke or death. Univariate and multivariable regression analyses were performed for statistical analysis. The slope of the linear regression line is given as the ß-value, and the rate parameter of the logistic regression is given as the adjusted OR (aOR). RESULTS: Prehospital delay was 0-2 days in 34.9%, 3-14 days in 29.5% and >14 days in 18.6%. Higher age (ß=-1.08, p<0.001) and a more severe index event (transitory ischaemic attack: ß=-4.41, p<0.001; stroke: ß=-6.05, p<0.001, Ref: amaurosis fugax) were determinants of shorter prehospital delay. Higher age (ß=0.28, p<0.001) and female sex (ß=0.09, p=0.014) were associated with a longer in-hospital delay. Index event after admission (aOR 1.23, 95% CI: 1.04 to 1.47) and an intermediate in-hospital delay of 2-3 days (aOR 1.15, 95% CI: 1.00 to 1.33) were associated with an increased POE risk. CONCLUSIONS: This study revealed that older age, higher American Society of Anesthesiology (ASA) stage, increasing severity of symptoms and ipsilateral moderate stenosis were associated with shorter prehospital delay. Non-specific symptoms were associated with a longer prehospital delay. Regarding in-hospital delay, older age, higher ASA stage, contralateral occlusion, preprocedural examination by a neurologist and admission on Fridays or Saturdays were associated with lagged treatment. A very short (<2 days) prehospital and intermediate in-hospital delay (2-3 days) were associated with increased risk of perioperative stroke or death.

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.

Age-related white matter change disease predicts long-term cerebrovascular morbidity following carotid endarterectomy.

PURPOSE: Cerebrovascular diseases remain a critical focus of medical research due to their substantial impact on global health. Carotid stenosis, often associated with atherosclerosis and advancing age, profoundly affects cerebral blood supply and white matter integrity. This study aims to assess how age-related white matter changes (ARWMC) score, applied to cortex and Basal Ganglia, relates to cardiovascular and cerebrovascular events in patients who underwent carotid endarterectomy (CEA). METHODS: Ninety patients undergoing CEA with regional anesthesia were prospectively enrolled from January 2012 to January 2022, and a post hoc analysis of patients with preoperative cerebral CT scans were reviewed, stratified by ARWMC score. Survival analysis and multivariate Cox regression were employed to assess time-dependent variables and independent predictors. RESULTS: A median follow-up of 51 months (Inter-quartile range [IQR [ [38.8-63.2] months) revealed higher ARWMC grades in the basal ganglia independently associated with significantly increased stroke risk (HR=5.070, 95% CI: 1.509-17.031, P=0.009), acute heart failure (HR=19.066, 95% CI: 2.038-178.375, P=0.01), major adverse cardiovascular events (MACE) (HR=2.760, 95% CI: 1.268-6.009, P=0.011), and all-cause mortality (HR=2.497, 95% CI:1.009-6.180, P=0.048). Polyvascular disease and chronic kidney disease emerged as additional predictors of MACE. CONCLUSION: Higher grades of ARWMC score in the basal ganglia were related to a significant increase in the risk of adverse cardiovascular events, such as stroke, MACE, AHF and all-cause mortality. This study suggests that ARWMC may have potential as a possible predictor of long-term cardio- and cerebrovascular events in patients undergoing CEA.

Quantitative evaluation using carotid Ultrasonography-Based High-Frame-Rate vector flow imaging in patients with low carotid stenosis.

OBJECTIVE: To explore the role of quantitative evaluation using carotid ultrasonography (US)-based high-frame-rate vector flow (V Flow) imaging in patients with low carotid stenosis. METHODS: This single-center cross-sectional study consecutively recruited volunteers without carotid plaque and patients with low carotid stenosis from August 2022 to May 2023. Patients were divided into symptomatic and asymptomatic groups according to their head CT or MRI results within eight weeks. All V Flow imaging examinations were performed using a Mindray Resona R9 US system. The wall shear stress (WSS) values, oscillatory shear index (OSI) values and turbulence (Tur) indexes in the normal common carotid artery (CCA), normal carotid bifurcation (CB), and on the upstream and downstream surface of carotid plaque were measured. Pearson Chi-square test and Fisher exact test were used for counting data according to their type. For measurement data, independent sample t test and non-parametric rank sum test were used. RESULTS: The results proved that patients have higher WSS values and Tur indexes of CB than volunteers, and higher WSS values were detected on the surface of the plaques in symptomatic patients. What's more, the downstream side of the plaque was more vulnerable to plaque rupture than the upstream side due to more dynamic blood flow. CONCLUSION: Therefore, carotid US-based high-frame-rate V Flow imaging provides reliable mechanical biomarkers for assessing the hemodynamic change in patients with low stenosis. Our study may provide a new imaging tool for monitoring the progression of atherosclerosis and aiding the management of early atherosclerotic patients.

Short-Term Statin Treatment Reduces, and Long-Term Statin Treatment Abolishes, Chronic Vascular Injury by Radiation Therapy.

BACKGROUND: The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration. METHODS AND RESULTS: C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca2+ activated K+ BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes. CONCLUSIONS: Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.

Outcomes of carotid revascularization stratified by procedure in eGFR<30 and dialysis patients.

OBJECTIVE: Renal failure is a predictor of adverse outcomes in carotid revascularization. There has been debate regarding the benefit of revascularization in patients with severe CKD or on dialysis. METHODS: VQI patients undergoing TCAR, tfCAS, or CEA between 2016 and 2023 with eGFR <30 ml/min/1.73m2 or on dialysis were included. Patients were divided into cohorts based on procedure. Additional analyses were performed for patients on dialysis only and by symptomatology. Primary outcomes were perioperative stroke/death/MI (SDM). Secondary outcomes included perioperative death, stroke, MI, CNI and stroke/death. Inverse probability of treatment weighting (IPW) was performed based on treatment assignment to TCAR, tfCAS, and CEA patients and adjusted for demographics, comorbidities, and pre-op symptoms. Chi-square and multivariable logistic regression analysis were used to evaluate the association of procedure with perioperative outcomes in the weighted cohort. Five-year survival was evaluated using Kaplan-Meier and weighted Cox regression. RESULTS: In the weighted cohort, 13,851 patients with eGFR of <30 (2,506 on dialysis) underwent TCAR (3,639, dialysis 704), tfCAS (1,975, 393) or CEA (8,237, 1,409) during the study period. Compared with TCAR, CEA had higher odds of stroke/death/MI (2.8% vs 3.6%, aOR 1.27 [1.00,1.61], p=.049), and MI (0.7% vs 1.5%, aOR 2.00 [1.31,3.05], p=.001)... Compared to TCAR, rates of SDM (2.8%vs5.8%), stroke (1.2%vs2.6%), death (0.9%vs2,4%)were all higher for tfCAS. In asymptomatic patients CEA patients had higher odds of MI (0.7% vs 1.3%, aOR 1.85[1.15, 2.97]p=.011) and CNI (0.3% vs 1.9%, aOR 7.23[3.28, 15.9] p<.001). Like the primary analysis, asymptomatic tfCAS patients demonstrated higher odds of death, and stroke/death. Symptomatic CEA patients demonstrated no difference in stroke, death or stroke/death. While tfCAS patients demonstrated higher odds of death, stroke, MI, stroke/death, and SDM. In both groups, 5-year survival was similar for TCAR and CEA (eGFR <30: 75.1% vs 74.2%, aHR1.06, p=.3) and lower for tfCAS (eGFR <30: 75.1% vs 70.4%, aHR1.44, p<.001) CONCLUSION: CEA and TCAR had similar odds of stroke and death and are both a reasonable choice in this population; however, TCAR may be better in patients with increased risk of MI. Additionally, tfCAS patients were more likely to have worse outcomes after weighting for symptom status. Finally, while patients with reduced eGFR have worse outcomes than their healthy peers, this analysis shows that the majority of patients survive long enough to benefit from the potential stroke risk reduction provided by all revascularization procedures.

Risk, prevention, screening and management of carotid artery stenosis in head & neck cancer patients-An evidence based review.

Our review aims to clarify the incidence of carotid artery stenosis, risks of development, screening, management, and primary prevention strategies documented in the literature after radiation therapy for head and neck cancers. The high prevalence of carotid stenosis after radiation therapy for head and neck cancers has made surveillance and risk stratification critical. In addition to general cardiovascular risk factors such as smoking, diabetes, and dyslipidemia, risk factors for carotid artery stenosis after head and neck radiation included total plaque score, radiotherapy use and dosage, length of time after radiotherapy, and age greater than 50. Cancer subtype, namely nasopharyngeal cancer, may be correlated with increased risk as well, though contrasting results have been found. Interestingly, however, no significant relationship has been found between radiotherapy dose and stroke risk. Surgical management of post-radiation carotid stenosis is similar to that of stenosis unrelated to radiation, with carotid endarterectomy considered to be the gold standard treatment and carotid artery stenting being an acceptable, less-invasive alternative. Medical management of these patients has not been well-studied, but antiplatelet therapy, statins, and blood pressure control may be beneficial. The mainstay of screening for radiation-induced stenosis has been Doppler ultrasound, with measurement of changes in the intima-media thickness being a primary marker of disease development. A literature review was carried out using the MeSH terms "Carotid Artery Stenosis," "Head and Neck Neoplasms," and "Radiotherapy."

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.

Machine Learning Detects Symptomatic Plaques in Patients With Carotid Atherosclerosis on CT Angiography.

BACKGROUND: This study aimed to develop and validate a computed tomography angiography based machine learning model that uses plaque composition data and degree of carotid stenosis to detect symptomatic carotid plaques in patients with carotid atherosclerosis. METHODS: The machine learning based model was trained using degree of stenosis and the volumes of 13 computed tomography angiography derived intracarotid plaque subcomponents (eg, lipid, intraplaque hemorrhage, calcium) to identify plaques associated with cerebrovascular events. The model was internally validated through repeated 10-fold cross-validation and tested on a dedicated testing cohort according to discrimination and calibration. RESULTS: This retrospective, single-center study evaluated computed tomography angiography scans of 268 patients with both symptomatic and asymptomatic carotid atherosclerosis (163 for the derivation set and 106 for the testing set) performed between March 2013 and October 2019. The area-under-receiver-operating characteristics curve by machine learning on the testing cohort (0.89) was significantly higher than the areas under the curve of traditional logit analysis based on the degree of stenosis (0.51, P<0.001), presence of intraplaque hemorrhage (0.69, P<0.001), and plaque composition (0.78, P<0.001), respectively. Comparable performance was obtained on internal validation. The identified plaque components and associated cutoff values that were significantly associated with a higher likelihood of symptomatic status after adjustment were the ratio of intraplaque hemorrhage to lipid volume (≥50%, 38.5 [10.1-205.1]; odds ratio, 95% CI) and percentage of intraplaque hemorrhage volume (≥10%, 18.5 [5.7-69.4]; odds ratio, 95% CI). CONCLUSIONS: This study presented an interpretable machine learning model that accurately identifies symptomatic carotid plaques using computed tomography angiography derived plaque composition features, aiding clinical decision-making.

Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI.

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.

William M. Feinberg Lecture: Asymptomatic Carotid Stenosis: Current and Future Considerations.

Asymptomatic high-grade carotid stenosis is an important therapeutic target for stroke prevention. For decades, the ACAS (Asymptomatic Carotid Atherosclerosis Study) and ACST (Asymptomatic Carotid Surgery Trial) trials provided most of the evidence supporting endarterectomy for patients with asymptomatic high-grade stenosis who were otherwise good candidates for surgery. Since then, transfemoral/transradial carotid stenting and transcarotid artery revascularization have emerged as alternatives to endarterectomy for revascularization. Advances in treatments against atherosclerosis have driven down the rates of stroke in patients managed without revascularization. SPACE-2 (Stent-Protected Angioplasty Versus Carotid Endarterectomy-2), a trial that included endarterectomy, stenting, and medical arms, failed to detect significant differences in stroke rates among treatment groups, but the study was stopped well short of its recruitment goal. CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) will be able to clarify whether revascularization by stenting or endarterectomy remains efficacious under conditions of intensive medical management. Transcarotid artery revascularization has a favorable periprocedural risk profile, but randomized trials comparing it to intensive medical management are lacking. Features like intraplaque hemorrhage on MRI and echolucency on B-mode ultrasonography can identify patients at higher risk of stroke with asymptomatic stenosis. High-grade stenosis with poor collaterals can cause hemispheric hypoperfusion, and unstable plaque can cause microemboli, both of which may be treatable risk factors for cognitive impairment. Evidence that there are patients with carotid stenosis who benefit cognitively from revascularization is presently lacking. New risk factors are emerging, like exposure to microplastics and nanoplastics. Strategies to limit exposure will be important without specific medical therapies.

ACR Appropriateness Criteria® Cerebrovascular Diseases-Stroke and Stroke-Related Conditions.

Cerebrovascular disease encompasses a vast array of conditions. The imaging recommendations for stroke-related conditions involving noninflammatory steno-occlusive arterial and venous cerebrovascular disease including carotid stenosis, carotid dissection, intracranial large vessel occlusion, and cerebral venous sinus thrombosis are encompassed by this document. Additional imaging recommendations regarding complications of these conditions including intraparenchymal hemorrhage and completed ischemic strokes are also discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Carotid atherosclerotic plaque microcalcification is independently associated with recurrent neurovascular events: a pilot study.

BACKGROUND: Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood. METHODS: We performed a post-hoc analysis of data from the ICARUSS study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ≥50% underwent 18F-sodium fluoride-positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBRmax). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for six months for recurrent ipsilateral neurovascular events. RESULTS: Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (OR 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (OR 1.12, 1.06-1.17 for each 100 unit increase). CONCLUSIONS: Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts.

Predicting Major Adverse Carotid Cerebrovascular Events in Patients with Carotid Stenosis: Integrating a Panel of Plasma Protein Biomarkers and Clinical Features-A Pilot Study.

Background: Carotid stenosis (CS) is an atherosclerotic disease of the carotid artery that can lead to devastating cardiovascular outcomes such as stroke, disability, and death. The currently available treatment for CS is medical management through risk reduction, including control of hypertension, diabetes, and/or hypercholesterolemia. Surgical interventions are currently suggested for patients with symptomatic disease with stenosis >50%, where patients have suffered from a carotid-related event such as a cerebrovascular accident, or asymptomatic disease with stenosis >60% if the long-term risk of death is <3%. There is a lack of current plasma protein biomarkers available to predict patients at risk of such adverse events. Methods: In this study, we investigated several growth factors and biomarkers of inflammation as potential biomarkers for adverse CS events such as stroke, need for surgical intervention, myocardial infarction, and cardiovascular-related death. In this pilot study, we use a support vector machine (SVM), random forest models, and the following four significantly elevated biomarkers: C-X-C Motif Chemokine Ligand 6 (CXCL6); Interleukin-2 (IL-2); Galectin-9; and angiopoietin-like protein (ANGPTL4). Results: Our SVM model best predicted carotid cerebrovascular events with an area under the curve (AUC) of >0.8 and an accuracy of 0.88, demonstrating strong prognostic capability. Conclusions: Our SVM model may be used for risk stratification of patients with CS to determine those who may benefit from surgical intervention.

Outcomes of carotid endarterectomy in octogenarians compared to their younger counterparts: a retrospective observational study.

Purpose: This study was performed to analyze the association between age and outcomes of carotid endarterectomy (CEA) by comparing postoperative outcomes between octogenarians and younger patients. Methods: From November 1994 to December 2022, 1,585 internal carotid arteries of 1,434 patients were enrolled. Patients were stratified into 2 groups: octogenarians (≥80 years old) and non-octogenarians (<80 years old). Primary endpoints were early (≤30 days) outcomes of ipsilateral stroke, any stroke, myocardial infarction, death, and major adverse cardiovascular events (MACE). We also compared overall any stroke and death between the 2 groups. Results: One of 132 octogenarians (0.8%) and 17 of 1,453 non-octogenarians (1.1%) experienced ipsilateral stroke within 30 days. Thirty-day MACE occurred in 4 of 132 octogenarians (3%) and 44 of 1,453 non-octogenarians (3%). There were no significant differences in any early (≤30 days) outcomes. Symptomatic status was associated with increased 30-day MACE (odds ratio [OR], 2.610; 95% confidence interval [CI], 1.450-4.696; P = 0.003) and 30-day any stroke (OR, 3.999; 95% CI, 1.627-9.828; P = 0.003). Symptomatic status was also associated with overall any stroke (hazard ratio [HR], 2.885; 95% CI, 1.865-4.463; P < 0.001), but age of ≥80 years was not associated with 30-day MACE, 30-day any stroke, or overall stroke. Age of ≥80 years was only associated with overall survival (HR, 2.644; 95% CI, 1.967-3.555; P < 0.001). Conclusion: CEA would be a safe and effective treatment for octogenarians with low 30-day complications and long-term stroke rates, comparable with that of younger counterparts. Advanced age is not a contraindication for CEA.

[Guideline for the management of symptomatic and asymptomatic internal carotid artery stenosis]. / Leitlinien zur Versorgung symptomatischer und asymptomatischer Stenosen der A. carotis interna.

BACKGROUND: Stenoses of the internal carotid artery (ICA) with a ≥ 50% degree of stenosis are common in the German population with a prevalence of approx. 4.2%. Furthermore, about 15% of ischemic strokes are due to stenosis or occlusion of the ICA. There are currently three approaches to the treatment of ICA stenoses: conventional therapy, endovascular treatment and surgical treatment. METHODS: Summary of the S3 guideline on the diagnosis, treatment and follow-up of extracranial carotid stenosis from 3 February 2020. RESULTS: Color-coded duplex sonography, computed tomography (CT) angiography and magnetic resonance (MR) angiography and, in exceptional cases, diagnostic subtraction angiography can be used to diagnose ICA stenoses, including the stenosis grade. The classification is into symptomatic and asymptomatic ICA stenoses. ICA stenoses can be treated conservatively, endovascularly with stenting or surgically by carotid endarterectomy. Invasive treatment should be carried out under inpatient conditions, whereby the hospital stay should be kept as short as possible. Color-coded duplex sonography should be performed regularly before discharge and at regular intervals thereafter to detect recurrent stenosis at an early stage and, if necessary, to initiate further invasive therapy. CONCLUSIONS: When choosing the treatment modality, particular attention must be paid to whether the stenosis is symptomatic or asymptomatic and the degree of stenosis. The S3 guideline on the diagnosis, treatment and follow-up of extracranial carotid stenosis from 3 February 2020 provides guidance here.

Exploring the relationship between embolic acute stroke distribution and supra-aortic vessel patency: key findings from an in vitro model study.

BACKGROUND: We investigated differences in intracranial embolus distribution through communicating arteries in relation to supra-aortic vessel (SAV) patency. METHODS: For this experimental analysis, we created a silicone model of the extracranial and intracranial circulations using a blood-mimicking fluid under physiological pulsatile flow. We examined the sequence of embolus lodgment on injecting 104 frangible clot analogues (406 emboli) through the right internal carotid artery (CA) as SAV patency changed: (a) all SAV patent (baseline), (b) emboli from a CA occlusion, (c) emboli contralateral to a CA occlusion and (d) occlusion of the posterior circulation. The statistical analysis included a descriptive analysis of thrombi location after occlusion (absolute and relative frequencies). Sequences of occlusions were displayed in Sankey flow charts for the four SAV conditions. Associations between SAV conditions and occlusion location were tested by Fisher's exact test. Two-sided p values were compared with a significance level of 0.05. RESULTS: The total number of emboli was 406 (median fragments/clot: 4 (IQR: 3-5)). Embolus lodgment was dependent on SAV patency (p<0.0001). In all scenarios, embolism lodging in the anterior cerebral artery (ACA) occurred after a previous middle cerebral artery (MCA) embolism (MCA first lodge: 96%, 100/104). The rate of ipsilateral ACA embolism was 28.9% (28/97) at baseline, decreasing significantly when emboli originated from an occluded CA (16%, 14/88). There were more bihemispheric embolisations in cases of contralateral CA occlusion (37%, 45/122), with bilateral ACA embolisms preceding contralateral MCA embolism in 56% of cases (14/25 opposite MCA and ACA embolism). CONCLUSIONS: All emboli in the ACA occurred after a previous ipsilateral MCA embolism. Bihemispheric embolisms were rare, except when there was a coexisting occlusion in either CA, particularly in cases of a contralateral CA occlusion.

Association between hospital ownership and patient selection, management, and outcomes after carotid endarterectomy or carotid artery stenting : - Secondary data analysis of the Bavarian statutory quality assurance database.

BACKGROUND: This study analyses the association between hospital ownership and patient selection, treatment, and outcome of carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS: The analysis is based on the Bavarian subset of the nationwide German statutory quality assurance database. All patients receiving CEA or CAS for carotid artery stenosis between 2014 and 2018 were included. Hospitals were subdivided into four groups: university hospitals, public hospitals, hospitals owned by charitable organizations, and private hospitals. The primary outcome was any stroke or death until discharge from hospital. Research was funded by Germany's Federal Joint Committee Innovation Fund (01VSF19016 ISAR-IQ). RESULTS: In total, 22,446 patients were included. The majority of patients were treated in public hospitals (62%), followed by private hospitals (17%), university hospitals (16%), and hospitals under charitable ownership (6%). Two thirds of patients were male (68%), and the median age was 72 years. CAS was most often applied in university hospitals (25%) and most rarely used in private hospitals (9%). Compared to university hospitals, patients in private hospitals were more likely asymptomatic (65% vs. 49%). In asymptomatic patients, the risk of stroke or death was 1.3% in university hospitals, 1.5% in public hospitals, 1.0% in hospitals of charitable owners, and 1.2% in private hospitals. In symptomatic patients, these figures were 3.0%, 2.5%, 3.4%, and 1.2% respectively. Univariate analysis revealed no statistically significant differences between hospital groups. In the multivariable analysis, compared to university hospitals, the odds ratio of stroke or death in asymptomatic patients treated by CEA was significantly lower in charitable hospitals (OR 0.19 [95%-CI 0.07-0.56, p = 0.002]) and private hospitals (OR 0.47 [95%-CI 0.23-0.98, p = 0.043]). In symptomatic patients (elective treatment, CEA), patients treated in private or public hospitals showed a significantly lower odds ratio compared to university hospitals (0.36 [95%-CI 0.17-0.72, p = 0.004] and 0.65 [95%-CI 0.42-1.00, p = 0.048], respectively). CONCLUSIONS: Hospital ownership was related to patient selection and treatment, but not generally to outcomes. The lower risk of stroke or death in the subgroup of electively treated patients in private hospitals might be due to the right timing, the choice of treatment modality or actually to better structural and process quality.