BACKGROUND:Severe atherosclerotic internal carotid artery stenosis may progress to complete internal carotid artery occlusion (ICAO). Therefore, ICAO represents an advanced form of carotid artery disease. We sought to investigate the association between ICAO with atherosclerotic disease in other arterial beds and vascular risk factors and to identify the patient implications of the diagnosis of ICAO. METHODS:Using the term "Internal carotid artery occlusion," a search of PubMed/MEDLINE, Scopus, and Embase between 1980 and 2025 revealed 10,588 results. After exclusion of case reports, letters to the Editor and Editorials, 5771 reports were identified. Following meticulous screening of the identified reports, 28 studies specifically addressing patient with ICAO cohorts were included in the final analysis. A quantitative and qualitative synthesis analysis was performed. A questionnaire was subsequently developed and sent out to 63 participants from the United States (n = 21) and several European countries (n = 42), aiming to achieve consensus regarding the optimal management of patients with ICAO. Three participants did not respond. The Consensus Coordinator abstained from voting to avoid introducing bias, resulting in a final voting panel of 60 participants. RESULTS:Across included studies, the proportion of patients with ICAO presenting with neurologic symptoms varied widely, ranging from 38% to 100%, whereas approximately 24% to 27% of patients were asymptomatic at the time of diagnosis. Consensus (≥75%) was achieved in 11 of the 17 (64.7%) prespecified statements. Most participants agreed that atherosclerotic ICAO represents a systemic manifestation of advanced atherosclerosis rather than isolated cerebrovascular pathology (56/60; 93.3%). Duplex ultrasound study should be used as the first-line diagnostic tool for suspected ICAO, with computed tomography angiography or magnetic resonance angiography confirmation if necessary (59/60; 98.3%). Optimal medical therapy (including antiplatelet, antihypertensives, statins, and glycemic control) remains the cornerstone of ICAO management (59/60; 98.3%). Lifestyle and metabolic risk factor optimization, smoking cessation, optimizing body weight, a healthy diet and exercise, should be strongly advised in all patients with ICAO (60/60; 100%). Most participants concurred that ICAO revascularization should be centralized in specialized vascular-neuro centers equipped for intraoperative neuromonitoring and advanced hemodynamic control (57/60; 95.0%). Finally, most participants agreed that current evidence for ICAO intervention is insufficient and that a global registry should be created to record outcomes and guide future trials (56/60; 93.3%). CONCLUSIONS:This international, multispecialty consensus highlights ICAO as a marker of advanced, systemic atherosclerosis. Management should emphasize comprehensive evaluation for multisystem vascular disease and aggressive modification of cardiovascular risk factors. Best medical therapy remains the cornerstone of the management of patients with ICAO, with conservative or invasive interventions considered selectively based on symptom status, anatomic considerations, procedural risk, and institutional expertise, to reduce the overall cardiovascular disease burden.

OBJECTIVE:Chronic venous disease is a progressive disease that often begins with venous symptoms even without visible signs. This systematic review and meta-analysis aimed to evaluate the effectiveness of micronized purified flavonoid fraction (MPFF) in patients with early stage chronic venous disease (Clinical, Etiological, Anatomical, and Pathophysiological C0s-C1). METHODS:A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MEDLINE, Embase, and Cochrane databases were searched from inception until November 2023. Prospective studies (randomized controlled trials and comparative, single-arm, and observational studies) assessing MPFF (1000 mg daily orally) in C0s-C1 patients were included. Outcomes included leg venous symptoms (pain, heaviness, and cramps) and quality of life (QoL). The data were analyzed using a random-effects meta-analysis model. RESULTS:Five studies involving 411 patients were analyzed. The patients' mean age was 40.1 (8.0) years, and 96.6% of them were female. Patients were classified as Clinical, Etiological, Anatomical, and Pathophysiological C1 (80%) and C0s (20%). MPFF significantly reduced pain intensity (mean change [MC], -2.3 cm; 95% confidence interval [CI], -3.1 to -1.6), reduced heaviness (MC, -2.8 cm; 95% CI, -3.5 to -2.1), and improved QoL (MC, -16.0; 95% CI, -20.7 to -11.3). Two studies reported complete resolution of symptoms for pain (100.0%), heaviness (87.9%), and cramps (97.8%). Two studies had a high risk of bias, and the heterogeneity level was frequently high among studies. CONCLUSIONS:The present meta-analysis reinforces the evidence supporting MPFF effectiveness in alleviating venous leg symptoms and improving QoL in C0s-C1 patients and supports the use of MPFF treatment in early disease management.

BACKGROUND: Popliteal Artery Entrapment Syndrome (PAES) is an uncommon but important cause of lower limb ischemia affecting young, active individuals without traditional atherosclerotic risk factors. The condition has an estimated prevalence of 0.17–3.5% in the general population and accounts for approximately 3–5% of claudication cases in patients under 40 years without atherosclerotic risk factors. PAES results from abnormal anatomical relationships between the popliteal artery and surrounding structures, causing compression and intermittent claudication. Early diagnosis is crucial to prevent complications such as thrombosis, aneurysm formation, or irreversible ischemia. CASE REPORT: A 36-year-old previously healthy male presented with right lower-limb claudication, limiting walking to less than 100 metres. Physical examination revealed absent right distal pulses, and Doppler ultrasound showed a peak systolic velocity of 400 cm/s in the right popliteal artery, corresponding to 90–99% stenosis. Magnetic resonance angiography confirmed type 3 PAES with sub-occlusive popliteal artery stenosis. Surgical treatment comprised myotomy of the lateral accessory head of the medial gastrocnemius muscle and popliteal artery interposition grafting from P1 to P3 using the contralateral inverted great saphenous vein via a posterior approach. The patient recovered uneventfully, with restored distal pulses, and remained symptom-free at one-year follow-up. CONCLUSION: This case highlights the importance of considering PAES in young patients presenting with claudication without atherosclerotic risk factors. Successful surgical management demonstrates that timely intervention yields excellent functional outcomes. The case emphasises the need for greater PAES awareness among healthcare providers, as early recognition and intervention improve patient outcomes and reduce the long-term burden of undiagnosed vascular disease.

BACKGROUND:A subset of patients with advanced chronic kidney disease (CKD) or kidney replacement therapy becomes ineligible for arteriovenous vascular access creation due to vascular exhaustion or comorbidity-driven contraindications. Outcomes following a negative surgical vascular access recommendation remain poorly characterized and may differ according to kidney replacement therapy status at assessment. METHODS:We retrospectively studied all patients evaluated by a multidisciplinary vascular access team (January 2022-December 2024) who received a negative surgical recommendation for autologous or prosthetic vascular access construction. Patients were primarily stratified as pre-dialysis CKD G4-5 or already receiving kidney replacement therapy. Reason for ineligibility was analyzed descriptively. RESULTS:Among 647 patients evaluated, 40 (6.2%) patients received a negative surgical vascular access recommendation; 20 were pre-dialysis CKD G4-5 and 20 were already receiving kidney replacement therapy. Vascular exhaustion accounted for 23 cases and comorbidity-driven contraindication for 17. Among pre-dialysis patients, 11/20 (55%) initiated kidney replacement therapy after index evaluation: 10 initiated hemodialysis and 1 initiated peritoneal dialysis. Non-planned hemodialysis initiation occurred in 9/10 (90%) patients who started hemodialysis as their first kidney replacement therapy modality, mainly due to acute cardiorenal or coronary syndromes. Among patients already receiving kidney replacement therapy, surgical ineligibility identified persistent absence of durable arteriovenous options: 18/20 (90%) received hemodialysis after index evaluation, with prolonged catheter exposure. Overall, 17/40 (43%) patients died, including 7/20 (35%) pre-dialysis patients and 10/20 (50%) already-kidney replacement therapy patients. CONCLUSIONS:Surgical vascular access ineligibility defines a high-risk clinical state whose implications differ by kidney replacement therapy status. Earlier identification, structured modality assessment, and timely palliative integration may better align care with prognosis, physiology, and patient goals.

INTRODUCTION:Chronic venous disease (CVD) is a widespread disease characterized by various clinical manifestations. This manuscript is Part II of a systematic literature review and meta-analysis assessing the effects of micronized purified flavonoid fraction (MPFF) on lower limb symptoms and signs in patients with CVD at all stages of the disease. Part I examined symptoms and Part II presented herein focused on signs. EVIDENCE ACQUISITION:A systematic literature review was conducted in November 2023 to identify studies investigating the efficacy of MPFF oral treatment (1000 mg daily for at least 1 month) on venous symptoms and signs in patients with CVD at all stages (C0s-C6). Databases searched included Medline, Embase, and Cochrane. Eligible studies included randomized controlled trials (RCTs) and non-RCTs (non-randomized comparative, single-arm, and observational studies) evaluating venous signs: edema, redness, ulcer healing and disease severity assessed by venous clinical severity score (VCSS). A single-group random-effects meta-analysis was used to estimate the mean change in sign intensity and the proportion of sign improvement or complete resolution from baseline to the final assessment. EVIDENCE SYNTHESIS:Out of 387 identified articles, 56 studies were included in the analysis, among which 33 reported CVD signs in 24,617 MPFF-treated patients. Included participants were mainly females (84.1%) with a mean age (±SD) of 48.6 (±8.8) years, and overweight with a mean BMI of 26.3 (±4.5) kg/m2. Significant reductions were observed in mean [95% confidence interval] ankle and calf circumferences (-7.6 mm [-9.1 to -6.2] and -8.0 mm [-11.2 to -4.8], respectively, P<0.001). Venous ulcers were healed in 48.9% [30.3% to 67.8%] or regressed in 73.4% [63.3% to 82.3%] of the patients (P<0.001). Significant improvements were also shown in redness and VCSS score (P<0.001). Twelve studies had a high risk of bias, while sensitivity analyses did not change the study results. Heterogeneity level was frequently high among studies. CONCLUSIONS:This comprehensive meta-analysis provides additional evidence supporting the effectiveness of MPFF in improving clinical signs of CVD across all stages of the disease.

Cigarette smoking is a major preventable risk factor for lower extremity arterial disease (LEAD) and is strongly associated with a higher risk of disease progression, worse post-procedural outcomes, and increased healthcare utilization. Smoking provokes the development of atherosclerotic through different mechanisms. Endothelial cell dysfunction, oxidative stress, inflammation, and arterial stiffness are among the key factors related to the development of atherogenesis due to smoking. Smoking cessation among patients with LEAD and the use of smoking cessation methods, including pharmacological treatment, are mandatory. Given that smoking cessation interventions remain underutilized. Therefore, in this narrative review we highlight the importance of incorporating smoking cessation treatments as part of the medical management of LEAD. Regulatory approaches to reduce tobacco use and support smoking cessation have the potential to reduce the burden of LEAD.

Background Transcarotid artery revascularization (TCAR) has emerged as an alternative therapeutic modality to carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) for the management of patients with carotid artery stenosis. However, certain issues regarding the indications and contraindications of TCAR remain unanswered or unresolved. The aim of this international, expert-based Delphi consensus document was to attempt to provide some guidance on these topics. Methods A 3-round Delphi consensus process was performed, including 29 experts. The aim of round 1 was to investigate the differing views and opinions of the participants. Round 2 was carried out after the results from the literature on each topic were provided to the participants. During round 3, the participants had the opportunity to finalize their vote. Results Most participants agreed that TCAR can or can probably or possibly be performed within 14 days of a cerebrovascular event, but it is best to avoid it in the first 48 hr. It was felt that TCAR cannot or should not replace TFCAS or CEA, as each procedure has specific indications and contraindications. Symptomatic patients >80 years should probably be treated with TCAR rather than with TFCAS. TCAR can or can probably be used for the treatment of restenosis following CEA or TFCAS. Finally, there is a need for a randomized controlled trial (RCT) to provide better evidence for the unresolved issues. Conclusions This Delphi consensus document attempted to assist the decision-making of physicians or interventionalists or vascular surgeons involved in the management of carotid stenosis patients. Furthermore, areas requiring additional research were identified. Future studies and RCTs should provide more evidence to address the unanswered questions regarding TCAR.

INTRODUCTION:The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. The current stratification of AsxCS patients based on the degree of stenosis alone does not always reflect ipsilateral ischemic stroke risk. We hypothesized that the presence of ≥1 "high-risk" carotid plaque feature may more accurately identify AsxCS patients at high risk for a future ipsilateral ischemic cerebrovascular event. EVIDENCE ACQUISITION:We reviewed the literature for evidence supporting an association between high-risk carotid plaque features with ipsilateral ischemic stroke risk. EVIDENCE SYNTHESIS:Certain carotid plaque features, such as intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, ulceration, or neovascularization, may more accurately stratify patients at low vs. high future stroke risk. The presence of ≥1 "high-risk" carotid plaque characteristics can inform decisions on the conservative vs. invasive management of AsxCS patients and target carotid revascularization procedures to those AsxCS patient subgroups at high stroke risk who are more likely to benefit from them. CONCLUSIONS:The present article presents the rationale supporting stratification of AsxCS patients not based on the degree of stenosis, but on the presence of one or more specific high-risk plaque features that increase the risk of a future ipsilateral ischemic cerebrovascular event.

Background: Autologous arteriovenous fistulae (AVF) are the vascular access (VA) of choice for most hemodialysis (HD) patients. Creating multidisciplinary VA teams (MDT) may improve access-related outcomes and patient survival. This study aims to evaluate our center’s MDT impact on matured AVFs. Methods: A retrospective case-control analysis was performed, comparing our center’s incident HD patients from years 2022 and 2019. An MDT was created in 2021. Patient data was collected from their electronic health record. The primary outcome was the VA typology used for HD initiation. Secondary outcomes were the prevalence of functioning AVFs 12 months after HD initiation and 24-month patient mortality. Clinical predictors of mortality were derived from a combined-year Cox proportional hazard regression model. Results: One hundred and sixty-nine and 184 incident HD patients were included from 2022 and 2019, respectively. There were no significant differences regarding demographic variables, comorbidities, prior nephrology and VA appointments, patients with VA constructed, and the number of non-programmed HD initiations. The number of patients starting HD with a matured AVF was higher in 2022 (50.9% vs 37.5%, p = 0.011), regardless of demographic variables and comorbidities. The number of functioning AVFs at the 12th month of HD was also greater in 2022 (85.2% vs 76.6%, p = 0.041). The cumulative number of AV interventions until 12 months post-HD was similar between years, with fewer AV construction surgeries in 2022 ( p < 0.001). Primary patency ( p = 0.020) and secondary patency ( p < 0.001) were higher in 2022. The 24-month cumulative mortality was lower in 2022 (17.8% vs 27.2%, p = 0.041), with no significant differences regarding the categorized cause of death. In our combined-cohort multivariable analysis, previous myocardial infarction (HR 1.86, p = 0.034) and dementia (HR 2.61, p = 0.016) were predictors of 24-month mortality. VA construction (HR 0.36, p = 0.013) was a negative predictor. Conclusion: In our center, the MDT creation was associated with a significantly increased number of matured AVFs at HD initiation and after 12 months of HD. Twenty-four-month patient mortality was lower post-MDT creation.

INTRODUCTION: Asymptomatic patients benefit from 3 to 6 hours of neurological and invasive blood pressure (BP) monitoring following carotid endarterectomy (CEA). Only a minority of patients will benefit from a prolonged stay in a high-dependency unit (HDU). The aim of this study was to externally validate previously described predictive variables of postoperative need for prolonged HDU stay. METHODS: To identify patients needing HDU stay, a composite outcome (CO) was created, including cardiac events, neurologic deterioration, postoperative aminergic/ventilatory support, and prolonged use of intravenous (IV) BP control therapy. A retrospective study was performed in one center: increased clamping time, preoperative systolic BP, systolic BP during pre-anesthetic procedure, maximum intraoperative mean arterial pressure (MAP), and eversion technique were significant predictors for the CO. We aimed to ascertain the validity of these factors in an independent population. Consecutive patients submitted to asymptomatic CEA in the same period were retrospectively analyzed in a second independent center. RESULTS: A total of 51 procedures were included (86.3% male; 69.2±7.9 years) and 11 (21.6%) presented with the CO. The presence of diabetes was associated with a higher incidence of the CO (p=0.011), and acetaminophen as intraoperative analgesia demonstrated an inverse correlation with the CO (p<0.001). Receiver operator characteristic curve analysis of predictive factors revealed that intraoperative maximum MAP had a strong correlation with the CO (area under the curve – AUC – 0.739, p=0.017). The remaining variables also did not reach statistical significance. CONCLUSIONS: In this analysis, the risk for CO development was consistently increased in patients who developed high MAP intra-operatively, highlighting the need for scrupulous BP management to reduce potential complications. However, we identified two previously unidentified associations: first, diabetics were more prone to develop complications and were more likely to benefit from HDU stay. Second, acetaminophen as intraoperative analgesia could have a protective role against CO development.

INTRODUCTION:Carotid endarterectomy is currently the gold standard treatment option for significant symptomatic carotid stenosis. Carotid artery stenting can be an alternative in selected patients, although with inferior results when compared with its open counterpart. Transcarotid artery revascularization (TCAR) emerged as a new option, with promising results. This study aims to systematically review current evidence of the safety of TCAR in patients with symptomatic carotid artery stenosis. EVIDENCE ACQUISITION:A systematic review of the literature was performed, according to PRISMA guidelines. Literature search was performed on the PubMed and Web of Science databases, which returned 178 studies. Eleven studies were selected. Data were extracted using predefined forms. EVIDENCE SYNTHESIS:A total of 28326 symptomatic patients undergoing TCAR were included for analysis. Reported TIA/stroke rates after TCAR ranged between 2.3-3.3% in-hospital and 1.2-4.3% at 30-days. Similarly, in-hospital post-operative mortality was reported in 0.5-0.7% of the cases, and 1-4.9% at 30 days. After 1 year, TIA/Stroke and death rates ranged between 3.5-3.7% and 2.5-13%, respectively. Postoperative cardiovascular events were observed in up to 2.9% of the patients among the included studies. Cranial nerve injuries were reported in up to 0.7% of the cases, while surgical and vascular access complications ranged between 1.2-6.1%. CONCLUSIONS:TCAR has shown promising results for significant symptomatic carotid stenosis treatment, and may be a relevant alternative to carotid endarterectomy, especially in high-risk patients. Further studies are required to assess the effectiveness of TCAR and its comparability with carotid endarterectomy.

INTRODUCTION:The optimal management of patients with asymptomatic (AsxCS) and symptomatic carotid stenosis (SxCS) is still debatable. The present article will discuss emerging technological advances for the diagnosis and management of patients with AsxCS. EVIDENCE ACQUISITION:PubMed/MedLine was searched until December 31, 2024 for studies in English discussing emerging technological advances in the diagnosis and management of patients with AsxCS. EVIDENCE SYNTHESIS:Several technological advances have recently been reported, among others, nanoplastics and microplastics, artificial intelligence and machine learning in predictive analytics for stroke prevention, digital twins for personalized monitoring, electronic tattoos for continuous non-invasive monitoring, stroke risk prediction through plaque morphology and late-phase contrast-enhanced ultrasound. A brief overview of each technological advance is presented and discussed. CONCLUSIONS:The technological advances discussed in the present article will aid the early diagnosis of AsxCS as well as the individualized optimal management of patients with AsxCS.

Diabetic microvascular complications (DmVCs) and chronic venous disease (CVD) share common risk factors and pathophysiological features. However, they are often assessed and managed as separate conditions. The study objective was to map the available clinical evidence of venoactive drugs (VADs), beyond their demonstrated effects on sign and symptoms of CVD, in the management of patients with diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN). We conducted a Scoping Review to map the clinical evidence on VADs recommended for treating CVD in the management of DR, DN and DPN to address VADs choices in clinics. PubMed and Cochrane Library databases were searched, studies in any language were included with no restriction on publication date. In total, 393 records were identified. Most included studies (N.=42) assessed clinical outcomes in DR (N.=33), followed by DN (N.=7) and DPN (N.=2). The median (range) publication date of the included studies was 2001 (1970-2022). Most studies were randomized trials (57%), followed by case series (17%), and case-control studies/systematic reviews (both 10%). Calcium dobesilate (CaD), was the most assessed VAD in DR (85%), DN (86%), and DPN (50%). CaD has shown significant improvements in DR and DN based on systematic-review data. Our findings suggest that VADs, in particular CaD, may represent a promising therapeutic option for the treatment of patients with both CVD and DmVC. Medical recommendations for VADs prescription should consider patients' microvascular status, evidence about VADs, as well as the multi-modal treatment approach.

Background: The optimal management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis is controversial and includes intensive medical management (i.e., best medical therapy [BMT]) with/without an additional carotid revascularization procedure (i.e., carotid endarterectomy [CEA], transfemoral carotid artery stenting [TFCAS] or TransCarotid Artery Revascularization [TCAR]). The aim of this international, expert-based, multispecialty Delphi Consensus document was to reconcile the conflicting views regarding the optimal management of AsxCS and SxCS patients. Methods: A three-round Delphi Consensus process was performed including 63 experts from Europe (n=37) and the United States (n=26). A total of 6 different clinical scenarios were identified involving patients with either AsxCS or SxCS. For each scenario, 5 treatment options were available: (i) BMT alone, (ii) BMT plus CEA, (iii) BMT plus TFCAS, (iv) BMT plus TCAR, or (v) BMT plus CEA/TFCAS/TCAR. Consensus was achieved when >70% of the Delphi Consensus participants agreed on a therapeutic approach. Results: Most participants concurred that BMT alone is not adequate for the management of a 70-year-old fit male or female patient with 80-99% AsxCS (52/63; 82.5% and 45/63; 71.5%, respectively). In contrast, most panelists would opt for BMT alone for an 80-year-old male AsxCS patient with several co-morbidities (48/63; 76.2%). The majority of participants would opt for BMT plus a carotid revascularization procedure for an 80-year-old male SxCS patient with a recent ipsilateral cerebrovascular event, an ipsilateral 70-99% SxCS and a 5-year predicted risk of ipsilateral ischemic event of 10% (54/63; 85.7%), 15% (59/63; 93.6%), or 20% (63/63; 100%). The opinion of U.S.-based participants varied from that of Europe-based respondents in some scenarios. Conclusions: The present Delphi Consensus document showed that a "one-size-fits-all" approach is not appropriate for patients with either AsxCS or SxCS. Patients should be stratified according to their future stroke risk and should be treated accordingly. ### Competing Interest Statement Dr. Michael C. Stoner has a Consultant agreement with Boston Scientific. Dr. Mahmoud B. Malas is a Consultant to Cordis and Bard. Dr. Peter A. Schneider is a Consultant to Surmodics, Medtronic, Boston Scientific, Cagent, Acotec, Abbott, Endologix, Shockwave, Healthcare Inroads, Inari and BD. Dr. Mark K. Eskandari is a paid consultant for W.L. Gore and Silkroad Medical (Boston Scientific). Dr. Meghan Dermody is a Consultant/speaker for Boston Scientific Vascular and Medtronic Aortic. Dr. Marc L. Schermerhorn is PI for Medtronic, Boston Scientific and Shape clinical trials. He also does research with Cook, Terumo and Gore. Dr. Gary Roubin is the Chair of the Interventional Management Committee of CREST-2. He is also InspireMD Inc. Director and stock holder. Dr. Sean P. Lyden is a Consultant for BD, Boston Scientific, Contego Medical, Cordis, Endologix, Inspire MD, Medtronic, Rapid Medical, Shockwave, Penumbra, Vivasure and Nectero. He has stock options in Inspire MD, Reva Medical and Centerline Biomedical. He is a Board Member for VIVA Physicians. He has performed Research Studies for Abbott, Endologix, Surmodics, W.L. Gore, Terumo Aortic, NIH, Boston Scientific, Merit, Contego Medical, Inspire MD, Reva Medical, Penumbra, Medalliance and Nectero. The other authors have no conflicts of interest. ### Funding Statement This work did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Not applicable I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data is available by Dr. Kosmas I. Paraskevas

Atherosclerosis is a chronic and progressive disease with a long preclinical (asymptomatic) period. The optimal management of patients with preclinical cardiovascular disease (CVD) includes behavioral counselling and lifestyle measures. Weight loss, regular exercise, interventions to modify sleep distubances and control of the modifiable cardiovascular risk factors (smoking, dyslipidemia, hypertension and diabetes mellitus), as well as adoption of a Mediterranean diet including 5 portions of vegetables and fruits per day, are of utmost importance in these patients. Timely initiation of appropriate medical therapy reduces cardiovascular events and disease progression. Medical therapy should be administered: (1) to lower blood pressure <130/80 mmHg in patients with hypertension (and even <120/80 mmHg if tolerated), (2) to reduce glycated hemoglobin values <7.0% (equivalent to <53 mmol/mol), and, (3) to lower low-density lipoprotein cholesterol values <70 mg/dL (1.8 mmol/L) for high-risk individuals and to <55 mg/dL (<1.4 mmol/L) for very high-risk patients. The present narrative review discusses the optimal management of individuals with preclinical cardiovascular disease (CVD), with a focus on carotid artery stenosis.

INTRODUCTION:The purpose of this review was to critically evaluate the current literature on AI applicability to developing prediction models for cerebrovascular events in patients with carotid artery stenosis using standardized tools. EVIDENCE ACQUISITION:A systematic review was performed in accordance with the Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Critical appraisal was conducted using PROBAST risk-of-bias and the TRIPOD-AI reporting adherence tools. EVIDENCE SYNTHESIS:A total of eight studies were included. Most studies were retrospective and single-center with unclear/high risk of bias and poor adherence to reporting standards. Discrimination area under the receiver operating characteristic curve (AUROC) ranged from 0.71-0.99 while software accuracy ranged from 0.725-0.95. Globally, AI prediction tools outperformed traditional regression model and were consistent in concluding that associating clinical and imageologic data reached the best accuracy and discrimination. Some studies identified risk factors inconsistent with our current understanding, such as high calcium burden in the carotid plaque. However, external validation and calibration data were scarce. CONCLUSIONS:Novel tools to predict individual prognosis and outcomes of patients with carotid artery stenosis would help improve patient care from a personalized medicine point of view. Up to date, studies on AI-based predictive models have identified potential risk factors we were previously unaware of. Although AI-based predictive models hold great promise, translation to real world practice remains limited.