Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

INTRODUCTION: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. AREAS COVERED: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. EXPERT OPINION: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Novel Biomarkers and Imaging Indices for the "Vulnerable Patient" with Carotid Stenosis: A Single-Center Study.

BACKGROUND: We investigated the relationship of matrix metalloproteinases (MMPs), cardio-ankle vascular index (CAVI), and Gray-Scale Median (GSM) score with the severity and vulnerability of carotid atherosclerosis and major adverse cardiovascular events (MACE) during follow-up of carotid artery revascularization. METHODS: We enrolled 262 patients undergoing carotid revascularization therapy (GRT), 109 asymptomatic patients with low-grade carotid stenosis (40-70%) receiving conservative treatment (GCT), and 92 age- and sex-matched control subjects without carotid atherosclerosis (GCO). All participants underwent carotid ultrasound and we assessed at baseline clinical parameters, metabolic profile, CAVI, GSM, and circulating levels of hsCRP, MMP-3,-7,-9, and TIMP-1. RESULTS: Both GRT and GCT presented with elevated CAVI, MMPs, and TIMP-1 levels compared to GCO (p < 0.001). The escalation highly correlated to the presence of symptoms or paralleled the degree of carotid stenosis (p < 0.001). During follow-up (mean duration: 55 months), 51 GRT patients experienced MACE unrelated to the revascularization procedure. Within GRT, diabetes (HR: 2.07; CI: 1.55-2.78, p < 0.001), smoking (HR: 1.67; CI: 1.35-1.95, p < 0.001), high CAVI (HR: 1.22; CI: 1.09-1.43, p = 0.023) and MMP-9 (HR: 1.44; CI: 1.29-2.15, p = 0.005), and low GSM (HR: 1.40; CI: 1.16-2.12, p = 0.002) independently predicted MACE occurrences, despite the optimum medical therapy. CONCLUSIONS: Novel imaging and biochemical biomarkers were positively associated with atherosclerosis severity, while CAVI, MMP-9, and low GSM showed a positive, independent relationship with MACE after carotid revascularization, describing "vulnerable patients".

[The effects of carotid revascularization on mood symptoms and quality of life in patients with high - grade carotid stenosis].

Carotid occlusive disease has been related to ischaemic strokes and cerebral hypoperfusion, thus affecting patients' quality of life, mainly because of cognitive decline and depressive symptoms. Carotid revascularization techniques [carotid endarterectomy (CEA) and carotid artery stenting (CAS)] may, postoperatively, have a positive impact on patients' quality of life and mental condition, though there have been also presented elusive findings and controversial results. The aim of the present study is to evaluate the effect of carotid revascularization (CEA, CAS) on patients' psychological condition and quality of life through a baseline and follow-up examination. We present data of a group of 35 patients (age range:60-80 years, ΜA=70,26-SD=9,05) with severe, left or right, carotid artery stenosis (>75%), presented with or without symptoms, who underwent surgical treatment with CEA or CAS. Baseline and follow-up (6 months post-surgery) evaluation was conducted in order to assess patients' depressive symptoms and quality of life, through completion of the Beck Depression Inventory and WHOQOL-BREF Inventory, respectively. No statistically significant (p < 0,05) effect of the revascularization process on mood or quality of life assessment could be documented for our patients, regardless of the applied technique (CAS or CEA). Our study supports existing evidence that all of the traditional vascular risk factors represent active participants in the inflammatory process, which has also been implicated in the pathophysiology of depression as well as in pathogenesis of atherosclerotic processes. Thus we have to illuminate new links between the two nosological entities, in the crossroads of psychiatry, neurology and angiology, through the pathways of inflammatory reactions and endothelium dysfunctions. Even though the effects of carotid revascularization on patient's mood and quality of life, are often characterized by opposing results, pathophysiological processes of "vascular depression" and "post stroke depression" remain a promising interdisciplinary medical domain, sharing both scientific and clinical interests between the fields of neurosciences and vascular medicine. Our results, regarding the bilateral connection of depression and carotid artery disease, advocate a most probable causality link between atherosclerotic process and depressive symptoms, rather than justifying a direct association between depressive disorders and carotid stenosis and inferred cerebral blood flow reduction per se.

Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Optimal periprocedural antithrombotic treatment in carotid interventions: An international, multispecialty, expert review and position statement.

BACKGROUND: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recently published studies. METHODS: The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel. RESULTS: For asymptomatic patients, we recommend low-dose aspirin (75-100 mg/day) or clopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAPT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAPT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking. CONCLUSIONS: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAPT (ticagrelor instead of clopidogrel) should be evaluated in future trials.

International Union of Angiology Position Statement on no-option chronic limb threatening ischemia.

This position paper, written by members of International Union of Angiology (IUA) Youth Committee and senior experts, shows an overview of therapeutical approaches for patients with chronic limb-threatening ischemia (CLTI) and absence of 'standard' solutions for revascularization. The aim was to demonstrate the accurate management of the 'no-option' CLTI patient including the wound treatment and the rehabilitation, considering always the goal of the increase of quality of life of the patients.

[The relationship of carotid artery disease with mental and neurocognitive disorders].

Carotid stenosis constitutes a common vascular disease that significantly affects cerebral blood flow and thus is associated with patients' cognitive functions. Carotid revascularization techniques [carotid endarterectomy (CEA) and carotid artery stenting (CAS)] may benefit cognition, though there are opposing findings, reporting an apparent decrement in cognitive function, no effect, or an apparent improvement after revascularization. A great number of studies are trying to evaluate the effect of carotid revascularization (CEA, CAS) on patients' cognitive functions, as well as on their psychological condition and quality of life through a baseline and follow-up neuropsychological examination. Recent reviews refer only to the narrow limits of cognitive deficits that may be attributed to carotid stenosis, rather than elucidating the outfit of all aspects of mental and cognitive correlations. Most of those findings depict controversy in current literature as far as the neuropsychological effects of carotid revascularization techniques are concerned, while clinical entities of "vascular dementia" and "vascular depression", as well as intercurrent vascular risk factors are also addressed. This might be taken into consideration, when determining the optimal therapeutic strategy for tackling carotid artery occlusive disease, while best practice clinical decisions should be still focused on stroke prevention and symptoms alleviation, until further research on the field of neuroangiology presents undisputable conclusions regarding the underlying effects of revascularization on mood and cognition. Τhe neurovascular interface, as far as mental and neurocognitive impact of carotid stenosis is concerned, also, comprises, the conceptual pathophysiological entity of "atheroinflammation", underscoring the association of vascular lesions with cognitive impairment, major depressive disorder and bipolar disorder. Chronic recurrent ischemia and chronic low perfusion are also addressed from neurocognitive aspect, regarding therapeutic strategies that might be preferred so as to reduce the burden of chronic cerebrovascular disease in both symptomatic and asymptomatic patients, given the fact that inflammatory processes of vascular complexion underlie both neuroinflammation and atherosclerosis, affecting cerebral perfusion as well as cortical blood flow.

Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease.

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.

From Ancient Hatei to Hubris Syndrome in SARS-CoV-2 Health Crisis Management.

COVID-19 pandemic has highlighted, in a very inflictive way, the need for less hubristic political leadership, revealing the menaces of arrogant decision making of those in power. Hubris Syndrome is associated with power and it is more likely to manifest itself the longer the person exercises power and the greater the power he exercises, while our modern times 'Hatei' (the goddess that blinded ancient leaders committing hubris) may be called positive illusion enhancement due to prolonged exposure to power. Hatei might also blurs the decision makers' vision through a hormonal pathway, since hormones seem to affect risk taking, as well as through serotonin, which is also involved in the regulation of decision making and processing punishment-related information, deficiencies of which could be relevant to Hubris Syndrome. Other findings may provide information regarding the neuro-anatomical 'location' of Hatei, since fronto-striatal and limbic-striatal dopaminergic pathways have been identified as important regulators of impulsive behaviors. Therefore we might consider choosing political leaders and state officials whose less illusionary character is more likely to become non-flammable against the fire of hubris, in periods of crisis like the current COVID-19 Pandemic. Especially in SARS-CoV-2 era we should bring whatever scientific data there may be to tackle the intoxicating effects of power, keeping also in mind that there are no anti-hubris medication and that it is unlikely to have this social construct improved via pharmacology. Before establishing constitutional procedures for the early diagnosis of hubris as well as for the subsequent constrain of our leaders' power, we should focus on the criteria by which we elect them and maybe include the pre-existence of depressive diathesis among those criteria, especially if we consider that those leaders might have to handle tough situations like the COVID-19 pandemic outbreak, that require increased empathy in decision making.

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

The Association of Arterial Stiffness With Significant Carotid Atherosclerosis and Carotid Plaque Vulnerability.

Arterial stiffness and its valid index, the cardio-ankle vascular index (CAVI), have emerged as predictors of adverse cardiovascular outcomes. We investigated the relationship of the CAVI with significant carotid stenosis (> 50%) and the related cerebrovascular symptoms or carotid plaque echogenicity, assessed by ultrasound gray-scale median (GSM) score, at baseline and after carotid artery stenting (CAS). We prospectively enrolled 113 patients with carotid stenosis (70-99% for asymptomatic and > 50% for symptomatic participants) eligible for CAS. Age- and sex-matched individuals (n = 38) served as controls (CON). Clinical data, CAVI, and biochemical profile were obtained at baseline. Clinical assessment and CAVI measurement were performed 6 months after CAS. Compared with the CON group, the CAS group had a higher incidence of co-morbidities (diabetes, hypertension, and hyperlipidemia), higher CAVI values (9.94 ± 2.14 vs 7.85 ± .97 m/sec, P < .001), but a better lipid profile due to increased prescription of statins. The symptomatic CAS subgroup showed higher CAVI (P < .001), high-sensitivity C-reactive protein (P = .048), and osteoprotegerin (P = .002) levels than the asymptomatic one. In multivariate analysis, CAVI at baseline was independently associated with the presence of significant carotid atherosclerosis (ß = .695, P < .001), cerebrovascular events (ß = .474, P < .001), and GSM score (ß = -.275, P = .042). Raised CAVI values were independently associated with significant carotid stenosis and plaque vulnerability.