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The CEAP classification constitutes the most important progress in the classification of Chronic Venous Diseases (CVD). It was proposed in 1994 and adopted worldwide to facilitate meaningful communication about CVD and serve as a basis for more scientific analysis of management alternatives. This classification, based on correct diagnosis, was also expected to serve as a systematic guide in clinical investigation of patients, as an orderly documentation system and as a basis for decisions regarding appropriate treatment. It is complete and well structured, provides a large number of advantages and it is superior to previous classifications. Some of problems of CEAP classification have been solved during the last 10 years. An international consensus meeting in Rome in 2001 suggested definitions and refinements of the clinical classification, the C in CEAP, which were published in 2003. Finally in 2004, the International Working Group published the first complete revision of the CEAP classification. The changes include additions to, or refinements of, several definitions used in describing CVD, refinement of the C classification of CEAP, addition of the descriptor n (no venous abnormality identified), incorporation of the date of classification and level of clinical investigation. In addition the description of 'basic CEAP,' was introduced as a simpler alternative to the full 'advanced' CEAP classification. Many questions about CEAP classification have been resolved but other questions are still open; further work is necessary. [ABSTRACT FROM AUTHOR]

This article briefly discusses the risk factors for the development of lower extremity artery disease, namely smoking, diabetes mellitus, hyperlipidemia/dyslipidemia and hypertension. Each of these risk factors will be discussed in detail in forthcoming articles of the journal.

Diabetes mellitus (DM) is a major risk factor for lower extremity arterial disease (LEAD) and about 20% of symptomatic patients with LEAD have DM. In subjects with DM, LEAD is a cause of morbidity and mortality. DM typically causes complications in the form of macro- and microangiopathy. In these patients, macroangiopathy manifests as atherosclerosis like in non-diabetic patients. However, its course is accelerated due to accompanying risk factors like hyperlipidemia and hypertension, with cumulative effects. Other factors are also relevant such as inflammation, endothelial dysfunction, platelet activation, blood rheological properties, hypercoagulability, and factors stimulating vascular smooth muscle cell proliferation. Additionally, DM is a risk factor for restenosis and amputation. DM is strongly associated with femoral-popliteal and tibial LEAD, which manifests earlier in patients with DM and may progress more rapidly to critical limb ischemia. Diabetic microangiopathy is characterized by arteriolosclerosis and interstitial fibrosis which additionally affects progression and outcomes of angiopathy of lower limbs. Glycemic control particularly decreases microangiopathic complications, while prevention of macrovascular complications requires treatment of accompanying risk factors like hypertension and dyslipidemia.

Background: Complex femoropopliteal artery disease represents a challenge. The Supera stent holds the promise of improving the results of endovascular therapy for complex femoropopliteal disease., Aims: We aimed at appraising the early and long-term effectiveness of the Supera stent after successful subintimal angioplasty (SuperSUB strategy) for complex femoropopliteal lesions., Methods: We conducted a multicenter, prospective, single-arm observational study including consecutive patients at participating centers in whom Supera was implanted after successful subintimal angioplasty for complex femoropopliteal lesions., Results: A total of 92 patients were included Femoropopliteal arteries were the most common target, and lesion length was 261 ± 102 mm. Most procedures were technically demanding, with antegrade femoral access in 35 (38%) and retrograde distal access in 55 (60%). Supera stent length was 281 ± 111 mm, with 4, 5, and 6 mm devices being most commonly used: 32 (35%), 35 (38%), and 23 (25%), respectively. Technical success was achieved in 100% of subjects, as was clinical success (per subject), whereas procedural success (per subject) was obtained in 98%. At 24 months, freedom from clinically driven target lesion revascularization was 93%, whereas primary patency was 87%. When compared with a similar historical cohort, Supera stent use appeared to be associated with a reduction in resources., Conclusion: Use of Supera stent after successful subintimal recanalization of complex lower limb arterial lesions yields favorable procedural results, which are maintained over follow-up, and are associated also with a favorable resource use profile., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Disclosures D.P.M. has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk. J.F.M. receives funding from the United States National Institute of Neurologic Disorders and Stroke for work related to running the CREST-2 clinical trial (U01NS080168) and the CREST-2 Long-term Observational Extension study (U01NS119169). E.A.S. has received research grants from the United States Food and Drug Administration, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic and Philips; has received consulting/speaking fees from Abbott, Bayer, BD, Boston Scientific, Cook, Cordis, CSI, Inari, Infraredx, Medtronic, Philips, Shockwave and VentureMed. H.-H.E. is a local Principal Investigator for the ROADSTER 2 trial and a scientific committee member of SPACE-1, SPACE-2 and ACST-2. T.R. is funded by grants from the National Institutes of Health (R01 MD012467, R01 NS029993, R01NS040807, 1U24NS107267), and the National Center for Advancing Translational Sciences (UL1 TR002736, KL2 TR002737). J.S.M. has received institutional research grants from Abbott, Cook, Endologix, Gore and Medtronic., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are increasingly recognised for their role in cardiovascular (CV) physiology. The GH-IGF-1 axis plays an essential role in the development of the CV system as well as in the complex molecular network that regulates cardiac and endothelial structure and function. A considerable correlation between GH levels and CV mortality exists even among individuals in the general population without a notable deviation in the GHIGF- 1 axis functioning. In addition, over the last decades, evidence has demonstrated that pathologic conditions involving the GH-IGF-1 axis, as seen in GH excess to GH deficiency, are associated with an increased risk for CV morbidity and mortality. A significant part of that risk can be attributed to several accompanying comorbidities. In both conditions, disease control is associated with a consistent improvement of CV risk factors, reduction of CV mortality, and achievement of standardised mortality ratio similar to that of the general population. Data on the prevalence of peripheral arterial disease in patients with acromegaly or growth hormone deficiency and the effects of GH and IGF-1 levels on the disease progression is limited. In this review, we will consider the pivotal role of the GH-IGF-1 axis on CV system function, as well as the far-reaching consequences that arise when disorders within this axis occur, particularly in relation to the atherosclerosis process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hypothyroidism and hyperthyroidism, both overt and subclinical, are associated with increased risk of cardiovascular morbidity and mortality. The association between thyroid-stimulating hormone levels and cardiovascular risk has been demonstrated in large epidemiological studies and meta-analyses and is now considered a U-shaped curve. Several pathophysiological mechanisms linking thyroid and cardiovascular disease are known; however, specific clinical complications of peripheral arterial disease as endpoints of clinical trials have not been adequately investigated. The potential mechanisms linking hypothyroidism and peripheral arterial disease are endothelial dysfunction, blood pressure changes, dyslipidemia, and low-grade systemic inflammation. The potential mechanisms linking hyperthyroidism and peripheral arterial disease are hyperdynamic circulation, elevated systolic blood pressure, hypercoagulability, and possibly increased arterial inflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atherosclerotic cardiovascular disease (ASCVD) is defined as coronary heart disease (CHD), cerebrovascular disease, or lower extremity arterial disease (LEAD) also named peripheral arterial disease (PAD). ASCVD is considered to be of atherosclerotic origin and is the leading cause of morbidity and mortality mainly for individuals with diabetes mellitus (DM). In this consensus document of the International Union of Angiology the authors discuss epidemiology, risk factors, primary and secondary prophylaxis, the correlation between diabetes mellitus and LEAD, conservative and surgical treatment.

Vascular compression syndromes (VCS) are rare diseases, but they may cause significant symptoms interfering with the quality of life (QoL) of patients who are often in their younger age. Given their infrequent occurrence, multiform clinical and anatomical presentation, and absence of dedicated guidelines from scientific societies, further knowledge of these conditions is required to investigate and treat them using modern imaging and surgical (open or endovascular) techniques. This consensus document will focus on known VCS, affecting the arterial and venous system. The position paper, written by members of International Union of Angiology (IUA) Youth Committee and senior experts, will show an overview of pathophysiology, diagnostic, and therapeutical approaches for patients with VCS. Furthermore, this document will provide also unresolved issues that require more research that need to be addressed in the future.

Varicose veins (VVs) mostly represent benign disease. However, in some cases, they can lead to serious complications including deep venous thrombosis (DVT) and pulmonary embolism (PE). Besides deteriorated blood flow caused by VVs inflammation is most probably a common denominator of VVs and DVT, which promotes a procoagulant state and thrombus formation also in deep veins. Patients with VVs have increased levels of interleukins, the most specific inflammatory markers of vascular wall inflammation that promote coagulation. The studies showed that VVs may increase the risk for DVT. However, the evidence of the risk and incidence of DVT in patients with VVs and without additional risk factors is poor. The increased risk is associated with previous venous thromboembolism (VTE), malignancy, estrogen use, pregnancy and postpartum, hospitalization in the last 6 months, age, and obesity. Varicose veins represent also an increased risk for VTE during long-term immobilization and long air travel or road trip. Further, superficial venous thrombosis is related to an increased risk for DVT, particularly if the thrombus in the superficial vein extends close to the saphenofemoral or femoropopliteal junction. Increased risk for DVT is increased during and after invasive treatment of VVs. Thromboprophylaxis after invasive procedures is recommended in subjects older than 60 years and those with another thrombophilic state.

Background: This prospective observational study was aimed at assessing early outcomes of inpatients with isolated distal deep vein thrombosis (IDDVT) and coexisting bleeding., Methods: Patients received enoxaparin 4000 units daily or intermediate doses, and ultrasound surveillance (US). Primary outcomes were extension to the popliteal vein (PDVT) or symptomatic pulmonary embolism (PE), bleeding complications during the treatment and the composite of PDVT and bleeding complications. Secondary outcomes were recurrent IDDVTs and death., Results: 90/95 patients completed the study period (30 days). PDVT occurred in 2/41 (4.9%) and in 3/45 (6.7%) subjects receiving enoxaparin 4000 units and intermediate doses respectively (OR 1.39; 95% CI: 0.22-11; P=0.72). PE occurred in only one of the 4 untreated subjects (25% vs. 0 patients taking enoxaparin 4000 units or intermediate doses; P=1.0). Recurrent IDDVTs occurred in 29 subjects (32.2%), more frequently during enoxaparin 4000 (19/29, 65.5%). Four patients died (4.4%). Bleeding complications occurred in 8 subjects (8.9%), all treated with intermediate doses (0 vs. 17.8%; P=1.0). Enoxaparin 4000 units significantly reduced the risk of the composite outcome compared with higher doses (4.9% vs. 24.4%; OR 6.31; 95% CI: 1.56-42.65; P=0.02). Major trauma significantly increased the risk of PDVT (OR 20.92; 95% CI: 2.82-427.51, P=0.01; logistic regression P=0.01). Patients with major trauma are also at increased bleeding risk (OR 5; 95% CI: 1.06-23.76, P=0.04; logistic regression P=0.03)., Conclusions: Enoxaparin 4000 units daily, supported by US, may be an option for selected patients.

Introduction: The aim of this review was to assess the evidence supporting an association between asymptomatic carotid stenosis (ACS) with impaired cognitive function due to chronic cerebral hypoperfusion and/or silent cerebral embolization., Evidence Acquisition: PubMed/Medline, Embase and the Cochrane databases were searched up to December 1, 2022 to identify studies focusing on the association between ACS and cognitive function, as well as the mechanisms involved., Evidence Synthesis: A total of 49 studies were identified. The evidence supports an association between ACS and progressive cognitive deterioration. The mechanisms involved in the cognitive decline associated with ACS include cerebral hypoperfusion and silent cerebral embolization. Irrespective of the mechanism involved, severe ACS is associated with a progressive decline in several aspects of cognitive function, including global cognition, memory and executive function., Conclusions: Patients with ACS are at increased risk of developing a progressive decline in their cognitive function. The evidence from the present systematic review suggests that it may be inappropriate to consider ACS patients developing cognitive dysfunction as "asymptomatic". Besides stroke, myocardial infarction and death rates, future studies should include evaluation of cognitive function as part of their outcomes.

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., Competing Interests: Declaration of Competing Interest All authors are members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATS; available at www.FACTCATS.org) with the shared goal of optimizing stroke prevention. The views of particular FACTCATS do not necessarily reflect the views of other FACTCATS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Peripheral artery disease (PAD), defined as lower extremity arterial disease, constitutes an underestimated aspect of the menopause-associated risk of atherosclerotic cardiovascular disease (ASCVD). Accumulation of ASCVD risk factors, such as atherogenic dyslipidaemia, diabetes, and arterial hypertension, after the transition to menopause may contribute to atherosclerotic plaque formation in peripheral arteries. However, inconsistency exists among studies as to whether transition to menopause increases the risk of PAD, although early menopause (<45 years) or premature ovarian insufficiency may accelerate peripheral atherosclerotic plaque formation. Menopausal hormone therapy may decrease the risk of PAD if administered early ( i.e. , within the first 5-6 years after last menstruation), whereas it has no effect in women with established ASCVD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder in women of reproductive age. It presents with gynaecologic, metabolic, and psychologic manifestations. The dominant drivers of pathophysiology are hyperandrogenism and insulin resistance. Both conditions are related to cardiometabolic risk factors, such as obesity, hypertension, dyslipidaemia, hyperglycaemia, type 2 and gestational diabetes, nonalcoholic fatty liver disease and obstructive sleep apnoea. Women with PCOS of reproductive age consistently demonstrated an elevated risk of subclinical atherosclerosis, as indicated by different measurement methods, while findings for menopausal age groups exhibited mixed results. Translation of subclinical atherosclerosis into the increased incidence of peripheral arterial disease and major cardiovascular (CV) events is less clear. Although several expert groups have advised screening, the CV risk assessment and prevention of CV events are frequently underdiagnosed and overlooked aspects of the management of PCOS. A combination of lifestyle management and pharmacotherapy, including the promising new era of anti-obesity medicine, can lead to improvements in cardiometabolic health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Testosterone levels in men begin declining in the early years of adulthood, with a 1-2% reduction/year. Low testosterone levels in men are associated with obesity, metabolic syndrome, diabetes mellitus, dyslipidaemia, hypertension and increased cardiovascular mortality. However, observational studies of testosterone levels in males and their relationship with peripheral arterial disease (PAD) have yielded mixed results; only some cohorts show a clear association with low free testosterone levels. This discrepancy may, in part, be due to methodological issues with estimating free testosterone but also to different effects of testosterone on the vessel wall and metabolism. While testosterone improves glycaemic control, has anti-obesity effects and induces vasodilation, it also stimulates platelet aggregation and increases the haematocrit. Androgen deprivation treatment for advanced prostate cancer may be associated with elevated cardiovascular risk, as is testosterone abuse for performance enhancement. On the other hand, judicious treatment of male hypogonadism or testosterone treatment of trans-men appears to be safe., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.

Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one's predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options.

This position paper, written by members of International Union of Angiology (IUA) Youth Committee, shows an overview of coagulation system and laboratory tests, analysis of medical therapies (older and newer), medication discontinuation/restart recommendations, bridging therapy recommendations, and an overview of hemostatic agents used in the operating room.

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.

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., Competing Interests: Declaration of Competing Interest Dr. Mikhailidis has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk. Dr. Chaturvedi reports consulting for Astra Zeneca and BrainGate and serving as an Associate Editor for Stroke, and as an Editorial Board Member of Neurology and Journal of Stroke and Cerebrovascular Diseases. The other authors report no conflicts., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%-20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atherosclerosis has a long preclinical phase, and the risk of cardiovascular (CV) events may be high in asymptomatic subjects. Conventional risk factors provide information for the statistical probability of developing CV events, but they lack precision in asymptomatic subjects. This review aims to summarize the role of some widely publicized indicators of early atherosclerosis in predicting CV events. The earliest measurable indicator of the atherosclerotic process is endothelial dysfunction, measured by flow-mediated dilation (FMD) of the brachial artery. However, reduced FMD is a stronger predictor of future CV events in patients with existing CV disease than in apparently healthy persons. Alternatively, measurement of carotid artery intima-media thickness does not improve the predictive value of risk factor scores, while detection of asymptomatic atherosclerotic plaques in carotid or common femoral arteries by ultrasound indicates high CV risk. Coronary calcium is a robust and validated help in the estimation of vascular changes and risk, which may improve risk stratification beyond traditional risk factors with relatively low radiation exposure. Arterial stiffness of the aorta, measured as the carotid-femoral pulse wave velocity is an independent marker of CV risk at the population level, but it is not recommended as a routine procedure because of measurement difficulties. Low ankle-brachial index (ABI) indicates flow-limiting atherosclerosis in the lower limbs and indicates high CV risk, while normal ABI does not rule out advanced asymptomatic atherosclerosis. Novel circulating biomarkers are associated with the atherosclerotic process. However, because of limited specificity, their ability to improve risk classification at present remains low., (Copyright © 2022. Published by Elsevier B.V.)

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients <75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.