Asymptomatic carotid stenosis and cognitive impairment.

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.

From varicose veins to venous thromboembolic events.

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.

Management and outcomes of calf deep vein thrombosis in patients with contraindication to full anticoagulation due to bleeding.

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.

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.

International Union of Angiology Position Statement on perioperative drug and hemostasis management in vascular surgery.

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.

Optimal management of asymptomatic carotid stenosis in 2021: the jury is still out. An international, multispecialty, expert review and position statement.

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.

Do we have a unified consensus on antithrombotic management of PAD?

Peripheral artery disease (PAD) is one of the most frequent manifestations of atherosclerosis with high rates of morbidity and mortality. Platelets and coagulation are involved in the progression of atherosclerosis and thromboembolic complications. PAD patients have increased prothrombotic potential, which includes platelet hyperaggregability and increased pro-coagulant state. Therefore, antithrombotic treatment is of utmost importance for the prevention of cardiovascular events in this group of patients. Aspirin is the basic antiplatelet drug, but with limited efficacy in PAD. In contrast to coronary artery disease, its effect on the prevention of cardiovascular events in PAD has been limited proven. Particularly in asymptomatic PAD, there is no evidence for risk reduction with aspirin. Clopidogrel and ticagrelor are more effective than aspirin. Clopidogrel is thus an effective alternative to aspirin for prevention of cardiovascular events in symptomatic PAD. In patients who are non-responders to clopidogrel, ticagrelor is indicated. Dual antiplatelet treatment (DAPT) with aspirin and ticagrelor in patients with coronary artery disease and concomitant PAD significantly decreased the rate of major adverse cardiovascular events, including adverse limb events. However, in the CHARISMA Trial, aspirin and clopidogrel were not more effective than aspirin alone and increased bleeding complications. Therefore, DAPT seems effective only in PAD accompanied by coronary artery disease. Anticoagulant treatment for symptomatic PAD with vitamin K antagonists alone or in combination with aspirin is not more effective than single antiplatelet treatment but increases the rate of major bleeding. Low dose rivaroxaban combined with aspirin in PAD patients significantly reduces cardiovascular events, including limb-threatening ischemia and limb amputations. Anticoagulation and antiplatelet treatment after percutaneous or surgical revascularization of PAD improve the patency of treated vessels. Aspirin with or without dipyridamole improved patency of infra-inguinal by-pass grafts at one year. The combination of clopidogrel with aspirin was more effective than aspirin alone in the prevention of prosthetic graft occlusions in patients undergoing below-knee by-pass-grafting. Oral vitamin K antagonists were not more effective than aspirin in the prevention of infra-inguinal by-pass occlusion. The combination of low dose rivaroxaban and aspirin was effective in preventing major adverse cardiovascular events and adverse limb events after infrainguinal endovascular or surgical revascularization in patients with intermittent claudication. However, the data on antithrombotic treatment after revascularization for limb-threatening ischemia is scanty and inconclusive. In conclusion: Antithrombotic treatment of PAD is a cornerstone for the management of these patients. Antiplatelet drugs prevent the initiation and progression of atherosclerosis and are effective also in the prevention of thromboembolic events. Simultaneous use of antiplatelet and anticoagulation drugs is accompanied by an increased risk of bleeding. However, combined treatment with aspirin and low-dose rivaroxaban is more effective than single antithrombotic treatment and safer than full-dose combined treatment.

Reasoned therapeutic protocol in outpatients with COVID-19.

BACKGROUND: Seventy percent of patients affected by SARS-COV-2 disease are asymptomatic or with symptoms that not required Hospitalization. A prodromal period lasting about 5 days can be identified. In this phase a patient with a positive swab for viral RNA may or may not evolve towards the phase of symptomatic disease. METHODS: In this paper we reviewed the literature related to COVID-19 therapy we propose a reasoned treatment protocols in outpatients according to the age and the comorbidity. RESULTS: The aim of this study was to reduce the impact of the virus by reducing its ability to attack cells and the inflammatory burden and the prothrombotic effects proposing two therapeutic schemes of proven efficacy according to the age of the patients and the comorbidities. CONCLUSIONS: We aimed to reduce worsening of clinical status and hospitalization while protecting patients at home.

How to manage patients with polyvascular atherosclerotic disease. Position paper of the International Union of Angiology.

Atherosclerosis is a systemic disease affecting multiple arterial territories. Patients with clinical atherosclerotic disease in one vascular bed are likely to have asymptomatic or symptomatic atherosclerotic lesions in other vascular beds. Specifically, peripheral arterial disease (PAD) often coexists with coronary and carotid disease. With progression of atherosclerotic disease in one vascular bed, the risk of clinical manifestations in other territories increases and the incidence of adverse cardiovascular events increases substantially with the number of affected vascular beds. Classical risk factors are associated with the development of polyvascular atherosclerotic disease (PVD) in different territories; however, to a different extent. Risk modification represents basic treatment of patients with PVD. All modifiable risk factors should be aggressively controlled by lifestyle modification and medication. Particular attention should be directed to patients with PAD who are often undertreated in spite of the proven benefits of guideline-based approach. There is currently no proof that identification of asymptomatic atherosclerosis and PVD improves clinical outcomes in patients who are already in prevention programs. Revascularization should be performed only in symptomatic vascular beds, using the least aggressive method according to consensual decision of a multidisciplinary vascular team.

Calf deep vein thrombosis: frequency, therapeutic management, early outcomes and all-causes mortality in a cohort of hospitalized patients.

BACKGROUND: Isolated distal deep vein thromboses (IDDVT) are frequent; however, their optimal management is still controversial. METHODS: We performed a retrospective study on inpatients undergoing ultrasound for suspected deep vein thrombosis (DVT) or with a particular risk profile, during 2016. This study aimed to assess the frequency of proximal deep vein thromboses (PDVT) and IDDVT; to evaluate therapeutic management and identify variables associated with early outcomes and mortality among IDDVT patients; to compare all-causes mortality between subjects with PDVT and IDDVT. RESULTS: Among 21594 patients hospitalized in the study period 251 IDDVT and 149 PDVT were diagnosed; the frequency was 1.2% and 0.7% respectively. 19% of IDDVT patients died compared to 25.5% of PDVT subjects (OR=0.72; 95% CI=0.44-1.17; P=0.19). In IDDVT patients, age ≥80, cancer and intracranial bleeding increased the risk of death (OR=2; 95% CI=1.07-3.75, P=0.001; OR=8.47; 95% CI=3.28-21.88, P=0.0000003; OR=2.33; 95% CI=1.18-4.58, P=0.0003). A significant association between intracranial hemorrhage and both proximal extension by using the Fisher's exact test (P=0.031; OR=16.11; 95% CI=0.80-321.2), and composite of propagation to popliteal or to other calf veins (OR=8.28, 95% CI=2.07-33 P=0.001) was observed. Standard anticoagulation significantly reduced the composite of propagation to popliteal or to other calf veins (OR=0.07; 95% CI=0.009-0.61, P=0.007), and all-causes mortality (OR=0.37; 95% CI=0.17-0.8; P=0.02), without a significant increase of bleeding. CONCLUSIONS: Among inpatients, IDDVT exceeded 60% of DVT. Mortality was not significantly different between IDDVT and PDVT subjects. Intracranial bleeding significantly increased the risk of propagation and death. Although standard anticoagulation decreased both these complications, further targeted studies are needed.

The vascular side of COVID-19 disease. Position paper of the International Union of Angiology.

The SARS-CoV-2 infection (COVID-19) is causing an ongoing pandemic and potentially fatal disease. Development of coagulopathy with thrombotic complications such as deep vein thrombosis and pulmonary embolism are emerging as factors for progression to severe disease and death. Also, a markedly increased level of D-dimer, a protein product of fibrin degradation, has been associated to mortality. Furthermore, activation of immune response due to virus infection may led to uncontrolled severe inflammation with damage to host cells and induction of endotheliitis and cellular apoptosis and pyroptosis. The use of low molecular weight heparin in early stage of the disease could prevent vascular complications and reduce the progression to severe stage of the disease. Aim of this paper was to summarize current evidence about vascular involvement in COVID-19 disease and potential antithrombotic therapy.

Venous hemodynamic changes in lower limb venous disease: the UIP consensus according to scientific evidence.

There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatmen by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.

A large Italian observational multicentre study on vascular ulcers of the lower limbs (Studio Ulcere Vascolari).

An observational study of 2 years was promoted by the Italian Association for Cutaneous Ulcers (AIUC) in order to monitor the epidemiology of leg ulcers, the trend of healing and the more frequent therapeutic approaches in lower limb ulcers. Fifty-nine sites in 14 different Italian regions involved in the study, with 1333 enrolled patients (1163 patients fully evaluated and followed up for 9 months). A prevalence of females (62%) was observed with a mean age of 70 years and a high rate of hypertension (62%), diabetes (38%) and obesity (29%). Venous ulcer was most frequent (55%), followed by mixed (25%) and diabetic (8·3%) ulcers. Basically, all patients received a local therapy (LT) (compression and advanced local therapies), while 63% of patients have an associated systemic pharmaceutical treatment. Ulcer healing rates progressively increased throughout the study and despite the type of observational study does not allow conclusions on the treatment, it was observed that the patients receiving additional systemic drugs were associated with a more rapid acceleration of healing rates of ulcers compared to LT alone (3 months: 39·7% versus 29·2%; 6 months: 62·0% versus 47·0%; 9 months: 74·7% versus 63·8%). In particular, the Studio Ulcere Vascolari (SUV) study showed that a combination treatment with sulodexide and compression therapy allows for a greater increase in the healing rates in venous ulcers.