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There is currently a degree of divergence among the main clinical practice guidelines on the management of risk factors for peripheral arterial disease (PAD). This project aims to gain understanding of the management of PAD risk factors in clinical practice and to reach a multidisciplinary consensus on the strategies to be followed in order to optimize its identification, treatment, and follow-up.A multidisciplinary consensus following the Delphi methodology.Professionals (n = 130) with extensive experience in PAD participated in this consultation. The results suggest that in order to optimize the control of risk factors, efforts should be aimed at: (1) promoting the involvement and awareness of all specialists in the identification of and screening for the disease; (2) guaranteeing the possibility of evaluating the ankle-brachial index (ABI) in all the medical specialties involved; (3) promoting strategies for patients to quit smoking through the use of drugs, programs, or referrals to specialized units; (4) promoting an appropriate Mediterranean-based diet and the prescription of daily exercise; (5) raising awareness of the importance of ensuring LDL cholesterol values below 70 mg/dL, especially in symptomatic but also in asymptomatic patients (55 mg/dL following the publication of the ESC/EAS guide); (6) recommending the use of antiplatelet therapy in asymptomatic patients with diabetes mellitus (DM) and/or a pathological ABI; and (7) protocolizing the annual evaluation of ABI in high-risk patients.This document presents the 22 agreed-upon strategies which are intended to help professionals optimize multidisciplinary management of PAD risk factors.

Objetivo: Se ha desarrollado una encuesta para comprender el conocimiento y la implementación actual del concepto de higiene de las heridas un año después de su difusión. También se analizaron los obstáculos para su implementación y los resultados. Método: La revista Journal of Wound Care (JWC), con la colaboración de ConvaTec, desarrolló una encuesta de 26 preguntas, compuesta por respuestas de opción múltiple y texto libre, que distribuyó globalmente por correo electrónico y en línea; la encuesta estuvo abierta unas 12 semanas. Debido a la naturaleza exploratoria de la investigación, se utilizó una técnica de muestreo no probabilístico. Los autores analizaron los resultados de la encuesta para sacar conclusiones de los datos. Resultados: Un total de 1478 participantes dio su consentimiento para el uso de sus datos combinados anonimizados. Casi el 90% era de Estados Unidos o el Reino Unido. La mayoría se desempeñaba como especialista en el cuidado de las heridas y estaba distribuido equitativamente entre centros de atención primaria y hospitales de agudos. El 66,6% había trabajado en el área de cuidado de las heridas durante más de 8 años. Los encuestados trabajaban con una amplia variedad de tipos de heridas. Más de la mitad (57,4%) había oído hablar del concepto de higiene de las heridas, y entre ellos, el 75,3% la había implementado; el 78,7% respondió que la aplicaba “siempre”, mientras que el 20,8% lo hacía “a veces”. Los tres principales obstáculos para su adopción fueron la confianza (39,0%), el deseo de que haya más estudios sobre la higiene de las heridas (25,7%) y la competencia (24,8%). En general, tras la implementación de la higiene de las heridas, el 80,3% informó que las tasas de cicatrización de sus pacientes habían mejorado. Conclusión: Los encuestados estuvieron totalmente de acuerdo en que la implementación de la higiene de las heridas es un método exitoso para el tratamiento del biofilm y un componente fundamental para mejorar las tasas de cicatrización en heridas de difícil cicatrización. Sin embargo, los obstáculos para su adopción e implementación demuestran que se necesitan cursos integrales de educación y capacitación, apoyo institucional para los cambios de política, protocolos, y más estudios clínicos para promover la higiene de las heridas.

Non-healing wounds are devastating for patients, potentially causing long-term morbidity and an impaired quality of life. They also incur a huge health economic burden for health-care services. Understanding of the causes of non-healing wounds has increased significantly. While the need to address the underlying aetiology has always been acknowledged, the role of biofilm in delaying or preventing healing is now accepted. There is a consensus on the need to debride the wound to remove biofilm and then prevent its reformation, to kickstart healing. The potential benefits of incorporating an antibiofilm component within the wound bed preparation framework are clear. However, such a strategy needs to be flexible enough so that it can be implemented by all practitioners, regardless of their expertise or specialty. Wound Hygiene does this. This supplement describes the Wound Hygiene protocol, and includes a selection of case studies on different wound types, demonstrating its ease of use and effectiveness in clinical practice.

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Objective: In light of the COVID-19 pandemic, which has resulted in changes to caseload management, access to training and education, and other additional pressures, a survey was developed to understand current awareness and implementation of the wound hygiene concept into practice one year on from its dissemination. Barriers to implementation and outcomes were also surveyed. Method: The 26-question survey, a mixture of multiple choice and free-text, was developed by the Journal of Wound Care projects team, in consultation with ConvaTec, and distributed globally via email and online; the survey was open for just over 12 weeks. Due to the exploratory nature of the research, non-probability sampling was used. The authors reviewed the outputs of the survey to draw conclusions from the data, with the support of a medical writer. Results: There were 1478 respondents who agreed to the use of their anonymised aggregated data. Nearly 90% were from the US or UK, and the majority worked in wound care specialist roles, equally distributed between community and acute care settings; 66.6% had been in wound care for more than 8 years. The respondents work across the spectrum of wound types. More than half (57.4%) had heard of the concept of wound hygiene, of whom 75.3% have implemented it; 78.7% answered that they ‘always’ apply wound hygiene and 20.8% ‘sometimes’ do so. The top three barriers to adoption were confidence (39.0%), the desire for more research (25.7%) and competence (24.8%). Overall, following implementation of wound hygiene, 80.3% reported that their patients' healing rates had improved. Conclusion: Respondents strongly agreed that implementing wound hygiene is a successful approach for biofilm management and a critical component for improving wound healing rates in hard-to-heal wounds. However, the barriers to its uptake and implementation demonstrate that comprehensive education and training, institutional support for policy and protocol changes, and more clinical research are needed to support wound hygiene.

Greater population life expectancy and consistent improvement in diagnostic techniques have increased the diagnosis of abdominal aortic aneurysms (AAAs) in the elderly population. The aim was to study the natural history of small (55 mm) incidental AAAs in octogenarian and nonagenarian patients to assess the need for follow up and/or invasive treatment.This was a retrospective analysis of a prospective registry. Patients ≥ 80 years old at the time of diagnosis of a55 mm AAA in 1988-2018 were selected. Clinical and anatomical characteristics were registered. Patients were divided in three groups: 30 - 39 mm, 40 - 49 mm, and 50 - 54 mm AAA. The outcome variables were aorto-iliac rupture, AAA reaching a surgical threshold (≥ 55 mm), and death. A descriptive statistical analysis was performed and life tables, Kaplan-Meier curves, and uni- and multivariable Cox regression were used.Three hundred and ten patients were included, 256 (82.6%) men, with mean index age of 84.5 years (standard deviation [SD] 3.5), and median follow up of 37.9 months (interquartile range [IQR] 18.2 - 65.4). Eighteen (5.8%) AAAs ruptured; four of these patients were operated on and only one survived. Sixty-two (20%) AAA reached a surgical size; eight were repaired electively, with 0% early mortality. The survival rates were 81%, 70%, and 38% at one, two, and five years. The rupture rates were 1%, 2%, and 6% and the AAAs reaching surgical threshold were 1%, 4%, and 19% for the same time periods. AAA size40 mm was an independent protective factor from rupture (0.13; 95% confidence interval [CI] 0.03 - 0.48), reaching surgical threshold (0.08; 95% CI 0.04 - 0.16) and death (0.63; 95% CI 0.42 - 0.95).The risk of late rupture of small incidental AAA diagnosed in octogenarian and nonagenarian patients is very small, especially when the AAA is40 mm in diameter. In contrast, global mortality is high. Conservative management seems sensible, with strict selection of the patients who would benefit from follow up and eventual repair.

European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis

Foreword. Wound Hygiene: the next stage Since a panel published the first consensus document on Wound Hygiene in March 2020, there has been a flurry of activity in support of this newly established concept in proactive wound healing. 1 The document concluded that all wounds, particularly hard-to-heal ones, will benefit from Wound Hygiene, which should be initiated at the first referral, following a full holistic assessment to identify the wound aetiology and comorbidities, and then implemented at every dressing change until full healing occurs. 1 The consensus has since been bolstered by educational webinars; competency-based skills training and support; development of international Wound Hygiene ambassadors; a survey of 1478 respondents, published in July 2021; 2 and a case study supplement, published in January 2022, featuring a range of wound types, anatomies and underlying conditions on the improvements in wound-healing progress that can be achieved. 3 Wound Hygiene has gained its own identity and is now a term in and of itself, that encompasses a 4-step protocol of care. It is an antibiofilm approach that is increasingly being used across wound care. The results of the survey 2 were particularly encouraging for seeing how far Wound Hygiene has come, and how quickly: More than half (57.4%) had heard of the concept of Wound Hygiene Of those, 75.3% have implemented Wound Hygiene Overall, following implementation of Wound Hygiene, 80.3% of respondents reported improved healing rates. 2 However, the top three barriers identified by the survey—lack of confidence, competence and research data—show that there is more to be done to support Wound Hygiene in practice. 2 As a result, a consensus panel of international key opinion leaders convened virtually in the summer of 2021 to discuss what has been done so far, the outputs of the survey, and ideas for addressing the unmet needs identified by the results. The result is this publication, which represents an addendum to the initial consensus document, broadening support for implementation of Wound Hygiene. This document will reflect on the reasons Wound Hygiene has been successful in its first two years of implementation, reiterating its DNA: Do not wait to treat hard-to-heal wounds Use a simple 4-step approach Enable all healthcare professionals to implement and use Wound Hygiene. The document will also discuss the evolution of the Wound Hygiene concept, focusing on how and when to implement Wound Hygiene on all tissue types of hard-to-heal wounds, and proposing what these are. The panel has expanded the framework in which Wound Hygiene is used, with the ultimate objective of introducing the concept of ‘embedding Wound Hygiene intro a proactive wound healing strategy.’ Key inefficiencies are often observed along the journeys of people living with hard-to-heal wounds. The limited number of specialised healthcare professionals and the resulting delays in reaching them may increase the likelihood of a hard-to-heal wound developing. In a world where so much is happening so quickly that we may, at times, feel powerless to drive change, the panel wants to provide further guidance to propel the use of Wound Hygiene. The concept of Wound Hygiene is resonating, and the panel wants you to know that in whatever region you work, in whatever area of clinical practice, you are enabled to make this change. Wielding the 4-step Wound Hygiene protocol consistently is a key action every healthcare professional in every care setting can take to tackle the global wound care crisis. Wound Hygiene has taken off—now, where do we want to land? In a place where Wound Hygiene is practised on all wounds, at every stage, until healing. The panel once again recognises that the community of global healthcare providers should consider their local standards and guidelines when applying the recommendations of this document. To this end, the panel has created a flexible 3-phase framework that situates Wound Hygiene as integral to proactive wound healing. The panel hopes you will continue to implement Wound Hygiene and see the benefits it can bring to people living with wounds, as well as those who care for them.

Background: Cardiovascular diseases (CVDs) are the main cause of death in first world countries, being atherosclerosis, a recurring process underlying their apparition. MicroRNAs (miRNAs) are small non-coding RNAs that modulate the expression of their target proteins. Therefore, they have emerged as key players in diseases like cancer, diabetes, or CVDs. Methods: Apolipoprotein E-deficient (ApoE-/-) mice fed a standard type diet (STD) or high fat diet (HFD) for 8 and 18 weeks was compared to wild type (WT) STD-fed groups for the same time. 18 miRNAs were selected (from Pubmed and GEO database) for their possible role in promoting atherosclerosis and were analysed by RT-qPCR in the aorta from the experimental model. Afterwards, the altered miRNAs in the aorta from 18 weeks-ApoE-/- mice were studied in human healthy aortic samples, human early aortic atherosclerotic plaques, and human advanced carotid atherosclerotic plaques. Results: From the 18 miRNAs analyzed, miR-155-5p was overexpressed and miR-143-3p was downregulated in mouse and human atherosclerotic lesions. In addition, a significant decrease of protein kinase B (AKT), target of miR-155-5p, and an increase of insulin-like growth factor type II receptor (IGF-IIR), target of miR-143-3p, were noted in aortic roots from ApoE-/- mice and in carotid plaques from ACA patients. Finally, both miRNAs were studied on vascular endothelial and smooth muscle cell lines. The overexpression of miR-155-5p reduced AKT levels and its phosphorylation in vascular smooth muscle cells. MiR-143-3p overexpression decreased IGF-IIR reducing apoptosis in vascular cells. Conclusions: Our results suggest that miR-155-5p and miR-143-3p may be implicated in insulin resistance and plaque instability by the modulation of their targets AKT and IGF-IIR, contributing to the progression of experimental and human atherosclerosis.Trial Registration: authorization numbers PFS09-007 and PI1442016.

Objectives Carotid stenosis patients are at risk of vascular events despite antiplatelet therapy. Data on prescribed antiplatelet regimens have not been comprehensively collated from trials to guide optimal therapy in this population. Methods This review was conducted in line with the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, Ovid, Embase, Web of Science, and Google Scholar from 1988 to 2018 were searched using the search terms “carotid stenosis”, “asymptomatic”, “symptomatic”, “antiplatelet”, and “anti-platelet” to identify randomised trials in patients with asymptomatic or symptomatic extracranial moderate–severe carotid stenosis on any form of antiplatelet therapy in which vascular events and pre specified composite outcome events were reported. Results Twenty-five studies were judged eligible for inclusion. Data from one randomised controlled trial showed no significant difference in benefit with aspirin versus placebo in asymptomatic carotid stenosis, but it is still reasonable to recommend aspirin (81–325 mg daily) for prevention of vascular events in these patients. Low to medium dose aspirin (81–325 mg daily) is superior to higher doses (>650 mg daily) at preventing recurrent vascular events in patients undergoing endarterectomy. Data from endovascular treatment (EVT) trials support peri-procedural treatment of asymptomatic and symptomatic patients with 81–325 mg of aspirin daily. The use of peri-procedural aspirin–clopidogrel in patients undergoing EVT is based on one pilot trial, but appears safe. Short-term aspirin–dipyridamole or aspirin–clopidogrel treatments are equally effective at reducing micro-embolic signals on transcranial Doppler ultrasound in patients with ≥50% symptomatic carotid stenosis. There is insufficient evidence to recommend routine aspirin–clopidogrel combination therapy to reduce the risk of recurrent clinical ischaemic events in patients with symptomatic moderate–severe carotid stenosis. Conclusions This comprehensive review outlines an evidence based approach to antiplatelet therapy in carotid stenosis patients. Future trials should randomise such patients to receive different antiplatelet regimens to assess their efficacy and safety and to optimise peri-procedural and long-term preventive treatment in this patient cohort.

Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia

Objective The aim of this paper was to provide recommendations for diagnosis and management in the setting of infection following open or endovascular reconstructions of the supra-aortic trunks. Methods A review of the Medline database was performed from 1997 to 2017 by a combined strategy of MeSh terms. Results The literature search identified 49 publications: 36 studies addressing prosthetic material infections and 13 studies addressing stent infections. A total of 140 cases of prosthetic material infections were reported, mostly involving carotid patches. Surgical treatment was mostly based on complete removal of the infected material followed by in situ arterial reconstruction (86 cases, 62.3%). Peri-operative complications included cranial nerve injury in 17 cases (12.5%), stroke in eight (6.7%), bleeding in four (2.9%), re-infection in five (3.6%), and cardiac failure in three cases (2.2%). Stent infections were reported in 12 patients: eight carotid stents, three subclavian stents and one tandem brachiocephalic subclavian stent. Treatment was not described for one case, was conservative in one case, consisted of stent removal with venous reconstruction in six cases, stent removal without reconstruction because of carotid thrombosis in two cases, and carotid embolisation in two cases. Complications included intra-operative death in one case (9.1%), stroke in two (18.2%), reinfection in one (9.1%), bleeding in one (9.1%), and cardiac failure in one case (9.1%). Conclusion Appropriate pre-operative imaging is mandatory and treatment modality should be determined by patient condition. Complete removal of the infected material, followed by in situ arterial reconstruction with venous material seems advisable, despite high morbidity. However, alternative strategies may be considered for fragile and high risk patients. A multidisciplinary approach is mandatory to ensure optimum results.

espanolIntroduccion: la arteria subclavia aberrante es la anomalia mas comun del arco aortico, aunque la clinica de disfagia lusoria aparece tan solo en el 0,5-2 % de los pacientes. No existe ningun consenso sobre su tratamiento. Caso clinico: se presenta el caso de una paciente de 86 anos con clinica de disfonia y disfagia de 1,5-2 anos de evolucion que asocia una perdida de peso de 10 kg en los ultimos 6 meses. En el escaner realizado durante el estudio se encuentra una arteria subclavia aberrante no dilatada que comprime el esofago a su paso retrocardial. Ademas, la paciente presentaba una estenosis del 60 % de la arteria carotida ipsilateral que le habia ocasionado un ictus 5 meses antes. Se realiza un bypass carotido-subclavio derecho con protesis PTFE de 6 mm y en la misma intervencion, tras el procedimiento anterior, se realiza una endarterectomia carotidea derecha y angioplastia quirurgica. El posoperatorio transcurrio sin complicaciones. La paciente se mantuvo asintomatica, sin eventos neurologicos; tampoco disfagia ni disfonia. Pudo retomar la ingesta normal de alimentos. En el CT de control a los 10 dias se observo la arteria subclavia derecha trombosada sin compresion residual, por lo que no se considero necesaria la exclusion de su origen con una endoprotesis toracica. Discusion: aunque en un primer momento se considero la posibilidad de realizar un tratamiento en dos tiempos (cirugia abierta y, posteriormente, endovascular toracico), el tratamiento quirurgico combinado permitio tratar la disfagia lusoria, asi como la estenosis carotidea sintomatica ipsilateral, durante la misma intervencion para no tener que someter a una paciente mayor a una cirugia excepcionalmente larga, ademas de omitir el uso de una endoprotesis toracica complementaria que finalmente no fue necesaria. EnglishIntroduction: the aberrant subclavian artery is the most common variation of the aortic arch but symptoms of dysphagia lusoria appear only in 0,5-2 % of the patients. There is no consensus on its treatment. Case report: we hereby present the case of an 86 year-old woman who had suffered dysphonia and dysphagia for 1.5-2 years associating a loss of 10 kg of weight in the last 6 months. An angioCT scan revealed a non-dilated aberrant right subclavian artery which compressed of the retrocardial esophagus, and a 60 % stenosis of the right carotid artery, which had caused an ipsilateral minor stroke 5 months before. We performed a right carotid-subclavian bypass using a 6 mm ePTFE graft, followed by a right carotid endarterectomy and Dacron patch angioplasty in the same procedure. The postoperative period was uneventful, the patient remained asymptomatic, with no neurological symptoms, dysphagia or dysphonia, and resumed normal oral intake. Ten days after the procedure the control CT revealed a thrombosed right subclavian artery with no residual esophageal compression, so an additional endovascular occlusion of the subclavian origin was deemed unnecessary. Discussion: although we first considered the possibility of performing a sequential hybrid treatment, with initial surgical bypass and secondary thoracic endovascular grafting, the combined open surgical technique allowed us to solve both the dysphagia lusoria and the symptomatic right carotid stenosis in one single procedure, and the complementary thoracic endografting was ultimately unnecessary.

Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

Abdominal aortic aneurysm (AAA) is a permanent dilation of the aorta due to excessive proteolytic, oxidative and inflammatory injury of the aortic wall. We aimed to identify novel mediators involved in AAA pathophysiology, which could lead to novel therapeutic approaches. For that purpose, plasma from four AAA patients and four controls were analysed by a label-free proteomic approach. Among identified proteins, paraoxonase-1 (PON1) was decreased in plasma of AAA patients compared with controls, which was further validated in a bigger cohort of samples by ELISA. The phenylesterase enzymatic activity of PON1 was also decreased in serum of AAA patients compared with controls. To address the potential role of PON1 as a mediator of AAA, experimental AAA was induced by aortic elastase perfusion in wild-type (WT) mice and human transgenic PON1 (HuTgPON1) mice. Similar to humans, PON1 activity was also decreased in serum of elastase-induced AAA mice compared with healthy mice. Interestingly, overexpression of PON1 was accompanied by smaller aortic dilation and higher elastin and vascular smooth muscle cell (VSMC) content in the AAA of HuTgPON1 compared with WT mice. Moreover, HuTgPON1 mice display decreased oxidative stress and apoptosis, as well as macrophage infiltration and monocyte chemoattractant protein-1 (MCP1) expression, in elastase-induced AAA. In conclusion, decreased circulating PON1 activity is associated with human and experimental AAA. PON1 overexpression in mice protects against AAA progression by reducing oxidative stress, apoptosis and inflammation, suggesting that strategies aimed at increasing PON1 activity could prevent AAA.

The European Society for Vascular Surgery (ESVS), in line with its mission, appointed the Vascular Access (VA) Writing Committee (WC) to write the current clinical practice guidelines document for surgeons and physicians who are involved in the care of patients with haemodialysis (HD) and VA. The goal of these Guidelines is to summarise and evaluate all the currently available evidence to assist physicians in selecting the best management strategies for all patients needing VA or for pathologies derived from a VA.

Carlos Lahoza,∗, Carlos Esteban Graciab, Leonardo Reinares Garciac, Sergi Bellmunt Montoyad, Angel Brea Hernandoe, Alvaro Fernandez Herederof, Manuel Suarez Tembrag, Marta Botas Velascoh, Carlos Guijarro i, Esther Bravo Ruiz j, Xavier Pintok, Melina Vega de Ceniga l y Guillermo Monux Ducajum, en representacion del grupo de prevencion secundaria de la Sociedad Espanola de Arteriosclerosis y de la seccion de medicina vascular de la Sociedad Espanola de Angiologia y Cirugia Vascular

Questions and Answers on Diagnosis and Management of Patients with Peripheral Arterial Diseases : A Companion Document of the 2017 ESC Guidelines for the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients (n=225) compared with the control group (n=100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA.

Background Ultrasound screening of abdominal aortic aneurysm (AAA) has proved to reduce mortality from AAA rupture and has been implemented in several countries. Recent reports show a decreasing prevalence of AAA in Western countries. We report the results from a screening program among 65-year-old men in a defined area in the North of Spain. Methods We invited the 1,413 men born in 1943 and registered in the health area under our care to participate in the study. We registered their medical history and cardiovascular risk factors and we performed an abdominal ultrasound scan. We diagnosed an AAA when the infrarenal aortic diameter was ≥3 cm. We performed univariate and multivariate analysis to assess independent factors associated with the development of an AAA, using logistic regression. Results The participation rate was 70.8%. The prevalence of active smoking, hypertension, diabetes, and hypercholesterolemia was 19.6%, 52.1%, 25.7%, and 76.9%, respectively. Including 3 previously known and repaired AAAs, the total prevalence of AAA was 4.7% ( n = 37). The mean diameter of the AAA was 35.7 ± 7.9 mm (range, 30–62 mm). Multivariate analysis confirmed the independent impact of active smoking (Exp[B], 3.47 [95% confidence interval {CI}: 1.67–7.22]), hypertension (Exp[B], 2.43 [95% CI: 1.08–5.45]), and peripheral arterial disease (Exp[B], 3.00 [95% CI: 1.16–7.80]) on the incidence of AAA. Conclusions The prevalence of AAA remains high in the studied area in the North of Spain. The potential benefit of lowering smoking rates has not been observed yet. The current international recommendations of screening for 65-year-old men are still applicable in our population.

OBJECTIVE: To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA). APPROACH AND RESULTS: Tissue-conditioned media from patients with AAA were analyzed by a mass spectrometry-based strategy using liquid chromatography coupled to tandem mass spectrometry. Global pathway analysis by Ingenuity software highlighted the presence of several circulating proteins, among them were proteins from the complement system. Complement C3 concentration and activation were assessed in plasma from AAA patients (small AAA, AAA diameter=3-5 cm and large AAA, AAA diameter >5 cm), showing decreased C3 levels and activation in large AAA patients. No association of a combination of single-nucleotide polymorphisms in complement genes between large and small AAA patients was observed. Intense extracellular C3 inmunostaining, along with C9, was observed in AAA thrombus. Analysis of C3 in AAA tissue homogenates and tissue-conditioned media showed increased levels of C3 in AAA thrombus, as well as proteolytic fragments (C3a/C3c/C3dg), suggesting its local deposition and activation. Finally, the functional role of local complement activation in polymorphonuclear (PMN) cell activation was tested, showing that C3 blockade by anti-C3 antibody was able to decrease thrombus-induced neutrophil chemotaxis and reactive oxygen species production. CONCLUSIONS: A decrease of systemic C3 concentration and activity in the later stages of AAA associated with local complement retention, consumption, and proteolysis in the thrombus could induce PMN chemotaxis and activation, playing a detrimental role in AAA progression. The article has been supported by the European Community, Fighting Aneurysmal Disease project (FP-7, HEALTH F2-2008–200647), the Spanish MICIN (SAF2010/21852), Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Red RIC (RD12/0042/00038), and biobancos (RD09/0076/00101), Fundación Lilly and Fundacion Pro Centro Nacional de Investigaciones. Sí

Resumen Fundamento y objetivo Analizar variables clinicas y serologicas (perfil lipidico, marcadores inflamatorios) como potenciales factores de riesgo para el desarrollo de eventos cardiovasculares y mortalidad a corto plazo en pacientes con claudicacion intermitente. Pacientes y metodo Incluimos todos los pacientes con diagnostico inicial de claudicacion intermitente vascular en nuestro centro durante 2005-2006. Analizamos datos clinicos, parametros serologicos (creatinina, colesterol total, colesterol unido a lipoproteinas de baja densidad [colesterol LDL], colesterol unido a lipoproteinas de alta densidad [colesterol HDL], apolipoproteina A1, apolipoproteina B100, lipoproteina(a), homocisteina, proteina C reactiva, velocidad de sedimentacion globular [VSG], fibrinogeno), eventos cardiovasculares y mortalidad durante el seguimiento a 1-3 anos. Resultados Incluimos 162 pacientes, de los que 143 (88,3%) eran varones. La edad media (DE) fue de 66 (10,4) anos (extremos 41-86), 76 (46,9%) eran fumadores activos, 96 (59,3%) hipertensos, 56 (34,6%) diabeticos y 129 (79,6%) hipercolesterolemicos. Registramos 16 (9,9%) eventos coronarios/cerebrovasculares, 18 (11,1%) eventos vasculares en extremidades inferiores y 9 (5,9%) muertes tardias durante el seguimiento (media de 18,2 [8] meses). La hipertension arterial fue el unico predictor de eventos coronarios o cerebrovasculares (p = 0,013); la cardiopatia y el colesterol HDL 20 mm/h a mortalidad (p = 0,008). Conclusiones Las cifras reducidas de colesterol HDL y elevadas de VSG han resultado factores de riesgo independientes para eventos vasculares perifericos y mortalidad a corto plazo.

Las enfermedades cardiovasculares son la primera causa de muerte en el mundo occidental. El proceso patologico que subyace a ellas es un engrosamiento de la pared arterial debido a la formacion de placas ateroscleroticas, las cuales se complican frecuentemente con un trombo y pueden dar lugar a sindrome coronario agudo o accidente cerebrovascular. Uno de los mayores retos de la medicina cardiovascular es encontrar la manera de predecir el riesgo de un sujeto de sufrir un evento trombotico agudo. En las ultimas decadas, hay un gran interes en la busqueda de biomarcadores diagnosticos y pronosticos que puedan ser identificados en sangre. Entre ellos, la proteina C reactiva es la mas conocida. Otros, como el ligando de CD40 soluble, pueden predecir eventos cardiovasculares. En cambio, hasta el momento no hay un biomarcador aceptado en la practica clinica. Actualmente, existen diversas tecnicas de alto rendimiento como la proteomica, que permite la deteccion de multiples biomarcadores potenciales. Estas aproximaciones pueden identificar en un futuro proximo nuevos biomarcadores que, junto con las tecnicas de imagen, pueden ayudar a mejorar la prediccion de eventos vasculares agudos.

There is increasing evidence of the importance of nutrition in the incidence, severity, and prognosis of peripheral arterial disease (PAD). PAD patients should be encouraged to reduce the consumption of dietary fat, saturated fat, cholesterol, and sodium, and to increase the daily intake of fiber, folate, and vitamins D and E, with a diet based on fruits, vegetables, nuts, and whole grains, low on meat and refined grain products, and with no added salt. Improving the everyday diet enhances the patient’s overall status and cardiovascular prognosis, and does not increase the number of pills prescribed. A systematic nutritional assessment should be included as part of the integral management of patients with critical limb ischemia, as anemia, iron, folate, and vitamins B12 and D deficiencies are common and can seriously affect patient outcome. To date, no solid recommendations can be offered regarding the systematic supplementation of folate, vitamins B or D, niacin, L-arginine, omega-3 essential fatty acids, oral amino acids, antioxidants, or any other specific compound, for either the prevention or the treatment of PAD until further evidence demonstrates efficacy.

Background Abdominal aortic aneurysms (AAAs) are currently followed with serial ultrasound or computed tomography scanning diameter measurements, but evidence shows that AAA expansion is mostly discontinuous and quite unpredictable in any given patient. A reliable predictive model of AAA growth and/or rupture risk could help individualize treatment, follow-up protocols, and cost-effectiveness. Our objective is to set a predictive model of short-term prospective AAA growth, after clinical, serologic, and anatomic data. Methods A prospective pilot cohort was designed. We recruited 96 consecutive, asymptomatic, infrarenal, atherosclerotic AAA patients. We registered clinical data (age, gender, cardiovascular risk factors, comorbidity, and statin intake), baseline aortic diameter, prospective 1-year AAA growth, and the concentration of metalloprotease-2, metalloprotease-9, cystatin C, α1-antitrypsin, myeloperoxidase, monocyte chemoattractant protein–1, homocysteine, D-dimer, plasmin–antiplasmin complex (PAP), and C-reactive protein in peripheral blood at the time of baseline assessment. With all these data, we elaborated predictive models for 1-year AAA growth assessed both as a continuous variable (mm/year) and a dichotomic one (defined as stability, if AAA growth rate was ≤2 mm/year, versus expansion, if AAA growth rate was >2 mm/year), using simple and multiple linear and logistic regression. Results The multivariate model confirmed the independent impact of D-dimer levels and chronic renal failure (CRF) on increasing AAA growth rates. Every increase by 1 ng/mL in the plasma concentration of D-dimer was related to a mean 1-year increase of 0.0062 mm in the AAA growth. Likewise, CRF increased the 1-year prospective AAA growth by a mean of 2.95 mm. When we assessed AAA growth as a dichotomic variable, the increase in the peripheral concentrations of PAP slightly increased the risk of AAA expansion (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00–1.02), but the presence of CRF increased the risk dramatically (OR: 14,523.62; 95% CI: 0–7.39E+40). Conclusions Plasma D-dimer and PAP levels seem promising biomarkers of short-term AAA activity. CRF is an important independent prognostic factor of AAA expansion. The dichotomic classification of AAA growth, as stability versus progression, can be useful in the development of management models and their clinical application.

Abdominal aortic aneurysm (AAA) is a significant health problem in the elderly. Efforts to limit the mortality rate depend on early detection and elective AAA repair. The benefit of early detection of AAAs, by ultrasound screening is limited since early repair of small AAA has been shown to provide no clinical advantage. There is currently no established pharmacotherapeutic treatment for small AAAs. In the first part of this review, we describe the potential mechanisms whereby statins can modulate the pathological processes associated to experimental and human AAA. Among them, statins are able to regulate leukocyte recruitment and immuno-inflammatory responses, platelet activation, oxidative stress, proteolysis and extracellular matrix breakdown. However, controversial results have been obtained in experimental models of AAA. In the second part of this review, we analyze the effect of statins in both, cardiovascular events on AAA patients and AAA growth. Although statin treatment is recommended for all AAA patients with the aim of reducing the incidence of cardiovascular events and death, controversial results have been shown between experimental and clinical studies regarding the potential preventive effect on AAA growth. One potential reason for these discrepancies could be related to the fact that statins reduce total cholesterol concentrations but do not modify HDL concentrations, the most sensitive predictor of AAA among lipid markers. In this respect, it could be of interest to test the effect of drugs modulating plasma HDL concentrations on AAA evolution.

Objective— In the search of novel biomarkers of abdominal aortic aneurysm (AAA) progression, proteins released by intraluminal thrombus (ILT) were analyzed by a differential proteomic approach. Methods and Results— Different layers (luminal/abluminal) of the ILT of AAA were incubated, and the proteins released were analyzed by 2-dimensional difference in-gel electrophoresis. Several differentially expressed proteins involved in main AAA pathological mechanisms (proteolysis, oxidative stress, and thrombosis) were identified by mass spectrometry. Among the proteins identified, peroxiredoxin-1 (PRX-1) was more released by the luminal layer compared with the abluminal layer of the ILT, which was further validated by Western blot, ELISA, and immunohistochemistry. We demonstrated increased PRX-1 serum levels in AAA patients compared with healthy subjects and also positive correlation among PRX-1 and AAA diameter, plasmin-antiplasmin, and myeloperoxidase levels. Finally, a prospective study revealed a positive correlation between PRX-1 serum levels and AAA expansion rate. Moreover, the combination of PRX-1 and AAA size had significantly additive value in predicting growth. Conclusion— Several proteins associated with AAA pathogenesis have been identified by a proteomic approach in ILT-conditioned medium. Among them, PRX-1 serum levels are increased in AAA patients and correlate with AAA size and growth rate, suggesting the potential use of PRX-1 as a biomarker for AAA evolution.

Cardiovascular disease is the principal cause of death in developed countries. The underlying pathological process is arterial wall thickening due to the formation of atherosclerotic plaque, which is frequently complicated by thrombus, thereby giving rise to the possibility of acute coronary syndrome or stroke. One of the major challenges in cardiovascular medicine is to find a way of predicting the risk that an individual will suffer an acute thrombotic event. During the last few decades, there has been considerable interest in finding diagnostic and prognostic biomarkers that can be detected in blood. Of these, C-reactive protein is the best known. Others, such as the soluble CD40 ligand, can be used to predict cardiovascular events. However, to date, no biomarker has been generally accepted for use in clinical practice. At present, there are a number of high-performance techniques, such as proteomics, that have the ability to detect multiple potential biomarkers. In the near future, these approaches may lead to the discovery of new biomarkers that, when used with imaging techniques, could help improve our ability to predict the occurrence of acute vascular events.

Neutrophil gelatinase-associated lipocalin (NGAL) plasma concentrations have been associated with cardiovascular diseases. We aimed to assess the association of NGAL with abdominal aortic aneurysm (AAA).NGAL concentrations were analyzed by Western blotting in conditioned medium of polymorphonuclear neutrophils (PMNs) from AAA patients (n=22) and controls (n=11), and also in aortic biopsies from AAA patients and healthy controls (n=10). Plasma NGAL concentrations were measured by ELISA in three groups of subjects from France (n=60), Spain (n=75) and Australia (n=100) and associated with AAA presence and growth.PMNs isolated from AAA patients secreted significantly greater amounts of NGAL than PMNs from controls. Luminal thrombus released large amounts of NGAL compared to abluminal AAA thrombus, AAA wall and healthy aortic media. Plasma NGAL concentrations were significantly higher in patients with AAA than controls from France [115 (78-200) vs. 94 (72-114) ng/ml, p0.001]. NGAL plasma concentrations in AAA patients from Spain correlated with other markers of thrombus activity (plasmin-antiplasmin complexes and D-dimer). Furthermore, a positive correlation between plasma NGAL and retrospective AAA growth (rho=0.4, p=0.01) was observed, which remained significant after adjusting for other risk factors. Plasma NGAL was only weakly associated with prospective growth in both Spanish and Australian patients.NGAL is released by PMNs and by the luminal part of AAA thrombus. NGAL plasma levels were increased in AAA patients compared with healthy subjects and correlated with retrospective AAA growth. Further studies in larger subjects groups are needed to confirm the association between NGAL and AAA presence and growth.