BACKGROUND:In venous malformations (VMs), postprocedural edema on T2-weighted (T2w) MRI can obscure true post-treatment changes, making reliable posttherapeutic imaging-based monitoring challenging. Current MRI evaluation is often qualitative and center-dependent, underscoring the need for standardized quantitative parameters. METHODS:We retrospectively analyzed patients with VMs treated at our hospital between 2018 and 2022 who underwent MRI with MR angiography (MRA) before and after ethanol sclerotherapy. VM volume was calculated from diameters measured in two orthogonal planes on T2w and MRA images. A new parameter, volumetric perfusion fraction (VPF), was calculated as the ratio of perfused MRA volume to total T2w volume. Parameters were compared using comparative tests and receiver operating characteristic (ROC) analysis reflecting each parameter's ability to distinguish baseline from post-sclerotherapy images. RESULTS:Thirty-six patients with VMs were included (median age 21 years; 7 - 59 years; 24 female; 66.7 %). Total malformation volume on T2w images decreased by 9.0 % (45.4 mL; 0.6 - 801.9 mL vs 30.9 mL; 0.1 - 802.4 mL; p = 0.056) after therapy, whereas perfused MRA volume decreased by 87.4 % (26.1 mL; 0.5 - 643.6 mL vs 4.5 mL; 0.0 - 352.4 mL; p < 0.001). VPF decreased by 68.1 % (74.0 %; 10.1 - 131.7 % vs 18.2 %; 0.0 - 85.3 %; p < 0.001) despite considerable interindividual variability. ROC analysis showed the strongest effect for VPF, with an area under the curve (AUC) of 0.91 (p < 0.001), followed by MRA-derived diameter and volume (AUC 0.75 and 0.79; both p < 0.001). T2w MRI parameters showed the lowest effect (AUC 0.57; p = 0.30). CONCLUSION:VPF showed the strongest discrimination of treatment effects compared with MRA and T2w measures. It may serve as a robust and objective MRI parameter for monitoring therapy-related changes in clinical routine and future trials.

Background:Pain is one of the most important symptoms affecting quality of life in patients with venous malformations. Alcohol embolization is a common approach among other treatment modalities. However, the benefits and complications of this therapy require rigorous evaluation in the face of emerging alternative treatments. The aim of this study was to evaluate the efficacy of alcohol embolization in pain management compared with non-invasive treatment, and to explore associated complications. Methods:We performed a retrospective, comparative study at the Vascular Malformation Center, University Hospital of Bern, from 2008 to 2022. Consecutive patients with peripheral venous malformations were included, one group underwent alcohol embolization and the other group received non-invasive treatment including counseling for compression stockings, physical therapy and anticoagulation. Decision to treat was made jointly by the clinician and the patient, after discussing the potential harms and benefits. Pain levels were measured using the 0-10 Numerical Rating Scale on every scheduled visit. Inverse probability of treatment weights were used to adjust for confounders such as severity of malformation indicated by number of tissues affected, localization, presence of hypertrophic tissue, history of thrombophlebitis, age, and level of pain at the initial visit. The primary outcome was change in maximal pain level, and secondary outcomes included changes in mean and minimal pain levels within 1 year of follow-up. Results:A total of 227 patients were included in the analysis, 86 in the intervention group and 141 in the control group. Over the course of one year, both the control and alcohol embolization groups experienced reductions in pain. The control group showed a reduction in maximal pain from 4.42 by 0.95 points, with an additional non-significant reduction of 0.99 points in the alcohol embolization group [estimate: -0.0027 per day, 95% confidence interval (CI): -0.0061, 0.0007, P=0.12]. However, alcohol embolization led to a more pronounced and significant reduction in mean and minimal pain, with additional reductions of 1.06 (-0.0029 per day, 95% CI: -0.0055, -0.0003, P=0.02) and 0.69 points per year (-0.0019 per day, 95% CI: -0.0035, -0.0004, P=0.01), respectively. Seven minor and five major complications occurred in the alcohol embolization group. Conclusions:Non-invasive treatment helps patients with venous malformations to manage maximal pain effectively. Alcohol embolization results in a faster and more pronounced reduction in mean and minimal pain levels, but we found no statistical evidence of an advantage of alcohol embolization for reducing maximal pain. Treatment efficacy did not appear to be influenced by gender, age, or previous treatment history. To adequately assess the efficacy of new therapies, future trials should include both disease-specific, patient-reported outcome measures and a control group.

Die akute Extremitätenischämie (ALI) ist eine Reduktion der arteriellen Perfusion mit potenzieller Bedrohung der Extremität und einer Symptomdauer von bis zu 14 Tagen. Die (ALI) ist ein vaskulärer Notfall. Die Mortalitäts (10 %)- und Amputationsraten (6–8 %) während des stationären Aufenthaltes sind hoch. Die häufigsten Ursachen sind kardial embolisch oder ein lokal thrombotischer Verschluss (in-situ Thrombose). Die Differenzierung der dilatativ-aneurysmatischen Gefässkrankheit als Ursache der (ALI) ist wichtig, da sich die Therapie unterscheidet. Eine primär lebensbedrohliche Sonderform ist der akute Verschluss der Aorta abdominalis (Leriche Syndrom). Pathophysiologisch sind das Ausmass der Hypoxämie und die Dauer für die Entstehung von Gewebeuntergang prognostisch entscheidend. Der Grad der Gewebeschädigung hängt von der Reichweite des Kollateralzirkulation ab. Systemisch können komplizierend eine Rhabdomyolyse, akutes Nierenversagen sowie ein konsekutives Lungenödem hinzukommen.

ZusammenfassungDie akute Extremitätenischämie (ALI) ist eine vaskuläre Notfallsituation. Die klinisch wichtigen Zeichen der ALI sind Schmerz (pain), Sensibilitätsstörung (paraesthesia), Pulslosigkeit (pulslessness), Hautblässe (palor), motorischer Ausfall (paralysis) und Schockzustand (prostration), die auch als die 6 P’s nach Pratt bezeichnet werden. Dringlichkeit und Prognose werden entsprechend des Rutherford Klassifikationssystems beurteilt. Die apparative Diagnostik darf keine relevante Verzögerung der Therapie mit sich führen. Die continuous wave (CW)-Dopplerdruckmessung auf Knöchelhöhe sowie die Duplexsonografie erlauben eine rasche Diagnostik am Patientenbett. Die kontrastmittelverstärkte computertomografische Angiografie ist aufgrund ihrer praktisch ubiquitären, durchgehenden Verfügbarkeit die häufigste bildgebende Notfalldiagnostik. Laborchemisch geben erhöhtes Kalium, Laktat, Myoglobin und Lactatdehydrogenase (LDH) Hinweise für eine bereits relevante ischämische Gewebeschädigung.

ZusammenfassungDie Behandlung der akuten Extremitätenischämie (ALI) sollte in Zentren mit umfassender Expertise in endovaskulärer wie chirurgischer Behandlung erfolgen und stellt immer eine Notfallsituation dar. Die Initialbehandlung umfasst eine Analgesie, ausreichende intravenöse Flüssigkeitszufuhr, Sauerstoffgabe, Anti-Trendelenburg-Position und intravenöse Gabe von unfraktioniertem Heparin (UFH). Das Management richtet sich nach dem Schweregrad der akuten Extremitätenischämie (ALI) entsprechend Rutherford Stadium. Die klassische chirurgische Behandlung ist die Thrombembolektomie nach Fogarty mit oder ohne Patchplastik. Die endovaskulären Therapieoptionen stehen aufgrund vergleichbarer Ergebnisse bei geringerer Mortalitätsrate zunehmend im Vordergrund. Technisch sind die Beherrschung der perkutanen loko-regionalen Katheterthrombolyse (catheter-directed thrombolysis, CDT), der perkutanen mechanischen Katheter-Thrombusaspiration (PMT, mit oder ohne Thrombolyse), und die Möglichkeit endovaskulär-chirurgische Hybridverfahren Grundvoraussetzungen zur Behandlung der akuten Extremitätenischämie (ALI).

Background: Venous malformation (VM) is the most frequent type of congenital vascular malformation. In terms of functional outcome local sclerotherapy remains the most important therapeutic tool. For planning and correct estimation and prevention of complications, an exact anatomical classification of the VM is crucial. Not only the drainage, as assessed in the established classification, but also the phlebographic aspect of the internal VM structure itself plays a decisive role. In order to integrate this aspect, we aim to validate a proposal for a revised phlebographic VM classification distinguishing non-lacunar (a) and lacunar (b) types. Methods: We retrospectively analyzed all patients with VM in whom a direct puncture phlebography was performed in our clinic between 2009 and 2018 to assess morphology and flow characteristics. Phlebographic assessment included: (I) differentiation of non-lacunar vs. lacunar type; (II) drainage assignment according to the existing classification; (III) adjusted classification combining both. Inter-reader agreement was measured in percentage as well as by the Cohen's kappa coefficient (kappa). Results: Overall 26 patients were classified as non-lacunar (a) and 41 patients as lacunar (b) VM. For this categorization, inter-reader agreement was 96% (kappa=0.91). Classical Puig classification into types I, II, III and IV showed 87% inter-reader agreement (kappa=0.78). For the adjusted classification adding the non-lacunar or lacunar characteristic to type I-IV an agreement of 82% (kappa=0.77) was achieved. Conclusions: Phlebographic differentiation into non-lacunar and lacunar VM is feasible and reliable to distinguish phenotypic subgroups of patients with VM. We therefore propose to integrate this parameter of the internal VM structure into the existing classification.

Arteriovenous malformations (AVM) are benign vascular anomalies prone to pain, bleeding, and progressive growth. AVM are mainly caused by mosaic pathogenic variants of the RAS-MAPK pathway. However, a causative variant is not identified in all patients. Using ultra-deep sequencing, we identified novel somatic RIT1 delins variants in lesional tissue of three AVM patients. RIT1 encodes a RAS-like protein that can modulate RAS-MAPK signaling. We expressed RIT1 variants in HEK293T cells, which led to a strong increase in ERK1/2 phosphorylation. Endothelial-specific mosaic overexpression of RIT1 delins in zebrafish embryos induced AVM formation, highlighting their functional importance in vascular development. Both ERK1/2 hyperactivation in vitro and AVM formation in vivo could be suppressed by pharmacological MEK inhibition. Treatment with the MEK inhibitor trametinib led to a significant decrease in bleeding episodes and AVM size in one patient. Our findings implicate RIT1 in AVM formation and provide a rationale for clinical trials with targeted treatments.

Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call “Whole Exome Genome Sequencing” (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7–2.0 times cheaper than standard WES (no-plexing), 1.8–2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.

Ankle Brachial Index Bare Metal Stent Coronary Artery Disease Confidence Interval Chronic Limb Threatening Ischaemia Cardiac Rehabilitation Computed Tomography Angiography Cardiovascular Dual Antiplatelet Therapy Drug Coated Balloon Drug Eluting Stent Digital Subtraction Angiography expanded PolyTetraFluoroEthylene European Society of Cardiology European Society for Vascular Surgery Guidelines Steering Committee Guideline Writing Committee Home Based Exercise Therapy Hazard Ratio Health Related Quality of Life Intermittent Claudication International Normalised Ratio Major Adverse Cardiovascular Events Major Adverse Limb Events Magnetic Resonance Angiography Odds Ratio Peripheral Arterial Disease Proprotein Convertase Subtilisin/Kexin type 9 Percutaneous Transluminal Angioplasty Patient Reported Outcome Measure Quality Adjusted Life Years Randomised Controlled Trial Risk Ratio Supervised Exercise Therapy Toe Brachial Index Toe Pressure The Active detection and Management of the Extension of atherothrombosis in high Risk coronary patients In comparison with standard of Care for coronary Atherosclerosis Bare Metal Stent Versus Paclitaxel Eluting Stent in the Setting of Primary Stenting of Intermediate Length Femoropopliteal Lesions BIOTRONIK’s First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularisation of infrapopliteal arteries CANagliflozin cardioVascular Assessment Study Clopidogrel versus vs.Aspirin in Patients at Risk of Ischaemic Events Clopidogrel and AcetylSalicylic acid in bypass surgery for Peripheral ARterial disease Cilostazol:A STudy in Long-term Effects Comparison and Evaluation of Cardiac Biomarkers in Patients with Intermittent Claudication Claudication:Exercise Vs. Endoluminal Revascularisation Covered Versus vs. Balloon Expandable Stent Trial the Danish Cardiovascular Screening trial Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease trial Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes Dutch Iliac Stent trial:COVERed balloon-expandable versus vs.uncovered balloon-expandable stents in the common iliac artery Bypass Oral anticoagulants or Aspirin Trial Comparing ELUVIA Versus vs.Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes Empagliflozin in Heart Failure with a Preserved Ejection Fraction Ticagrelor versus vs. Clopidogrel in Symptomatic Peripheral Artery Disease Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk German Epidemiological Trial on Ankle Brachial Index Heart Outcomes Prevention Evaluation Heart Protection Study The Nord-Trøndelag Health Survey Self-Expanding Versus vs.Balloon-Expandable Stents for Iliac Artery Occlusive Disease Invasive revascularisation or not in intermittent claudication Management of peripheral arterial interventions with mono or dual antiplatelet therapy Self-Assessment Method for Statin side-effects Or Nocebo Prevalence of peripheral Arterial disease in patients with a non-high cardiovascular disease risk, with No overt vascular Diseases nOR diAbetes mellitus Prevention Of Progression of Arterial Disease And Diabetes PAD Awareness, Risk, and Treatment: NEw Resources for Survival Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome Stents versus vs.angioplasty for the treatment of iliac artery occlusions Supervised Exercise Therapy vs. Endovascular Revascularisation for Intermittent Claudication Caused by Iliac Artery Obstruction Viborg Vascular Trial VIABAHN endoprosthesis versus vs.bare nitinol stent implantation for complex superficial femoral artery occlusive disease Viabahn endoprosthesis with PROPATEN bioactive surface versus vs.bare nitinol stent in the treatment of long lesions in superficial femoral artery occlusive disease Rivaroxaban in Peripheral Artery Disease after Revascularisation YUKON-drug-eluting Stent Below The Knee ZILVER PTX Stent versus vs.Bypass Surgery in Femoropopliteal Lesions Zilver PTX randomised trial of paclitaxel-eluting stents for femoropopliteal artery disease The European Society for Vascular Surgery (ESVS) continuously develops clinical practice guidelines for patients with vascular diseases. This is the first guideline that specifically covers the diagnosis and treatment of patients with atherosclerotic lower extremity peripheral arterial disease (PAD, see also section 2.1) falling within the following clinical stages: (1) asymptomatic lower limb PAD (Rutherford grade 0/Fontaine stage I); and (2) intermittent claudication (IC, Rutherford grade I–III/Fontaine stage IIa and IIb). Thus, the management of patients with chronic limb threatening ischaemia (CLTI) falls outside the primary purpose of this guideline, as the management of such patients is already covered by other recent guidelines from the Society.1Conte M.S. Bradbury A.W. Kolh P. White J.V. Dick F. Fitridge R. et al.Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia.Eur J Vasc Endovasc Surg. 2019; 58: S1-S109Abstract Full Text Full Text PDF PubMed Scopus (648) Google Scholar Throughout the guideline, the term lower limb PAD refers to both aforementioned patient categories, whereas the terms asymptomatic PAD and IC are used where a certain section or recommendation only applies to that particular subcategory. Within the context of this guideline, the term PAD includes atherosclerotic disease from the infrarenal aorta to the toes. The primary aim of the guideline is to assist clinicians and patients in their selection of an optimal diagnostic and therapeutic pathway for PAD during patient centred shared decision making. A secondary aim is to contribute to an aligned management and research process of the disease across European countries and globally. Both the diagnostic and the therapeutic landscapes have evolved markedly within the PAD space during recent years with the introduction of new diagnostic modalities, imaging protocols, and therapeutic options. These include increased understanding and utilisation of non-interventional treatment options such as exercise therapy and secondary preventive pharmacotherapy and continuous advancements in endovascular therapeutic options that are becoming available to an increasing number of PAD patients. The scope of this guideline is to provide comprehensive, evidence based and clear recommendations on as many as possible of the different steps and decisions that fall within the clinical PAD patient management process. The term patient as used in the guideline is all encompassing, including people of all sex identities, and in general, these guidelines apply to adults over the age of 18 years. The clinician responsible for a PAD patient’s care will also differ by country, and will among others include vascular surgeons, angiologists, cardiologists, interventional radiologists, vascular physicians, primary care physicians, and exercise rehabilitation specialists. The guidelines were therefore developed by a multidisciplinary group of specialists in the field (see Appendix B) to promote a high standard of care based on the highest quality evidence available. This guideline should not be considered as a legal standard of care. The document provides guidance and support, and the choice of therapy will ultimately depend on the individual patient and treatment setting and fall within the responsibility of the treating physician. All ESVS guidelines, including app based smartphone and tablet versions, can be downloaded free of charge from the ESVS website (https://www.esvs.org/journal/guidelines/). The AGREE reporting standards for clinical practice guidelines were used throughout the guideline process and the AGREE II checklist is included as supplementary material (Appendix A).2Brouwers M.C. Kerkvliet K. Spithoff K. AGREE Next Steps ConsortiumThe AGREE Reporting Checklist: a tool to improve reporting of clinical practice guidelines.BMJ. 2016; 352: i1152Crossref PubMed Scopus (436) Google Scholar The development of these guidelines also followed the principal steps suggested for the ESVS guidelines development cycle, and was further informed by the ESVS Clinical Practice Guideline Development Scheme.3Antoniou G.A. Bastos Goncalves F. Bjorck M. Chakfe N. Coscas R. Dias N.V. et al.Editor's Choice - European Society for Vascular Surgery Clinical Practice Guideline Development Scheme: An Overview of Evidence Quality Assessment Methods, Evidence to Decision Frameworks, and Reporting Standards in Guideline Development.Eur J Vasc Endovasc Surg. 2022; 63: 791-799Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Members of the Guideline Writing Committee (GWC) were selected by the guideline chairs in collaboration with the ESVS Guideline Steering Committee (GSC) to represent an expert clinician group deeply involved in the management of PAD. This included representation from the disciplines of vascular surgery, angiology, physiotherapy, and vascular medicine (Appendix A). Members of the GWC have provided annual disclosure statements regarding relationships which might be perceived as conflicts of interest. These are available from ESVS headquarters upon request ([email protected]). Members of the GWC received no financial support from any pharmaceutical, medical device, or industry body to develop these guidelines. Videoconference software support along with travel and accommodation costs for mandatory meetings to develop the guideline were funded by the ESVS. The ESVS GSC was responsible for undertaking the review process which also included several independent external experts outside of the ESVS organisation. The final version was checked and approved by all members of both the GWC and the GSC. Following the completion of the second draft of the guideline on 15 January 2022, the GWC sent out the Guideline draft for review by the Swedish Heart and Lung Association (https://www.hjart-lung.se/om-oss/about-us/); a non-profit Swedish national patient organisation formed in 1939 that strives to improve the quality of life for persons with cardiovascular and lung diseases and works to ensure that patients with heart, vascular, and lung disease receive the care they need. This organisation was invited to review and provide comments from the patient and public perspectives on the full guideline content. After reading through the guideline document the response received stated that, as the organisation does not have medically trained personnel, neither among elected representatives nor civil servants, they could not comment on the specific medical content of the guidelines. They, however, welcomed the work done by the ESVS to design a compilation of knowledge, and in the guidelines propose the best possible care and treatment, based on science and clinical experience. Overall, the guideline content received a positive opinion from the patient organisation. The GWC held an introductory meeting on 23 and 24 June 2021 by video conference, where the list of topics and author assignments was determined by consensual agreement. The GWC met monthly by videoconference to discuss the writing process and any ongoing issues. After the first draft was completed and internally reviewed, the GWC met again on 21 and 22 April 2022 to review and approve the wording and content of each recommendation. If any of the GWC members disagreed with the content of a particular recommendation during this meeting, an open vote was held (where all GWC members participated and had the same voting rights) where a simple majority decision was decisive for acceptance of the recommendation. Detailed search strategies for the different topic specific sections of the guideline are available in Supplementary material. Members of the GWC performed literature searches in Medline/PubMed, Embase, and the Cochrane Library from inception up to the date specified in the search for peer reviewed publications. Hand searching of included references was also performed. As per the ESVS guideline development process cycle, all systematic literature searches were last updated in November 2022 when the GWC worked with the first revision of the guideline draft. The last literature search was done in July 2023. Selection of studies for inclusion was based on the titles and abstracts of retrieved studies. The selection process followed the pyramid of evidence with systematic review and meta-analysis of randomised trials at the top, followed by individual randomised trials, meta-analysis of observational studies, and finally observational studies. Case reports, abstracts, and in vitro studies were excluded leaving expert opinion at the base of the pyramid. Other guideline documents were considered only if they applied a systematic approach for literature searches and or produced their own meta-analyses of existing literature. For section 3.3 where no suitable systematic review or consensus document was available, an extensive DELPHI expert consensus process on the use of patient reported outcome measures was arranged and published separately to support this part of the guideline.4Arndt H. Nordanstig J. Bertges D.J. Budtz-Lilly J. Venermo M. Espada C.L. et al.A Delphi Consensus on patient reported outcomes for registries and trials including patients with intermittent claudication: recommendations and reporting standard.Eur J Vasc Endovasc Surg. 2022; 64: 526-533Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar For section 6.4 of the guidelines where there was no appropriate systematic review and meta-analysis available, such a study was performed by members of the GWC.5Koeckerling D. Raguindin P.F. Kastrati L. Bernhard S. Barker J. Quiroga Centeno A.C. et al.Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis.Eur Heart J. 2023; 44: 935-950Google Scholar The studies that underpin each recommendation are shown directly in the individual recommendation table, and further details are given for each in more comprehensive tables of evidence Supplementary material. The European Society of Cardiology (ESC) system was used for grading the level of evidence and the accompanying class of each recommendation. For each guideline recommendation, the level of evidence was graded from A to C (Table 1) with A being the highest. The strength (class) of each recommendation was graded from I to III with I as the strongest (Table 2). The class II subcategory was also further subcategorised into IIa and IIb based on an overall assessment of the strength and robustness of available evidence alongside concurrent clinical experience and expert consensus opinion within the GWC.Table 1Levels of evidence adapted from the European Society of Cardiology evidence grading system.Level of Evidence AData derived from multiple randomised trials or meta-analyses of randomised trialsLevel of Evidence BData derived from a single randomised trial or large non-randomised studiesLevel of Evidence CConsensus opinion of experts and or small studies, retrospective studies, registries Open table in a new tab Table 2Class of recommendations from the European Society of Cardiology evidence grading system.ClassDefinitionWordingIEvidence and or general agreement that a given treatment or procedure is beneficial, useful, effectiveis recommendedIIaConflicting evidence and or divergence of opinion about the usefulness or efficacy of the given treatment or procedure: weight of evidence or opinion is in favour of usefulness or efficacyshould be consideredIIbConflicting evidence and or divergence of opinion about the usefulness or efficacy of the given treatment or procedure: usefulness or efficacy is less well established by evidence or opinionmay be consideredIIIEvidence or general agreement that a given treatment or procedure is not useful or effective and in some cases may be harmfulis not recommended, should not be done Open table in a new tab This is the first ESVS guideline focusing on asymptomatic PAD and IC. However, the ESC/ESVS 2017 Guidelines on the Diagnosis and Treatment of PAD included several relevant sections and recommendations that potentially overlap with this guideline.6Aboyans V. Ricco J.B. Bartelink M.E.L. Bjorck M. Brodmann M. Cohnert T. et al.Editor's Choice - 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2018; 55: 305-368Abstract Full Text Full Text PDF PubMed Scopus (608) Google Scholar Furthermore, this guideline does not cover acute lower limb PAD presentations, as these are already covered by the ESVS 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia.7Bjorck M. Earnshaw J.J. Acosta S. Bastos Goncalves F. Cochennec F. Debus E.S. et al.Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia.Eur J Vasc Endovasc Surg. 2020; 59: 173-218Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar The ESVS 2023 Clinical Practice Guidelines on Antithrombotic Therapy for Vascular Diseases contains comprehensive recommendations on antithrombotic therapies for both asymptomatic PAD and IC patients, and the recommendations from that guideline are aligned with this as far as possible; however, an updated literature search was done on this topic to account for potential new evidence that may have emerged following the publication of the antithrombotic guideline. When this guideline changes or updates a previous recommendation from any of these previous guidelines, it is discussed in the relevant section, and all changed or updated recommendations are also briefly summarised below (Table 3).Table 3Brief overview of differences between previous cardiovascular guideline recommendations and this guideline.GuidelineYear of printed publicationRecommendation in previous guidelinesESVS lower limb PAD and intermittent claudication guideline recommendationReasons for differencesCanadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease2022We suggest against routine PAD testing for inferring global cardiovascular risk, in patients without symptoms of PAD, who have clinically symptomatic atherosclerosis in another vascular territory (Weak Recommendation;Moderate quality evidence).Recommendation 4:For clinically asymptomatic individuals at increased risk of lower limb peripheral arterial disease, focused screening for peripheral arterial disease with ankle brachial index measurements based on the lowest recorded ankle pressure may be considered, to support secondary prevention strategies. (IIb, B)They suggest against screening in patients who already manifested atherosclerotic symptoms from other vascular territories than the legs (and thus are already considered having a high cardiovascular risk).European Society for Vascular Medicine (ESVM) Guideline on Peripheral Arterial Disease2019It is recommended that patients with diabetes should be screened for PAD (Class I Level B)Recommendation 4:For clinically asymptomatic individuals at increased risk of lower limb peripheral arterial disease, focused screening for peripheral arterial disease with ankle brachial index measurements based on the lowest recorded ankle pressure may be considered, to support secondary prevention strategies. (IIb, B)They recommend PAD screening only for patients with diabetes whereas the ESVS guideline suggest focused screening in a broader high risk population (see section 3.1.1.2).2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)2018In patients with coronary artery disease, screening for lower extremity atherosclerotic disease (LEAD) by ABI measurement may be considered for risk stratification. (IIb, B)Screening for LEAD may be considered in patients with heart failure. (IIb, C)Recommendation 4:For clinically asymptomatic individuals at increased risk of lower limb peripheral arterial disease, focused screening for peripheral arterial disease with ankle brachial index measurements based on the lowest recorded ankle pressure may be considered, to support secondary prevention strategies. (IIb, B)They recommend PAD screening only for patients with manifest coronary artery disease or heart failure whereas this guideline suggests focused screening in a broader high risk population (see section 3.1.1.2).2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)2018Measurement of the ABI is indicated as a first line non-invasive test for screening and diagnosis of lower extremity atherosclerotic disease (LEAD). (Class 1 Level C)Recommendation 5:The ankle brachial index is recommended as the appropriate test to establish the diagnosis of lower limb peripheral arterial disease.(I, B)Current evidence level supports upgrading from level C to B, based on two review studies, one systematic Cochrane review, one meta-analysis, and one clinical trial (see section 3.1.3.1)Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: Management of asymptomatic disease and claudication2015Recommendation 2.1We recommend using the ABI as the first line non-invasive test to establish a diagnosis of PAD in individuals with symptoms or signs suggestive of disease. When the ABI is borderline or normal (> 0.9) and symptoms of claudication are suggestive, we recommend an exercise ABI. (Grade 1 Level A)Recommendation 5:The ankle brachial index is recommended as the appropriate test to establish the diagnosis of lower limb peripheral arterial disease.(I, B)Current evidence level supports a downgrading from level A to B. (see section 3.1.3.1)European Society for Vascular Medicine (ESVM) Guideline on Peripheral Arterial Disease2019Measurement of the ABI by non-invasive measurements using Doppler occlusion pressure is indicated as an appropriate test to verify PAD. (Class 1 Level C)Recommendation 5:The ankle brachial index is recommended as the appropriate test to establish the diagnosis of lower limb peripheral arterial disease.(I, B)Current evidence level supports upgrading from level C to B, based on two review studies, one systematic Cochrane review, one meta-analysis and one clinical trial (see section 3.1.3.1)European Society for Vascular Medicine (ESVM) Guideline on Peripheral Arterial Disease2019It is recommended that ABI values ≤ 0.9 are evidence of significant PAD. (Class I Level B)Recommendation 6:It is recommended that an ankle brachial index cutoff value at ≤ 0.9 is used for lower limb peripheral arterial disease diagnosis, and that a value ≥ 1.4 be considered inconclusive.(I, C)A cutoff value has been added for incompressible ankle arteries (ABI ≥ 1.4) which led to an overall downgrading of evidence to level C. No references are provided in support of the level B evidence level in the ESVM guideline.European Society for Vascular Medicine (ESVM) Guideline on Peripheral Arterial Disease2019It is recommended that the ABI score with the highest ankle artery pressure value is to be used for the calculation of ABI. (Class I Level C)Recommendation 7:When the ankle brachial index is used to estimate the severity of lower limb peripheral arterial disease in symptomatic patients or is being used during follow up after revascularisation, it is recommended to be calculated by dividing the highest systolic pressure at the ankle level by the highest systolic arm pressure. (I, B)The recommendation has been upgraded to level B based on two observational studies and one review. The level C evidence statement suggested by ESVM refers to the scientific statement from the American Heart Association. (Aboyans et al. Circulation 2012) that in turn suggested a Grade I Level A recommendation.Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease2022We recommend smoking cessation interventions ranging from intensive counselling, nicotine replacement therapy, bupropion, varenicline, and sometimes nicotine e-cigarettes (Strong Recommendation; High quality Evidence).Recommendation 22:For patients with lower limb peripheral arterial disease who smoke, councelling as part of intensive smoking cessation intervention is recommended. (I, B)Recommendation 23:For patients with lower limb periperal arterial disease who smoke, varenicline, either alone or in combination with nicotine replacement therapy, is recommended as the first line pharmacological smoking cessation treatment due to its higher effectiveness as compared to other pharmacological alternatives. (I, B)We considered the current evidence base differently, especially for bupropion. We also considered the potential harm of e-cigarettes (see chapter 4.1.1.1)Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease2022Statin add on therapies (ezetimibe and or PCSK-9 inhibitors) if receiving maximally tolerated dose of statin therapy and the low density lipoprotein cholesterol is ≥ 1.8 mmol/L, non-high density lipoprotein cholesterol ≥ 2.4 mmol/L or apolipoprotein B 100 ≥ 0.7 mg/dL.Recommendation 32:For patients with lower limb peripheral arterial disease, it is recommended to reduce the low density lipoprotein cholesterol concentrations to < 1.4 mmol/L (< 55 mg/dL) and decrease it by ≥ 50% if baseline values are within 55–110 mg/dL. (I, B)We recommended a slightly lower low density lipoprotein cholesterol threshold, although we recognise that the current evidence for a lower threshold is mainly based on heterogeneous cohorts and was mainly driven by positive data from recent trials on PCSK-9 inhibitors.2021 ESC Guidelines on cardiovascular disease prevention in clinical practice2021Considered to be at high risk:Documented atherosclerotic cardiovascular disease (ASCVD), clinical or unequivocal on imaging. Documented clinical ASCVD includes previous AMI, ACS, coronary revascularisation and other arterial revascularisation procedures, stroke and TIA, aortic aneurysm and PAD.Symptomatic or asymptomatic lower extremity atherosclerotic disease (LEAD) (ABI < 0.90) is associated with a doubling of the 10 year rate of coronary events, CV mortality, and total mortality.Recommendation 44For patients with lower limb peripheral arterial disease, even if asymptomatic, it is recommended to consider an ankle brachial index ≤ 0.9 or ≥ 1.4 a risk enhancing factor for a cardiovascular event and for an increased all cause mortality. (I, A)The ESC document classifies PAD as a documented ASCVD, and further emphasises the high cardiovascular risk associated with PAD.In our document we have suggested a diagnostic method for PAD which is not given in the ESC guideline.European Society for Vascular Medicine (ESVM) Guideline on Peripheral Arterial Disease2019It is recommended that recognition be given that patients with PAD have a high risk of vascular events in other vascular beds, and as such these patients should always be considered very high risk for further events. (Class I Level A)andIt is recommended that ABI values ≤ 0.9 are evidence of significant PAD (Class I Level B)Recommendation 44:For patients with lower limb peripheral arterial disease, even if asymptomatic, it is recommended to consider an ankle brachial index ≤ 0.9 or ≥ 1.4 a risk enhancing factor for a cardiovascular event and for an increased all cause mortality. (I, A)The two quoted recommendations from ESVM together provide a similar message to recommendation 43 in this guideline.Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: Management of asymptomatic disease and claudication2015Recommendation 5.5We recommend the selective use of BMS or covered stents for aorto-iliac angioplasty for common iliac artery or external iliac artery occlusive disease, or both, due to improved technical success and patency. (Grade 1 Level B)Recommendation 55:For patients with disabling intermittent claudication undergoing revascularisation, primary bare metal stenting is recommended over primary balloon angioplasty for iliac artery occlusions due to the lower risk of distal embolisation. (I, B)We have also considered the risk of distal embolisation when performing balloon angioplasty on iliac artery occlusions why we did not recommend selective use of stents for iliac artery occlusions. We also considered the results from the recently published DISCOVER trial that did not show any benefit of covered vs. uncovered stents in the common iliac artery (see chapter 6.4).Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: Management of asymptomatic disease and claudication2015Recommendation 5.6We recommend the use of covered stents for treatment of AIOD in the presence of severe calcification or aneurysmal changes where the risk of rupture may be increased after unprotected dilation. (Grade 1 Level C)Recommendation 57:For patients with disabling intermittent claudication undergoing revascularisation who have Trans-Atlantic Inter-Society Consensus Document II C/D iliac lesions, covered stent placement may be considered over bare metal stents due to higher patency rates. (IIb, B)Our recommendation more precisely targets complex (i.e., TASC II C and D) aorto-iliac lesions, where the risk of vessel rupture is substantially higher. We also considered the results of the recently published

TIPS is the most effective treatment for portal hypertension. Patient selection remains important to achieving optimal post-TIPS outcomes. The study evaluates 1-year mortality factors in cirrhotic patients receiving TIPS. METHODS:87 cirrhotic patients received a TIPS between 2015 - 2021. Predictors of 1-year and overall mortality were assessed by estimating cumulative incidence functions and Grey's test to adjust for liver transplantation as a risk competing with mortality. Variables with p < 0.05 were checked for collinearity and included in the multivariate Cox proportional hazards model. Model discrimination was evaluated by calculating the area under the ROC curve. RESULTS:87 patients were included (68% men; 22% ≥70 years). ALD was the primary cirrhosis cause. Most patients were Child-Pugh class B, MELD-Na score was 13.6 ± 6.0 points. The most frequent indication for TIPS was bleeding (51.7%), followed by refractory ascites (42.5%). The variables positively associated with mortality in univariate analysis were ascites, clinically overt sarcopenia and MELD-Na score, while ongoing nutritional supplementation improved survival. In the multivariate analysis, only clinically overt sarcopenia and MELD-Na score remained independently associated with mortality. A MELD-Na/sarcopenia model demonstrated a good discrimination, AUROC: 0.86 (95% CI 0.77 - 0.95). CONCLUSION:MELD-Na score, and sarcopenia were significantly associated with 1-year survival in cirrhotic patients who received TIPS.

PIK3CA variants are known to cause vascular malformations. We were interested in studying the phenotypic spectrum, the location within the PIK3CA gene, and the variant allele frequency (VAF) of somatic PI3KCA variants in vascular malformations. Clinical data of consecutive patients with extracranial/extraspinal vascular malformations were collected in the context of the VASCOM cohort (2008-2022, n = 558). Starting October 2020, biopsy samples were tested with the TSO500 gene panel (Illumina). All consenting patients with PIK3CA variants were included in this study. Eighty-nine patients had available genetic results by June 2022. PIK3CA variants (n = 25) were found in 16 simple/combined (nonsyndromic) vascular malformations and in nine vascular malformations associated with other anomalies (syndromic). Four hotspot variants in exons 9 and 20 (c.1624G>A, c.1633G>A, c.3140A>G, c.3140A>T) were identified in 16/25 patients (VAF 0.9%-9.7%). Six non-hotspot variants (c.328_330del, c.323_337del, c.353G>A, c.1258T>C, c.3132T>A, c.3195_3203delinsT) were detected in nine patients (VAF 3.6%-31.7%). Non-hotspot variants were more frequent in syndromic than nonsyndromic vascular malformations (p = 0.0034) and exhibited a higher VAF than hotspot variants (p = 0.0253). Our study contributes to the growing body of knowledge of the genetic background in vascular malformations. Further studies will enrich the ever-growing list of pathogenic PIK3CA variants associated with vascular malformations.

OBJECTIVE:Predictive models for reintervention may guide clinicians to optimize selection, education, and follow-up of patients undergoing endovascular iliac revascularization. Although the impact of lesion- and device-related characteristics on iliac restenosis and reintervention risk is well-defined, data on patient-specific risk factors are scarce and conflicting. This study aimed to explore the value of patient-related factors in predicting the need for clinically driven target-vessel revascularization (CD-TVR) in patients undergoing primary endovascular treatment of iliac artery disease. METHODS:Consecutively enrolled patients undergoing endovascular revascularization for symptomatic iliac artery disease at a tertiary vascular referral center between January 2008 and June 2020 were retrospectively analyzed. Primary and secondary outcomes were CD-TVR occurrence within 24 months and time to CD-TVR, respectively. Patients who died or did not require CD-TVR within 24 months were censored at the date of death or at 730 days, respectively. Multiple imputation was used to account for missing data in primary analyses. RESULTS:A total of 1538 iliac interventions were performed in 1113 patients (26% females; 68 years). CD-TVR occurred in 108 limbs (74 patients; 7.0%) with a median time to CD-TVR of 246 days. On multivariable analysis, increasing age was associated with lower likelihood of CD-TVR (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.50-0.83; P = .001) and decreased risk of CD-TVR at any given time (hazard ratio [HR], 0.66; 95% CI, 0.52-0.84; P = .001). Similarly, a lower likelihood of CD-TVR (OR, 0.75; 95% CI, 0.59-0.95; P = .017) and decreased risk of CD-TVR at any given time (HR, 0.73; 95% CI, 0.58-0.93; P = .009) were observed with higher glomerular filtration rates. Lastly, revascularization of common vs external iliac artery disease was associated with lower likelihood of CD-TVR (OR, 0.48; 95% CI, 0.24-0.93; P = .030) and decreased risk of CD-TVR at any given time (HR, 0.48; 95% CI, 0.25-0.92; P = .027). No associations were observed between traditional cardiovascular risk factors (sex, hypertension, higher low-density lipoprotein cholesterol, higher hemoglobin A1c, smoking) and CD-TVR. CONCLUSIONS:In this retrospective cohort study, younger age, impaired kidney function, and external iliac artery disease were associated with CD-TVR. Traditional markers of cardiovascular risk were not seen to predict reintervention.

Objective: Generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), kaposiform lymphangiomatosis (KLA), and central conducting lymphatic anomaly (CCLA) are rare, multisystem lymphatic disorders, referred to as complex lymphatic anomalies (CLAs). Their etiology remains poorly understood; however, somatic activating mutations have recently been discovered, and the results of targeted treatments are promising. This study aimed to elaborate on the phenotypic description of CLA.Methods: Thirty-six consecutive patients were recruited for the "GLA/GSD Registry" of the University Hospital of Freiburg, Germany (2015-2021). Clinical data were prospectively collected provided that a signed informed consent form was obtained. The latest proposed diagnostic guidelines were retrospectively applied.Results: Thirty-two patients (38% males) were included in the study; 15 GLA, 10 GSD, 3 KLA, and 4 CCLA patients were identified. Eighty-four percent already had symptoms by the age of 15 years. Osteolysis and periosseous soft-tissue infiltration were associated with GSD (p < 0.001 and p = 0.011, respectively), ascites and protein-losing enteropathy with CCLA (p = 0.007 and p = 0.004, respectively), and consumption coagulopathy with KLA (p = 0.006). No statistically significant differences were found in organ involvement, distribution of osteolytic lesions, number of affected bones and fractures. Twenty-five patients had complications; one patient with GLA died despite multimodal treatment. Spontaneous regression was seen in one patient with untreated KLA.Conclusions: CLA are rare, and their overlapping clinical presentations make differential diagnosis difficult. The characterization of our case series contributes to the phenotypic description and differentiation of these four clinical entities. A further understanding of their pathogenesis is crucial for evaluating targeted therapies and optimizing medical care.

Objective: In recent years, genotypic characterization of congenital vascular malformations (CVMs) has gained attention; however, the spectrum of clinical phenotype remains difficult to attribute to a genetic cause and is rarely described in the adult population. The aim of this study is to describe a consecutive series of adolescent and adult patients in a tertiary center, where a multimodal phenotypic approach was used for diagnosis.Methods: We analyzed clinical findings, imaging, and laboratory results at initial presentation, and set a diagnosis ac-cording to the International Society for the Study of Vascular Anomalies (ISSVA) classification for all consecutively registered patients older than 14 years of age who were referred to the Center for Vascular Malformations at the University Hospital of Bern between 2008 and 2021.Results: A total of 457 patients were included for analysis (mean age, 35 years; females, 56%). Simple CVMs were the most common (n = 361; 79%), followed by CVMs associated with other anomalies (n = 70; 15%), and combined CVMs (n = 26; 6%). Venous malformations (n = 238) were the most common CVMs overall (52%), and the most common simple CVMs (66%). Pain was the most frequently reported symptom in all patients (simple, combined, and vascular malformation with other anomalies). Pain intensity was more pronounced in simple venous and arteriovenous malformations. Clinical problems were related to the type of CVM diagnosed, with bleeding and skin ulceration in arteriovenous malformations, localized intra-vascular coagulopathy in venous malformations, and infectious complications in lymphatic malformations. Limb length difference occurred more often in patients with CVMs associated with other anomalies as compared with simple or com-bined CVM (22.9 vs 2.3%; P < .001). Soft tissue overgrowth was seen in one-quarter of all patients independent of the ISSVA group. Conclusions: In our adult and adolescent population with peripheral vascular malformations, simple venous malfor-mations predominated, with pain as the most common clinical symptom. In one-quarter of cases, patients with vascular malformations presented with associated anomalies on tissue growth. The differentiation of clinical presentation with or without accompanying growth abnormalities need to be added to the ISSVA classification. Phenotypic characterization considering vascular and non-vascular features remains the cornerstone of diagnosis in adult as well as pediatric patients.

Background:Transarterial chemoembolization (TACE) is the accepted therapy for intermediate hepatocellular carcinoma (HCC). Although recent data suggests that bland transarterial embolization (TAE) is equally effective in intermediate HCC, not much is known about the efficacy in very early and early HCC not amenable for ablation or resection. We aimed to compare the outcome of patients with very early and early HCC treated by drug-eluting beads TACE (DEB-TACE), a specific technique of TACE using DC beads, and TAE using microparticles with a size of 100 µm up to 700 µm.Methods:Clinical data of totally 95 patients with very early and early HCC not amenable for surgery or ablation, treated between 2009 and 2019 at the Department of Visceral Surgery and Medicine and the Interdisciplinary Center of Vascular Interventions, University Hospital Bern, Switzerland, were retrospectively analyzed (52 patients in DEB-TACE and 42 patients in TAE group, respectively). All images were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Primary endpoint was overall survival (OS). Secondary endpoints were local response rate and time to local progression.Results:Most patients presented with Child-Pugh A. Thrombocytes were significantly lower in patients treated by TAE. Minor side effects occurred equally in both groups. No differences were detected in terms of OS, local tumor recurrence and response rate.Conclusions:Compared with DEB-TACE, TAE is an equally effective and save therapy for very early and early HCC not amenable for resection or ablation without differences in local tumor control and OS.

Objectives:. Parkes Weber syndrome (PWS) is a rare disorder that combines overgrowth, capillary malformations, and arteriovenous malformations (AVM)/arteriovenous fistulas, for which underlying activating mutations in the ras/mitogen-activated protein kinase/extracellular-signal-regulated kinase signaling pathway have been described. The clinical overlap with Klippel-Trenauny syndrome, associated with mutations in PIK3CA, is significant. This case series aimed to elaborate on the phenotypic description of PWS, to underline its clinical overlap with Klippel-Trenauny syndrome and nonsyndromic AVM, and to evaluate the contribution of genotypic characterization to the diagnosis. Methods:. All patients diagnosed with PWS upon enrollment in the Bernese VAScular COngenital Malformations (VASCOM) cohort were included. The diagnostic criteria of PWS were retrospectively reviewed. A next-generation sequencing (NGS) gene panel (TSO500, Illumina) was used on tissue biopsy samples. Results:. Overall, 10/559 patients of the VAScular COngenital Malformations cohort were initially diagnosed with PWS. Three patients were reclassified as nonsyndromic AVM (Kristen Rat Sarcoma Viral oncogene homolog [KRAS], KRAS+tumor protein p53, and protein tyrosine phosphatase non-receptor type 11). Finally, 7 patients fulfilled all clinical diagnostic criteria of PWS. Genetic testing was available in 5 PWS patients. Only 1 patient had the classic RASA1 mutation; another patient had mutations in G protein subunit alpha q (GNAQ) and phosphatase and tensin homolog. In a third case, a PIK3CA mutation was detected. In 2 patients, no mutations were identified. Conclusion:. Overgrowth syndromes with vascular malformations are rare and their clinical overlap hampers the classification of individual phenotypes under specific syndrome labels, sometimes even despite genetic testing. To provide optimal patient care, an accurate phenotypic description combined with the identification of molecular targets for precision medicine may be more meaningful than the syndrome classification itself.

ObjectiveAtherosclerosis expression varies across not only coronary, cerebrovascular, and peripheral arteries but also within the peripheral vascular tree. The underlying pathomechanisms of distinct atherosclerosis phenotypes in lower extremity peripheral artery disease (PAD) is poorly understood. We investigated the association of cardiovascular risk factors (CVRFs) and atherosclerosis distribution in a targeted approach analyzing symptomatic patients with isolated anatomic phenotypes of PAD.MethodsIn a cross-sectional analysis of consecutive patients undergoing first-time endovascular recanalization for symptomatic PAD, data of patients with isolated anatomic phenotypes of either proximal (iliac) or distal (infrageniculate) atherosclerosis segregation were extracted. We performed a multivariable logistic regression model with backward elimination to investigate the association of proximal and distal PAD with CVRFs.ResultsOf the 637 patients (29% females) with endovascular recanalization, 351 (55%) had proximal and 286 (45%) had distal atherosclerosis. Female sex [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.20–0.54, p = 0.01], active smoking (OR 0.16, 95% CI 0.09–0.28, p < 0.001), and former smoking (OR 0.33, 95% CI 0.20–0.57, p < 0.001) were associated with proximal disease. Diabetes mellitus (DM) (OR 3.25, 95% CI 1.93–5.46, p < 0.001), chronic kidney disease (CKD) (OR 1.18, 95% CI 1.08–1.28, p < 0.001), and older age (OR 1.31, 95% CI 1.06–1.61, p = 0.01) were associated with distal disease.ConclusionFemale sex, particularly in the context of smoking, is associated with clinically relevant, proximal atherosclerosis expression. Our additional findings that distal atherosclerosis expression is associated with DM, CKD, and older age suggest that PAD has at least two distinct atherosclerotic phenotypes with sex-specific and individual susceptibility to atherogenic risk factors.

ObjectiveThe aim of the study is to evaluate the cross-sectional and longitudinal association of early natural menopause with changes in cardiovascular risk factors (CVRFs).MethodsPostmenopausal women from the Swiss CoLaus study, reporting age at natural menopause (ANM) and having CVRFs measurements (blood lipids, blood pressure, glucose, homeostatic model assessment for insulin resistance [HOMA-IR], and inflammatory markers) at baseline (2003-2006) and first follow-up (2009-2012) were eligible for analysis. Age at natural menopause was analyzed as a continuous variable and in categories (ANM <45 and >= 45 y old). Linear regression analysis and linear mixed models were used to assess whether ANM is associated cross-sectionally and longitudinally with changes in CVRFs. Models were adjusted for demographic characteristics, lifestyle-related factors, time since menopause, medication, and clinical conditions.ResultsWe analyzed 981 postmenopausal women. The cross-sectional analysis showed that women with ANM younger than 45 years had lower diastolic blood pressure (beta = -3.76 mm Hg; 95% confidence interval [CI] = -5.86 to -1.65) compared with women whose ANM was 45 years or older. In the longitudinal analysis, ANM younger than 45 years was associated with changes in log insulin (beta = 0.26; 95% CI = 0.08 to 0.45) and log homeostatic model assessment for insulin resistance levels (beta = 0.28; 95% CI = 0.08 to 0.48). No associations were found between ANM and other CVRFs.ConclusionsEarly menopause may be associated with changes in glucose metabolism, while it may have little to no impact on other CVRFs. Larger longitudinal studies are needed to replicate our findings.