Abstract Objective To assess the natural history of saphenous and non-saphenous varicose veins using the results of the Bonn Vein Studies and data published in literature. Methods We used the data of the Bonn Vein Studies (BVS) 1 and 2 to assess if preexisting non-saphenous varicose veins (NSVV) in persons who had no saphenous varicose veins (SVV) at baseline have an impact on the incidence of SVV during the follow-up of 6.6 years and vice versa. SVV where defined as tortuous or not-tortuous refluxing saphenous veins. The statistical evaluation was performed using SAS version 9.4 (SAS Institute, Cary, North Carolina). In addition, we performed a review of publications concerning the natural history of varicose veins (VV) using PubMed. Results In the BVS the overall incidence of SVV within the follow-up time of 6.6 years was 8.0 % (n = 133 of 1661; 95 % CI: 6.8–9.4). 7.2 % (n = 107 of 1492) without VV in BVS 1 and 19.8 % (n = 26) of patients with preexisting NSVV developed SVV. The relative risk for the development of SVV in patients with preexisting NSVV was 2.44 (95% CI: 1.64–3.64) adjusted for age and sex. The overall incidence of NSVV was markedly higher with 13.3 % (n = 226 of 1661; 95 % CI: 11.8–15.1). During follow-up 148 patients (9.9 %) without VV in BVS 1 developed NSVV. 48.5 % (n = 78) of patients with preexisting SVV developed NSVV during follow-up. The relative risk for the development of NSVV in patients with preexisting SVV was 4.10 (95% CI: 3.26–5.16), adjusted for age and sex. In published studies the development of VV is preceded by venous reflux. Initial VV may develop at any segment and the results from literature suggest that the location of VV and reflux at the time of the investigation depends on age. In younger individuals more distal location are reported with an ascending progression in the majority but also descending progression is possible. Conclusions Based on the results of the Bonn Vein Studies 1 and 2 we could demonstrate, that preexisting SVV increase the risk of developing NSVV and preexisting NSVV increase the risk of developing SVV in a similar way. Venous reflux may initially occur in any segment of the venous system and may progress in antegrade and/or retrograde fashion. In younger adults initial VV seem to be localized more often in distal parts of the legs with an antegrade progression over time.

The authors regret there was a mistake in Figure 6 and 13. In Figure 6, it should read ‘Compression’ for oedema, to include inelastic compression as well (green box); in Figure 13, the pressure at the ankle should read ‘≤ 40 mm Hg’, for small and recent onset ulcer (yellow box):

Compared with the 2015 version of the guidelines on the management of chronic venous disease (CVD),1 the global structure of the document has been modified considerably in an attempt to make it more practical and user friendly. Special subsections on management strategy with accompanying flowcharts have been added to the different chapters.•An extensive chapter has been entirely dedicated to superficial venous incompetence. A new subsection on evidence supporting endovenous non-thermal ablation has been included. A new subsection on incompetence of perforating veins has been added, as well as a subsection on practical strategies for special anatomical presentations. The management of recurrent varicose veins is discussed at the end of this chapter.•Deep venous pathology is discussed in a separate chapter, with an emphasis on the increasing evidence in the field of managing iliofemoral and iliocaval obstruction. In addition, new topics in this chapter are the combination of superficial and deep venous problems, aneurysms of the deep veins and popliteal vein entrapment syndrome.•An entirely new chapter has been dedicated to the management of patients with venous leg ulcers.•A new chapter describes the management of patients with varicose veins, related to underlying pelvic venous disorders.•A new chapter considers special patient characteristics and their potential influence on management strategy.•Gaps in evidence and future perspectives are briefly discussed in a separate chapter.•A lay summary of the guidelines provides useful information for patients.

OBJECTIVES:Medical compression therapy is used for non-invasive treatment of venous and lymphatic diseases. Medical compression therapy-associated adverse events and contraindications have been reported, although some contraindications are theoretically based. This consensus statement provides recommendations on medical compression therapy risks and contraindications. METHODS:A systematic literature search of medical compression therapy publications reporting adverse events up until November 2017 was performed. A consensus panel comprising 15 international experts critically reviewed the publications and formulated the recommendations. RESULTS:Sixty-two publications reporting medical compression therapy adverse events were identified. The consensus panel issued 21 recommendations on medical compression therapy contraindications and adverse event risk mitigation, in addition to reviewing medical compression therapy use in borderline indications. The most frequently reported non-severe medical compression therapy-associated adverse events included skin irritation, discomfort and pain. Very rare but severe adverse events, including soft tissue and nerve injury, were also identified. CONCLUSION:This consensus statement summarises published medical compression therapy-associated adverse events and contraindications, and provides guidance on medical compression therapy. Severe medical compression therapy-associated adverse events are very rarely encountered if compression is used correctly and contraindications are considered.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation–like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

IntroductionSulodexide is a widely used glycosaminoglycan derived drug for oral (antithrombotic) and parenteral (anticoagulant) indications and is composed of fast moving heparin (80%) and dermatan sulfate (20%). In view of the current shortage of porcine heparin supply sulodexide may be a potential substitute for heparin for surgical and interventional anticoagulation. The purpose of this study is to compare the anticoagulant activities of sulodexide with heparin in simulated studies to mimic surgical and interventional anticoagulation.Materials and MethodsPowder versions of sulodexide were obtained from Alfasigma (Bologna, Italy). Powder versions of porcine mucosal heparin were obtained from Medefil (Glendale Heights, IL, USA). Stock solution of both heparin and sulodexide were prepared in sterile saline at 10mg/ml. Sterile solutions were made at 1.0 and 0.1mg/ml. USP potency for both drugs were measured, cross referenced against US pharmacopiel standard and expressed as units per milligram. Whole blood activated clotting time was measured in healthy human volunteers at graded concentrations of both drugs. Plasma based anticoagulant assays such as activated partial thromboplastin time (APTT) and thrombin time (TT) were measured. Protamine neutralization studies were also carried out in the different assays used.ResultsThe USP potency of sulodexide range from 90 – 105 U/mg whereas the porcine heparin exhibited a potency range of 180 – 200 U/mg as measured by the anti‐Xa activity. In the ACT assays USP potency adjusted sulodexide and heparin produced concentration dependent prolongation of this test which were comparable to heparin. Both the sulodexide and heparin produce concentration dependent anticoagulant effects in the APTT and TT assays. Protamine sulfate produced effective neutralization of the anticoagulant effects of both the sulodexide and heparin.ConclusionsThese results suggest that at USP potency equated levels sulodexide is capable of producing similar anticoagulant effects as unfractionated heparin. The USP potency of sulodexide can be adjusted at a comparable potency to porcine heparin to obtain comparable anticoagulant responses in the in vitro setting. Additional in vivo studies are warranted to compare the potency adjusted sulodexide with heparin.

Objectives: Reflux assessment with ultrasound (U/S) is usually qualitative. Quantitative measurements of superficial venous insufficiency (SVI) include the venous arterial flow index (VAFI), recirculation index (RCI), venous filling index (VFI), and the postural diameter change (PDC) of the saphenous trunk. The aim was to investigate their relationship. Materials and methods: This was an observational study performed on patients with varicose veins and hospital employees. Four haemodynamic parameters were measured in 21 legs from 16 subjects. Legs were divided into no reflux (n = 7) and reflux (n = 14). The VAFI is the U/S ratio of common femoral vein volume flow divided by the common femoral artery volume flow, performed supine. The RCI is the U/S ratio of reflux volume over antegrade volume within the saphenous trunk after calf compression, standing. The VFI is the rate of calf volume increase on dependency measured in mL/s, using air plethysmography. The PDC is the percentage reduction of the saphenous trunk diameter from standing to lying, using U/S. Results: The clinical part of the CEAP classification was: C-0 = 3, C-1 = 4, C-2 = 5, C-3 = 1, C-4a = 1, C-4b = 6, C-5 = 1. All four tests demonstrated significant differences between the two groups with minimal overlap (Mann Whitney U test): VAFI (p =.028), RCI (p < .0005), VFI (p =.001), and PDC (p = .014). Furthermore, significant correlations were observed with the tests: VAFI vs. RCI (r = .532, p = .015), VFI (r = .489, p = .025) and PDC (r = -.474, p = .030); RCI vs. VFI (r = .446, p = .043) and PDC (r = -.527, p = .014). Conclusions: Superficial venous drainage insufficiency should not be confined to an U/S assessment of the presence of reflux, which is qualitative. Quantitative data may be provided using the VAFI, RCI, VFI, and PDC. Understanding why there are significant correlations among these parameters and the preferred objective reference test requires further work.

ZusammenfassungDurch die Möglichkeit der Stenteinlage in iliakale Venen scheint die Behandlung der zentralen Obstruktion ein leichtes Unterfangen geworden zu sein. Allerdings bedingt diese Behandlung eine zumindest vorübergehende Antikoagulation – und der Stent wird lebenslang im Bein verbleiben. Und die Evaluation der Ergebnisse ist noch nicht gut etabliert. Auch die Indikationsstellung ist nicht immer objektivierbar gegeben, wenn man bedenkt, dass 25 % der Bevölkerung eine Stenose der linken V. iliaca von über 50 % aufweisen, auch wenn sie meist keine Symptome haben. Erschwerend kommt hinzu, dass die venöse chronische Insuffizienz als klinisches Syndrom (CVI) mehrere Ursachen haben kann, wie Varikose, Obstruktion oder Refluxe der tiefen Achse und die Behandlung eines einzelnen, anatomischen Befundes nicht unbedingt die Klinik nachhaltig verbessern muss. Die Luft-Plethysmographie (Air Plethysmography, APG) bietet in diesem Zusammenhang eine objektive, vom Untersucher und vom Patienten unabhängige Auswertungsmöglichkeit für die venöse Drainage und für die venöse Wiederauffüllzeit, die in jedem Fall vor einem Eingriff der zentralen Venen und zur Evaluation des Ergebnisses gefordert werden sollte.

Introduction: In the majority of reports on the endovascular management of May Thurner syndrome, measurements have been performed in axial computed tomography (CT) images. However, area measurement obtained by intravascular ultrasound (IVUS) is considered in current practice the gold standard for assessing these lesions. Furthermore, there is increasing awareness that due to the irregular shape of veins, especially when compressed, diameter measurements are less accurate than area measurements. The debate regarding the definition of a significant iliofemoral vein stenosis is ongoing. Any attempt to treat obstruction should be preceded by an accurate and reproducible measurement of the degree of stenosis. The theoretical relationship between a diameter stenosis of 50% is a 75% area stenosis in arterial disease. In collapsible veins with a constant perimeter, a 50% diameter reduction is in theory only a 33% area stenosis because of elliptical transformation. The difference between diameter and area for irregular May Thurner lesions has never been assessed. The aim of our study was to investigate potential differences between assessment of stenosis in May Thurner syndrome by measurements of diameter versus area in CT imaging. Methods: This was a retrospective study that included the first 50 consecutive outpatients with evidence of May-Thurner syndrome in prescheduled abdominal contrast-enhanced CTs, performed for reasons unrelated to venous disease. Patients with history of deep venous thrombosis were excluded. Three measurement techniques were employed: 1) diameter measurement in axial CT images 2) diameter measurement in multiplanar reconstructions (MPR) orthogonal to the line of blood flow 3) manual measurement of the cross-sectional area in reconstructions orthogonal to the line of blood flow. The percentage of compression of the common iliac vein was measured by comparing it with the diameter/cross sectional area measured above the ipsilateral confluence of the external and internal iliac vein. Differences among the three methods of assessment were assessed by analysis of variance (ANOVA). Results: ANOVA showed statistically significant differences among the three methods of assessment (F=121.7, p<0.001). More specifically, mean percentage of stenosis assessed by axial imaging (54.8+/- 12.9%) was significantly higher compared to mean percentage of stenosis assessed by area (20.2+/-14.2%); p<0.001. Similarly, mean percentage of stenosis assessed by MPR (51.5+/-9.1%) was also higher than mean percentage of stenosis assessed by area (p<0.001). No statistically significant difference was found between mean degree of stenosis assessed by axial imaging and MPR (p=0.54). Conclusion: Diameter measurements in CT scans for assessment of May Thurner syndrome tend to overestimate stenoses when compared to area measurements. Area measurements in reconstructions orthogonal to the line of blood flow may provide a more accurate method of assessing these lesions and should be validated against other methods, such as IVUS. Based on our findings, the use of diameter measurements as a method of assessing iliac venous lesions should be reconsidered.

Air plethysmography (APG) is a small, lightweight device that measures change in calf volume in response to various maneuvers. Of these, elevation and dependency are the most important because they are gravitational maneuvers and, without gravity, venous insufficiency would be rare. The hypothesis underpinning the value of APG is that rapid calf expansion on dependency or a slow reduction in calf volume on leg elevation are a failure of our natural defense mechanisms against gravity. The APG parameters quantifying this are termed the venous filing index (VFI) and the venous drainage index (VDI), respectively. They are measured in mL/s for consistency and comparability and they serve to quantify the observations of Trendelenburg. The VFI and VDI may have relationships to ultrasound phenomena or imaging in individual veins, like reflux or iliac occlusion. However, APG assesses the calf as a global unit, providing the rate of volume change. In this way, it behaves as a pure test, uncorrupted by words like reflux, resistance, pressure, and wall tension, which are difficult to measure and are only part of any venous pathology. If the pathology is considered a chronic insufficiency of venous drainage of the leg, then APG is the noninvasive, objective test to quantify this whenever insufficiency is suspected.

Evidence that medical compression stockings (MCS) prevent deep venous thrombosis (DVT) is weak. Furthermore, the body position that predisposes to DVT is not fully known. It is assumed that standing is protective through involuntary leg muscle contractions and that lying stationary may provoke DVT. Previous work using ultrasound has shown the presence of venous sludge in the popliteal veins, in both positions. The aim was to investigate the effect of standing, lying, and compression on thrombogenicity.

Foot infections are the commonest complication of diabetes mellitus requiring hospitalisation. Despite local osteomyelitis being the most frequent sequel of a diabetic foot infection, there is emerging evidence to suggest that local disease may lead to distant infections. In this report we present a case of recurrent thoracic spine spondylodiscitis due to left hallux osteomyelitis in a man with type 2 diabetes. This case illustrates the importance of considering spondylodiscitis as a differential diagnosis in patients presenting with diabetic foot infection and complaining of acute severe back pain.

Professor Evi Kalodiki (1956–2018) died aged 62 on New Year’s eve after a long illness. She achieved more during her life than most people could ever imagine. The account below serves only to illustrate a few facets of her which made her stand apart. Evi was born in Larnaca, Cyprus, the birthplace of Aphrodite. She was the daughter of eminent parents who both made successful careers as lawyers. At school, she was recognised for her first prizes in the disc throwing events. When educational activities became boring, she would leave the class and contemplate life sitting high on a roof water storage container. Her radiant beauty turned the heads of many men, but none could ever tame her sufficiently for a relationship. She was awarded an MA in English literature from the University of Athens after four years’ study. It was after this that her medical career began. Her surgical activities started working up through the grades for the godfather of vascular surgery in Greece, Prof P Balas, at the 1st Surgical Unit of the University of Athens. In 1984, she relocated to the UK and positioned herself at St Mary’s Hospital, Paddington, for almost two decades. During this time, she worked for eminent surgeons including Prof HAF Dudley, Mrs M Ghilchik, Mr JHN Wolfe and Mr RD Rosin. Prof G Stansby supported her innovative research for the Surgical Research Society and Prof Nicolaides provided her with opportunities for advancing the Irvine Laboratory at St Mary’s. Two people must be commended for mentoring her throughout the years. The first is Dr Jawed Fareed from Loyola University Chicago who awarded her visiting professor for her work for Loyola and dedication to the International Union of Angiology (IUA) over several decades. The second is Prof Pier Luigi Antignani who awarded her the Mauro Bartolo lifetime achievement award in 2016 for outstanding scientific contributions in vascular diseases throughout the world. Evi was co-director of the Josef Pflug vascular Laboratory at Ealing Hospital. This was an initiative set up by Prof George Geroulakos, her former mentor. The majority of her publications during her last 10 years originated from this laboratory, now part of the West London Vascular and Interventional Centre. She was the queen of air-plethysmography and her best work was the Discord Outcome Analysis (DOA) as a reporting standard in clinical trials on venous interventions. The DOA is pivotal in highlighting the discrepancies between different outcomes, interrogates the process of reporting and is instrumental in ensuring that interventions are appropriate. Internationally, Evi was the front for the Hellenic Phlebological Society. Evi was a founding member of the Hellenic society, Paddington Street, the centre of Greek culture in London. She was a founder also of the Giorgos Sarantaris (1908–1941) poet society whose headquarters are in Cyprus. Socially, Evi gave generously to charities. Her friendly manner and timeless unconditional interest in other people made her well known to all the venous community. She sat in the first four rows at conferences and had a reserved seat at the front at Saint Sophia’s cathedral, every Sunday. Her funeral was held at the Greek orthodox cathedral of St Sophia in Bayswater, the burial was at the 1st Cemetery in Athens where she was placed second shelf on the right in a reserved mausoleum with her ancestors, and the 40 days memorial service was held at her birthplace in Larnaca. She will be remembered forever for her enthusiasm for taking photographs. She is pictured shaking hands with the king of Sweden, Kojak, the Sultan of Malaysia and the Archbishop of Melbourne. She leaves behind her husband Christopher Lattimer, her sister Maria and her special nephew Phaedon and two nieces, Vereniki and Eva. May her soul rest in peace.

Introduction - Currently there is no study prospectively examining the association of the anatomic finding of non thrombotic iliac vein lesions, identified with imaging methods and signs and symptoms of venous disease. The objective of our study was to investigate the incidence and clinical significance of non thrombotic iliac vein lesions assessed by contrast CT scans of the abdomen and pelvis. Methods - This was a prospective study of 100 consecutive ambulatory outpatients, without any history of deep venous thrombosis, presenting to the radiology department for prescheduled abdominal contrast-enhanced CT for reasons unrelated to venous disease. Patients underwent thorough physical examination, while demographics and C class of the CEAP classification were documented. Diameter and percentage compression of the common iliac vein compared with the adjacent ipsilateral and the contralateral common iliac vein at the same level, were measured. Results - Mean age of the study population was 60.8±14.8 years. 53 were males. A ≥50% stenosis of the common iliac vein was detected in 15 and a ≥70%stenosis in 4 of the cases when compared to the caudal unilateral or the contralateral iliac vein. In 13 cases the stenosis was on the left side, in one case it was right sided and 1 case had bilateral iliac stenosis. The mean diameter of the right and left normal common iliac veins was 1.26±0.19 cm and 1.18±0.21 cm respectively. The mean diameter of the common iliac vein at the level of stenosis for the patients with a ≥50% stenosis was 0.64±0.12 cm. There were 57 patients classified as C0, 28 as C1, 12 as C2, 2 as C3, 1 with C4a and none as C4b, C5 or C6. All 15 subjects with ≥50% stenosis were classified as ≤C1, apart from one who was classified as C2 while none of the 3 patients with C3 or C4 disease had a stenosis greater than 50%. The difference in the calf and supramalleolar circumference between the two legs was not found to be significantly different between the patients with an iliac vein stenosis ≥50% and those without a stenosis (P 0.24, P 0.94). Conclusion - A more than 50% non thrombotic iliac vein compression is a relatively common anatomic variant that is rarely associated with signs and symptoms of chronic venous disease. These findings raise caution for the increasing number of iliac venous stenting procedures in minimally symptomatic patients.

D. Rastel and B. Lun should be congratulated for their evidence as to why low strength 18–23 mmHg medical compression stockings (MCS) do not significantly compress or occlude deep calf veins in the standing position.1Rastel D. Lun B. Lower limb deep vein diameters beneath medical compression stockings in the standing position.Eur J Vasc Endovasc Surg. 2019; 57: 276-282Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar This is contrary to the results of compression specialists who claim, using standing MRI, that low strength compression stockings alone can significantly compress or occlude the deep veins of the calf.2Partsch H. Mosti G. Uhl J.F. Unexpected venous diameter reduction by compression stocking of deep, but not of superficial veins.Veins Lymphat. 2012; 1: e3Crossref Google Scholar The authors used ultrasound through a transparency of a hybrid (elastic + non-elastic) pneumatic pressure device in nine standing patients (all limbs classified C1-3). Pressures of 43.1 ± 16.2 mmHg (mean, SD) were required to occlude deep veins. They went on to examine seven standing patients, bearing equal weight, first wearing a 20–36 mmHg MCS and then without a MCS. There was no significant difference in diameter change with the stocking. Additionally, six patients were examined without compression with the leg: (i) off-loaded, (ii) bearing equal weight, and then (iii) bearing full weight. Deep venous diameters reduced significantly (p = .009) from off-loading to equal weight bearing by 11.8% (range 0–54%). From equal weight bearing to full weight bearing all deep veins collapsed completely. They concluded that the observed deep vein diameter reductions under compression in the standing position are caused by the isometric muscle tension necessary for weight bearing and not by the compression effect of the stocking. The deep veins of the calf are surrounded by muscles that form the pumping chamber. It is not surprising that any pressure changes in this compartment would have a significant effect on venous diameter. This was acknowledged recently in an attempt to explain the “paradox” effect of MCS on deep versus superficial veins.3Uhl J.F. Benigni J.P. Cornu-Thenard A. Fournier J. Blin E. Relationship between medical compression and intramuscular pressure as an explanation of a compression paradox.Phlebology. 2015; 30: 331-338Crossref PubMed Scopus (17) Google Scholar However, weight bearing requires powerful isometric muscle contractions. Furthermore, a transfer of body weight from one leg to the other, which occurs in walking and standing, is the most efficient natural pumping mechanism recognised to date.4Lattimer C.R. Franceschi C. Kalodiki E. Optimizing calf muscle pump function.Phlebology. 2018; 33: 353-360Crossref PubMed Scopus (11) Google Scholar If the hypothesis that a MCS compresses deep veins independently of the systolic and diastolic activities of the calf pump is correct, then a real paradox arises: how can collapsed veins result in better pumping with an improved ejection fraction?2Partsch H. Mosti G. Uhl J.F. Unexpected venous diameter reduction by compression stocking of deep, but not of superficial veins.Veins Lymphat. 2012; 1: e3Crossref Google Scholar, 5Mosti G. Partsch H. Is low compression pressure able to improve venous pumping function in patients with venous insufficiency?.Phlebology. 2010; 25: 145-150Crossref PubMed Scopus (38) Google Scholar The work presented by the authors supports that a MCS does not significantly compress the deep veins of the calf alone and that any effects observed are from muscle pumping activity. There is no paradox. Lower Limb Deep Vein Diameters Beneath Medical Compression Stockings in the Standing PositionEuropean Journal of Vascular and Endovascular SurgeryVol. 57Issue 2PreviewThe mechanism by which compression therapy works is still discussed, especially at calf level. Whether lower limb deep vein diameters change under compression stockings is a matter of debate: no change versus great change. New study material helps to address this question. Full-Text PDF Open Archive

Objective/background: Unlike most systemic chronic diseases, chronic venous insufficiency (CVI) is ideal to study using endogenous biomarkers. The stimulus causing damage can be turned on and off with gravitational positioning and venous blood samples can be taken locally. Annexin V (apoptosis) and microparticles (cell membrane debris) were used as markers of cell destruction, with matrix metalloproteinases (MMPs) as markers of tissue remodelling. The aim of this proof of concept study was to validate a gravitational model by investigating whether standing induced biochemical stress and whether recovery occurs on lying and after compression. Methods: Fourteen patients (C4a-b) and 14 volunteers (C0-1) were tested under three supervised laboratory conditions for 1 h on separate days: (i) stationary standing on a small paper square; (ii) lying with both legs elevated 20 degrees; (iii) compression standing using a 23-32 mmHg below knee stocking. Immediately after each condition, venous blood was withdrawn from the ankle. Commercial enzyme linked immunosorbent assay kits were used for batch analysis of the plasma samples. Results: Median (interquartile range [IQR]) values of annexin V (AU/mL) and microparticles (nM) standing were as follows: volunteers 2.9 (2 - 3.4) and 10.2 (8.8 - 13.8), and patients 2.2 (1.3 - 6) and 11.3 (7.7 - 20), respectively. Significant reductions were observed lying: volunteers 2.1 (1.5 - 2.7; p = .019) and 8.5 (7.4 - 9.4; p = .041), patients 1.7 (1.2 - 2.7; p = .004) and 8.5 (7.0 - 11.4; p = .041), respectively. Globally, all median MMP values in the patients reduced with lying and with compression versus standing (p = .004). Individually, significant reductions occurred in MMPs 2 and 13 with compression and MMPs 3, 7, 8, 9, 10, and 12 on lying. Lying was more effective at reducing MMP levels than compression. Conclusion: Annexin V and microparticle concentrations are responsive to elevation and compression after 1 h. In the patients, all the tested MMPs decreased after lying and with compression versus standing. This model provides evidence supporting gravitational protection in the treatment of CVI. (C) 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.