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Background: Varicose veins and chronic venous disease are common, and some funding bodies ration treatment based on a minimum diameter of the incompetent truncal vein. This study assessed the effect of maximum vein diameter on clinical status and patient symptoms., Methods: A prospective observational cohort study of patients presenting with symptomatic varicose veins to a tertiary referral public hospital vascular clinic between January 2011 and July 2012. Patients underwent standardized assessment with venous duplex ultrasonography, and completed questionnaires assessing quality of life (QoL) and symptoms (Aberdeen Varicose Vein Questionnaire, EuroQol Five Domain QoL assessment and EuroQol visual analogue scale). Clinical scores (Venous Clinical Severity Score (VCSS) and Clinical Etiologic Anatomic Pathophysiologic (CEAP) class) were also calculated. Regression analysis was used to investigate the relationship between QoL, symptoms and vein diameter., Results: Some 330 patients were assessed before surgery. The median maximum vein diameter was 7·0 (i.q.r. 5·3-9·2) mm overall, 7·9 (6·0-9·8) mm for great saphenous vein and 6·0 (5·2-8·9) mm for small saphenous vein. In linear regression analysis, vein diameter was shown to have a significant association with VCSS (P = 0·041). For every 1-mm increase in vein diameter, there was a 2·75-fold increase in risk of being in CEAP class C4 compared with C2. No other QoL or symptom measures were related to vein diameter., Conclusion: Incompetent truncal vein diameter was associated with increasing VCSS, but not a variety of other varicose vein disease-specific and generic patient-reported outcome measures., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objective: A randomized clinical trial assessing the difference in quality of life and clinical outcomes between delayed and simultaneous phlebectomies in the context of endovenous truncal vein ablation., Background: Endovenous ablation has replaced open surgery as the treatment of choice for truncal varicose veins. Timing of varicosity treatment is controversial with delayed and simultaneous pathways having studies advocating their benefits. A previous small randomized study has shown improved outcomes for simultaneous treatment., Methods: Patients undergoing local anesthetic endovenous thermal ablation were randomized to either simultaneous phlebectomy or delayed varicosity treatment. Patients were reviewed at 6 weeks, 6 months, and 1 year with clinical and quality of life scores completed, and were assessed at 6 weeks for need for further varicosity intervention, which was completed with either ultrasound-guided foam sclerotherapy or local anesthetic phlebectomy. Duplex ultrasound assessment of the treated trunk was completed at 6 months., Results: 101 patients were successfully recruited and treated out of 221 suitable patients from a screened population of 393. Patients in the simultaneous group (n = 51) showed a significantly improved Venous Clinical Severity Score at all time points, 36% of the delayed group required further treatment compared with 2% of the simultaneous group (P < 0.001). There were no deep vein thromboses, with 1 superfificial venous thrombosis in each group., Conclusions: Combined endovenous ablation and phlebectomy delivers improved clinical outcomes and a reduced need for further procedures, as well as early quality of life improvements.

Objectives: Although the clinical benefits of endovenous thermal ablation are widely recognized, few studies have evaluated the health economic implications of different treatments. This study compares 6-month clinical outcomes and cost-effectiveness of endovenous laser ablation (EVLA) compared with radiofrequency ablation (RFA) in the setting of a randomized clinical trial., Methods: Patients with symptomatic primary varicose veins were randomized to EVLA or RFA and followed up for 6 months to evaluate clinical improvements, health related quality of life (HRQOL) and cost-effectiveness., Results: A total of 131 patients were randomized, of which 110 attended 6-month follow-up (EVLA n = 54; RFA n = 56). Improvements in quality of life (AVVQ and SF-12v2) and Venous Clinical Severity Scores (VCSS) achieved at 6 weeks were maintained at 6 months, with no significant difference detected between treatment groups. There were no differences in treatment failure rates. There were small differences in favor of EVLA in terms of costs and 6-month HRQOL but these were not statistically significant. However, RFA is associated with less pain at up to 10 days., Conclusions: EVLA and RFA result in comparable and significant gains in quality of life and clinical improvements at 6 months, compared with baseline values. EVLA is more likely to be cost-effective than RFA but absolute differences in costs and HRQOL are small.

Background: Recurrent varicose veins (RVV) occur in 13% to 65% of patients following treatment, and remain a debilitating and costly problem. RVV were initially thought largely to be due to inadequate intervention, however, more recently neovascularization and other factors have been implicated. This review aims to provide an overview of the current understanding of the etiology and pathogenesis of RVV., Methods: A systematic search of the PubMed database was performed using the search terms including "recurrent," "varicose veins," and "neovascularization.", Results: Three types of RVV have been reported, namely residual veins, true RVV, and new varicose veins, although the definitions varied between studies. RVV are attributable to causes including inadequate treatment, disease progression, and neovascularization. Using duplex ultrasonography, neovascularization has been observed in 25% to 94% of RVV. These new vessels appear in various size, number, and tortuosity, and they reconnect previously treated diseased veins to the lower limb venous circulation. Histologically, these vessels appear primitive with incomplete vein wall formation, decreased elastic component, and lack of valves and accompanying nerves. Although the rate of RVV following open surgery and endovenous treatment appears similar, neovascularization seems less common following endothermal ablation. Other causes of RVV following endovenous treatment include recanalization and opening of collaterals., Conclusions: Recurrence remains poorly understood following treatment of varicose veins. Neovascularization is an established and common cause of RVV, although other factors may contribute., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Venous disorder is common in the general population. Uncomplicated varicose veins represent a significant proportion of the disease burden, and can impact considerably on quality of life, producing a wide spectrum of symptoms. Little is known about the natural course of the disease at this stage and the treatment strategy employed is often not based on robust scientific evidence. The aim of this article is to elucidate the options to manage uncomplicated varicose veins. There are likely to be significant geographic differences in the treatment strategy employed, and it is hoped that we will arouse discussion among physicians regarding the management of this very common medical condition. The reader will be asked for their preferred treatment choice for a given clinical case vignette., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Sclerotherapy has been shown to be an effective and increasingly popular therapeutic strategy for the treatment of varicose veins. However, recent reports of serious side effects, including cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), as well as speech and visual disturbances, have caused serious concern regarding its use. This review evaluated the reported incidences of neurological side effects associated with the use of sclerotherapy., Methods: A systematic search of the data bases MEDLINE, OVID Embase, and Google Scholar was undertaken by two independent reviewers. Articles reporting neurological side effects in humans following foam and liquid sclerotherapy were included; animal studies, laboratory studies, and review articles were excluded. Additional references were also obtained using the related articles function., Results: The search yielded 1023 articles, of which 41 studies were found to meet the inclusion criteria. A total of 10,819 patients undergoing sclerotherapy were reviewed. There were 12 case reports of CVA with confirmatory brain imaging and nine reports of TIA. There were 97 (0.90%) reports of neurological events overall, including TIA, visual and speech disturbances, and 29 cases of reported migraine (0.27%). Symptoms occurred at times ranging from minutes to several days following sclerotherapy. Eleven patients with TIA or CVA were found to have a right to left cardiac shunt, usually a patent foramen ovale., Conclusions: Neurological side effects following sclerotherapy are a rare occurrence; however, CVA associated with the use of sclerotherapy is clearly documented. The pathologic mechanisms resulting in CVA are likely to be different to those leading to migraine and visual disturbances; however, care should be exercised in patient selection, particularly in those with known cardiac defects., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Hypoxia-inducible factor-1 (HIF-1) is a nuclear transcription factor that is upregulated in hypoxia and co-ordinates the adaptive response to hypoxia by driving the expression of over 100 genes. In facilitating tissues to adapt to hypoxia, HIF-1 may have a role in reducing the cellular damage induced by ischaemia, such as that seen in peripheral arterial disease (PAD), or following acute ischaemic insults such as stroke and myocardial infarction. This therefore raises the possibility of HIF-1 modulation in such contexts to reduce the consequences of ischaemic injury. HIF1 has further been implicated in the pathogenesis of atherosclerosis, abdominal aortic aneurysm (AAA) formation, pulmonary hypertension and systemic hypertension associated with obstructive sleep apnoea. Through a better understanding of the role of HIF-1 in these disease processes, novel treatments which target HIF-1 pathway may be considered. This review summarises the role of HIF-1 in arterial disease, specifically its role in atherosclerosis, ischaemic heart disease, in-stent restenosis following coronary revascularisation, stroke, PAD, AAA formation, pulmonary artery hypertension and systemic hypertension. The potential for exploiting the HIF-1 signalling pathway in developing therapeutics for these conditions is discussed, including progress made so far, with attention given to studies looking into the use of prolyl-hydroxylase inhibitors.

Objective: The wide variety of outcome measures to evaluate patients with varicose veins poses significant difficulties when comparing clinical trials. In addition, the relationship between different outcome measures is poorly understood. The aim of this study was to compare anatomical, hemodynamic, and clinical outcomes with disease-specific quality-of-life tools in patients undergoing treatment for varicose veins., Methods: Patients undergoing treatment for symptomatic veins in a single unit were studied. Assessments included duplex ultrasonography, digital photoplethysmography, evaluation of Venous Clinical Severity Scores and CEAP scores, generic (Short Form 12 [SF12]) and disease-specific (Aberdeen Varicose Vein Questionnaire [AVVQ], and Specific Quality-of-life and Outcome Response-Venous [SQOR-V]) questionnaires. Patients were reviewed at 6 weeks when hemodynamic, clinical, and quality-of-life assessments were repeated. The relationships between these outcomes were assessed., Results: The AVVQ showed a strong positive correlation with the SQOR-V (Spearman coefficient 0.702; P < .001) and weaker, but significant correlations with the SF12 physical and mental component scores and the Venous Clinical Severity Score (VCSS) (P < .001, P = .019, and P < .001, respectively, Spearman correlation). No correlations were observed between the AVVQ and photoplethysmography results (Spearman coefficient -0.042; P = .606), and weak correlations were observed with the AVVQ and anatomical reflux. At 6 weeks, functional, clinical, and hemodynamic measurements were all responsive to changes following interventions; however, correlations observed between changes in disease-specific quality-of-life and generic, clinical, and hemodynamic outcomes were weak., Conclusions: Both the AVVQ and SQOR-V questionnaire are sensitive and responsive disease-specific questionnaires, which correlate with generic and clinical outcomes to some extent. Anatomical and hemodynamic measurements correlated poorly with functional outcomes both preoperatively and following interventions., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Venous hypoxia has long been postulated as a potential cause of varicosity formation. This article aimed to review the development of this hypothesis, including evidence supporting and controversies surrounding it. Vein wall oxygenation is achieved by oxygen diffusing from luminal blood and vasa vasorum. The whole media of varicosities is oxygenated by vasa vasorum as compared to only the outer two-thirds of media of normal veins. There was no evidence that differences exist between oxygen content of blood from varicose and non-varicose veins, although the former demonstrated larger fluctuations with postural changes. Studies using cell culture and ex vivo explants demonstrated that hypoxia activated leucocytes and endothelium which released mediators regulating vein wall remodelling similar to those observed in varicosities. Venoactive drugs may improve venous oxygenation, and inhibit hypoxia activation of leucocytes and endothelium. The evidence for hypoxia as a causative factor in varicosities remains inconclusive, mainly due to heterogeneity and poor design of published in vivostudies. However, molecular studies have shown that hypoxia was able to cause inflammatory changes and vein wall remodelling similar to those observed in varicosities. Further studies are needed to improve our understanding of the role of hypoxia and help identify potential therapeutic targets., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: This study aimed to assess the trends and regional variations in secondary care treatment of patients with varicose veins in National Health Service (NHS) England based on data published by the Hospital Episode Statistics which was freely and readily available to the public and health-care policy-makers., Methods: Hospital Episode Statistics data for patients being treated for varicose veins, and UK Statistics Authority population estimates in all 28 Strategic Health Authorities (SHAs) in England from 2002 to 2006 were retrieved and analysed., Results: Between 2002 and 2006 there was a 20% overall reduction (46,190-37,135) in the total number of varicose vein procedures performed in NHS England per year. The number of varicose vein procedures performed per 100,000 population per year varied significantly across the SHAs (P < 0.0001). Similarly, significant regional variations were also noted in the frequency of primary procedures of greater and small saphenous vein (P < 0.0001). During this time, injection sclerotherapy was only performed in 15 (53.6%) SHAs. The annual proportion of varicose vein procedures performed as daycases had increased from 56% to 64% during the period., Conclusion: From 2002 to 2006 there was an overall reduction in the total number of varicose vein procedures performed in NHS England with major regional variations.

Background: Endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) are both associated with excellent technical, clinical and patient-reported outcomes for the treatment of varicose veins. The aim of this study was to compare the techniques in a randomized clinical trial., Methods: Consecutive patients with primary great saphenous vein reflux were randomized to EVLA (980 nm) or RFA (VNUS ClosureFAST) at a single centre. The primary outcome measure was postprocedural pain after 3 days. Secondary outcome measures were quality of life at 6 weeks, determined by the Aberdeen Varicose Vein Questionnaire (AVVQ) and Short Form 12 (SF-12), and clinical improvement assessed by the Venous Clinical Severity Score (VCSS). Analyses were performed on the basis of intention to treat using multivariable linear regression., Results: Some 131 patients were randomized to EVLA (64 patients) or RFA (67). Mean(s.d.) pain scores over 3 days were 26.4(22.1) mm for RFA and 36.8(22.5) mm for EVLA (P = 0.010). Over 10 days, mean(s.d.) pain scores were 22.0(19.8) mm versus 34.3(21.1) mm for RFA and EVLA respectively (P = 0.001). The mean(s.d.) number of analgesic tablets used was lower for RFA than for EVLA over 3 days (8.8(9.5) versus 14.2(10.7); P = 0.003) and 10 days (20.4(22.6) versus 35.9(29.4) respectively; P = 0.001). Changes in AVVQ, SF-12 and VCSS scores at 6 weeks were similar in the two groups: AVVQ (P = 0.887), VCSS (P = 0.993), SF-12 physical component score (P = 0.276) and mental component score (P = 0.449)., Conclusion: RFA using VNUS ClosureFAST was associated with less postprocedural pain than EVLA. However, clinical and quality-of-life improvements were similar after 6 weeks for the two treatments.

Objective: To evaluate patient satisfaction following endothermal ablation for varicose veins (VVs)., Methods: A 12-question survey was sent to consecutive patients treated with endothermal ablation--questions related to preprocedure symptoms, recurrence, further treatments, and patient satisfaction., Results: Questionnaires sent a median 12 (range 6-22) months postintervention were returned by 177 (60.0%) of 295 patients; 63 (35.6%) of 177 received treatment for recurrent VVs. Preintervention symptoms included aching (141 [79.7%] of 177), swelling (86 [48.6%] of 177), and heaviness (72 [40.7%] of 177). Improvements in preoperative symptoms were reported by 82.5% (146 of 177). Postintervention recurrence was reported by 87 (49.4%) of 177; 61 (70.1%) of 87 reported a few recurrent varicosities only. Further treatment was required by 11 (6.2%) of 177; 79 (44.6%) of 177 of patients reported no complications. The majority (151 [85.8%] of 176) were satisfied with their treatment. In all, 16 (25.4%) of 62 of patients treated for recurrent VVs were dissatisfied versus 9 (7.9%) of 114 of those with primary VVs (P = .0026)., Conclusions: The majority of patients are satisfied with results following endothermal ablation. Dissatisfaction may be more likely following treatment for recurrent VVs.

Objectives: A number of modalities are now available for the treatment of varicose veins. The aim of the study was to investigate the factors considered important by patients when contemplating treatment of their varicose veins., Methods: Consecutive new patients referred to a vascular surgery service were invited to complete a short anonymous questionnaire prior to their consultation. The questionnaire consisted of 13 multiple choice questions relating to symptoms, potential varicose vein treatments and patient knowledge of existing therapies., Results: Of 111 patients, there were 83 complete responses (75%). Symptoms of pain or aching were reported as moderate or severe by 77/103 (75%) of patients and significantly limited the activities of 47/101 (47%). Although the majority (89/103 [86%]) of patients were aware of surgery, only 52/103 (51%) knew of the existence of endothermal ablation (either laser or radiofrequency) and only 23/103 (22%) were aware of foam sclerotherapy. Some 58/92 (63%) were in favour of local anaesthetic treatment. Most patients (74/103, 72%) felt inadequately informed to express a preference regarding treatment type prior to their consultation, although 24/103 (23%) expressed a preference for endovenous treatment. Interestingly, 74/92 (80%) stated that the opinion of their vascular surgeon would be likely to or definitely influence their treatment decision and the majority of patients stated that what they had read in magazines (54/80, 64%) or on the Internet (51/85, 60%) would have no influence on their decision regarding treatment, respectively., Conclusion: Only a minority of patients referred with varicose veins were aware of endovenous treatments or felt adequately informed to express a treatment preference prior to consultation. Over half of patients expressed a preference for local anaesthetic therapy and a preference for a single visit treatment, although most would be strongly influenced by the opinion of their vascular surgeon and not influenced by media advertising.

Objectives: The aim of this study was to evaluate postoperative pain following endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) and identify risk factors for increased pain., Methods: Patients undergoing either segmental RFA (VNUS Closure Fast, VNUS Medical Technologies, San Jose, California) or EVLA (980 nm) for varicose veins completed a preoperative disease-specific quality-of-life questionnaire (Aberdeen Varicose Vein Questionnaire [AVVQ]) and a diary card recording postoperative pain, return to normal activities, and return to work. Median 3- and 10-day pain scores were calculated., Results: In all, 81 patients returned diary cards (RFA = 45, EVLA = 36). Patients receiving RFA reported less postoperative pain than those receiving EVLA at 3 days (14.5 vs 25.8 mm, P = .053, Mann-Whitney U test) and 10 days (13 vs 23.3 mm, P = .014, Mann-Whitney U test) and returned to work earlier than those receiving EVLA (median 5 vs 9 days, P = .022)., Conclusions: Patients treated with segmental RFA had less postoperative pain and returned to work quicker than those treated with EVLA.

Introduction: This paper aims to summarize the scientific rationale and future perspectives in the development of effective matrix metalloproteinase (MMP) modulators in the management of patients with arterial and venous disease., Methods: Pubmed, Embase and Cinahl databases were searched using the search terms 'MMP', 'matrix metalloproteinase', 'arterial disease', 'venous disease', 'aneurysm', 'vascular disease', 'atherosclerosis' and 'varicose veins'. Articles focussing on aneurysm disease, peripheral arterial disease, carotid stenosis and venous disorders were included., Results: Animal studies assessing MMP expression have demonstrated that MMP-2 and MMP-9 may contribute to arterial aneurysm formation and in atherosclerosis. Human studies and animal models have shown that MMP-3 and MMP-9 may have a protective role against plaque development and destabilization whereas MMP-12 might promote these changes. In venous disease, increased expression of MMP-1, MMP-9 and MMP-13 have been shown in human varicose veins. MMP-2 and MMP-9 were also shown to be upregulated in experimentally induced venous hypertension and higher concentrations of MMP-2 in wound exudate and biopsies have been shown to correlate with impaired venous ulcer healing. The use of statins has become widespread in patients with arterial disease and MMP inhibition is likely to contribute to the mechanism of action. More selective MMP modulators are currently being developed, although clinical studies are currently lacking., Conclusions: MMPs have been directly implicated in the pathophysiology of many arterial and venous disorders and remain an important potential therapeutic target. Studies are needed to further develop and demonstrate the clinical benefits of MMP modulating agents.

Peripheral arterial disease is commonly caused by atherosclerosis, and symptoms depend on the location and size of the affected artery, metabolic demands on the tissue, and the presence or absence of a collateral circulation. This article reviews the current evidence for the diagnosis and management of peripheral arterial disease.

Objectives: To review the mechanisms, diagnosis and treatment options for symptomatic iliac artery compression in cyclists., Methods: Pubmed, Medline, Embase and Google were searched using combinations of the terms 'iliac artery disease', 'iliac artery compression', 'iliac artery stenosis', 'cyclists' and 'athletes'., Results: Tethering of the iliac artery by the psoas arterial branch and fibrous tissue, and muscular hypertrophy predispose the vessel to kinking and compression during cycling. Symptoms may only be present on maximal exercise in the cycling position. Provocative exercise tests using a cycling ergometer with ankle brachial pressure index measuring has a sensitivity of 85% to detect arterial insufficiency. Magnetic resonance imaging is increasingly being used as the investigation of choice to confirm the diagnosis, although digital subtraction angiography and colour duplex ultrasonography may also help. Conservative measures including adjustments to the cycling posture and bicycle setup should be recommended to all patients. The evidence for surgical and endovascular treatments is limited and the use of prosthetic graft should be avoided., Conclusions: Iliac artery compression should be recognised as an important differential diagnosis in competitive cyclist presenting with lower limb symptoms. Although the optimal treatment strategy remains unclear, early diagnosis may reduce unnecessary investigations, and enable the cyclist to make appropriate adjustments and decisions in treatment management.

Circadian rhythms in stomatal aperture and in stomatal conductance have been observed previously. Here we investigate circadian rhythms in apertures that persist in functionally isolated guard cells in epidermal peels of Vicia faba, and we compare these rhythms with rhythms in stomatal conductance in attached leaves. Functionally isolated guard cells kept in constant light display a rhythmic change in aperture superimposed on a continuous opening trend. The rhythm free-runs with a period of about 22 hours and is temperature compensated between 20 and 30 degrees C. Functionally isolated guard cell pairs are therefore capable of sustaining a true circadian rhythm without interaction with mesophyll cells. Stomatal conductance in whole leaves displays a more robust rhythm, also temperature-compensated, and with a period similar to that observed for the rhythm in stomatal aperture in epidermal peels. When analyzed individually, some stomata in epidermal peels showed a robust rhythm for several days while others showed little rhythmicity or damped out rapidly. Rhythmic periods may vary between individual stomata, and this may lead to desynchronization within the population.