Manjit S. Gohel

The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression

High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.

Post‐thrombotic syndrome: a clinical review

Up to half of patients with proximal deep vein thrombosis (DVT) will develop post‐thrombotic syndrome (PTS) despite optimal anticoagulant therapy. PTS significantly impacts upon quality of life and has major health‐economic implications. This narrative review describes the pathophysiology, risk factors, and diagnosis, prevention and treatment of PTS, to improve our understanding of the disease and guide treatment. Relevant articles were identified through systematic searches of the PubMed, EMBASE and Cochrane databases between 1966 and November 2011. Studies were included for detailed assessment if they met the following criteria: published in English, human study participants, study population aged > 18 years, and lower limb post‐thrombotic syndrome. All non‐systematic reviews and single patient case reports were excluded. Recurrent thrombosis, thrombus location and obesity are major risk factors, whereas the importance of gender and age remain uncertain. The diagnosis of PTS is based on clinical findings in patients with a known history of DVT. Several clinical scales have been described, with the Villalta Score gaining increasing popularity. Adequate anticoagulation and use of elastic compression stockings (ECS) following DVT can reduce the incidence of PTS. Catheter‐directed thrombolysis and mechanical thrombectomy of acute DVT may preserve valvular function. Studies to date of these techniques are encouraging, and have reported improved hemodynamics and a reduced incidence of PTS. The management of established PTS is challenging. Compression therapy, aimed at reducing the underling venous hypertension, remains the mainstay of treatment. This is despite a paucity of high‐quality evidence to support its use. Pharmacologic and surgical treatments have also been described, with a number of studies citing symptomatic improvement.

Pharmacological treatment in patients with C4, C5 and C6 venous disease

Background A range of surgical, endovenous, physical and medical treatments are available for patients with chronic venous disease. The aim of this review was to evaluate the evidence for pharmacological agents used for the treatment of chronic venous disease. Methods A literature search was performed using Pubmed, Embase, Cochrane and Google Scholar databases. The initial search terms ‘varicose vein’, ‘venous ulcer’, ‘venous disease’ and ‘lipodermatosclerosis’ were used to identify relevant clinical studies of pharmacotherapy in patients with chronic venous disease (C4–C6). Results A huge range of naturally occurring and synthetic drugs have been studied in patients with chronic venous disease. For patients with C4 venous disease, micronized purified flavonoid fraction (MPFF), oxerutin, rutosides and calcium dobesilate may reduce venous symptoms and oedema. MPFF and pentoxifylline have been shown to improve venous ulcer healing when used in addition to multilayer compression bandaging. The clinical benefits of other medications remain unproven. Reliability of meta-analyses was limited by study heterogeneity, small sample sizes and lack of long-term follow-up. Conclusions In prospective randomized studies, MPFF (Daflon®), other flavonoid derivatives and pentoxifylline have demonstrated clinical benefits in patients with C4–C6 venous disease. Pharmacotherapy should be part of a range of treatment options in the modern management of patients with chronic venous disorders.

Venous Hypoxia: A Poorly Studied Etiological Factor of Varicose Veins

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.

The treatment of varicose veins: an investigation of patient preferences and expectations

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.

Identification of patient safety improvement targets in successful vascular and endovascular procedures: analysis of 251 hours of complex arterial surgery.

OBJECTIVES To investigate failures in patient safety for patients undergoing vascular and endovascular procedures to guide future quality and safety interventions. DESIGN Single centre prospective observational study. METHODS 66 procedures (17 thoracoabdominal and 23 abdominal aortic aneurysms, 4 carotid and 22 limb procedures) were observed prospectively over a 9-month period (251 h operating time) by two trained observers. Event logs were recorded for each procedure. Two blinded experts identified and independently categorised failures into 22 types (using a validated category tool) and severity (5-point scale). Data are expressed as median (range). Statistical analysis was performed using Mann-Whitney U, Kruskal-Wallis and Spearmans Rank tests. RESULTS 1145 failures were identified with good inter-assessor reliability (Cronbachs alpha 0.844). The commonest failure types related to equipment (including unavailability, configuration and other failures) (269/1145 [23.5%]) and communication (240/1145 [21.0%]). A comparatively lower number of technical and psychomotor failures were identified (103 [9.0%]). The number of failures correlated with procedure duration (rho = 0.695, p < 0.001) but not anatomical site of the procedure or pathology of the disease process. Failure rate was higher in patients undergoing combined surgical/endovascular procedures compared to open surgery (median 5.7/h [IQR 4.2-8.1] vs 3.0/h [2.5-3.5]; p < 0.001). The severity of failures was similar (1.5/5 [1-2] vs 1/5 [1-2] respectively; p = 0.095). For combined procedures, failure rates were significantly higher during the endovascular phase (9.6/h [7.5-13.7]) compared to the non-endovascular phase (3.0/h [1.0-5.0]; p < 0.001). CONCLUSIONS Failures in patient safety are common during complex arterial procedures. Few failures were severe, although minor failures during critical stages and accumulation of multiple minor failures may potentially be important. Failures occurred especially during the endovascular phase and were often related to equipment or communication aspects. Interventions to improve procedural safety and quality of care should primarily target these specific areas.

A Review of Familial, Genetic, and Congenital Aspects of Primary Varicose Vein Disease

Varicose veins are a common manifestation of chronic venous disease (CVD) and present as excessively dilated, tortuous, and elongated superficial veins in the lower limbs. Varicose veins arise either secondary to vein wall remodeling or valvular incompetence leading to blood stasis and venous hypertension.1 Patients may experience lower limb pain, muscle cramps, bleeding, swelling, and skin changes, which include lipodermatosclerosis and eventual ulceration.2 To date, no specific cause for the development of varicose veins has been identified. However, various genetic and environmental risk factors have been ascribed to their formation. Primary varicose veins have been shown to affect up to one third of the Western adult population and are a major cause of morbidity. Estimates of prevalence range from 2% to 56% in men and 1% to 60% in women.3,4 This inconsistency between reports may be due to heterogeneity of study populations, study designs, and experimental methodologies used as well as actual variations in the general population. Some reports suggest that varicose veins are more common in women than men,5–8 whereas others have shown the opposite.2,3,9,10 A cross-sectional survey in Edinburgh, UK, involving a total of 1566 patients, showed an age-adjusted prevalence of Grade 1 truncal varices in 33.3% of men compared with 26.2% of women.10 It has also been reported that there is a significant correlation between CVD onset and sex with females showing first symptoms at a mean age of 30.8 years and males at 36.8 years.8 Besides sex, the prevalence of varicose veins increases with age. The Edinburgh Vein Study reported the prevalence of varicose veins increases from 11.5% in 18 to 24 year olds age to 55.7% in 55 to 64 year olds.10 Similarly, other studies have reported …

A study of patient satisfaction following endothermal ablation for varicose veins.

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.

Secondary care treatment of patients with varicose veins in National Health Service England: at least how it appeared on a National Health Service website

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.

Heterogeneity of Reporting Standards in Randomised Clinical Trials of Endovenous Interventions for Varicose Veins

AIMS The efficacy of endovenous treatments for venous reflux has been demonstrated in numerous randomised clinical trials, although significant heterogeneity may exist between studies. The aim of this study was to assess the heterogeneity in reporting between randomised clinical trials investigating endovenous treatments for patients with varicose veins. METHODS A literature search of the Pubmed, Cochrane and Google Scholar databases was performed using appropriate search terms. Randomised clinical trials published between January 1968 and June 2009 evaluating endovenous interventions for varicose veins were included and relevant abstracts and full text articles were reviewed. Published study reports were evaluated against recommended reporting standards published by the American Venous Forum in 2007. RESULTS Twenty-eight randomised trials fulfilled the inclusion criteria. Median patient age (reported in 20/28 studies) ranged from 33 to 54 years. The CEAP classification was presented in 17/28 studies and the proportion of patients with C2 disease ranged from 6.3% to 83.5%. A total of 31 different outcome measures were utilised. This included 13 different questionnaires, varicose vein recurrence at 38 time points and 30 categories of complications. Duplex ultrasonography was used in 21/28 trials to assess recurrence. Quality of life was only evaluated in 11 studies and the follow-up period ranged from 3 weeks to 10 years. CONCLUSIONS Meaningful comparison across randomised studies of endovenous treatments is made difficult by considerable variations in study populations and outcome measures between trials. This highlights the need for the use of prospectively agreed population selection, and reporting standards for outcome measures in randomised clinical assessments of new treatments.