Incidence and risk factors for venous reflux in the general population: Edinburgh Vein Study.

OBJECTIVE/BACKGROUND: Chronic venous disease (CVD) is common, but the incidence of venous reflux, a precursor to this condition, is unknown. This study measured the incidence of venous reflux and associated risk factors, and examined the association between venous reflux and the incidence of CVD. METHODS: In the Edinburgh Vein Study, a random sample of 1566 men and women aged 18-64 years were examined at baseline. Eight hundred and eighty of these patients were followed up 13 years and underwent an examination comprising clinical classification of CVD and duplex scanning of the deep and superficial systems to measure venous reflux ≥0.5 s. RESULTS: The 13-year incidence of reflux was 12.7% (95% confidence interval [CI] 9.2-17.2), equivalent to an annual incidence of 0.9% (95% CI 0.7-1.3). The 13-year incidence of isolated superficial, isolated deep, and combined deep and superficial reflux was 8.8% (95% CI 5.6-12.0), 2.6% (95% CI 1.2-5.0), and 1.3% (95% CI 0.4-3.2), respectively. The highest incidence was in the great saphenous vein in the lower thigh (8.1%, 95% CI 5.4-11.8). There were no age or sex differences (p > .050). The risk of developing reflux was associated with being overweight (odds ratio [OR] 2.1, 95% CI 1.0-4.4) and with history of deep vein thrombosis (OR 11.3, 95% CI 1.0-132.3). Venous reflux at baseline was associated with new varicose veins at follow up (p < .001): the age- and sex-adjusted OR was 4.4 (95% CI 1.8-10.8) in those with isolated superficial reflux and 7.3 (95% CI 2.6-22.5) in those with combined deep and superficial reflux. CONCLUSION: For every year of follow-up, around 1% of this adult population developed venous reflux. In two thirds of cases, the superficial system was affected. Venous reflux increased the risk of developing varicose veins, especially when combined deep and superficial reflux was present.

Telangiectasia in the Edinburgh Vein Study: epidemiology and association with trunk varices and symptoms.

OBJECTIVE: Little research has been devoted to telangiectasia. The purpose of this study was to analyse the data in the Edinburgh Vein Study to determine the prevalence of telangiectasia in the general population, to analyse the demographic characteristics and association with symptoms and to compare the findings to those relating to varices of the saphenous systems. DESIGN: Cross-sectional population study. SETTING: Twelve general practices with catchment areas geographically and socioeconomically distributed throughout Edinburgh. PARTICIPANTS: An age stratified random sample of 1566 people (699 men and 867 women) aged 16-64 selected from computerised age-sex registers of participating practices. METHODS: Included in the population screening was a clinical examination, photography and duplex ultrasonography of the superficial veins and the deep veins down to popliteal level. Telangiectases and varicose veins were graded 1-3 according to severity. RESULTS: A total of 1322 (84%) of the population were classified as having telangiectasias in their right legs; 555 (79%) of men and 767 (88%) of women; 1226 (92%) as grade 1 and 96 (8%) as grades 2 and 3. There were no significant differences between left and right legs (p=0.144). The commonest locations for telangiectases were the postero-medial aspects of the thigh, popliteal fossa and upper one third of calf. There was a highly significant association between the degree of severity of varicose veins and the grade of telangiectasia (p<0.001). Less than 1% of subjects with grades 2-3 trunk varices were free of telangiectasia, but 51% of subjects with grades 2-3 telangiectasia had no clinical evidence of varicose veins. There was a significant linear trend in the proportion of subjects reporting heaviness, swelling, aching and cramps being highest among those with neither telangiectasia nor varicose veins, lower in those with telangiectasia or varicose veins only and lowest in subjects having both. The highest frequency of most symptoms was found in subjects with both telangiectasia and varicose veins. CONCLUSIONS: Telangiectasia is so common in the general population, especially in women, as to represent the norm. The anatomical distribution is entirely different from the distribution of the skin and subcutaneous manifestations of chronic venous insufficiency. Our confirmation of a strong association between trunk varices and grades 2-3 telangiectasia suggests the need for controlled studies into which condition should be treated. We found no evidence that telangiectasia per se was entirely responsible for leg symptoms.

Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms.

BACKGROUND: Two clinical trials, one British and one American, have shown that early, prophylactic elective surgery does not improve five-year survival among patients with small abdominal aortic aneurysms. We report long-term outcomes in the United Kingdom Small Aneurysm Trial. METHODS: We randomly assigned 1090 patients, 60 to 76 years of age, with small abdominal aortic aneurysms (diameter, 4.0 to 5.5 cm) to one of two groups: 563 were assigned to undergo early elective surgery, and 527 were assigned to undergo surveillance by ultrasonography. Patients were followed in the trial until June 1998 and thereafter until August 2001; the mean duration of follow-up was 8 years (range, 6 to 10). RESULTS: The mean duration of survival was 6.5 years among patients in the surveillance group, as compared with 6.7 years among patients in the early-surgery group (P=0.29). The adjusted hazard ratio for death from any cause in the early-surgery group as compared with the surveillance group was 0.83 (95 percent confidence interval, 0.69 to 1.00; P=0.05). The 30-day operative mortality in the early-surgery group (5.5 percent) led to an early disadvantage in terms of survival. The survival curves crossed at three years, and at eight years, mortality in the early-surgery group was 7.2 percentage points lower than that in the surveillance group (P=0.03). There was no evidence that age, sex, or the initial size of the aneurysm modified the hazard ratio or that delayed surgery in the surveillance group increased 30-day postoperative mortality. Death was attributable to a ruptured aneurysm in 19 of the 411 men who died (5 percent) and in 12 of the 85 women who died (14 percent) (P=0.001). The rate of early cessation of smoking was higher in the early-surgery group than in the surveillance group. CONCLUSIONS: Among patients with a small abdominal aortic aneurysm, we found no long-term difference in mean survival between the early-surgery and surveillance groups, although after eight years, total mortality was lower in the early-surgery group. This difference may be attributed in part to beneficial changes in lifestyle adopted by members of the early-surgery group.

Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial.

BACKGROUND: The treatment of rest pain, ulceration, and gangrene of the leg (severe limb ischaemia) remains controversial. We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty in such patients. METHODS: We randomly assigned 452 patients, who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease, to receive a surgery-first (n=228) or an angioplasty-first (n=224) strategy. The primary endpoint was amputation (of trial leg) free survival. Analysis was by intention to treat. The BASIL trial is registered with the National Research Register (NRR) and as an International Standard Randomised Controlled Trial, number ISRCTN45398889. FINDINGS: The trial ran for 5.5 years, and follow-up finished when patients reached an endpoint (amputation of trial leg above the ankle or death). Seven individuals were lost to follow-up after randomisation (three assigned angioplasty, two surgery); of these, three were lost (one angioplasty, two surgery) during the first year of follow-up. 195 (86%) of 228 patients assigned to bypass surgery and 216 (96%) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median (IQR) of 6 (3-16) and 6 (2-20) days after randomisation, respectively. At the end of follow-up, 248 (55%) patients were alive without amputation (of trial leg), 38 (8%) alive with amputation, 36 (8%) dead after amputation, and 130 (29%) dead without amputation. After 6 months, the two strategies did not differ significantly in amputation-free survival (48 vs 60 patients; unadjusted hazard ratio 1.07, 95% CI 0.72-1.6; adjusted hazard ratio 0.73, 0.49-1.07). We saw no difference in health-related quality of life between the two strategies, but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy. INTERPRETATION: In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty, a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angioplasty.

A comparison of acylated streptokinase-plasminogen complex and streptokinase in healthy volunteers.

The in vivo effects on the fibrinolytic and coagulation system of infusion acylated streptokinase-plasminogen complex (BRL 26921; 5, 7 and 12 mg) or streptokinase (250,000 u) were determined in healthy male volunteers. While this dose of streptokinase resulted in depletion of plasminogen and antiplasmin, and in some cases of fibrinogen and coagulation factors V and VIII, the equivalent 7 mg dose of BRL 26921 had little effect on these parameters. 12 mg BRL 26921 had some systemic effects on the fibrinolytic system. For initial clinical studies a dose of 10 mg BRL 26021 would seem appropriate. Both drugs induced an anamnestic rise in streptokinase antibody, whereas no change in liver function tests were observed. A delayed mild febrile reaction was observed in some subjects following infusion of streptokinase or BRL 26921. Clinical, laboratory, and subjective monitoring revealed no other adverse effects with either drug.

Smoking and risk factors in deep vein thrombosis.

The incidence of deep vein thrombosis (DVT) as diagnosed by the 125I fibrinogen test (125IFT) was determined in a series of 300 newly admitted medical and 201 surgical patients. 6 medical patients died before 125IFT screening could be completed. The incidence of DVT was 14% in medical patients and 18% in surgical patients. Increasing age, a malignant condition and a past history of thromboembolism all increased the risk of DVT. Increasing levels of cigarette smoking were found to be associated with a reduced incidence of DVT. Although statistical significance was achieved at only the 10% level for this finding it is in agreement with the results from studies on patients with myocardial infarction. The protective effect of cigarrette smoking was observed at all ages, and in both medical and surgical patients.

beta-thromboglobulin and deep vein thrombosis.

The measurement of plasma beta-thromboglobulin as a potential diagnostic test for venous thrombosis has been investigated in 16 normal volunteers, 24 patients presenting with deep vein thrombosis (DVT) or pulmonary embolism and 46 patients screened by 125I fibrinogen test (IFT) for post-operative DVT. The normal mean was 33 ng/ml (range 15-117 ng/ml). Of the 24 patients with clinical thrombotic disease 22 presented with DVT confirmed by phlebogram or IFT and 2 presented with embolism confirmed by lung scan. At the time of first presentation 12 out of 24 had betaTG values greater than 70 ng/ml. All except 3 of this group of 24 patients had values of greater than 70 ng/ml at some stage during a subsequent week of daily sampling. DVT was detected in 13 out of 46 screened post-operative patients. There was a rise om betaTG observed within 24 hr of the IFT becoming positive but the mean rise did not reach significance at the 5% level. An association between DVT and high betaTG values has been confirmed. However, its clinical value cannot yet be fully elucidated until factors, probably related to blood sampling and clearance, are further investigated.

Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population.

Intermittent claudication has been studied in cardiovascular surveys but limited information is available on asymptomatic peripheral arterial disease. The purpose of this paper is to describe the prevalence of both asymptomatic and symptomatic disease and relation to ischaemic heart disease in the Edinburgh Artery Study. A cross-sectional survey was conducted on an age-stratified sample of men and women aged 55 to 74 years selected from age-sex registers in ten general practices in the city. Arterial disease was assessed in 1592 participants by means of the WHO questionnaire on intermittent claudication and measurement of the ankle brachial systolic pressure index (ABPI) and change in ankle systolic pressure during reactive hyperaemia. The prevalence of intermittent claudication was 4.5% (95% confidence interval (CI): 3.5%-5.5%). Major asymptomatic disease causing a significant impairment of blood flow occurred in 8.0% (95% CI: 6.6%-9.4%). A further 16.6% (95% CI: 14.6%-18.5%) had criteria considered abnormal in clinical practice: 9.0% had ABPI less than 0.9 and 7.6% had reactive hyperaemia pressure reduction greater than 20%. Intermittent claudication was equally common in both sexes. The ABPI and reactive hyperaemia results suggested a slight preponderance of asymptomatic disease in males and were consistent with an increasing prevalence with age and lower social class. Mean ABPI was higher in normal men than women, and was lower in the left leg than the right suggesting a unilateral predisposition to disease. Subjects with major asymptomatic disease had more evidence of ischaemic heart disease than in the normal population (relative risk (RR) 1.6; 95% CI: 1.3-1.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Lifestyle risk factors for lower limb venous reflux in the general population: Edinburgh Vein Study.

BACKGROUND: Varicose veins occur commonly in the general population but the aetiology is not well established. Varicosities are associated frequently with reflux of blood in the leg veins due to valvular incompetence. Our aim was to determine in the general population which lifestyle factors were related to reflux and thus implicated in the aetiology of varicose veins. METHODS: In the Edinburgh Vein Study, 1566 men and women aged 18-64 years were sampled randomly from the general population in the city of Edinburgh, Scotland, and had duplex scans to measure reflux in eight venous segments in each leg. A self-administered questionnaire enquired about occupation, mobility at work, smoking, obstetric history, dietary fibre intake and bowel habit. A bowel record form was completed subsequently. RESULTS: In women, venous reflux was associated with decreased sitting at work (odds ratio [OR] = 0.76, 95% CI : 0.61-0.94), previous pregnancy (OR = 1.20, 95% CI : 0.93-1.54), and a lower prior use of oral contraceptives (OR = 0.84, 95% CI : 0.66-1.06). Mean body mass index was greater in women with superficial reflux compared to those with no reflux: 26.2 kg/m(2) (95% CI : 25.5-27.0) versus 25.2 kg/m(2) (95% CI : 24.8-25.6). On age adjustment, sitting at work remained related to reflux (OR = 0.78, 95% CI : 0.63-0.98) and prior use of oral contraceptives to superficial reflux (OR = 0.71, 95% CI : 0.50-1.01). In age-adjusted analyses in men, height was related to reflux, (OR = 1.13, 95% CI : 1.02-1.26) and straining at stool was related to superficial reflux (OR = 1.94, 95% CI : 1.12-3.35). No associations were found in either sex between reflux and social class, lifetime cigarette consumption, dietary fibre intake and intestinal transit time. CONCLUSIONS: This population study did not identify strong and consistent lifestyle risk factors for venous reflux although previous pregnancy, lower use of oral contraceptives, obesity and mobility at work in women and height and straining at stool in men may be implicated.

Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population.

BACKGROUND: Intermittent claudication is associated with a poor prognosis, but less is known of the risks associated with asymptomatic peripheral arterial disease. The aims of this study were to determine the incidence and natural history of claudication, and the incidence of cardiovascular events in symptomatic and asymptomatic peripheral arterial disease. METHODS: In 1988, 1592 subjects aged 55-74 years were selected randomly from the age-sex register of 10 general practices in Edinburgh, Scotland. The presence of peripheral arterial disease was determined by the World Health Organization questionnaire on intermittent claudication, the ankle brachial pressure index and a reactive hyperaemia test. This cohort was followed prospectively over 5 years for subsequent cardiovascular events and death. RESULTS: One hundred and sixteen new cases of claudication were identified (incidence density 15.5 per 1000 person-years). Of those with claudication at baseline, 28.8% and still had pain after 5 years, 8.2% underwent vascular surgery or amputation, and 1.4% developed leg ulceration. Claudicants had a significantly increased risk of developing angina compared with normals (RR: 2.31, 95% CI: 1.04-5.10), and asymptomatic subjects had a slightly increased risk of myocardial infarction and stroke. Deaths from cardiovascular disease were more likely in both claudicants (RR: 2.67, 95% CI: 1.34-5.29) and subjects with major (RR: 2.08, 95% CI: 1.13-3.83) or minor asymptomatic disease (RR: 1.74, 95% CI: 1.09-2.76). Subjects with major asymptomatic disease also had an increased risk of non-cardiovascular death (RR: 2.19, 95% CI: 1.33-3.59), and therefore had the highest overall risk of death (RR: 2.44, 95% CI: 1.59-3.74). CONCLUSIONS: Subjects with asymptomatic peripheral arterial disease appear to have the same increased risk of cardiovascular events and death found in claudicants.

Water vapour transmission rates in burns and chronic leg ulcers: influence of wound dressings and comparison with in vitro evaluation.

One of the main functions of wound dressings is to control water vapour transmission rate (WVTR) from wounded skin. In this paper, the influence of hydrocolloid, knitted viscose and gauze dressings was evaluated through in vivo measurement of WVTR in burns and chronic leg ulcers utilizing an evaporimeter. The results suggest that the evaporative water vapour loss from exposed skin wounds depends mainly on the wound depth, and that chronic leg ulcers have the same level of the WVTR as full thickness burns. Compared with the knitted viscose and gauze dressings, hydrocolloid dressing has a greater effect on reducing evaporative water loss, with WVTR being 20-30% of that of exposed wounds under the conditions used in this study. This result is in agreement with that obtained in an in vitro evaluation.

Atherosclerotic plaque at the carotid bifurcation: CT angiographic appearance with histopathologic correlation.

BACKGROUND AND PURPOSE: The likelihood that carotid plaque will give rise to cerebral ischemia probably relates to the degree of arterial stenosis and to plaque morphology. The aim of this study was to assess whether features seen at CT angiography might be used to predict carotid plaque stability by comparing CT angiograms with histopathologic examinations of the carotid artery bifurcation. METHODS: Nine patients with symptomatic severe carotid stenosis at intraarterial angiography had CT angiography of the carotid bifurcation before carotid endarterectomy. After endarterectomy, multiple sections of the specimens through the carotid bifurcation were examined histologically. Plaque characteristics recorded included the proportion of necrotic/lipid core, presence of hemorrhage, extent of fibrosis, ulceration, calcification, inflammatory cell infiltrate, and fibrous cap thickness. Corresponding CT angiograms were assessed for plaque size, distribution, and radiodensity as well as presence of calcific density and ulceration. Histologic findings and CT angiograms were compared. RESULTS: Plaque with a large necrotic/lipid core, which was often hemorrhagic, was found in 16 of 23 sections, and in 15 of these this histologic appearance corresponded with patchy or homogeneous low density on CT angiograms. Six of seven predominantly fibrous plaques were of soft-tissue density on CT angiograms. High density consistent with calcification was seen more frequently on CT angiograms than it was detected histologically, but CT angiography depicted plaque ulceration poorly (four ulcers at histology; two false-positive and two false-negative findings at CT angiography). CONCLUSION: CT angiography is a promising method for assessing the lumen and wall of the carotid artery. The apparent correlation between histologic appearance and plaque density on CT angiograms has important implications for the prediction of plaque stability, even though ulceration is shown inconsistently.

Variability of ankle and brachial systolic pressures in the measurement of atherosclerotic peripheral arterial disease.

The aim of this study was to determine the variability of measurements of ankle and brachial systolic pressures and ankle brachial ratios in order to assess their suitability for use in epidemiological studies of arterial disease in the lower limbs. Thirty-six subjects had repeat measurements taken by four observers on two separate days using a Doppler probe and random zero sphygmomanometer. The variability in the measurement of ankle systolic pressure was comparable to that for brachial systolic pressure. The 95% confidence limits of one measurement of the ankle brachial ratio was estimated to be +/- 16%, reducing to +/- 10% for the mean of four measurements taken by two observers on two days. Analysis of variance indicated that the variability in the measurement of ankle brachial ratios attributable to observers, days, timing of measurements on the same day, and repeat measurements was considerably less than the "biological" variability between subjects and between legs. These results suggest that repeatability of the ankle brachial ratio is such that a single measurement is suitable for most epidemiological studies of atherosclerotic peripheral arterial disease.

Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study.

STUDY OBJECTIVE: To determine the prevalence of varicose veins and chronic venous insufficiency (CVI) in the general population. DESIGN: Cross sectional survey. SETTING: City of Edinburgh. PARTICIPANTS: Men and women aged 18-64 years selected randomly from age-sex registers of 12 general practices. MAIN RESULTS: In 1566 subjects examined, the age adjusted prevalence of trunk varices was 40% in men and 32% in women (p < or = 0.01). This sex difference was mostly a result of higher prevalence of mild trunk varices in men. More than 80% of all subjects had mild hyphenweb and reticular varices. The age adjusted prevalence of CVI was 9% in men and 7% in women (p < or = 0.05). The prevalence of all categories of varices and of CVI increased with age (p < or = 0.001). No relation was found with social class. CONCLUSIONS: Approximately one third of men and women aged 18-64 years had trunk varices. In contrast with the findings in most previous studies, mainly conducted in the 1960s and 1970s, chronic venous insufficiency and mild varicose veins were more common in men than women. No evidence of bias in the study was found to account for this sex difference. Changes in lifestyle or other factors might be contributing to an alteration in the epidemiology of venous disease.

Haemostatic factors and risk of varicose veins and chronic venous insufficiency: Edinburgh Vein Study.

Despite much research, the aetiology of venous disease is still poorly understood. Since haemostatic factors are involved in the processes of fibrinolysis and platelet aggregation, it is conceivable that such processes may be implicated in the pathology of varicose veins and chronic venous insufficiency (CVI). The Edinburgh Vein Study examined 1566 men and women aged 18-64 years that were randomly selected from the lists of 12 general practitioners. Each subject completed a questionnaire, underwent a comprehensive clinical examination and had a blood sample taken for the analysis of plasma fibrinogen, tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) antigens. Subjects with trunk varicose veins and those with CVI had higher levels of each haemostatic factor compared with those with no trunk varices and no CVI. Although unit increases in t-PA and vWF were initially associated with a significantly increased risk of CVI in men, and both factors with an elevated risk of trunk varices in women, multiple adjustment for age, smoking status and body mass index reduced the odds ratios to non-significance. However, this does not entirely rule out the possibility of a pathogenic role for haemostatic factors in venous disease, but rather indicates the need for further experimental and epidemiological studies.

Doppler waveform analysis and percutaneous dilatation of arteries in ischaemia of the lower limb.

Percutaneous transluminal dilatation of narrowed atheromatous arteries using the inflatable Gruntzig catheter is becoming an accepted non-surgical treatment for patients with disabling intermittent claudication of the lower limb. The use of doppler ultrasound to study limb blood flow in a group of patients having aortic or iliac dilatation is described.

Case report: infected false aneurysm at the site of an iliac stent.

False aneurysm formation at the site of iliac artery stent placement is an uncommon but serious complication of the procedure. We report a case of infected false aneurysm at the site of an iliac stent, complicated by renal failure.

Epidemiology of varicose veins. A review.

Disease of the venous system is a major problem affecting western societies, resulting in considerable morbidity in the population and cost to the health service. In many countries "varicose veins are probably the commonest disorder presenting to general surgeons" and an average of 30% of district nursing time is estimated to be spent caring for patients with venous ulcers. For the patient with varicose veins or leg ulceration, there is often persistent discomfort and disability extending over long periods of time. Despite this, little epidemiological research has been carried out on venous disease, perhaps partly because of society's perception that venous disease is not a major problem and it is not normally a cause death. More recently however, efforts have been made to conduct structured epidemiological studies to identify risk factors and to clarify the geographical variations suggested in the past by anecdotal evidence. This article reviews recent epidemiological studies, discusses the prevalence of varicose veins and presents evidence for and against the differing theories of causation.

Socioeconomic impact of chronic venous insufficiency and leg ulcers.

Chronic venous insufficiency affects approximately 5% and chronic leg ulcer approximately 1% of the adult population of developed countries. Not only do recent quality of life studies highlight major disability and social impairment but, since this is a condition characterized by chronicity and relapse, it gives rise to massive health care expenditure amounting in the UK to around Pounds 400 million per annum. Venous disease consumes 1-2% of the health care budgets of European countries. Imprecise disease classifications and codings impede the acquisition of accurate data but there is a compelling need for better quality socioeconomic data concerning this long-neglected health care problem.

Review of classic research: Community clinics for leg ulcers.

These three critiques discuss the influence of the frequently referenced classic paper, cited below, on the management of leg ulcers.