TASC II document on the management of peripheral arterial disease.
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Guideline Adherence↗
Biomedical subjects
A W Bradbury
Publications and source records attributed to A W Bradbury.
Obesity and thrombosis.
OBJECTIVES: To describe the pathophysiological mechanisms by which obesity increases the propensity to thrombosis, the leading cause of death in the Western World, with particular emphasis on the role of inflammation, oxidative stress, dyslipidaemia, insulin resistance and the coagulation cascade. DESIGN: Review article. MATERIALS AND METHODS: Medline (1966-2005) and Cochrane library review of literature examining the relationship between obesity and thrombosis. Search terms included obesity, overweight, body mass index, thrombosis, cardiovascular disease, venous thromboembolism, peripheral arterial disease, and coronary heart disease. RESULTS: Obesity is an important and growing public health issue that is estimated to affect more than half of the UK adult population. Obesity, in particular central (visceral) obesity, is associated with significant, and largely preventable, morbidity and mortality including an increased incidence and prevalence of arterial and venous thrombotic events. The various mechanisms by which obesity may cause thrombosis include: the actions of so-called adipocytokines from adipose tissue, e.g. leptin and adiponectin; increased activity of the coagulation cascade and decreased activity of the fibrinolytic cascade; increased inflammation; increased oxidative stress and endothelial dysfunction; and disturbances of lipids and glucose tolerance in association with the metabolic syndrome. CONCLUSIONS: Obesity appears to be associated with thrombosis via several mechanisms. These pro-thrombotic factors are all improved by weight loss.
Adiponectin↗
The low incidence of surgery for non-cardiac vascular disease in UK Asians may be explained by a low prevalence of disease.
AIMS: Firstly, to compare rates of surgery for non-cardiac vascular disease in Caucasians and Asians and secondarily to assess the prevalence of peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA) in the male UK Asian population. METHODS: Analysis of a prospective database followed by an epidemiological survey of 100 unselected Pakistani males, in which demographic and anthropometric data were collected alongside aortic ultrasonography and measurement of ankle: brachial pressure index (ABPI). RESULTS: Although 14.1% of our catchment area is Asian, after correction for age, they only accounted for 64/2268 (2.8%) of procedures for PAD and AAA. Specifically, Asians were 10 times less likely to undergo AAA repair and 3 times less likely to undergo procedures for lower limb peripheral bypass, amputation and endovascular intervention. In the epidemiological study, 26 subjects had a significant history of ischaemic heart disease, 21 were diabetic, 32 had hypertension and 60 were current or ex-smokers. Median aortic diameter [IQR] was 17.6 mm [16.3-19.1 mm] and no subject had an AAA. In 200 limbs, median ABPI [IQR] was 1.12 [1.04-1.21]. Only 2 patients had an ABPI < 0.9. CONCLUSION: Despite a high prevalence of cardiovascular risk factors and ischaemic heart disease, the prevalence of PAD and AAA is much lower than would have been expected in an age- and sex-matched Caucasian population. These data suggest that the reduced incidence of surgery for PAD and AAA in UK Asians is due to a low prevalence of disease.
Aged↗
A comparison between the short term and long term benefits of screening for abdominal aortic aneurysms from the Huntingdon Aneurysm screening programme.
BACKGROUND: The UK Multicentre Aneurysm Screening Study (MASS) showed a 44% reduction in AAA-related mortality after 4 years and predicted an increased number of deaths prevented in the longer term. We aim to compare the 5 and 13 years benefit from aneurysm screening in the Huntingdon Aneurysm screening programme. METHODS: Incidence and mortality of ruptured AAA (RAAA) after 5 and 13 years of screening in a population based aneurysm screening program. RESULTS: Five years of screening resulted in a reduction in the incidence of RAAA of 49% (95% CI: 3-74%). Nine out of 11 ruptures in the invited group did not survive (mortality 82%; 95% CI: 48-98%) compared to 38 non-survivors from 51 ruptures in the control group (mortality 75%; 95% CI: 60-86%). Five years of screening resulted in an RAAA-related mortality reduction of 45% (95% CI: -15 to 74%). After 13 years of screening the incidence of RAAA was reduced by 73% (95% CI: 58-82%). Twenty-one out of 29 ruptures in the invited group did not survive (mortality 72%; 95% CI: 53-87%) compared to 64 non-survivors from 82 ruptures in the control group (mortality 78%; 95% CI: 68-86%). Thirteen years screening resulted in a reduction of mortality from RAAA of 75% (95% CI: 58-84%). The number needed to screen to prevent one death reduced from 1380 after 5 years to 505 after 13 years. The number of elective AAA operations needed to prevent one death reduced from 6 after 5 years to 4 after 13 years. CONCLUSION: AAA screening becomes increasingly beneficial as screening continues over the longer term. Benefits continue to increase after screening has ceased.
Aortic Aneurysm, Abdominal↗
Hypotensive resuscitation in patients with ruptured abdominal aortic aneurysm.
BACKGROUND: The technique of hypotensive resuscitation in haemorrhagic shock involves resuscitation to below normotensive blood pressures achieving the minimum perfusion pressure that will adequately perfuse vital organs until definitive arrest of haemorrhage. AIM: To summarise the evidence for the use of hypotensive resuscitation in patients with uncontrolled haemorrhagic shock and ruptured abdominal aortic aneurysm (AAA). METHODS: A MEDLINE (1966-2004) and Cochrane library search for articles relating to hypotensive resuscitation was undertaken; see text for further details. RESULTS: Several animal studies exist using an abdominal aortotomy model of ruptured AAA. These have demonstrated improved tissue perfusion, decreased blood loss and improved survival associated with hypotensive resuscitation compared with aggressive resuscitation. There are several human studies advocating delayed rather than immediate resuscitation in trauma patients but careful review of the literature reveals no prospective studies of hypotensive resuscitation in patients with ruptured AAA. CONCLUSIONS: Animal studies demonstrate superiority of hypotensive resuscitation over aggressive resuscitation but further research is required to assess its efficacy in patients with ruptured AAA.
Aneurysm, Ruptured↗
Management of severe ischaemia of the leg.
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Catheterization↗
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.
Aged↗
The association between raised coagulation factor levels and venous thrombo-embolism.
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Blood Coagulation Factors↗
Peri-operative myocardial injury in patients undergoing surgery for critical limb ischaemia.
INTRODUCTION: Although up to a half of patients undergoing abdominal aortic aneurysm (AAA) repair suffer myocardial injury, as indicated by a rise in cardiac troponin I (cTnI), this is infrequently accompanied by a rise in creatine kinase (CK)-MB fraction or electrocardiogram (ECG) changes. This study compares for the first time peri-operative cTnI, CK-MB and ECG changes in patients undergoing surgery for critical lower limb ischaemia (CLI). METHODS: Twenty-nine patients (20 men, median age 75 [range, 57-95] years) were studied prospectively. cTnI, CK/CK-MB ratio and ECG were performed pre-operatively and on post-operative days 1, 2 and 3. RESULTS: Eleven (38%) patients had an elevated cTnI >0.5 ng/ml. Five (17%) patients had an elevated CK-MB fraction >4% and all of these patients had an elevated cTnI. Eleven (38%) patients had ischaemic changes on ECG including seven of 11 (64%) patients with elevated cTnI and all five patients with elevated CK-MB fraction. There was no relationship between pre-operative cardiac status, antiplatelet use or type of anaesthesia and post-operative cTnI rise. Patients with a cTnI rise were younger (p=0.01), and were more likely to have presented with gangrene (p=0.04) and have a longer operation time (p=0.01) than patients who did not demonstrate a cTnI rise. Four patients developed clinically apparent cardiac complications: cardio-pulmonary arrest (n=1), cardiogenic shock (n=1), acute CCF (n=1) and rapid atrial fibrillation (n=1). Survival at 6 months was 26 of 29 (90%) patients. CONCLUSION: These data demonstrate that over a third of patients operated for CLI sustain peri-operative myocardial injury, many of which are not clinically apparent. Pre-operative medical optimisation may improve prognosis in this group of patients.
Aged↗
The validity, reliability, reproducibility and extended utility of ankle to brachial pressure index in current vascular surgical practice.
BACKGROUND: Despite the increasing sophistication of vascular surgical practice, more than three decades after its introduction to clinical practice, the ankle to brachial pressure index (ABPI) remains the cornerstone of non-invasive assessment of the patient with symptomatic peripheral arterial disease (PAD). AIM: To summarise what is known about ABPI and critically appraise its validity, reliability, reproducibility and extended utility. METHODS: A MEDLINE (1966-2004) and Cochrane library search for articles relating to measurement of ABPI was undertaken; see text for further details. RESULTS: There is considerable disagreement as to how ABPI should be measured. Furthermore, various factors, including the type of equipment used, and the experience of the operator, can result in significant inter- and intra-observer error. As such, care must be taken when interpreting data in the literature. ABPI is valuable in the assessment of patients with atypical symptoms, venous leg ulcers and after vascular and endovascular interventions. However, absolute pressures are probably more valuable in patients with critical limb ischaemia. ABPI is also useful in subjects with asymptomatic PAD where it correlates well with, and may be used in screening studies to quantify, cardiovascular risk. CONCLUSIONS: While its apparent simplicity can beguile the unwary, ABPI will continue to have a key role in the assessment of symptomatic PAD. ABPI is also likely to have extended utility in health screening and institution of best medical therapy in asymptomatic subjects.
Ankle↗
Serum lactate and base deficit as predictors of mortality after ruptured abdominal aortic aneurysm repair.
OBJECTIVE: Whole body hypoperfusion and lower torso ischaemia-reperfusion contribute to post-operative organ dysfunction in patients undergoing repair of ruptured abdominal aortic aneurysm (AAA). Serum lactate and base deficit are markers of tissue ischaemia and are used to assess the adequacy of resuscitation. This study examines the prognostic value of immediate post-operative levels of serum lactate and base deficit in ruptured AAA. METHODS: Thirty patients (24 men and 6 women of median age 74, range 51-85, years) who survived to at least 12h after ruptured AAA repair were studied retrospectively. The relationship between immediate post-operative lactate, base deficit and mortality was determined. RESULTS: Fifteen patients (50%) died, all from organ failure. An elevated lactate (>2.1 mmol/l) and base deficit (<-2 mmol/l) were present in 20 (67%) and 27 (90%) patients, respectively. Lactate (p<0.001) and base deficit (p=0.003) were significantly higher in non-survivors compared with survivors. Lactate (p=0.021) and base deficit levels (p=0.028) were independently significant for predicting mortality and a significant interaction existed between lactate and base deficit levels for predicting mortality (p=0.027). The sensitivity and specificity of lactate > or =4.0 mmol/l was 13 of 15 (87%) and 12 of 15 (80%), respectively, and base deficit < or =-7 mmol/l was 12 of 15 (80%) and 12 of 15 (80%), respectively. The likelihood ratios for a positive result with the defined cut-off values for lactate and base deficit were 4.3 and 4.0, respectively. Lactate > or =4.0 mmol/l and base deficit or =-7 mmol/l were associated with a 4% probability of death. CONCLUSION: These data demonstrate that an immediate post-operative serum lactate > or =4.0 mmol/l and base deficit < or =-7 mmol/l are good predictors of outcome after ruptured AAA repair. The prognostic value of these simple and inexpensive tests require corroboration in a larger prospective study.
Acid-Base Imbalance↗
Coagulopathy and hyperfibrinolysis in ruptured abdominal aortic aneurysm repair.
Perioperative hemorrhage is one of the principal causes of death in patients with ruptured abdominal aortic aneurysm (AAA). This study examines perioperative coagulation and fibrinolysis in patients undergoing ruptured AAA repair complicated by coagulopathy. Eight patients (8 men of median age 74, range 69-87, years) who developed clinical and laboratory evidence of coagulopathy during attempted repair of ruptured infrarenal AAA were prospectively studied. Platelet count, fibrinogen, clotting times, prothrombin fragment (PF) 1+2, and tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) activities were measured preoperatively, immediately before, and 5 min and 24 hr after aortic declamping. Six patients died, three intraoperatively, one within 24 hr, and two in the late postoperative period. All patients had thrombocytopenia and prolonged clotting times intraoperatively with evidence of increased thrombin generation (as demonstrated by elevated PF 1+2). Five patients had increased systemic fibrinolysis (as demonstrated by elevated t-PA activity) preoperatively and/or before aortic declamping and all of these patients died. Three patients had perioperative inhibition of systemic fibrinolysis (as demonstrated by elevated PAI activity) and two survived. These data demonstrate that coagulopathy in ruptured AAA repair may be associated with a hyperfibrinolytic state. Further research is required to determine if (a) a causal relationship exists between hyperfibrinolysis and coagulopathy and (b) whether antifibrinolytic agents can improve outcome if targeted at this group of patients.
Aged↗
Nerve injuries and varicose vein surgery.
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Catheter Ablation↗
ACE inhibitors increase type III collagen synthesis: a potential explanation for reduction in acute vascular events by ACE inhibitors.
INTRODUCTION: Large trials have shown that angiotensin converting enzyme inhibitor (ACE-I) therapy reduces the risk of myocardial infarction and stroke. Acute vascular events are thought to be initiated by plaque rupture. Animal models of atherosclerosis show an increase in extra cellular matrix when given ACE-I therapy. ACE-I therapy could influence collagen synthesis, one of the major constituents of the atherosclerotic cap. METHODS: A nested case-control study was performed within the Huntingdon Aneurysm Screening Project. Subjects were assessed for arterial disease, drug history and smoking. Blood samples were taken for a measure of collagen synthesis, the amino-terminal propeptide of type III procollagen (PIIINP), lipid levels, iron metabolism and cotinine levels. RESULTS: Information was available for 420 subjects. Thirty-five were taking ACE-I therapy and 385 were not. Mean serum PIIINP level was 3.5 microg/l (sd 1.3 microg/l, range: 1.7-16.5 microg/l. There was a marked increase in mean collagen turnover between subjects taking ACE-I therapy compared to those not. Mean PIIINP level for cases and controls was 4.26 microg/l (95% CI: 3.73-4.79 microg/l) versus 3.61 microg/l (95% CI: 3.48-3.75 microg/l). No differences were found for patients taking other antihypertensive drugs. After adjusting for age, weight, height, lipid levels and ferritin, PIIINP levels remained significantly higher in cases than controls: 4.14 microg/l (95% CI: 3.72-4.57 microg/l) versus 3.62 microg/l (95% CI: 3.49-3.75 microg/l) (P-value 0.02). DISCUSSION: These results suggest that ACE-I therapy up-regulates collagen synthesis, and could improve plaque stabilisation. This may provide an explanation for the decrease in acute vascular events observed in patients on ACE-I therapy.
Acute Disease↗
The effect of long saphenous vein stripping on deep venous reflux.
BACKGROUND: The addition of long saphenous vein (LSV) stripping to sapheno-femoral junction (SFJ) disconnection and multiple stab avulsions (MSAs) in the course of varicose vein (VV) surgery is associated with a significant reduction in recurrence, and a significant improvement in quality of life. It is hypothesised that these benefits relate, at least in part, to a favourable effect of stripping on deep venous reflux. OBJECTIVE: To examine the effect of long saphenous vein (LSV) stripping on deep venous reflux (DVR). METHODS: This was prospective study of 62 consecutive patients (77 limbs) CEAP class 2-6, undergoing SFJ disconnection and MSAs, with and without successful stripping of the LSV to the knee. A duplex ultrasound examination was performed pre-operatively and at a median (IQR) of 24 (23-25) months post-operatively. Completely stripped limbs were defined as those in whom complete stripping of the LSV to the knee was confirmed on post-operative duplex. Reflux >/=0.5 s. was considered pathological. RESULTS: Pre-operatively, 32 (42%) limbs had deep venous reflux (DVR). Post-operative duplex at 24 months revealed that the LSV had been completely stripped in 29 (38%) limbs. In patients with pre-operative DVR, complete stripping was associated with a significant reduction in the prevalence of superficial femoral vein (SFV) (p<0.001) and popliteal vein (PV) (p=0.016), McNemar test) on post-operative duplex. By contrast, in patients without pre-operative DVR, incomplete stripping was associated the development of SFV (p=0.031) and PV (p=0.008) reflux. CONCLUSIONS: Complete LSV stripping abolishes DVR in a significant proportion of limbs, whereas failure to strip is frequently associated with the development of new DVR. These data support for routine stripping and suggest that the benefits of stripping may relate, at least in part, to a favourable impact on deep venous function.
Aged↗
The effect of superficial venous surgery on generic health-related quality of life.
BACKGROUND: Superficial venous surgery (SVS) is associated with a significant improvement in disease-specific health related quality of life (HR-QoL) but the effect on generic HR-QoL remains uncertain. The aim of this study was to determine the effect of SVS on responses to the Short Form [SF]-36, the most widely used generic HR-QoL instrument. METHOD: Two hundred and three patients undergoing SVS completed the SF-36 pre-operatively and 24 months post-operatively. Scores for the 8 SF-36 domains [physical (PF) and social functioning (SF), role limitation due to physical (RP) and emotional (RE) problems, mental health (MH), vitality (V), pain (P), and general health perception (HP)] were calculated and normalised using UK standard data. RESULTS: Pre-operatively, patients scored significantly lower (worse) than the general UK population in PF, RP and P. Surgery was associated with a significant improvement in PF and P (45.3 vs. 42.5 and 48.9 vs. 43.8 postop vs. preop, p<0.001, WSR) at 2 years. CONCLUSION: SVS leads to a statistically and clinically significant improvement in the physical components of the SF-36. These data will allow the clinical benefits of SVS to be compared with other interventions so helping informing decisions about how venous surgery should be prioritised appropriately within the NHS.
Adult↗
Manipulation of the renin angiotensin system in peripheral arterial disease.
The Heart Outcomes Prevention Evaluation (HOPE) study has provided evidence for the use of ramipril for secondary cardiac prevention for patients with peripheral arterial disease. Despite this many vascular surgeons and general practitioners are reluctant to prescribe ACE inhibitors in a group of patients perceived to have a high incidence of renal artery stenosis. This review aims to review the pathophysiology of the renin-angiotensin system and make evidence based recommendations for commencing ACE inhibitors as part of a comprehensive delivery of best medical therapy to patients with peripheral arterial disease.
Algorithms↗
The role of cilostazol in the treatment of intermittent claudication.
This paper represents a review, by experts, of current opinion and information on intermittent claudication (IC) and the role that cilostazol plays in its treatment. IC is a common and debilitating condition that has a significant adverse impact on health-related quality of life (HR-QoL). It is currently under-recognised as a powerful marker of increased cardiovascular (CV) risk. The clinical priority is secondary prevention -- sometimes referred to as best medical therapy aimed at reducing CV risk. However, the priority for most patients (often overlooked by clinicians) is symptom relief: an increase in walking distance leading to an improvement in HR-QoL. The symptoms of IC may be improved by exercise, pharmacotherapy, and when these are unsuitable or unsuccessful, endovascular or surgical intervention. Cilostazol is indicated for the improvement of maximal and pain-free walking distance in patients with IC who do not have rest pain or tissue necrosis. In clinical trials, cilostazol improved symptoms both objectively and subjectively, and also improved HR-QoL. Cilostazol is usually well tolerated, with adverse events being generally mild to moderate in intensity, and transient or resolved after symptomatic treatment (e.g. non-prescription analgesics). Such events only infrequently require permanent drug withdrawal. There are no interactions with other drugs commonly prescribed in patients with IC, such as statins and anti-platelet agents. Cilostazol also has a range of potentially beneficial effects that may in the future be proven to decrease CV risk and modify the underlying process of atherosclerosis. Cilostazol represents the best evidence-based pharmacological therapy available for the symptoms of IC and should be the first-line treatment for symptom improvement in appropriate patients. Based on the available treatment strategies, the paper presents a suggested algorithm for the management of IC highlighting the role of cilostazol.
Algorithms↗