Bypass surgery for chronic lower limb ischaemia.

BACKGROUND: Surgical bypass of an occluded arterial segment is one of the mainstay treatments for patients with critical limb ischaemia (CLI). However, it was introduced without formal evaluation. OBJECTIVES: To determine the effects of bypass surgery in patients with CLI. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group (PVD) searched their trials register (last searched November 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched Issue 4, 2007). Principal trial investigators were also contacted. SELECTION CRITERIA: All randomised controlled trials (RCTs) of bypass surgery versus control or any other treatment. DATA COLLECTION AND ANALYSIS: For the update one author and PVD editorial staff extracted data and assessed trial quality. Unpublished data were obtained from trial investigators. Data were analyzed using Peto odds ratio (OR) or weighted mean difference (fixed and random effects models). MAIN RESULTS: Nineteen trials were identified. Eight involved a total of just over 1200 patients. Four trials compared bypass surgery with angioplasty (PTA) and one each with thromboendarterectomy, thrombolysis, exercise, and spinal cord stimulation. Four included patients with intermittent claudication (IC) and CLI, two were restricted to claudicants, and two to CLI. Vein grafts were used for distal reconstructions and synthetic prostheses for aorto-iliac or ilio-femoral bypasses. Six trials included mortality. In general, trial quality was good; blinding was not possible. Mortality and amputation rates did not differ significantly between bypass surgery and PTA; primary patency was significantly higher in the bypass group after 12 months (Peto OR 1.6, 95% CI 1.0 to 2.6) but not after four years (P = 0.14). In patients with lower CLI, surgery was associated with increased surgical complications (Peto OR 2.69, 95% CI 1.87 to 3.86) and longer hospital stays during the first year, mean stay 46.1 days (SD 53.9) compared with 36.4 days (SD 51.4) for those receiving PTA (P < 0.0001). Amputation rates were significantly lower in bypass compared with thrombolysis (Peto OR 0.2, 95% CI 0.1 to 0.6); mortality rates did not differ. Blood flow restoration was significantly greater in bypass than in thromboendarterectomy patients (Peto OR 9.2, 95% CI 1.7 to 50.6); mortality and amputation rates did not differ. Bypass surgery outcomes did not differ significantly from exercise or spinal cord stimulation. AUTHORS' CONCLUSIONS: There is limited evidence for the effectiveness of bypass surgery compared with other treatments; no studies compared bypass to no treatment. Further large trials are required.

Lipid-lowering for peripheral arterial disease of the lower limb.

BACKGROUND: Lipid-lowering therapy is recommended for secondary prevention in people with coronary artery disease. It may also reduce cardiovascular events and/or local disease progression in people with lower limb peripheral arterial disease (PAD). OBJECTIVES: To assess the effects of lipid-lowering therapy on all-cause mortality, cardiovascular events and local disease progression in patients with PAD of the lower limb. SEARCH STRATEGY: The authors searched The Cochrane Peripheral Vascular Diseases Group's Specialised Register (last searched February 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 2, 2007) for publications describing randomised controlled trials of lipid-lowering therapy in peripheral arterial disease of the lower limb. SELECTION CRITERIA: Randomised controlled trials of lipid-lowering therapy in patients with PAD of the lower limb. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trial quality and extracted data. MAIN RESULTS: Eighteen trials were included, involving a total of 10,049 participants. Trials differed considerably in their inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Only one trial (PQRST) reported a detrimental effect of active treatment on blood lipid/lipoprotein levels. The pooled results from all eligible trials indicated that lipid-lowering therapy had no statistically significant effect on overall mortality (Odds Ratio (OR) 0.86; 95% Confidence Interval (CI) 0.49 to 1.50) or on total cardiovascular events (OR 0.8; 95% CI 0.59 to 1.09). However, subgroup analysis which excluded PQRST showed that lipid-lowering therapy significantly reduced the risk of total cardiovascular events (OR 0.74; CI 0.55 to 0.98). This was primarily due to a positive effect on total coronary events (OR 0.76; 95% CI 0.67 to 0.87). Greatest evidence of effectiveness came from the use of simvastatin in people with a blood cholesterol >/= 3.5 mmol/litre (HPS). Pooling of the results from several small trials on a range of different lipid-lowering agents indicated an improvement in total walking distance (Weighted Mean Difference (WMD) 152 m; 95% CI 32.11 to 271.88) and pain-free walking distance (WMD 89.76 m; 95% CI 30.05 to 149.47) but no significant impact on ankle brachial index (WMD 0.04; 95% CI -0.01 to 0.09). AUTHORS' CONCLUSIONS: Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD. It may also improve local symptoms. Until further evidence on the relative effectiveness of different lipid-lowering agents is available, use of a statin in people with PAD and a blood cholesterol level >/=3.5 mmol/litre is most indicated.

Screening for abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is found in 5% to 10% of men aged 65 to 79 years. The major complication is rupture which presents as a surgical emergency. The mortality after rupture is high, 80% for patients reaching hospital and 50% for those undergoing surgery for emergency repair. Currently elective surgical repair is recommended for aneurysms discovered to be larger than 5.5 cm to prevent rupture. There is interest in population screening to detect, monitor and repair abdominal aortic aneurysms before rupture. OBJECTIVES: To determine the effects of screening asymptomatic individuals for AAA on mortality, subsequent treatment, quality of life and cost effectiveness of screening. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Trials Register (last searched 26 January 2007) and CENTRAL (last searched Issue 1, 2007). SELECTION CRITERIA: Randomised controlled trials of population screening for AAA. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials and extracted data. MAIN RESULTS: Four studies involving 127,891 men and 9,342 women were included in this review. Only one study included women. Results for men and women were analysed separately. Three to five years after screening there was no significant difference in all-cause mortality between screened and unscreened groups for men or women (men, odds ratio (OR) 0.95; 95% Confidence interval (CI) 0.85 to 1.07; for women OR 1.06; 95% CI 0.93 to 1.21). There was a significant decrease in mortality from AAA in men (OR 0.60; 95% CI 0.47 to 0.78), but not for women (OR 1.99; 95% CI 0.36 to 10.88). In this analysis mortality includes death from rupture and from emergency or elective surgery for aneurysm repair. There was also a decreased incidence of ruptured aneurysm in men (OR 0.45; 95% CI 0.21 to 0.99) but not in women (OR 1.49; 95% CI 0.25 to 8.94). There was a significant increase in surgery for AAA in men (OR 2.03; 95% CI 1.59 to 2.59). This was not reported in women. There were no data on life expectancy, complications of surgery or subjective quality of life. AUTHORS' CONCLUSIONS: There is evidence of a significant reduction in mortality from AAA in men aged 65 to 79 years who undergo ultrasound screening. There is insufficient evidence to demonstrate benefit in women. The cost effectiveness may be acceptable, but needs further expert analysis. These findings need careful consideration in judging whether a co-ordinated population-based screening programme should be introduced.

Steroid sex hormones for lower limb atherosclerosis.

BACKGROUND: There is accumulating evidence that steroid sex hormones have a beneficial effect on a number of risk factors for peripheral arterial disease. OBJECTIVES: The objective of this review was to determine whether exogenous steroid sex hormones are an effective treatment for patients with lower limb atherosclerosis. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group trials register was searched, together with reference lists from relevant articles and reviews obtained through searches of Embase and Medline (up to May 2001). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of steroid sex hormones in patients with lower limb atherosclerosis were selected. DATA COLLECTION AND ANALYSIS: Both reviewers extracted data and assessed trial quality independently. Whenever possible investigators were contacted to obtain information needed for the review that could not be found in published reports. MAIN RESULTS: Four trials appeared to meet the inclusion criteria, but one was excluded because of poor methodology. The three remaining trials compared testosterone treatment with placebo in a total of 109 subjects with intermittent claudication or critical leg ischaemia. The most recent trial to meet the inclusion criteria dated from 1971. No trials were available which investigated the potentially beneficial effects of oestrogenic hormones in women with lower limb atherosclerosis. Testosterone therapy produced no significant improvement in tests of walking distance or in a variety of other objective tests for peripheral arterial disease, including venous filling time, muscle blood flow and plethysmography. The relative risk for subjective improvement in symptoms using the combined trial results was also non-significant (relative risk 1.10, 95% confidence interval 0.81 to 1.48). REVIEWER'S CONCLUSIONS: There is no evidence to date that short-term testosterone treatment is beneficial in subjects with lower limb atherosclerosis. However, this might reflect limited data rather than the lack of a real effect.

Femoral atherosclerosis in an older British population: prevalence and risk factors.

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.

Bypass surgery for chronic lower limb ischaemia.

BACKGROUND: Surgical bypass of an occluded arterial segment is the mainstay of treatment for patients with critical limb ischaemia. As with many surgical interventions, however, it was introduced without formal evaluation. OBJECTIVES: The objective of this review was to determine the effects of bypass surgery in patients with chronic lower limb ischaemia. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, MEDLINE, EMBASE, reference lists of relevant articles, and contacted principal trial investigators. SELECTION CRITERIA: All randomised controlled trials of bypass surgery versus control, or versus any other form of treatment. DATA COLLECTION AND ANALYSIS: At least two reviewers extracted data and assessed trial quality independently. The reviewers contacted investigators to obtain information or data needed for the review that could not be found in published reports. Dichotomous data were analysed using the Peto odds ratio (OR), and continuous data with the weighted mean difference (fixed effect and random effects models). MAIN RESULTS: Eight trials were identified which appeared to meet the inclusion criteria, but two were subsequently excluded. The remaining six trials involved a total of just over 700 patients, two trials comparing bypass surgery with angioplasty (PTA), and one with each of thromboendarterectomy, thrombolysis, exercise, and spinal cord stimulation. Four trials included patients with a range of disease severity (intermittent claudication and critical limb ischaemia), one was restricted to claudicants only and another to only critical limb ischaemia. The type of bypass procedure performed in each trial was similar: vein grafts for distal reconstructions; synthetic prostheses for aorto-iliac or ilio-femoral bypasses. The outcome measures varied, but four of the six trials included mortality and operative failure. In general the quality of the trials was good, but none was blinded because of the nature of the intervention. There were no clear differences between bypass surgery and PTA. Mortality and amputation rates did not differ significantly, although primary patency was significantly higher in the bypass group after 12 months (Peto OR 1. 6, 95% CI 1.0, 2.6) but not after four years (p=0.14). Compared with thrombolysis, amputation rates were significantly lower in the bypass group (Peto OR 0.2, 95% CI 0.1, 0.6), but mortality rates did not differ. Compared with thromboendarterectomy, restoration of blood flow was significantly greater in the bypass patients (Peto OR 9.2, 95% CI 1.7, 50.6), but mortality and amputation rates did not differ. Bypass did not differ significantly from exercise or spinal cord stimulation. REVIEWER'S CONCLUSIONS: There is limited evidence for the effectiveness of bypass surgery and further large trials are required.

Garlic for peripheral arterial occlusive disease.

BACKGROUND: Commercially available preparations of garlic have been reported to have beneficial effects on some of the risk factors associated with atherosclerosis. OBJECTIVES: The objective of this review was to assess the effects of garlic (both dried and non-powdered preparations) for the treatment of peripheral arterial occlusive disease. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, AMED, EMBASE, BIDS ISI, abstracts of relevant symposia and reference lists of relevant articles up to August 1998. The reviewers also contacted pharmaceutical companies, investigators and experts in garlic therapies. SELECTION CRITERIA: Randomised trials of garlic therapy in patients with lower limb atherosclerosis. The main outcomes were objective measures of progression of underlying atherosclerosis (e.g. ankle pressure measurements, treadmill testing) and subjective measures (e.g. symptom progression). DATA COLLECTION AND ANALYSIS: At least two reviewers extracted data and assessed trial quality independently. The reviewers contacted investigators to obtain information needed for the review that could not be found in published reports. MAIN RESULTS: One eligible trial with 78 participants was found. Both men and women (aged 40-75) were included. The follow-up period was short, 12 weeks only. After twelve weeks of treatment, pain free walking distance increased from 161 to 207 m in the group on garlic and from 172 to 203 m in the placebo group. This was not a statistically significant difference. There was no difference in change of systolic or diastolic blood pressure, heart rate, ankle and brachial pressures. No severe side effects were observed and nine patients taking garlic (28%) and four patients taking placebo (12%) complained of a noticeable garlic smell. REVIEWER'S CONCLUSIONS: One small trial of short duration found no effect on walking distance.

Lipid-lowering for lower limb atherosclerosis.

BACKGROUND: Raised lipid levels, including cholesterol, are important risk factors in the development of lower limb arterial disease (atherosclerosis). OBJECTIVES: The objective of this review was to assess the effects of lipid lowering therapy in patients with lower limb atherosclerosis. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, Embase, reference lists of relevant articles, and contacted trial investigators in Europe and pharmaceutical companies. SELECTION CRITERIA: Randomised trials of lipid-lowering therapy in patients with lower limb atherosclerosis. The main outcomes were mortality, non-fatal events, direct tests of disease progression, indirect measurements of disease, and subjective measures. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed trial quality independently. The reviewers contacted investigators to obtain information needed for the review that could not be found in published reports. MAIN RESULTS: There were nine eligible trials, but two were excluded because of poor methodology. The seven remaining trials involved a total of 698 participants from seven different countries. Men and women participated in all but one trial and were generally middle aged to elderly. The follow-up period varied from four months to three years. The overall quality of the included trials was high. The trials were heterogeneous in terms of inclusion criteria, type of drugs used and outcomes measured. Lipid-lowering therapy produced a marked but non-significant reduction in mortality (odds ratio 0.21, 95% confidence interval 0. 03 to 1.17), but little change in non-fatal events (odds ratio 1.21, 95% confidence interval 0.80 to 1.83). In two trials there was a significant overall reduction in disease progression on angiogram (odds ratio 0.47, 95% confidence interval 0.29 to 0.77). The changes in ankle brachial pressure index and walking distance were inconsistent, although trials showed a general improvement in symptoms that could not be combined in a meta-analysis. Side effects were generally mild, with the exceptions of liver toxicity produced by betapyridil and the adverse effect of probucol on lipoprotein profile. REVIEWER'S CONCLUSIONS: Lipid-lowering therapy may be useful in preventing deterioration of underlying disease and alleviating symptoms. These results cannot determine whether one lipid-lowering regimen is better than another.

Steroid sex hormones for lower limb atherosclerosis.

BACKGROUND: There is accumulating evidence that steroid sex hormones have a beneficial effect on a number of risk factors for peripheral arterial disease. OBJECTIVES: The objective of this review was to determine whether exogenous steroid sex hormones are an effective treatment for patients with lower limb atherosclerosis. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group trials register was searched, together with reference lists from relevant articles and reviews obtained through searches of Embase and Medline. SELECTION CRITERIA: Randomised controlled trials of steroid sex hormones in patients with lower limb atherosclerosis were selected. DATA COLLECTION AND ANALYSIS: Both reviewers extracted data and assessed trial quality independently. Whenever possible investigators were contacted to obtain information needed for the review that could not be found in published reports. MAIN RESULTS: Four trials appeared to meet the inclusion criteria, but one was excluded because of poor methodology and another is awaiting translation into English. The two remaining trials compared testosterone treatment with placebo in a total of 83 men with intermittent claudication. No trials were available which investigated the potentially beneficial effects of oestrogenic hormones in women with lower limb atherosclerosis. Testosterone therapy produced no improvement in tests of walking distance or in a variety of other objective tests for peripheral arterial disease, including venous filling time, muscle blood flow and plethysmography. The odds ratio for subjective improvement in symptoms using the combined trial results was also non-significant (odds ratio 1.28, 95% confidence interval 0.61 to 2.65). REVIEWER'S CONCLUSIONS: There is no evidence to date that short-term testosterone treatment is beneficial in male subjects with lower limb atherosclerosis. However, this might reflect limited data rather than the lack of a real effect.

Exercise for intermittent claudication.

BACKGROUND: Exercise is an inexpensive, low risk option compared with other more invasive therapies for leg pain on walking (intermittent claudication). OBJECTIVES: The objective of this review was to determine the effects of exercise for leg pain. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, Embase, reference lists of relevant articles, and contacted principal investigators of trials. SELECTION CRITERIA: Randomised trials of exercise regimens in patients with leg pain on walking (intermittent claudication). DATA COLLECTION AND ANALYSIS: At least two reviewers extracted and assessed data trial quality independently. The reviewers contacted investigators to obtain information or data needed for the review that could not be found in published reports. MAIN RESULTS: Fifteen trials were identified that met the inclusion criteria, but five were subsequently excluded because of poor quality. The remaining ten trials involved a total of almost 250 male and female patients with stable leg pain. The follow-up ranged from 12 weeks to 15 months. There was also some variation in the exercise regimens used, although all recommended at least two weekly sessions of, mostly, supervised exercise. All trials used a treadmill walking test as one of the outcome measures. The overall quality of the included trials was generally good, though the trials were all small (20-49 patients). Exercise therapy significantly improved maximal walking time (minutes) (weighted mean difference 6.51, 95% confidence interval 4.36 to 8.66, fixed effect model [FE]), with an overall improvement in walking ability of approximately 150% (range 74% to 230%). Exercise produced significant improvements in walking time compared with both angioplasty at six months (weighted mean difference 3.30, 95% confidence interval 2.21 to 4.39, FE) and antiplatelet therapy (weighted mean difference 1.06, 95% confidence interval 0.15 to 1.97, FE), and did not differ significantly from surgical treatment. In one small trial, exercise was less effective than pentoxifylline (weighted mean difference -0.45, 95% confidence interval -0.66 to -0.24, FE). REVIEWER'S CONCLUSIONS: Exercise is of significant benefit to patients with leg pain.

Essential fatty acids and cardiovascular disease: the Edinburgh Artery Study.

The aim of this study was to determine whether plasma and red cell fatty acid levels were associated with cardiovascular disease, and whether any association was independent of other major risk factors. Over 1100 subjects were examined in a random sample survey of the general population (the Edinburgh Artery Study). Fatty acids were measured in three plasma fractions (triglyceride, cholesteryl ester and phospholipid) and in red cell phospholipids. Fatty acid levels in groups with cardiovascular disease (myocardial infarction (MI), angina and lower limb disease) were compared with a no disease group. In the cholesteryl ester and phospholipid fractions there were significantly lower levels of eicosapentaenoic acid in the MI group on univariate analysis (p<0.05), but not when adjusted for age, sex, smoking and systolic blood pressure using logistic regression. In the red cell fraction, alpha-linolenic acid was significantly lower in those with stroke (p<0.01) and lower limb disease (p<0.05). Linoleic acid was significantly raised in the triglyceride fraction in those with MI, probably reflecting recent dietary changes. There were significant increases in dihomo-gamma-linolenic acid in the phospholipid and red cell fractions in those with MI, and in the phospholipid fraction in the stroke group. These results do not support the hypothesis that n-6 fatty acids are protective against cardiovascular disease, although there may be some beneficial effects of the n-3 fatty acid, alpha-linolenic acid. Results from cross-sectional surveys must, however, be interpreted with caution because the presence of disease may affect dietary intake.

Is the emergency readmission rate a valid outcome indicator?

OBJECTIVES: The principal aim was to determine whether the emergency readmission rate varies between medical specialties, and to identify whether differences in emergency readmission rates between hospital trusts can be reduced by standardising for specialty. Possible factors influencing emergency readmission were also investigated, including frequency of previous admission and cause of readmission. DESIGN: Emergency readmission rates were obtained from the Scottish Morbidity Record scheme (SMR1) using record linkage, standardised for age and sex. Rates throughout Scotland were analysed by specialty, and rates for general medicine compared among teaching hospital trusts. Cause of emergency readmission was determined from hospital records in a random sample (177 patients). SETTING: Medical specialties throughout Scotland. SUBJECTS: All patients readmitted as an emergency within 28 days of discharge (October 1990 to September 1994). RESULTS: Emergency readmissions varied markedly between medical specialties, with highest rates in nephrology (24.2%, 95% CI 23.5 to 24.8) and haematology (20.4%, 95% CI 19.9 to 20.9), and the lowest in homeopathy (2.2%, 95% CI 1.6 to 2.7) and metabolic diseases (3.5%, 95% CI 2.4 to 4.5). The largest number of emergency readmissions was in general medicine, accounting for 63% of the total. Restricting emergency readmission rates to general medicine significantly altered previous rates. In the year preceding the emergency readmission, 59% of all patients had been admitted to hospital at least once, and most emergency readmissions (73.3%) resulted from a chronic underlying condition. CONCLUSIONS: Significant variations in emergency readmission rates occurred between medical specialties, suggesting that differences between hospital trusts are influenced by differences in specialties and thus case mix. The majority of emergency readmissions occurred in patients with an underlying chronic condition, and many had a history of multiple previous hospital admissions. The emergency readmission rate is therefore unlikely to be a valid outcome indicator reflecting quality of care until routine data are available for standardisation by case mix.

Smoking, hemorheologic factors, and progression of peripheral arterial disease in patients with claudication.

PURPOSE: The purpose of the current study was to determine whether hemostatic and rheologic factors are associated with the deterioration of peripheral arterial disease in patients with intermittent claudication and the influence of smoking and severity of underlying disease on these relationships. METHODS: We conducted a prospective cohort study with a 6-year follow-up period of a consecutive series of 607 patients with uncomplicated intermittent claudication. The study setting was the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. The main outcome measures were peripheral vascular intervention or onset of severe chronic leg ischemia (rest pain, ulceration, gangrene). RESULTS: A total of 210 patients died during follow-up. Two hundred three patients did not have a vascular event or deterioration of limb ischemia, 45 patients underwent a peripheral vascular intervention, and 64 progressed to severe chronic leg ischemia. Median levels (interquartile ranges) of whole blood viscosity were significantly higher in the vascular intervention group (3.75 mPa/sec; range, 3.38 to 4.13 mPa/sec) than in those who did not deteriorate 3.48 mPa/sec; range, 3.06 to 3.83 mPa/sec) (p < or = 0.05), and plasma von Willebrand factor was higher in those with severe chronic leg ischemia (154.0 IU/dl; range, 122.0 to 187.0 IU/dl) than in those who did not deteriorate (131.0 IU/dl; range, 106.0 to 165.0 IU/dl) (p < or = 0.01). After adjustment for age, sex, cigarette smoking, and ankle brachial pressure index, the levels of plasma fibrinogen and blood and plasma viscosities were each associated with an increased risk of vascular intervention (all p < or = 0.05). There were no significant associations between any of the hemorheologic factors and the risk of severe chronic leg ischemia on multivariate analyses. CONCLUSION: Elevations in rheologic factors may have important effects on further reduction of blood flow in the legs of patients with claudication and promote worsening ischemia and clinical progression of symptoms.

Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants.

Thrombotic risk factors may be important in determining cardiovascular outcome in patients with symptomatic peripheral arterial disease. A cohort study with a 6-year follow-up period was established to determine the relationships between haemostatic and rheological factors and incident ischaemic heart disease (IHD) and stroke events in patients with peripheral arterial disease. A consecutive series of 607 patients with intermittent claudication was examined between 1989 and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial infarction (MI), coronary death and total coronary events. A total of 210 patients died during follow-up. 203 patients did not experience a vascular event or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and whole blood viscosity were significantly higher in those who experienced an event compared with those who did not. After adjusting for age and sex, fibrin D-dimer was significantly associated with risk of non-fatal myocardial infarction (RR 1.50, 95% CI 1.09-2.06, P < or = 0.01). Both fibrinogen and fibrin D-dimer were associated with risk of total coronary events (P < or = 0.05). The risk of stroke was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04-3.34, P < or = 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07-1.65, P < or = 0.01). All the relationships became weaker and statistically non-significant after further adjustment for cigarette smoking, systolic blood pressure, glucose and baseline IHD. The associations of these factors to IHD and stroke may therefore be partly related to cardiovascular risk factors, but are likely to be important in the pathogenesis of future atherothrombotic events in subjects with peripheral arterial disease.

Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease.

BACKGROUND AND AIMS: epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis. The aim of this study was to perform a randomized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis. Main outcome measures were: cholesterol and lipoprotein concentrations; haemostatic and rheological variables; the ankle brachial pressure index; walking distance; and cardiovascular events and death. METHODS: 120 men and women with stable intermittent claudication were randomized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids, or placebo. RESULTS: 39 (65.0 cent) of those taking fatty acids and 36 (60.0 cent) of those taking placebo completed the trial. Lipid concentrations did not differ significantly during the trial. In those taking fatty acids, haematocrit was significantly higher than in the placebo group after 6 months (46.1 cent compared with 44.6 cent, P 0.05). CONCLUSIONS: a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure, but no other significant benefits on risk factors. The trend towards fewer coronary events in those taking fatty acids warrants further investigation.

Alterations in plasma lipids, lipoproteins and high density lipoprotein subfractions in peripheral arterial disease.

The concentrations of the major lipoprotein classes and of high density lipoprotein (HDL) subfractions in 63 male patients with arteriosclerosis of the lower limbs (claudication) were determined and compared with values from 63 healthy controls. The patients with peripheral arterial disease (PAD) had reduced levels of total HDL-cholesterol and HDL2b of large particle size, increased levels of small HDL3c particles and a high ratio of total plasma-cholesterol to HDL-cholesterol (coronary risk factor). The PAD patients, however, had lower levels of low density lipoprotein (LDL)-cholesterol but higher concentrations of very low density lipoprotein (VLDL)-cholesterol and plasma triglyceride than healthy subjects. This study therefore suggests that in PAD, the protective effect of HDL may be more important than the atherogenic effect of LDL. It further suggests that while HDL-cholesterol HDL2b and the ratio of total plasma-cholesterol to HDL-cholesterol may provide valid indices for identifying individuals at risk of PAD, other factors, such as LDL and total cholesterol, may not provide such an appropriate risk indicator.

Smoking, atherosclerosis and risk of abdominal aortic aneurysm.

AIMS: The role of cardiovascular risk factors and atherosclerosis in the aetiology of abdominal aortic aneurysms is not well understood. The aim of this study was to determine the association between atherosclerosis and aortic aneurysm in the general population and the extent to which cardiovascular risk factors might increase the risk of aneurysm independently of an effect on atherosclerotic disease. METHODS AND RESULTS: In the Edinburgh Artery Study, 1592 men and women aged 55-74 years were followed prospectively over a period of 5 years. Forty subjects were identified as having an abdominal aortic aneurysm and, for each, five controls were randomly selected. Case showed a higher prevalence of cardiovascular disease (P < or = 0.001) and had a lower ankle brachial pressure index (P < or = 0.01). Current and recent ex-cigarette smokers had an increased risk of aortic aneurysm compared with long time ex-smokers and never smokers (odds ratio 3.08, 95% CI 1.53 to 6.21). Adjustment for concurrent atherosclerotic disease reduced the odds ratio to 2.63 (95% CI 1.26 to 5.45). The risk of aortic aneurysm was not related to elevation in diastolic blood pressure or in serum cholesterol. CONCLUSIONS: These findings indicate that atherosclerotic disease is associated with risk of aortic aneurysm in the general population. In addition, cigarette smoking appears to have a direct effect on the risk of aortic aneurysm which is independent of atherosclerosis.