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PubMed2004

Helicobacter pylori seropositivity is associated with enhanced platelet activation in patients with intermittent claudication.

OBJECTIVE: Patients with intermittent claudication have a significantly increased risk of mortality from cardiovascular and cerebrovascular causes. Helicobacter pylori infection and abnormal platelet function have been shown to be associated with atherosclerosis as well as with acute ischemic events. The aim of this study was to assess for the first time the relation between H pylori serology status, platelet activation, and endothelial injury in patients with intermittent claudication. Design of study : A prospective observational study of 125 patients with intermittent claudication suitable for angioplasty was conducted at the Vascular Unit of the Aberdeen Royal Infirmary. Main outcome measures Main outcome measures were (1) H pylori serology using ELISA kit for immunoglobulin G antibody to H pylori and (2) whole blood flow cytometric analysis of resting platelet P-selectin expression and fibrinogen binding as measures of platelet activation. Results are presented as platelet percentage. von Wildebrand factor levels were measured using ELISA as a marker of endothelial injury. Carstair deprivation scores were calculated for all patients. RESULTS: H pylori serology was positive in 62 patients (49.6%), negative in 56 (44.8%) and equivocal in 7 (5.6%). Median P-selectin expression was significantly increased in H pylori-positive patients compared with seronegative patients (0.815 vs 0.65; P =.039). Median platelet fibrinogen binding was higher in seropositive patients, but this failed to reach statistical significance (2.135 vs 1.85%; P =.11). There was no difference in von Wildebrand factor levels between the two groups (P =.51). There was no difference in socioeconomic status between the two groups. CONCLUSION: Patients with intermittent claudication who are H pylori positive show enhanced platelet activation that does not appear to be mediated by means of endothelial cell injury.

Aged↗
PubMed1993

Serum lipoproteins and hemostatic function in intermittent claudication.

Normoglucemic men with intermittent claudication (n = 41), mean age of 63 years, and sex-, age-, body mass index-, and smoking habit-matched controls (n = 75) were compared for plasma lipoprotein and hemostatic variables. The patients had significantly lower levels of large high-density lipoprotein (HDL) particles (HDL2b, HDL2a, and HDL3a) and elevated lipoprotein(a) [Lp(a)] concentrations than the control subjects. Of the hemostatic variables, plasminogen activator inhibitor-1 (PAI-1), plasma antiplasmin, plasma fibrinogen, and urine beta-thromboglobulin concentrations were significantly elevated in patients. In intermittent claudication patients Lp(a) correlated significantly with activation of the coagulation system, ie, with the levels of plasma fibrinogen and urine fibrinopeptide A. No correlations between the values for Lp(a) and PAI-1 or plasma alpha 2-antiplasmin were seen. The PAI-1 activity showed significant univariate correlations to the levels of HDL3b, HDL2b (inverse), and very-low-density lipoprotein triglycerides, of which the positive correlation to HDL3b persisted in multivariate analysis (r = .48, P < .001). Independent characteristics for intermittent claudication estimated by multiple regression analysis were PAI-1, plasma fibrinogen, and HDL3a, with a combined R2 of .36. The intermittent claudication subgroup that was being treated with beta-blockers/thiazides had a higher frequency of coronary heart disease compared with the other patients. In addition, the patients taking beta-blockers/thiazides had elevated triglyceride concentrations, lower HDL cholesterol with a size shift toward smaller particles, and a tendency toward raised PAI-1 and plasma alpha 2-antiplasmin levels compared with the patient group that did not take these medications.

Blood Coagulation↗
PubMed2001

Anticoagulants (heparin, low molecular weight heparin and oral anticoagulants) for intermittent claudication.

BACKGROUND: Anticoagulant treatment for intermittent claudication might improve functional capacity, and prevent acute cardiovascular complications caused by peripheral obstructive arterial disease. OBJECTIVES: To assess the effects of anticoagulant drugs (heparin, low molecular weight heparin (LMWH) and oral anticoagulants) in patients with intermittent claudication (Fontaine stage II) in terms of improving walking capacity (pain-free walking distance or absolute walking distance), mortality, cardiovascular events, ankle/brachial pressure index, progression to surgery, amputation-free survival and side effects of these drugs. SEARCH STRATEGY: Randomised trials of anticoagulants for intermittent claudication were sought using the search strategy described by the Cochrane Peripheral Vascular Diseases Review Group. Additional trials were sought through: reference lists resulting from this search; recent conference proceedings; contact with authors of published trials and pharmaceutical companies producing anticoagulants. SELECTION CRITERIA: All randomised trials of anticoagulants used to treat patients with intermittent claudication. DATA COLLECTION AND ANALYSIS: Thirteen trials were initially considered eligible for inclusion in the review. Two studies evaluated oral anticoagulants, five evaluated standard heparin, and six evaluated LMWHs. Only three studies (two evaluating oral anticoagulants, one evaluating heparin) met the high quality methodological inclusion criteria and were included in the primary analysis. Four other studies were included in the sensitivity analysis. The reviewers extracted the data independently. MAIN RESULTS: No significant difference was observed between heparin treatment and control groups for pain-free walking distance or maximum walking distance at the end of treatment. There were no data to indicate that LMWHs benefit walking distance. Revascularisation or amputation-free survival rates were reported in one study only with a five year follow-up. No study reported a significant effect on overall mortality or cardiovascular events and the pooled odds ratios were not significant for these outcomes either. Major and minor bleeding events were significantly more frequent in the group treated with oral anticoagulants compared to control, with a non-significant increase in fatal bleeding events. No major bleeding events were reported in the study evaluating heparin, while a non-significant increase in minor bleeding events was reported. REVIEWER'S CONCLUSIONS: No benefit of heparin, LMWHs or oral anticoagulants has been established for intermittent claudication. An increased risk of major bleeding events has been observed especially with oral anticoagulants. The use of anticoagulants for intermittent claudication cannot be recommended at this stage.

Administration, Oral↗
PubMed2003

The effect of peripheral percutaneous transluminal angioplasty on quality of life in patients with intermittent claudication.

BACKGROUND AND OBJECTIVE: intermittent claudication is associated with a significant reduction in quality of life. Treatment of claudicants aims to reduce mortality from cardio- and cerebro-vascular events and to improve quality of life. Quality of life assessment should be used to guide and evaluate treatment in this group of patients. Peripheral percutaneous transluminal angioplasty (PTA) is now widely used in the treatment of intermittent claudication. The aim of this review is to examine the effect of PTA on quality of life (QOL) in patients with intermittent claudication. METHODS: a review was conducted of prospective clinical trials assessing the effect of peripheral PTA on QOL. Publications were retrieved by searching Medline and PreMedline, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of systematic reviews, AMED and CINAHL. The reference lists of the relevant publications were also searched. RESULTS: seven prospective studies (10 publications) on the effect of PTA on QOL in claudicants were identified. Several different questionnaires were used to measure quality of life (Nottingham Health Profiile, SF-36, EuroQol) none of which were disease specific. All the studies showed some improvement in QOL after PTA at follow-up periods of between 6 weeks and 24 months, except for one which showed some improvement at 6 months but not at 24 months. CONCLUSIONS: despite the fact that studies on the effect of PTA on QOL in claudicants have used generic QOL questionnaires which are relatively insensitive, the findings suggest that PTA may result in some improvement in QOL in these patients, although level I evidence to support this is lacking. The availability of disease-specific questionnaires should enable a more accurate assessment of PTA on QOL in these patients.

Angioplasty, Balloon↗
PubMed1994

Epidemiology of intermittent claudication in middle-aged men.

Intermittent claudication, myocardial infarction, and angina pectoris share many epidemiologic and biologic features. Yet few large cohort studies describing the prevalence, incidence, and risk factors for intermittent claudication have been done. The authors evaluated intermittent claudication in 10,059 Israeli men aged 40-65 years, of whom 8,343 were free of coronary heart disease and symptoms of peripheral vascular disease; this latter group was followed for 5 years from 1963 to 1968. Prevalent and incident cases of intermittent claudication were defined by the London School of Hygiene Cardiovascular Disease Questionnaire, and all cardiovascular disease risk factor evaluations were standardized. Baseline prevalence was 27.0/1,000 (211/10,029). A total of 360 previously healthy men developed intermittent claudication for a crude 5-year incidence rate of 43.1/1,000 (360/8,343) or a crude annual incidence of 8.6/1,000. Following univariate analysis with demographic, physiologic, psychosocial, and other cardiovascular disease variables, logistic regression was used to identify risk factors for intermittent claudication. These were the following: > 20 cigarettes per day, odds ratio (OR) = 2.02, 95% confidence interval (CI) 1.54-2.66; serum cholesterol (50-mg/dl difference), OR = 1.35, 95% CI 1.18-1.54; 11-20 cigarettes per day, OR = 1.69, 95% CI 1.24-2.30; anxiety (high vs. low), OR = 1.85, 95% CI 1.29-2.65; socioeconomic status, OR = 1.82, 95% CI 1.26-2.64; and diabetes, OR = 1.85, 95% CI 1.25-2.75. Other significant predictors of smaller magnitude included in the regression were age, psychosocial coping factors, Quetelet's index, and exsmoking. The risk factors for intermittent claudication were a blend of those related to myocardial infarction (smoking, cholesterol, diabetes, but not hypertension) and others related to angina pectoris but not to myocardial infarction (stress and coping variables). There is reason to believe that preventing or modifying these factors will prove effective in altering the natural history and clinical outcomes of peripheral vascular disease as shown in other forms of atherosclerosis.

Adult↗
PubMed1991

Intermittent claudication.

The natural history of intermittent claudication is generally benign. Clear indications for revascularization in patients with intermittent claudication are rest pain and necrotic tissue. Disabling claudication in patients who are at low operative risk is another acceptable indication for surgical treatment. Young patients with intermittent claudication from aortoiliac occlusion constitute a subset of patients in whom a more aggressive approach is justified. Nevertheless, in most patients, the management of intermittent claudication should be conservative.

Female↗
PubMed1995

Influence of clinical resources on the treatment of intermittent claudication.

Management of intermittent claudication varies between surgeons, even after adjustment for case-mix, and could be related to the availability of clinical resources. The aim of this study was to ascertain whether vascular surgeons perceived deficiencies in the resources available to them for the management of claudication and to determine whether an association existed between reported deficits and patient management. Over a six month period, 28 vascular surgeons in Scotland completed recording forms on their treatment intentions for 1,180 claudicants. Subsequently, the surgeons were interviewed about resources available for vascular surgery. The majority of surgeons reported deficiencies in resources, predominantly insufficient operating lists (71%) and staff shortages (71%). Although considered less important than clinical factors or patient wishes, resources were independently associated with treatment. Surgeons reporting insufficient operating lists were less likely to opt for surgical treatment (p < 0.05), and those working with reluctant or inexperienced radiologists were less likely to consider percutaneous transluminal angioplasty (p < 0.05) and more likely to offer surgery (p < 0.001). However, case-mix and resources explained only some of the variations in treatment. The residual variation was likely to reflect an underlying lack of agreement among surgeons on the most appropriate management of claudication. Randomised controlled trials to address this issue would be welcomed by the majority of surgeons questioned.

Angioplasty, Balloon↗
PubMed1996

Quality of life in patients with intermittent claudication.

OBJECTIVE: As intermittent claudication (IC) infrequently progresses to limb loss many clinicians adopt a conservative approach to treatment. Recently percutaneous transluminal angioplasty (PTA) has been applied to patients with IC. If this were to become the first line treatment for IC it would have major implications in terms of hospital facilities as well as cost. A measure is required, therefore, to decide on rationing of limited financial resources. "Quality of life" may be more influential in determining demand on services since objective medical criteria cannot give an insight into the patients feelings of well being. DESIGN: We applied the Nottingham Health Profile, by post, to a group of claudicants and age/sex matched controls. 70% responded from both groups. Claudicants who had recently received intervention were excluded, as were controls complaining of any leg pains on walking. RESULTS: The results showed that claudicants have greater perceived problems in the areas of energy, pain, emotional reactions, sleep, and physical mobility compared to controls (p < 0.05; Mann-Whitney Test). This was reflected by a significantly greater positive response rate to problems with activities of daily living (0.05 > p > 0.02; Chi-square Test) in the claudicant group. CONCLUSION: Because of the cost and resource implications of introducing measures such as PTA to the treatment of vast numbers of patients with IC, we suggest that trials are needed to compare various treatments using quality of life measurements in addition to traditional efficacy/safety parameters.

Activities of Daily Living↗
PubMed1979

Intermittent claudication--pathophysiological considerations.

Intermittent claudication is a non-pathognomic symptom elicited by an inbalance between the metabolic demands of the exercising skeletal muscle and its blood supply. In normal conditions hyperemia to the working muscles will be impaired during the exercise by mechanical compression of the microvessels. The resulting anaerobic metabolism will cause further vasodilatation. Both phenomena (exercise and reactive hyperemia) contribute to a maximal increase in local blood flow as soon as the exercise is stopped. If the local circulation is impaired by occluding arterial disease (eventually complicated by aggravating factors) the tolerance to skeletal work is lowered and the circulatory reserves are entirely exhausted as demonstrated by the ischemic exercise-test. In the case of a major obstruction and poor collateralisation, a "steel phenomenon" may occur. The pharmacotherapeutic possibilities to cope with in this situation are briefly discussed.

Adenosine Triphosphate↗
PubMed1990

Effect of surgery on the systemic inflammatory response to intermittent claudication.

The hypothesis that intermittent claudication initiates a systemic inflammatory response was investigated by studying the effect of exercise on markers of neutrophil activation and vascular permeability in 25 claudicants and 10 controls. Urinary albumin excretion, previously demonstrated to reflect vascular permeability, increased significantly after exercise in claudicants and was associated with decreased neutrophil filterability and increased serum lysozyme activity. No similar exercise-induced changes were seen in controls or in claudicants after successful arterial bypass surgery. These results suggest that intermittent claudication is associated with potentially deleterious systemic manifestations that are surgically reversible.

Aged↗
PubMed2002

Vitamin C prevents endothelial dysfunction induced by acute exercise in patients with intermittent claudication.

In patients with intermittent claudication, exercise is associated with a marked increase in oxidative stress, likely responsible for systemic endothelial perturbation. In 31 claudicant patients, we assessed the effect of vitamin C administration on the acute changes induced by maximal and submaximal exercise in endothelium-dependent, flow-mediated dilation (FMD), and in plasma levels of thiobarbituric acid-reactive substances (TBARS) and soluble intercellular adhesion molecule-1 (sICAM-1). In 16 claudicants, maximal exercise reduced FMD (from 8.5+/-0.9 to 3.7+/-0.8%, P<0.01), and increased plasma levels of TBARS (from 1.93+/-0.06 to 2.22+/-0.1 nmol/ml, P<0.02) and of sICAM-1 (from 282+/-17 to 323+/-19 ng/ml, P<0.01). In eight of these patients, randomized to vitamin C, exercise-induced changes in FMD and biochemistry were abolished. This beneficial effect was not observed in the eight patients randomized to saline. In 15 patients, who walked until the onset of claudication pain (submaximal exercise), and in ten control subjects, who performed maximal exercise, no changes were observed with exercise. Thus, in claudicants, vitamin C prevents the acute, systemic impairment in endothelial function induced by maximal exercise. This finding provides a rationale for trials investigating antioxidant therapy and cardiovascular risk in patients with intermittent claudication.

Antioxidants↗
PubMed1981

Home-training of patients with intermittent claudication.

Fifteen patients with intermittent claudication but without angina pectoris underwent a training programme consisting of three months of home-training followed by three months of supervised in-hospital training. Detailed information and instruction preceded the start of the training. There was a significant increase in maximal walking distance and also in physical activity during the home-training period. There was no difference in the increase in walking distance between this group and an earlier, comparable, group that had undergone a similar period of supervised in-hospital training. A further significant increase in maximal walking distance was obtained after three months of supervised in-hospital training. The physical activity during leisure time was, however, not further increased. Smoking habits were affected. After one year, one out of twelve smokers had stopped smoking and eight had reduced their consumption by 30-75%. Home-training after a careful instruction and with control of results is an alternative to supervised in-hospital training for a large group of patients with intermittent claudication but without angina pectoris.

Activities of Daily Living↗
PubMed1985

The effect of hemodilution upon patients with intermittent claudication.

Seventeen patients with stable intermittent claudication and a PCV of more than 0.45 were venesected until a PCV of 0.35 was achieved. Only patients that were not considered candidates for surgical treatment were entered into the study. Each patient acted as their own control and was studied twice before the venesection at a mean PCV of 0.49 then after achieving a PCV of 0.35 or less (mean PCV of 0.33), and finally one month after the last venesection (mean PCV of 0.37). Angina developed in one patient after the third venesection and was withdrawn from the study. In the remaining sixteen patients, blood flow of the calf muscle during exercise increased significantly after venesection from 5.90 to 8.84 milliliters per 100 grams per minute (p = 0.02). This was measured by xenon 133 clearance and a cadmium telluride detector. There was also a substantial decrease (p less than 0.001) in whole blood viscosity at both low and high shear stresses, but there was no change in plasma viscosity or plasma fibrinogen. Treadmill claudication distance improved in only two patients. Ten patients were tired when the PCV decreased to 0.35 and subjective claudication distance deteriorated in four of these patients. Subsequent isovolemic venesection with dextran 70 volume replacement to a PCV of 0.35 did not improve the response in the six patients restudied. We conclude that venesection did not benefit these patients with intermittent claudication and there was an unacceptable incidence of side effects. Therefore, we suggest that reducing the PCV to 0.35 should be avoided in patients with intermittent claudication who have been refused surgical treatment.

Adult↗
PubMed1998

A randomized, double-blind, placebo-controlled, crossover study to assess the immediate effect of sublingual glyceryl trinitrate on the ankle brachial pressure index, claudication, and maximum walking distance of patients with intermittent claudication.

PURPOSE: The goal of the present study was to assess the immediate effect of sublingual glyceryl trinitrate (GTN) in patients with intermittent claudication. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover study. Inclusion criteria consisted of history of intermittent claudication, resting ankle brachial pressure index (ABPI) of 1.00 or less, a 20% or greater fall in ABPI after exercise, and maximum walking distance (MWD) of less than 250 m. Patients already receiving nitrates were excluded. In study 1, patients (n = 25) underwent a standard exercise test after randomization to receive either 800 microg of sublingual GTN or placebo. The postexercise ABPI was recorded. Then, the crossover portion of the study was performed. In study 2, patients (n = 22) had their claudication distance and MWD measured. They then were randomized to receive either GTN or placebo spray, and the exercise test was repeated, with the claudication distance and MWD recorded, followed by the crossover portion of the study. Statistical analysis was performed with the Wilcoxon matched pairs signed ranks test and the Mann-Whitney U test. RESULTS: In study 1, the median postexercise ABPIs for placebo and GTN were 0.29 and 0.36 (P =.0001). In study 2, the median claudication distance for both placebo and GTN groups was 70 m (P =.59). The median MWD for the placebo and GTN groups was 105 and 125 m (P =.0084) CONCLUSION: GTN can decrease the fall in ABPI after exercise and increase the MWD.

Administration, Sublingual↗
PubMed1989

Walking and cycling tests in neurogenic and intermittent claudication.

The walking and cycling tolerance of 19 patients with neurogenic claudication and 11 with intermittent claudication was assessed, first in the upright and then in 30 degrees of flexion, repeating the tests on a second day. The flexed posture improved the walking and cycling distance, respectively, in 11 and six patients with neurogenic claudication. In two of the 11 patients, this posture significantly improved by more than 100% of both walking and cycling distances. In addition, one patient had claudication pain when he was walking, but could cycle unlimited distance. Only one of the patients with intermittent claudication could walk or cycle further in the flexed position. Although some patients with neurogenic claudication increase their walking distance by flexing forwards, we conclude that posture-related walking and cycling are insufficiently sensitive tests to distinguish between neurogenic and intermittent claudication.

Exercise↗
PubMed1999

Vascular surgical society of great britain and ireland: review of 94 tibial bypasses for intermittent claudication

BACKGROUND: The management of intermittent claudication is usually non-operative. Most surgeons accept, however, that intervention may be warranted for those with debilitating symptoms. Such interventions are limited to above-knee bypass or balloon angioplasty. However, the authors have performed almost 4500 bypasses for limb salvage, with careful audit of results, and suggest that, in very carefully selected cases, tibial bypass can also be performed for intermittent claudication. The present study aimed to review the results of infrainguinal bypass in this unit; to compare the results for above-knee, below-knee popliteal and tibial bypass in claudicants using either in situ or excised vein as the conduit; and to examine the indications and long-term follow-up for those undergoing tibial bypass for claudication. METHODS: A database has been maintained prospectively in this unit since 1986. Details of all patients undergoing infrainguinal bypass for claudication were retrieved. In-hospital charts were also reviewed and cross-referenced with the computer database. In addition to demographic details, data were extracted on operative indication and procedure, postoperative complications, return to desired level of activity and long-term graft patency. RESULTS: From 1987 to 1997, 409 infrainguinal reconstructions were performed for intermittent claudication (9 per cent of all infrainguinal reconstructions). Of these 73 per cent were in men and 27 per cent in women with a mean age of 64 (range 24-91) years. The operative procedures comprised 165 above-knee popliteal grafts, 150 bypasses to the below-knee popliteal artery and 94 to tibial arteries. There were no operative deaths. However, one of 165 patients who had an above-knee popliteal graft underwent an amputation. Primary and secondary patency rates at 4 years were 62 and 64 per cent for above-knee popliteal bypass, 77 and 81 per cent for below-knee popliteal bypass, and 86 and 90 per cent for tibial bypass. Cumulative survival was 93 per cent at 4 years. CONCLUSION: Tibial bypass for severely disabling claudication can be performed with minimal morbidity and mortality rates, and is at least as durable as more commonly performed bypasses. These data indicate that concern over limb loss, death and limited life span may be exaggerated.

Journal Article↗
PubMed1996

Spinal intermittent claudication due to cervical and thoracic degenerative spine disease.

STUDY DESIGN: Neurogenic intermittent claudication can be caused by spinal cord compression. In this study, 20 patients with spinal intermittent claudication due to degenerative spine diseases were evaluated. OBJECTIVES: This study clarified the clinical features and pathomechanism of spinal intermittent claudication due to degenerative spine diseases. SUMMARY OF BACKGROUND DATA: Spinal intermittent claudication may either be produced by intrinsic or extrinsic lesions. Little is known about spinal intermittent claudication due to extrinsic lesions such as spinal cord compression. Twenty patients with spinal intermittent claudication, caused by cervical or thoracic lesions, who were given surgical treatment except for one, were studied. Their main subjective symptoms were tightness, weakness, and numbness in the lower limbs and a strangulated sensation in the trunk to lower limbs. The objective findings were occurrence and/or aggravation of spinothalamic signs. METHODS: The gait loading test was performed on these 20 patients. Selective spinal angiography was performed on the patients with thoracic myelopathy and its therapeutic effects were evaluated. A radiographic assessment was made in all patients. RESULTS: The subjective symptoms and objective findings were reproduced by the gait loading test. Selective spinal angiography temporarily relieved or improved the spinal intermittent claudication due to the thoracic myelopathy. Spinal intermittent claudication disappeared immediately after surgical treatment. CONCLUSIONS: Circulatory impairment of the spinal cord seems to be closely related to the etiology of spinal intermittent claudication. Besides providing diagnostic information, selective spinal angiography may also have a temporary therapeutic effect.

Adult↗