Intermittent claudication and vascular spasm. III. A new theory to explain some phenomena in intermittent claudication often interpreted as being due to vasospasm.
Explore the source record for details and available documents.
SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
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.
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.
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.
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.
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.
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.
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.
Patients with intermittent claudication have a high risk of concomitant cardiovascular disease, and their risk factors should be identified and treated. The prognosis for the leg symptoms is relatively benign, as 75% of patients will stabilize or improve. Physical training, perhaps combined with pharmacotherapy, can usually increase walking distance substantially. The patient should be referred to a vascular surgeon for possible endovascular or surgical treatment if the symptoms significantly impair the patient's social life or working ability.
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.
Intermittent claudication (IC) is defined by leg muscle pain, cramping and fatigue brought on by ambulation/exercise; relieved on rest; and caused by inadequate blood supply and is the primary symptom of peripheral arterial disease (PAD). PAD has a detrimental effect on the quality of life. PAD is a debilitating atherosclerotic disease of the lower limbs and is associated with an increased risk of cardiovascular morbidity and mortality. IC is an extremely important marker of atheroma. Up to 60% patients with IC have significant underlying coronary and/or carotid disease and 40% of all patients suffering from IC die or suffer a stroke within 5 years of presentation. The therapeutic intervention of IC essentially aims at providing symptomatic relief and reducing the systemic cardiovascular complications. Although exercise therapy is one of the most efficacious conservative treatments for claudication, the pharmacotherapeutic goals can be best achieved through an increase in the walking capacity to improve quality of life and a decrease in rates of amputation. In the development of treatment for IC, an aggressive non-pharmacological intervention and pharmacological treatment of the risk factors associated with IC are considered. In the next 2 years, the results of major trials of drugs that stabilize and regress atherosclerosis such as statins and angiotensin converting enzyme inhibitors, and anti-platelet agents, recombinant growth factors and immune modulators will be available for IC. Levocarnitine (l-carnitine) and a derivative, propionyl levocarnitine, are emerging agents that increase the pain-free walking and improve the quality of life in IC patients by working at the metabolism and exercise performance of ischemic muscles. This article provides a comprehensive review of the pathophysiology involved, diagnosis of IC and existing and emerging pharmacotherapies with rationale for their use in its treatment.
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.
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.
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.
In patients with intermittent claudication, treadmill exercise may cause acute deterioration of endothelial function and increase in plasma concentrations of adhesion molecules. The authors evaluated the efficacy of intravenously administered propionylcarnitine (PLC)in preventing these phenomena. Thirty-six claudicants with postexercise decrease in brachial artery flow-mediated dilation (FMD)were randomized to either placebo or PLC (600 mg as a single bolus followed by 1 mg/kg/min for 60 minutes).In the 18 patients randomized to placebo, FMD markedly decreased with exercise before (from 6.8 +/-0.4% to 4.0 +/-0.4%; p < 0.001) and after treatment (from 6.5 +/-0.4% to 4.4 +/-0.5%; p < 0.001). By contrast, in the PLC group, FMD significantly decreased with exercise before treatment (from 8.0 +/-0.7% to 4.4 +/-0.4%; p < 0.001), but not after active drug administration (from 7.1 +/-0.7% to 6.0 +/-0.6%; p = 0.067). The difference between treatments was not significant (p = 0.099; ANOVA). However, in the PLC group, the authors found that the greater the exercise-induced deterioration in endothelial function before treatment, the greater the capacity of PLC to prevent a postexercise decrease in FMD (r = -0.50, p = 0.034). Accordingly, they analyzed data in the 19 patients with a baseline exercise-induced decrease in FMD >or=45% (ie, the median FMD reduction in the entire group of 36 patients), and found that the exercise-induced FMD decrease was less after PLC than after placebo (p = 0.046, ANOVA). In the same subgroup, the exercise-induced increase in plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) was significantly higher before than after treatment in patients randomized to PLC (23.4 +/-5% vs 15.3 +/-7%, p = 0.007). In conclusion, in patients with intermittent claudication suffering from a greater endothelial derangement after treadmill, PLC administration provided a protective effect against deterioration of FMD and increase of sVCAM-1 induced by exercise.