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Flavonol and flavone intake and the risk of intermittent claudication in male smokers.

The objective of this study was to investigate the association between flavonol and flavone intake and the risk of intermittent claudication in male smokers. The study population consisted of participants of the Finnish alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study, who were free of intermittent claudication at study entry. These 25,041 male smokers were 50-69 years old at baseline. Participants completed a validated dietary questionnaire at baseline. The occurrence of intermittent claudication was assessed by annual administration of the Rose questionnaire. During the median follow-up of 4.1 years, 2412 new cases of intermittent claudication were observed. Dietary intake of flavonols and flavones was inversely associated with the risk of intermittent claudication when adjusted for cardiovascular risk factors (relative risk, RR in the highest vs. lowest quintile of intake 0.86, 95% confidence interval, CI: 0.75-0.98, p for trend 0.007). However, after further adjustment for intakes of vitamins C and E and total carotenoids, the association was attenuated (RR: 0.93, 95% CI: 0.81-1.08, p for trend 0.12). The risk of intermittent claudication was lower among men in the highest quintile of vegetable consumption (RR: 0.78, 95% CI: 0.69-0.89, p for trend 0.0001) and among wine drinkers (RR: 0.63, 95% CI: 0.41-0.98). Adjustment for flavonol and flavone intake only marginally changed these associations. In conclusion, flavonol and flavone intake was not independently associated with the risk of intermittent claudication.

Aged↗

Vitamin E for intermittent claudication.

BACKGROUND: It is thought that vitamin E may improve tolerance to intermittent claudication (i.e. pain caused by ischaemia in the muscles of the leg during exercise), thereby relieving the pain, through a variety of mechanisms. OBJECTIVES: The objective of this review was to determine the effects of vitamin E on people with intermittent claudication. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register, reference lists of relevant articles and a library specialising in literature on vitamins. SELECTION CRITERIA: Controlled trials comparing vitamin E with placebo, or other interventions, in patients with intermittent claudication. DATA COLLECTION AND ANALYSIS: Both reviewers extracted data and assessed study quality independently. MAIN RESULTS: Five eligible studies were found with a total of 265, predominantly male, participants. The average age was 57 years. The follow-up varied from 12 weeks to 18 months. The trials were small and generally of poor quality. The people studied were reasonably homogeneous but five different doses of vitamin E were used and four different physical outcomes were measured. No trials were identified that compared vitamin E with treatments other than placebo. All trials showed positive effects on one of their main outcomes. No serious adverse effects of vitamin E were reported. Two trials that lasted approximately eight months and used similar doses reported patients' subjective evaluation of the treatment. The relative risk for the combined results of these two trials using a random effects model was 0.57 with a 95% confidence interval of 0.28 to 1.15. REVIEWER'S CONCLUSIONS: While vitamin E - which is inexpensive and has had no serious side effects reported with its use - may have beneficial effects, there is insufficient evidence to determine whether it is an effective treatment for intermittent claudication.

Humans↗

[Measurement of quality of life in intermittent claudication. Clinical validation of a questionnaire].

OBJECTIVES: Functional limitation in patients with intermittent claudication impairs their quality of life. In order to measure this new evaluation parameter, we developed a self-administered questionnaire: Artemis. METHODS: The questionnaire was composed of a general instrument (SF-36) and a specific one. A cross sectional study was performed in 177 patients with intermittent claudication (mean age 68 +/- 10 years, 77% males) who stated their walking distance was limited within 50 to + 2000 meters. The acceptability, reliability and sensitivity of the questionnaire were tested. RESULTS: In patients who had a walking distance greater than 500 m (n = 96), the scores obtained were significantly higher (better quality of life) than in patients whose walking distance was limited to less than 500 m (n = 81) (p < 0.05). Intermittent claudication had a global effect on the different parameters of the quality of life evaluated by the questionnaire including physical performance and psychological and social aspects. CONCLUSION: The Artemis questionnaire as shown its ability to describe patients with intermittent claudication. It can be used in clinical trials as a tool for measuring quality of life.

Activities of Daily Living↗

The Bambuí health and aging study (BHAS). Prevalence of intermittent claudication in the aged population of the community of Bambuí and its associated factors.

OBJECTIVE: To assess the prevalence of intermittent claudication in the aged population of Bambuí, Brazil, and to identify the factors associated with this disease. METHODS: Population-based cross-sectional study of the aged population (>/= 60 years of age) of Bambuí. Participants were interviewed and examined, after written consent. Intermittent claudication was defined based on a standardized questionnaire. Analysis was performed using multiple logistic regression. RESULTS: Of the 1,742 elderly living in Bambuí, 1,485 (85.2%) were enrolled in the study. Thirty-seven individuals (2.5%) with intermittent claudication were identified: 28 (1.9%) males and 9 (0.6%) females. Their age brackets were: 16 (1.08%) individuals between 60 and 69 years of age, 17 (1.15%) between 70 and 79 years, and 4 (0.27%) >/= 80 years. A significant association between intermittent claudication and the following characteristics was found: male sex (OR=5.1; CI 2.4-11.0), smokers (OR=3.1; CI 1.2-8.5), ex-smokers (OR=3.4; CI 1.3-8.7), and more than 2 hospital admissions in the last 12 months (OR=2.8; CI 1.1-7.2). CONCLUSION: Disease prevalence was similar to that of other countries. The association between intermittent claudication and smoking strengthens the significance of tobacco in peripheral artery disease pathogenesis. The association of intermittent claudication and a higher number of hospital admissions suggests greater morbidity in the elderly affected.

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The role of comorbidity in the assessment of intermittent claudication in older adults.

The prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.

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Risk factors affecting the natural history of intermittent claudication.

To determine the prognostic significance of the level of arterial disease in claudicators, risk factors affecting the progression of intermittent claudication, including hemodynamic variables obtained from noninvasive vascular laboratory examinations, were assessed. We identified 378 patients with intermittent claudication by characteristic history and the presence of abnormal treadmill exercise examination results. Results of serial examinations were available for 195 of these patients, who had 310 claudicating limbs. Life-table analysis revealed that after eight years, 41% of these patients had progressed to critical ischemia, defined as rest pain or tissue loss, and 50% had died. Cox proportional hazards general linear regression analysis found that at a patient's first examination in the vascular laboratory, the ankle-brachial index and the decrease in ankle-brachial index after exercise were significantly associated with the subsequent development of critical ischemia. The level of disease at the initial examination in the vascular laboratory was not a significant risk factor for progression to critical ischemia and therefore should not be used as an indicator for or against operation in patients with intermittent claudication.

Adult↗

[Consensus diagnosis and treatment of arterial intermittent claudication. Central Guidance Organization for Peer Review].

Intermittent claudication is an indicator of increased risk of cardiac and cerebrovascular morbidity and mortality and as such a reason to look for modifiable risk factors for atherosclerosis. A vascular anamnesis and physical examination can reliably exclude presence of peripheral arterial occlusive disease in the lower extremities, but cannot reliably demonstrate its presence. Certainty about presence or absence of peripheral arterial occlusive disease can be obtained by determination of an ankle-brachial blood pressure index. The main method for the diagnosis of severity and localisation of stenoses and occlusions in the arteries to the legs is the echo-Doppler (duplex) examination. With this method the feasibility of percutaneous transluminal angioplasty (PTA) can also be determined. Consequently, angiography has lost importance as a diagnostic method and is only still indicated as part of an interventional treatment (operation or PTA). Treatment should be aimed at both amelioration of symptoms and reduction of risk factors for atherosclerosis. A key-stone of the treatment is cessation of smoking. The role of pharmacotherapy in reducing symptomatology is only limited. Walking exercise can have a positive effect on walking distance and should always be tried. PTA is the treatment modality of first choice for stenoses in the aortoiliac and femoropopliteal arteries. For segmental occlusions in the iliac pathway, also recanalisation by means of PTA (in combination with stent placement) is a justifiable treatment option. In all other cases operative revascularisations give good functional results. Invasive treatments for patients with intermittent claudication should be performed within a multidisciplinary team.

Angiography↗

The impact of intermittent claudication on quality of life evaluated by the Sickness Impact Profile technique.

Unselected patients suffering from intermittent claudication (n = 148) were invited to take part in a prospective study. Physical examination and several circulatory investigations were performed including a treadmill walking test, bicycle ergometry and a quality of life examination (Sickness Impact Profile, SIP, technique). The SIP has been reported to be sensitive enough to identify specific dysfunction profiles in several clinical conditions, but it has not been used on patients with intermittent claudication. The aim of this study was to determine to what extent quality of life was influenced by reduced walking ability in patients with intermittent claudication. If so, the SIP technique should then be a useful tool for determination of the degree of reduced exercise capacity in patients who may benefit from surgery instead of conservative treatment. A majority of the SIP categories, Sleep and rest, Emotional behaviour, Body care and movement, Home management, Mobility, Social interaction, Ambulation and Overall SIP were shown to be useful in confirming objective dysfunctions in our patients. The correlation between maximum walking ability and SIP scores indicated an approximate cut-off limit at 70 W walking capacity. Thus, significant reductions in everyday life function were demonstrated in patients with maximum walking ability below 70 W. Patients with intermittent claudication also suffered from several other dysfunctions in addition to walking disability. These factors may, as well, impact on quality of life without walking disability. Our results demonstrated that quality of life assessment by the SIP technique was a sensitive method for evaluation of overall dysfunction in patients with intermittent claudication.(ABSTRACT TRUNCATED AT 250 WORDS)

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[Padma-28, a herbal preparation, increases walking distance in patients with intermittent claudication].

Thirty-six patients with stable intermittent claudication were randomized in a doubleblind study either to treatment with two tablets of Padma-28 twice daily (containing 340 mg dried herbal mixture composed according to an ancient lamaistic prescription) or placebo for four months. Effect of treatment was quantified by measurements of systemic and peripheral systolic blood pressures, and pain-free and maximal walking distances on a tread-mill. The actively treated group attained a significant increase in pain-free walking distance from 115 m (72-218) to 227 m (73- >1000, p < 0.05). The placebo group did not show significant changes in either pain-free or maximal walking distance. Significant changes in systemic or peripheral blood pressures could not be demonstrated in any of the groups. In conclusion, our study has shown that treatment with Padma-28 over a four month period significantly increases the walking distance in patients with stable intermittent claudication of long duration.

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The fate of patients with intermittent claudication managed nonoperatively.

Of 100 patients with intermittent claudication, followed an average of six years, a surprising 78 per cent either showed improvement or remained stable regarding the presenting complaint. However, 39 per cent showed evidence of further progression of atherosclerosis. In patients with femoropopliteal occlusion in one leg, almost 40 per cent had occlusion in the one leg, almost 40 per cent had occlusion in the other leg after two to six years. The amputation rate was 7 per cent but six of these seven patients had severe diabetes. This study suggests that we are not causing limb loss by adhering to stringent criteria for bypass grafting. It also suggests that the patient with intermittent claudication without associated grave signs has a better than 50 per cent chance of improving and a better than 60 per cent chance that his disease will not show evidence of significant progression during a five to six year period. Such data should be taken into consideration when patients are considered for arterial reconstruction.

Adult↗

Beneficial effects of intermittent suction and pressure treatment in intermittent claudication.

The present study reports on the effects of a physical treatment modality in patients with intermittent claudication. During this treatment a major part of the skin surface is subjected to intermittent suction and pressure. In a previous, preliminary study the authors found a beneficial effect of this treatment in intermittent claudication. The study included 34 patients with moderate, stable intermittent claudication. Twenty-two patients participated in a double-blinded, randomized trial comparing the effects of 25 treatments to 25 placebo applications given over a period of two months. Twelve patients participated in an open trial investigating the possible effects of the treatment on platelet aggregation and fibrinolysis. Pain-free and maximal walking distances were measured on a treadmill, and systolic blood pressure was measured on the upper limb, the ankle, and the first toe bilaterally. The threshold for adenosine diphosphate (ADP)-induced platelet aggregation was tested, and the fibrinolytic activity was estimated from the euglobulin clot lysis time. Active treatment resulted in significant improvements in pain-free and maximal walking distances, whereas no changes could be found during placebo administration. The treatment caused significant increments in the ADP thresholds for platelet aggregation, while the effects on fibrinolysis were uncertain. It is concluded that intermittent suction and pressure treatment offers a new approach for conservative treatment of intermittent claudication.

Aged↗

Urinary microalbumin as a marker for intermittent claudication.

OBJECTIVE: The urinary microalbumin concentration was analysed in patients with intermittent claudication in order to investigate its usefulness as a marker for intermittent claudication. MATERIALS AND METHODS: Urinary samples were collected prior to and following exercise in 15 patients with claudication. The patients walked on a treadmill as far as possible until they were stopped by pain. Urinary microalbumin concentration was measured by a latex agglutination system, and the result was considered abnormal when the concentration exceeded 10 mg/g creatinine. The ankle brachial pressure index (ABI) at rest and the time taken for the ankle pressure to return to the resting level following exercise (ABI recovery time) also were measured. RESULTS: In seven (47%) of the patients, the urinary microalbumin concentration was elevated to more than 10 mg/g creatinine following exercise, while in eight (53%) it remained normal. The ABI recovery time was significantly longer in the patients in whom the microalbumin concentration was elevated, compared to that in patients without an elevated concentration. The urinary microalbumin concentration following exercise was reduced significantly when the walking distance was decreased 50% or 15%. Following vascular bypass surgery, the elevation in urinary microalbumin concentration was reduced. CONCLUSIONS: The use of urinary microalbumin as a diagnostic marker for intermittent claudication is limited. However, in cases where the concentration is elevated, it can be used to follow the course of the disease.

Albuminuria↗

Lack of influence of propranolol and metoprolol on walking distance in patients with chronic intermittent claudication.

Ten patients with chronic intermittent claudication were included in a double-blind, randomized cross-over study of placebo, propranolol 80 mg b.i.d. and metoprolol 100 mg b.i.d., each given for two months. At the end of each treatment period, the patients were tested on a treadmill and the time to first claudication pain and to intolerable claudication pain was noted. There was no decrease in time to first claudication pain or to intolerable pain with either propranolol or metoprolol as compared to placebo.

Chronic Disease↗

Supervised exercise therapy versus non-supervised exercise therapy for intermittent claudication.

BACKGROUND: Although exercise therapy is considered to be of significant benefit to people with leg pain (intermittent claudication), almost half of those affected do not undertake any exercise therapy. OBJECTIVES: To evaluate the effects of supervised versus non-supervised exercise therapy on the maximal walking time or distance for people with intermittent claudication. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialized Register (last searched November 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL) database in The Cochrane Library (last searched Issue 4, 2005). In addition, we handsearched the reference lists of relevant articles for additional trials. There was no restriction on language of publication. SELECTION CRITERIA: Randomized and controlled clinical trials comparing supervised exercise programs with non-supervised exercise programs for people with intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors (BB and EMW) independently selected trials and extracted data. One author (BB) assessed trial quality and this was confirmed by a second author (MP). For all continuous outcomes we extracted the number of participants, the mean differences, and the standard deviation. If data were available, the standardized mean difference was calculated using a fixed-effect model. MAIN RESULTS: We identified twenty-seven trials, of which 19 had to be excluded because the control group received no exercise therapy at all. The remaining eight trials involved a total of 319 male and female participants with intermittent claudication. The follow up ranged from 12 weeks to 12 months. In general, the supervised exercise regimens consisted of three exercise sessions per week. All trials used a treadmill walking test as one of the outcome measures. The overall quality of the included trials was good, though the trials were all small with respect to the number of participants, ranging from 20 to 59. Supervised exercise therapy showed statistically significant and clinically relevant differences in improvement of maximal treadmill walking distance compared with non-supervised exercise therapy regimens, with an overall effect size of 0.58 (95% confidence interval 0.31 to 0.85) at three months. This translates to a difference of approximately 150 meters increase in walking distance in favor of the supervised group. AUTHORS' CONCLUSIONS: Supervised exercise therapy is suggested to have clinically relevant benefits compared with non-supervised regimens, which is the main prescribed exercise therapy for people with intermittent claudication. However, the clinical relevance has not been demonstrated definitely and will require additional studies with a focus on the improvements in quality of life.

Directly Observed Therapy↗

The effect of withdrawal of drugs treating intermittent claudication.

BACKGROUND: Pharmacologic treatment for intermittent claudication is a management option. This study evaluated the effect of withdrawal of drug therapies, cilostazol and pentoxifylline, on the walking ability of peripheral artery disease patients. METHODS: Single-blind placebo crossover from a randomized, double-blind trial; 45 claudication patients received either cilostazol 100 mg orally twice daily (n = 16), pentoxifylline 400 mg orally three times daily (n = 13), or placebo (n = 16) for 24 weeks. After 24 weeks of double-blind therapy, treatment for all groups was placebo only, and follow-up continued through week 30. Treatment efficacy was established with treadmill testing. RESULTS: Profile analysis demonstrated a highly significant loss of treatment benefit after crossover (P = 0.001) for cilostazol-treated patients, but no significant change after crossover was observed with pentoxifylline. CONCLUSIONS: Drug withdrawal worsened the walking of claudicants who had benefited from cilostazol therapy. This decline with crossover to placebo suggests that the initial improvement with cilostazol treatment was due to the drug's action. Withdrawal of pentoxifylline did not adversely affect walking.

Administration, Oral↗

[Intermittent claudication. Synthesis and conclusions].

The intermittent claudication is a symptom. By itself, it does not justify surgical treatment. On the other hand, it is advisable when accompanied by a threat of trophic disorders. Direct arterial surgery is often necessary in the case of suprainguinal, aorto-iliac lesion, rarely in the leg. Indeed, under the inguinal area, nature tends to compensate for occlusions of the trunk by the formation of a parallel network. A logical treatment is to contribute to this tendency, by increasing the upward and downward pressure gradient through muscular exercise and lumbar sympathectomy. In practice, the choice between hyperemia surgery and reconstructive surgery rests on functional data, that make it possible to evaluate the potential of the parallel network and of the peripheral vascular bed.

Humans↗

The effectiveness of isoxsuprine in patients with intermittent claudication.

Sixty male patients with intermittent claudication were investigated in a randomized, double-blind, placebo-controlled study in order to determine the effectiveness of Isoxsuprine. The analysis of the results was made on the basis of subjective assessment of symptoms by the patients themselves and also on the results of segmental blood-pressure measurements and ankle/arm indices at rest and after standardised exercise. Significant differences were demonstrated between the active and placebo groups as regards pain-free walking distance although arterial pressure measurements did not show statistically significant differences between the two groups. Isoxsuprine appears to be significantly beneficial only for patients with obstructions at the femoro-popliteal level.

Adult↗

Effects of cilostazol on resting ankle pressures and exercise-induced ischemia in patients with intermittent claudication.

During exercise, patients with intermittent claudication (IC) have decreased limb arterial blood pressure that recovers during rest. A novel method for assessing dynamic recovery of function is measurement of the hemodynamic response after exercise. Cilostazol (Pletal), a new agent for the treatment of IC, increases walking distance and may decrease ischemic burden. The objective of this study was to assess the effect of cilostazol versus placebo on hemodynamic measurements after exercise-induced ischemia in patients with IC. Two double-blind, placebo-controlled studies with similar inclusion/exclusion criteria and duration (24 weeks) were pooled. Patients walked on a treadmill at 2.0 miles/h (3.2 km/h) on a 12.5% grade until the claudication-limited maximal walking distance (MWD) was reached. Anterior and posterior tibial pressures were measured with Doppler ultrasound at baseline and at 1, 5, and 9 min during recovery. Area under the curve (AUC), a measure of the time course of recovery of systolic pressure after exercise-induced ischemia, and ankle-brachial index (ABI) were calculated and compared using analysis of variance (ANOVA). All three treatment groups (308 patients randomized to cilostazol 100 mg bid, 303 to cilostazol 50 mg bid, and 299 to placebo) had similar baseline characteristics. Mean post-exercise AUC for cilostazol 100 mg and 50 mg bid versus placebo increased by 0.31 (p = 0.001) and 0.26 (p = 0.004), respectively. Mean resting ABI increased by 0.03 (p = 0.0039) and 0.04 (p = 0.0001) in the cilostazol 100 mg and 50 mg bid groups, respectively. In conclusion, following 24 weeks of treatment, cilostazol increased the ABI at rest and improved the recovery time of ankle pressures post-exercise.

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