Intermittent claudication and hypertension. Ankle pressure and walking distance in patients with well-treated and non-treated hypertension.
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We examined the effect of cilostazol, a type III phosphodiesterase inhibitor, on pain-free and maximal walking distance and quality of life measures. The present study examined adverse effects in 2,702 patients with stable, moderate to severe claudication enrolled in 8 randomized, double-blind, placebo-controlled trials. Treatment duration ranged from 12 to 24 weeks. Cilostazol therapy increased maximal and pain-free walking distances by 50% and 67%, respectively. In subgroup analysis, cilostazol increased pain-free and maximal walking distance similarly in men and women, in older (>/=65 years) and younger patients, and in patients with and without diabetes. Quality-of-life assessments revealed enhanced scores for physical well-being. Cilostazol-treated patients reported a higher incidence of headache, bowel complaints, and palpitations than patients given placebos. Cilostazol decreased triglycerides by 15.8% and increased high-density lipoprotein cholesterol by 12.8%, but there were no deleterious effects on any hematologic or serum markers. We conclude that cilostazol significantly increases walking distance and quality-of-life measures in patients with claudication without major adverse effects.
AT-1015 is a novel selective 5-HT2A serotonin receptor antagonist that is known to impair platelet aggregation and vasoconstriction. Serotonin has been hypothesized to contribute to claudication symptoms in individuals with peripheral arterial disease (PAD) via microvascular vasoconstrictor and thrombotic effects. AT-1015 was thus evaluated in 439 patients with claudication who were randomized in a double-blind, placebo-controlled trial comparing 10 mg, 20 mg, and 40 mg BID versus placebo for 24 weeks. Treadmill walking performance was assessed by peak walking time (PWT) and pain-free walking time (PFWT). Quality of life (QoL) was measured by the Walking Impairment Questionnaire (WIQ) and the Health Status Survey SF-36. Limb hemodynamics was assessed with the ankle-brachial index (ABI). The 40 mg arm was terminated prematurely by recommendation of the Data Safety Monitoring Committee due to an excess number of non-fatal myocardial infarctions. At study conclusion, there were no statistically significant differences in the mean change of PWT, PFWT, ABI and QoL between the 10 mg and 20 mg BID treatment groups compared with placebo. The proportion of patients who experienced an adverse event (AE) was similar across all treatment groups. Antimuscarinic and gastrointestinal AEs were more common in the AT-1015 treatment groups. Two deaths occurred: one in the placebo group and the other in the AT-1015 20 mg group. Although a prolongation of the QTc interval was observed in all groups, this was not clinically significant (QTc > 500 ms). Mean supine pulse rates were significantly increased in all AT-1015 treatment groups, consistent with predicted antimuscarinic effects. Population pharmacokinetic analysis fit a one-compartment model with first-order absorption and elimination. These data indicate that selective serotonin receptor blockade does not improve exercise tolerance or quality of life in individuals with claudication.
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The effect of 5 min treadmill exercise was investigated in claudicant patients and healthy controls; systemic neutrophil count, plasma thromboxane and von Willebrand's factor (a marker for endothelial injury) were measured. Median (interquartile range (i.q.r.)) resting neutrophil count was 5.6 (5.2-6.0) x 10(6) cells l-1 in claudicants and 2.8 (2.6-3.2) x 10(6) l-1 in controls (P < 0.05); this increased in those with claudication to 7.1 (6.2-7.7) x 10(6) l-1 immediately after exercise (P < 0.05). The resting plasma thromboxane level was 32.1 (25.0-60.0) pg ml-1 in claudicants and rose to 135.0 (104.0-141.3) pg ml-1 15 min after exercise, compared with a rise from 25.0 (22.0-33.5) to 55.5 (33.0-67.0) pg ml-1 in controls (P < 0.05). The resting serum von Willebrand's factor level was 127 (110-135) units dl-1 in claudicants compared with 60 (48-71) units dl-1 in controls; this difference persisted after exercise (P < 0.01). In patients with claudication, the level of von Willebrand's factor increased to 150 (140-156) units dl-1 60 min after exercise (P < 0.05). Free radical scavenging capacity was also investigated by measuring the plasma antioxidant activity of glutathione peroxidase and its essential non-metal cofactor selenium. Scavenging capacity was lower in claudicant patients whose median (i.q.r.) glutathione peroxidase activity (change in absorbance per min per ml plasma) was 2.84 (2.39-3.61) versus 3.24 (3.06-3.79) in controls (P < 0.05). Similarly, plasma concentrations of selenium were lower in claudicants at a median (i.q.r.) of 75.0 (58.0-81.0) micrograms l-1 compared with 88.0 (75.0-92.5) micrograms l-1 in controls (P < 0.05). Exercise in claudicant patients leads to neutrophilia and thromboxane production with subsequent endothelial injury. The antioxidant activity of glutathione peroxidase is reduced in patients with claudication and may allow the unopposed action of free radicals to damage endothelium.
The topic dealt with is about frequency and causes of the neural claudication intermittens among patients of our neurological department as a specific clinical form of lumbosacral disorder syndromes. Concluding special attention is given to diagnostical and therapeutical problems.
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In the light of the current controversy surrounding the use of hemorheologic and vasodilator drugs in the treatment of peripheral arteriosclerosis, a comparative study was designed in order to evaluate the efficacy of pentoxifylline, buflomedil, and nifedipine in 45 patients with peripheral arterial disease (Fontaine stage II). The patients in this prospective randomized study were divided into three groups: 15 patients received pentoxifylline treatment (1,200 mg/day), 15 were treated with buflomedil (600 mg/day), and 15 with nifedipine (60 mg/day). Response to treatment was assessed at the start of the study and after forty-five and ninety days, by clinical examination, Doppler test, strain test, and digital occlusion plethysmography using a strain gauge ring. Pentoxifylline was significantly more effective (P < 0.05) than buflomedil and nifedipine at ninety days in improving walking performance, resting toe pressure, resting and postexercise ankle/brachial pressure ratio, and basal/postischemic toe-pulse ratio. Significant differences within groups were also noted for initial claudication, toe peak-flow time, pulse reappearance time (PRT/2), and maximum postischemic flow time, together with significant intergroup variables. In conclusion, pentoxifylline proved more effective than the other drugs tested in: 1. improving distal pressure and resting microcirculatory blood flow; 2. increasing postexercise distal flow, ratios, and pressures and enabling faster recuperation of basal pulse rates; 3. increasing initial claudication distance in the strain test within the test group and achieving a greater absolute subjective claudication distance than that obtained using the other treatments.
Peripheral arterial disease (PAD), when accompanied by claudication, is a disabling disease that affects 12 percent of the population of the United States (US). PAD is associated with increased mortality as well as decreased functional status and quality of life. Smoking cessation and treatment of diabetes are key aspects of risk factor modification for the PAD patient as well as controlling other cardiovascular risk factors. Typically, only the most severely diseased patients with PAD receive surgery for the indication of claudication and other therapeutic options are being sought. Exciting developments are taking place in the area of drug development for instance. The benefits of a supervised walking exercise program have been consistently demonstrated in persons with PAD and therefore, exercise rehabilitation constitutes an important form of therapy for these persons. Unfortunately, in the US, exercise rehabilitation is not always reimbursed which may lessen its utility presently. All therapies which are used to treat claudication should incorporate measures of functional status and quality of life in addition to treadmill walking in order to ascertain the benefit of a given treatment for patients with PAD.
OBJECTIVES: To measure changes in claudicant's quality of life after surgery, angioplasty or unsupervised exercise. To explore the relationship between clinical indicators of limb perfusion and patient's perception of health change. DESIGN: Prospective study. SETTING: University Hospital vascular outpatients. MATERIALS AND METHODS: 202 claudicants referred for Duplex of lower limb arterial disease over a 12 month period. The short form 36 questionnaire was used to determine quality of life. Ankle pressures and walking distances were determined. MAIN RESULTS: The SF-36 was completed by 186 patients (92%) before and after treatment (34 operative patients, 74 angioplasty and 78 treated by exercise alone). Baseline quality of life was worse in surgical patients. Unsupervised exercise produced minimal changes in quality of life. Angioplasty and operation produced similar, significant improvements in physical functioning and pain. Changes in physical function or pain scores were unrelated to changes in ankle pressure. CONCLUSIONS: Unsupervised exercise programs are unlikely to significantly improve patient's quality of life. The benefits of surgery and angioplasty support a relaxation in the indications for investigation and treatment of claudicants. Patients with impaired perceived health should not be denied treatment on the basis of preintervention ankle pressure or walking distance alone.
Mechanisms for increased claudication distance following physical training were studied in ten patients with peripheral arterial insufficiency. The exercise capacity on a bicycle ergometer increased by an average of 26% after 3--4 months of training (P less than 0.05). Neither maximum lower leg blood flow during the exercise test nor oxygen uptake at exhaustion changed significantly after training (-8% and +5%, respectively), whereas popliteal-venous O2-saturation was lower at exhaustion after the training than before (8.5 +/- 3.2 and 11.4 +/- 4.6, respectively, P less than 0.05). Anaerobic glycolysis, as evidenced by the lactate release, was also lowered after the training (P less than 0.05). In conclusion, the present study shows that the increased exercise capacity following physical training in claudicants is associated with an increased local aerobic working capacity despite a virtually unchanged blood flow. This increased aerobic exercise capacity might partly be explained by an increased O2 extraction in the lower leg during exercise.
Reducing the risk factors of people with cardiovascular disease can be beneficial to their health. This article reports on a study into the effectiveness of a health education programme in helping people to reduce their risk factors.
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