Absolute Claudication Distance Research Articles

Training Rather Than Walking The Test In - Train Out Program for Home-Based Rehabilitation in Peripheral Arteriopathy

Exercise training reduces walking disability in peripheral arterial disease (PAD). This non-randomized study evaluates the effects on walking ability and hemodynamic parameters of a novel approach to home-based rehabilitation, the test in -train out program (Ti-To), compared with the traditional home-based free walking exercise (Tr-E). A total of 143 patients with claudication (117 men, average age 68+/-10 years), were included in a Ti-To (n=83) or Tr-E program (n=60). Evaluations, which were carried out upon entry and at 1, 2, 3, 4 and 6 months, included: self-reported claudication, walking ability (ie, absolute claudication distance, pain threshold speed), resting/exercise heart rates (HR), systolic/diastolic brachial pressure (SBP/DBP), ankle pressure (AP), ankle-brachial index (ABI). Ti-To involved 2 daily 10-min home walking sessions at maximal asymptomatic speed and the patient attending monthly check-ups at hospital. Tr-E involved 20-30 min of daily walking at self-selected speeds up to pain tolerance. A total of 126 patients (Ti-To, n=74; Tr-E, n=52) completed the program. Ti-To induced better relief from claudication (p=0.001). Functional parameters improved significantly for both groups (p<0.0001) with significant intergroup difference for Ti-To (p<0.0001). SBP and exercise HR decreased significantly in both groups, with Ti-To improving resting HR (p=0.0002), DBP (p=0.003), lowest AP worse limb (p=0.004) and ABI worse limb (p=0.0002). In patients with PAD, a Ti-To program had more positive effects on perceived claudication, and functional and hemodynamic parameters than did a Tr-E program.

Mild peripheral neuropathy prevents both leg muscular ischaemia and activation of exercise-induced coagulation in Type 2 diabetic patients with peripheral artery disease

To study the influence of peripheral neuropathy on intermittent claudication in patients with Type 2 diabetes (T2DM). Twenty-five patients with T2DM were grouped according to the ankle/brachial index (ABI): 10 with ABI > 0.9 without peripheral artery disease (PAD; group T2DM) and 15 with ABI < 0.9 with PAD (group T2DM + PAD). Twelve individuals without T2DM with PAD (group PAD without T2DM) were also enrolled. Tests for peripheral neuropathy were performed in all patients. ABI, rate pressure product, prothrombin fragments 1 + 2 (F1+2), thrombin-anti-thrombin complex (TAT), and d-dimer were measured before and after a treadmill test. During exercise both initial and absolute claudication distance and electrocardiogram readings were recorded. We found mild peripheral neuropathy in 20% of group T2DM and 46.7% of group T2DM + PAD (P < 0.01). After exercise, the rate pressure product increased in each group; ABI fell in T2DM + PAD (P < 0.0001) and in PAD without T2DM (P = 0.0005); the fall was greater in the latter group. Initial and absolute claudication distances were similar in PAD patients. In group T2DM + PAD, absolute claudication distance was longer in the subgroup without peripheral neuropathy (P < 0.05), whereas ABI and rate pressure products were similar. F1+2 values at rest were higher in group T2DM + PAD. After exercise, F1+2 values and TAT increased only in group PAD without T2DM. Only group PAD without T2DM experienced muscular ischaemia, whereas group T2DM + PAD did not. Mild peripheral neuropathy may have prevented them from reaching the point of muscular ischaemia during the treadmill test, because they stopped exercising with the early onset of pain. Reaching a false absolute claudication distance may induce ischaemic preconditioning. These findings suggest a possible protective role of mild peripheral neuropathy in T2DM patients with intermittent claudication, by preventing further activation of coagulation during treadmill testing.

The effect of current cigarette smoking on calf muscle hemoglobin oxygen saturation in patients with intermittent claudication

The purpose of this study was to compare calf muscle hemoglobin oxygen saturation response during exercise between smokers and non-smokers with peripheral arterial disease. Patients limited by intermittent claudication who were smokers (n = 12) were compared with those who had not smoked (n = 28) for at least 1 year prior to investigation. Ankle/brachial index (ABI) measurements were obtained with Doppler ultrasound, and maximal calf blood flow was measured by venous occlusion plethysmography. Hemoglobin oxygen saturation (StO2) of the calf muscle, initial claudication distance (ICD), and absolute claudication distance (ACD) were obtained during a graded treadmill test. Smokers refrained from smoking on the morning of the test. Smokers had similar ABI values compared with non-smokers (0.70 +/- 0.26 vs 0.73 +/- 0.23 [mean +/- SD]; p = 0.808), whereas the smokers had lower values for maximal calf blood flow (8.71 +/- 5.76 %/min vs 11.48 +/- 4.46 %/min; p = 0.038), ICD (122 +/- 123 m vs 243 +/- 177 m; p = 0.023), and ACD (284 +/- 170 m vs 452 +/- 263 m; p = 0.023). Additionally, smokers had lower calf muscle StO2 values at the end of 1 minute (16 +/- 15% vs 37 +/- 19%; p = 0.002) and 2 minutes of exercise (16 +/- 16% vs 35 +/- 25%; p = 0.008), and at the occurrence of ICD (17 +/- 17% vs 32 +/- 23%; p = 0.033) and ACD (16 +/- 16% vs 32 +/- 24%; p = 0.024). After adjusting for blood flow, calf muscle StO2 values remained lower in the smokers (p < 0.05). Finally, calf muscle StO2 at the end of the first minute of exercise was related to ICD (r = 0.611, p < 0.001) and ACD (r = 0.443, p < 0.01). In conclusion, smokers limited by intermittent claudication have lower calf muscle StO2 during exercise than nonsmokers, and lower StO2 during exercise is associated with shorter ICD and ACD.

Poor health-related quality of life in patients with peripheral arterial disease: Type D personality and severity of peripheral arterial disease as independent predictors

Peripheral arterial disease (PAD) is associated with poor health-related quality of life (HRQOL), but individual differences in this patient-based outcome are not fully understood. We examined the impact of PAD severity, invasive treatment, and type D personality, defined as tendencies to experience negative emotions and be socially inhibited, on HRQOL in a 1-year follow-up study. At their first visit to the department of surgery at the St. Elisabeth Hospital in Tilburg, The Netherlands, 203 consecutive PAD patients completed the DS14 type D personality and RAND-36 questionnaires (all self-report). Clinical data were derived from patients' medical files and included ankle-brachial index (ABI), initial and absolute claudication distance (ICD, ACD), and invasive treatment. The main outcome was HRQOL at 1-year follow-up. HRQOL improved between baseline and follow-up, and invasive treatment led to significant improvements in the subscales Physical Functioning (P = .005) and Pain (P = .003). Type D patients were severely impaired in their HRQOL compared with other patients at baseline (P < .01) and at follow-up (P < .05). ABI and ACD also predicted HRQOL at follow-up. After adjusting for ABI and ACD, invasive treatment and type D personality independently predicted all HRQOL domains, except for Physical Functioning. Overall, type D personality predicted increased risk for both poor General Health (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.69 to 8.08; P = .001) and poor Mental Health (OR, 6.01; 95% CI, 2.44 to 14.79, P < .0001) at 1 year after the PAD diagnosis. Despite an overall improvement, type D patients remained more impaired in 1-year HRQOL than other patients, adjusting for ABI and ACD. Type D personality is a psychologic risk factor that predicts poor patient-based outcomes in PAD and should be taken into account when HRQOL in PAD is evaluated.

L -Arginine Supplementation in Peripheral Arterial Disease

L-arginine is the precursor of endothelium-derived nitric oxide, an endogenous vasodilator. L-arginine supplementation improves vascular reactivity and functional capacity in peripheral arterial disease (PAD) in small, short-term studies. We aimed to determine the effects of long-term administration of L-arginine on vascular reactivity and functional capacity in patients with PAD. The Nitric Oxide in Peripheral Arterial Insufficiency (NO-PAIN) study was a randomized clinical trial of oral L-arginine (3 g/d) versus placebo for 6 months in 133 subjects with intermittent claudication due to PAD in a single-center setting. The primary end point was the change at 6 months in the absolute claudication distance as assessed by the Skinner-Gardner treadmill protocol. L-arginine supplementation significantly increased plasma L-arginine levels. However, measures of nitric oxide availability (including flow-mediated vasodilation, vascular compliance, plasma and urinary nitrogen oxides, and plasma citrulline formation) were reduced or not improved compared with placebo. Although absolute claudication distance improved in both L-arginine- and placebo-treated patients, the improvement in the L-arginine-treated group was significantly less than that in the placebo group (28.3% versus 11.5%; P=0.024). In patients with PAD, long-term administration of L-arginine does not increase nitric oxide synthesis or improve vascular reactivity. Furthermore, the expected placebo effect observed in studies of functional capacity was attenuated in the L-arginine-treated group. As opposed to its short-term administration, long-term administration of L-arginine is not useful in patients with intermittent claudication and PAD.

Exercise performance in patients with peripheral arterial disease who have different types of exertional leg pain

This study compared the exercise performance of patients with peripheral arterial disease (PAD) who have different types of exertional leg pain. Patients with PAD were classified into one of four groups according to the San Diego Claudication Questionnaire: intermittent claudication (n = 406), atypical exertional leg pain causing patients to stop (n = 125), atypical exertional leg pain in which patients were able to continue walking (n = 81), and leg pain on exertion and rest (n = 103). Patients were assessed on the primary outcome measures of ankle-brachial index (ABI), treadmill exercise measures, and ischemic window. All patients experienced leg pain consistent with intermittent claudication during a standardized treadmill test. The mean (+/- SD) initial claudication distance (ICD) was similar (P = .642) among patients with intermittent claudication (168 +/- 160 meters), atypical exertional leg pain causing patients to stop (157 +/- 130 meters), atypical exertional leg pain in which patients were able to continue walking (180 +/- 149 meters), and leg pain on exertion and rest (151 +/- 136 meters). The absolute claudication distance (ACD) was similar (P = .648) in the four respective groups (382 +/- 232, 378 +/- 237, 400 +/- 245, and 369 +/- 236 meters). Similarly, the ischemic window, expressed as the area under the curve (AUC) after treadmill exercise, was similar (P = .863) in these groups (189 +/- 137, 208 +/- 183, 193 +/- 143, and 199 +/- 119 AUC). PAD patients with different types of exertional leg pain, all limited by intermittent claudication during a standardized treadmill test, were remarkably similar in ICD, ACD, and ischemic window. Thus, the presence of ambulatory symptoms should be of primary clinical concern in evaluating PAD patients regardless of whether they are consistent with classic intermittent claudication.

Supervised exercise therapy for intermittent claudication in a community-based setting is as effective as clinic-based

This cohort study was conducted to determine the effect on walking distances of supervised exercise therapy provided in a community-based setting. The study included all consecutive patients presenting at the vascular outpatient clinic with intermittent claudication, diagnosed by a resting ankle brachial index<0.9, who had no previous peripheral vascular intervention for peripheral arterial disease, no major amputation, and sufficient command of the Dutch language. The exclusion criterion was the inability to walk the baseline treadmill test for a minimum of 10 m. The intervention was a supervised exercise therapy in a community-based setting. A progressive treadmill test at baseline and at 1, 3, and 6 months of follow-up measured initial claudication distance and absolute claudication distance. Changes were calculated using the mean percentages of change. From January through October 2005, 93 consecutive patients with claudication were eligible. Overall, 37 patients discontinued the supervised exercise therapy program. Eleven stopped because of intercurrent diseases, whereas for 10, supervised exercise therapy did not lead to adequate improvement and they underwent a vascular intervention. Three patients quit the program, stating that they were satisfied with the regained walking distance and did not require further supervised exercise therapy. Ten patients were not motivated sufficiently to continue the program, and in three patients, a lack of adequate insurance coverage was the reason for dropping out. Data for 56 patients were used and showed a mean percentage increase in initial claudication distance of 187% after 3 months and 240% after 6 months. The mean percentage of the absolute claudication distance increased 142% after 3 months and 191% after 6 months. Supervised exercise therapy in a community-based setting is a promising approach to providing conservative treatment for patients with intermittent claudication.

The effect of supervised exercise and cilostazol on coagulation and fibrinolysis in intermittent claudication: A randomized controlled trial

The prothrombotic, hypofibrinolytic state that develops in patients with intermittent claudication (IC) upon walking due to ischemia-reperfusion injury (IRI) of the leg muscles may contribute to the high incidence of life- and limb-threatening thrombotic events observed in this patient group. Treatments, such as angioplasty, that obtund the IRI also ameliorate the procoagulant diathesis. The effect on this diathesis of supervised exercise and cilostazol, both of which provide symptomatic benefit in IC, but without significantly obtunding IRI, is unknown. Thirty-four patients (27 men and 7 women; median age, 67 years; range, 63-72 years) were randomized to receive best medical therapy (BMT) plus supervised exercise (n = 9), BMT plus cilostazol (n = 9), BMT plus supervised exercise plus cilostazol (n = 7), or BMT alone (n = 9) in a 2 x 2 factorial design. Thrombin-antithrombin complex and prothrombin fragments 1 and 2, both markers of thrombin generation; plasminogen activator inhibitor antigen and tissue plasminogen activator antigen, both markers of fibrinolysis; ankle-brachial pressure index (ABPI); and initial and absolute claudication distance (ACD) were measured at baseline and then 3 and 6 months after randomization. At 6 months, when compared with receiving BMT only, supervised exercise and cilostazol resulted in improvements in ABPI of 18% and 13% and in ACD of 40% and 64%, respectively. The effects on ABPI and ACD of combining supervised exercise and cilostazol were additive. Supervised exercise, cilostazol, and supervised exercise combined with cilostazol had no significant effect on any of the four hemostatic markers. Treatment of IC by supervised exercise or cilostazol results in significant improvements in ABPI and ACD but has no demonstrable effect on the prothrombotic diathesis. This suggests that supervised exercise and cilostazol, unlike angioplasty, are unlikely to have a long-term beneficial effect on the thrombotic risks faced by these patients.

The Relationship Between Ankle-Brachial Index and Leisure-Time Physical Activity in Patients With Intermittent Claudication

The purpose of the study was to examine the relationship between ankle-brachial index (ABI) and leisure-time physical activity (LTPA) in patients with peripheral arterial disease limited by intermittent claudication. Patients included 342 sedentary men and women between the ages of 45 and 85 with intermittent claudication confirmed by a resting ABI of less than 0.90. Patients were categorized into either a low ABI group (ABI <0.50; n=84), a middle ABI group (ABI = 0.50 to 0.69; n=164), or a high ABI group (ABI = 0.70 to 0.89; n=94). The Minnesota LTPA questionnaire was used to estimate physical activity patterns, and a treadmill test, 6- minute walk test, and Walking Impairment Questionnaire were used to measure ambulatory function. A progressive decrease (p=0.030) in the total LTPA was observed among the high ABI (180 +/-131 kcal/day; mean +/- SD), middle ABI (138 +/-127 kcal/day), and low ABI (110 +/-89 kcal/day) groups. Progressive decrements in LTPA spent at moderate intensity (p=0.016) and high intensity (p=0.009), as well as the mean intensity of LTPA (p=0.024) were observed among the three respective ABI groups. Group differences in the LTPA measurements were no longer present (p>0.05) after adjusting for group differences in the absolute claudication distance during a treadmill test, and the 6-minute walk distance. The decline in total daily LTPA with progressively lower ABI in patients with intermittent claudication was due to their decreased participation in physical activities requiring moderate and high intensities. In addition, group differences in the LTPA measurements were explained by differences in ambulatory function.

Quality of life improvement after hospital- based rehabilitation or home-based physical training in intermittent claudication

The magnitude of potential changes in Quality-of-Life (QoL) after structured institution-based or home-based peripheral arterial disease (PAD) rehabilitation programs are largely unknown at present. This pilot study provides first QoL data after PAD rehabilitation or a home-based PAD training. In a non-randomized, open-label pilot study three groups of out-patients were compared: group 1 (n = 18) PAD rehabilitation; group 2 (n = 17) PAD rehabilitation + clopidogrel 75 mg once daily; group 3 (n = 20) home-based training. The training period was 3 months, which was followed by a 3-month observation phase (without prescribed training). The institution-based rehabilitation program consisted of 3 training hours per week whereas patients training at home were instructed to walk for 1 hour per day on an outdoor track. QoL assessment was performed using MOS SF-36, PAVK-86 and PAD-WIQ questionnaires. At baseline background variables, demographics and claudication distances were comparable between groups. After three months of training the percentage changes for the initial and the absolute claudication distance (ICD, ACD) for groups 1, 2, and 3 amounted to 164%, 201%, 44% (ICD) and 83%, 131%, 5% (ACD), respectively. Statistically significant QoL improvements were recorded for physical functions, pain and disease related anxiety in all three study groups; statistically significant inter-group differences were not found. In sharp contrast to the development of the claudication distances the improvement in QoL, found after 3 months of training, was comparable and not consistently different between the groups.

Metabolic syndrome impairs physical function, health-related quality of life, and peripheral circulation in patients with intermittent claudication

This study was conducted to (1) examine the effect of metabolic syndrome on intermittent claudication, physical function, health-related quality of life, and peripheral circulation in patients with peripheral arterial disease (PAD), and (2) determine whether peripheral vascular function was predictive of intermittent claudication and physical function in patients with metabolic syndrome. Patients limited by intermittent claudication and who had metabolic syndrome (n = 133) were compared with those without metabolic syndrome (n = 201). Patients were assessed on metabolic syndrome characteristics, PAD-specific measures consisting of ankle/brachial index and claudication distances, physical function measures, health-related quality of life, and calf blood flow and transcutaneous oxygen tension responses after 3 minutes of vascular occlusion. Initial claudication distance (mean +/- SD) was 29% shorter (P = .018) in patients with metabolic syndrome than in the controls (128 +/- 121 meters vs 180 +/- 166 meters), and absolute claudication distance was 22% shorter (P = .025) in those with metabolic syndrome (319 +/- 195 meters vs 409 +/- 255 meters). Furthermore, patients with metabolic syndrome had lower peak oxygen uptake (P = .037), a shorter 6-minute walk distance (P = .027), lower values on six domains of health-related quality of life (P < .05), reduced calf hyperemia (P = .028), and greater calf ischemia (P < .001) after vascular occlusion. In the group with metabolic syndrome, calf ischemia was correlated with initial claudication distance (r = 0.30, P = .004), absolute claudication distance (r = 0.40, P < .001), and peak oxygen uptake (r = 0.52, P < .001). Metabolic syndrome worsens intermittent claudication, physical function, health-related quality of life, and peripheral circulation in patients with PAD. Calf ischemia in those with metabolic syndrome was predictive of intermittent claudication and physical function. The additive burden of metabolic syndrome thus places patients who are limited by intermittent claudication at an even greater risk for living a functionally dependent lifestyle. Aggressive risk-factor modification designed to treat components of metabolic syndrome should be evaluated for efficacy in modifying physical and vascular function in patients with intermittent claudication.

Sarpogrelate, a 5-HT2A receptor antagonist in intermittent claudication. A Phase II European study

This was a multinational, multicentre, double-blind Phase II study in Europe to evaluate the efficacy and safety of two dose regimens (200 mg bid and 200 mg tid) of sarpogrelate (MCI-9042, 5-HT2A receptor antagonist) compared to placebo in patients with stable, moderately severe intermittent claudication. Following a single-blind placebo run-in period of 6 weeks, 364 (309 male and 55 female) patients (59.2 +/- 8.4 years, mean +/- SD) were randomized to receive sarpogrelate 200 mg bid, 200 mg tid or placebo for 24 weeks with a follow-up of 8 weeks. The primary objective was the increase of absolute claudication distance (ACD) at the end of treatment (week 24) compared to placebo. Analysis of covariance (ANCOVA) was performed on the log-transformed percentage of baseline ACD: loge(ACD/baseline). A responder analysis (defined as a > or = 50% improvement in ACD) was also performed. There was a marked training/placebo effect on the ACD which persisted up to 16 weeks. At 24 weeks the primary objective did not reach statistical significance (200mg bid vs placebo, p = 0.225; 200mg tid vs placebo, p = 0.580). In the responder analysis, 200 mg bid showed a statistically significant difference vs placebo (p = 0.035). In the exploratory analysis with completers (patients completing all treadmill tests), there was a statistical difference in ACD/baseline change for 200 mg bid (p = 0.035) and in the responder analysis for 200 mg tid (p = 0.044) at 24 weeks compared to placebo. Both treatments showed a carry-over effect for ACD during the 8-week follow-up (weeks 28-32). The treatment was well tolerated and no clinically significant safety concerns were reported. In conclusion, the study results confirm that sarpogrelate is well tolerated and although the primary endpoint failed to reach statistical significance, the responder analysis showed an increased absolute walking distance, which makes a further trial warranted, including a larger population, and possibly also a longer treatment period.

Metabolic Syndrome Impairs Function, Health-Related Quality of Life, and Peripheral Circulation in Patients with Intermittent Claudication

Patients limited by intermittent claudication have multiple co-morbid conditions and are sendentary, thereby increasing their risk of having metabolic syndrome. Metabolic syndrome's possible negative effects on ambulation and peripheral circulation in these patients are of particular importance. PURPOSE: To examine the effect of metabolic syndrome on intermittent claudication and peripheral circulation in patients with peripheral arterial disease (PAD), and to determine whether peripheral vascular function was predictive of the severity of intermittent claudication in patients with metabolic syndrome. METHODS: Patients limited by intermittent claudication who had metabolic syndrome (n = 155) were compared to those without metabolic syndrome (n = 428). Patients were assessed on metabolic syndrome characteristics, ambulatory function, and peripheral vascular function. RESULTS: Initial claudication distance (ICD) was 30% shorter (p = 0.007) in patients with metabolic syndrome than in the controls (133 ± 119 vs. 189 ± 165 m; mean ± SD), and absolute claudication distance (ACD) was 21% shorter (p = 0.028) (327 ± 194 vs. 413 ± 248 m). Furthermore, patients with metabolic syndrome had greater calf ischemia (p = 0.016) following a vascular occlusion test. Calf ischemia was correlated with ICD (r = 0.28, p = 0.031), and ACD (r = 0.39, p = 0.003) in the group with metabolic syndrome. CONCLUSION: Metabolic syndrome worsens intermittent claudication and peripheral circulation in patients with PAD. Thus, the additive burden of metabolic syndrome places patients limited by intermittent claudication at even greater risk for living a functionally dependent lifestyle. Supported by NIH (R01-AG-16685, K01-00657).

Assessing foot pathology using multi-segment foot models: Implications for clinical practice

There is a subset of older adults with peripheral arterial disease (PAD) who are unable to complete current walking exercise therapy guidelines due to the severity of claudication, presence of foot pathology, arthritis and/or other co-morbidities. Our aim was to therefore systematically review the evidence for the effectiveness of all forms of exercise on claudication in PAD, and subsequently compare walking to alternative modes.An electronic search of the literature was performed from earliest record until March 2011 using a variety of electronic databases. To be included trials must have been a randomized controlled trial of an exercise intervention for adults with intermittent claudication and have reported at least one claudication parameter such as initial (ICT/D) and/or absolute claudication time or distance (ACT/D) measured via a treadmill protocol. Assessment of study quality was performed using a modified version of the Physiotherapy Evidence Database Scale (PEDro). Mean difference and relative effect sizes (ESs) were calculated and adjusted via Hedges’ bias-corrected for small sample sizes.Thirty-six trials reported on walking distance in PAD: 32 aerobic (including 20 walking); 4 progressive resistance training (PRT) or graduated weight lifting exercise. In total 1644 subjects (73% male) were studied (1183 underwent exercise training); with few over 75. Most modes and intensities of exercise, irrespective of pain level, significantly improved walking capability (ACD/T Relative ES range 0.5–3.53). However, overall quality of the trials was only modest with on average 6 of the 11 PEDro quality criteria being present (mean 5.8 ± 1.3), and on average sample sizes were small (mean 44 ± 51).Modes of aerobic exercise other than walking appear equally beneficial for claudication and the benefits of PRT and upper body exercise appear promising, but little data are published on these modalities. Additional studies of high quality are required to validate these alternative prescriptions and their efficacy relative to walking.

Effect of Intermittent Pneumatic Compression of Foot and Calf on Walking Distance, Hemodynamics, and Quality of Life in Patients with Arterial Claudication. A Prospective Randomized Controlled Study With 1-Year Follow-up

The authors evaluated the effect of intermittent pneumatic compression on the walking ability, peripheral hemodynamics and quality of life in patients with claudication. Forty-one patients with claudication were randomized to intermittent compression and aspirin or aspirin alone. Inflation for 4 seconds at 3 impulses per minute, calf inflate delay 2 second was used for 5 months for at least 2.5 hours daily. The claudication patients who had intermittent pneumatic compression had improved initial and absolute claudication distance on treadmill testing and improved ankle-brachial index measurements compared with those who did not. The authors concluded that intermittent pneumatic compression was effective method for improving walking ability and pressure indices.

A pilot study of l-arginine supplementation on functional capacity in peripheral arterial disease

Peripheral arterial disease (PAD) impairs walking capacity and is often associated with a profound endothelial vasodilator dysfunction, characterized by reduced bioactivity and/or synthesis of endothelium-derived nitric oxide (NO). Previous studies have suggested that dietary supplementation of L-arginine, the precursor of NO, improves endothelium-dependent vasodilation, limb blood flow and walking distance. However, these studies have been small, and have used large intravenous doses of L-arginine. The optimal dose of L-arginine has not been determined. Accordingly, this pilot study was conducted to establish the lowest effective oral dose of L-arginine to improve walking distance in preparation for the definitive study. Patients with PAD and intermittent claudication (n = 80) participated in this study. Eligibility criteria included: (1) ankle-brachial index (ABI) at rest < or = 0.90; (2) post-exercise reduction in ABI > or = 25%; and (3) difference in absolute claudication distance of < or = 25% between two consecutive treadmill tests. Treadmill testing was performed using the Skinner-Gardner protocol and community-based walking was assessed using the walking impairment questionnaire. Patients were randomly assigned to oral doses of 0, 3, 6 or 9 g of L-arginine daily in three divided doses for 12 weeks. Treadmill testing was performed prior to administration of the study drug and again after 12 weeks of treatment. The study drug was well tolerated, with no significant adverse effects of L-arginine therapy. The safety laboratory studies were unremarkable, except for a statistically significant reduction in hematocrit in the L-arginine-treated groups. There was no significant difference observed in absolute claudication distance between the groups. However, a trend was observed for a greater increase in walking distance in the group treated with 3 g L-arginine daily, and there was a trend for an improvement in walking speed in patients treated with L-arginine. This pilot study provided data for safety, for power calculation and for dosing for the larger definitive trial that is now underway.

The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication

The purpose of this randomized trial was to compare the efficacy of a low-intensity exercise rehabilitation program vs a high-intensity program in changing physical function, peripheral circulation, and health-related quality of life in peripheral arterial disease (PAD) patients limited by intermittent claudication. Thirty-one patients randomized to low-intensity exercise rehabilitation and 33 patients randomized to high-intensity exercise rehabilitation completed the study. The 6-month exercise rehabilitation programs consisted of intermittent treadmill walking to near maximal claudication pain 3 days per week at either 40% (low-intensity group) or 80% (high-intensity group) of maximal exercise capacity. Total work performed in the two training regimens was similar by having the patients in the low-intensity group exercise for a longer duration than patients in the high-intensity group. Measurements of physical function, peripheral circulation, and health-related quality of life were obtained on each patient before and after the rehabilitation programs. After the exercise rehabilitation programs, patients in the two groups had similar improvements in these measures. Initial claudication distance increased by 109% in the low-intensity group (P < .01) and by 109% in the high-intensity group (P < .01), and absolute claudication distance increased by 61% (P < 0.01) and 63% (P < .01) in the low-intensity and high-intensity groups, respectively. Furthermore, both exercise programs elicited improvements (P < .05) in peak oxygen uptake, ischemic window, and health-related quality of life. The efficacy of low-intensity exercise rehabilitation is similar to high-intensity rehabilitation in improving markers of functional independence in PAD patients limited by intermittent claudication, provided that a few additional minutes of walking is accomplished to elicit a similar volume of exercise.

The impact of type 2 diabetes and peripheral arterial disease on quality of life

Peripheral arterial disease (PAD) is associated with impaired walking distance as the result of claudication and reduced quality of life (QOL). Diabetes mellitus (DM) is commonly associated with PAD. The combined effect of DM and PAD versus PAD alone on walking distance and QOL is not well understood. This prospective, descriptive study examined walking distance and QOL associated with DM and PAD compared with PAD alone. Walking distance was assessed by an exercise treadmill test to determine initial claudication distance and absolute claudication distance and by self-report using the Walking Impairment Questionnaire. QOL was measured using the Short Form-36. The overall sample consisted of 92 men and women with PAD and DM or PAD alone. Of the total sample, 74 participants had PAD with ABI less than 0.9 mm Hg and 18 subjects had PAD and uncontrolled DM with hemoglobin A1c 7.0 mg/dL or greater. The mean age was 72 years (standard deviation [SD] = 7) for the PAD only group and 75 years (SD = 8) (not significant) for the PAD and DM groups. Initial claudication distance was greater in subjects with PAD only (186.9 m, SD = 136.4) than in diabetic subjects with PAD (127.3 m, SD = 70.0, P = .01). Absolute claudication distance was higher in patients with PAD only (461.3 m, SD 308) than in diabetic subjects with PAD (279.1 m, SD = 100, P = .01). Self-reported walking speed was reduced in patients with DM and PAD compared with patients with PAD only (P = .05). Diabetic patients with PAD reported impaired role function (P = .007), general health (P = .03), and social function (P = .04) compared with patients with PAD only. We conclude that DM has a significant detrimental impact on walking distance and QOL in patients with PAD. These findings suggest that diabetic patients with PAD are at greater risk for experiencing social isolation, impaired role function, reduced overall perceptions of general health, and impaired functional capacity. Future studies with larger sample sizes are needed to identify factors that contribute to these perceptions in diabetic patients with PAD.

Improvement of the Walking Ability in Intermittent Claudication due to Superficial Femoral Artery Occlusion with Supervised Exercise and Pneumatic Foot and Calf Compression: A Randomised Controlled Trial

Objectives To compare the effect of unsupervised exercise, supervised exercise and intermittent pneumatic foot and calf compression (IPC) on the claudication distance, lower limb arterial haemodynamics and quality of life of patients with intermittent claudication. Methods Thirty-four eligible patients with stable intermittent claudication were randomised to IPC ( n=13, 3 h/d for 6 months), supervised exercise ( n=12, three hourly sessions/week for 6 months) or unsupervised exercise ( n=9). In each patient, initial claudication distance (ICD), absolute claudication distance (ACD), resting ankle brachial pressure index (ABPI), and resting hyperaemic calf arterial inflow were measured before, 6 weeks, 6 months and 1 year after randomisation. Quality of life was assessed with the short form (SF)-36, walking impairment (WIQ) and intermittent claudication questionnaires (ICQ). Results Compared with unsupervised exercise, both IPC and supervised exercise, increased ICD and ACD, up to 2.83 times. IPC increased arterial inflow ( p<0.05 at 6 weeks) and ABPI. Supervised exercise decreased arterial inflow and increased ABPI ( p<0.05 at 6 months). Unsupervised exercise had no effect on arterial inflow or ABPI. IPC improved significantly the ICQ score and the speed score of the WIQ, while supervised exercise improved the WIQ claudication severity score. At 1 year clinical effectiveness of supervised exercise and IPC was largely preserved. Conclusions IPC, by augmenting leg perfusion, achieved improvement in walking distance comparable with supervised exercise. Long-term results in a larger number of patients will provide valuable information on the optimal treatment modality of intermittent claudication.

Rapid foot and calf compression increases walking distance in patients with intermittent claudication: Results of a randomized study

The aim of our pilot study was to determine the usefulness of rapid, high-pressure, intermittent pneumatic calf and foot compression (IPCFC) in patients with stable intermittent claudication, with reference to the end points of improvement in initial claudication distance (ICD) (distance at which patient feels pain or discomfort in the legs), and improvement in absolute claudication distance (ACD) (distance at which patient stops walking because the pain or discomfort becomes severe). Thirty male patients presenting with stable, intermittent claudication (ACD between 50 and 150 meters on treadmill testing at 3.8 km/h, 10 degrees gradient) were recruited into this pilot study from a single center. Fifteen patients were randomized to treatment with IPCFC (applied for 1 hour twice daily in the sitting position) and were also advised to have daily exercise, and 15 patients served as controls, who were advised exercise alone. All patients received aspirin and had resting and postexercise ankle/brachial index (ABI) measured at enrollment along with ICD and ACD on treadmill testing (3.8 km/h, 10 degrees gradient). The mean age, baseline ICD, and ACD of the treatment and control groups were 70.4 +/- 7 years and 70.7 +/- 9 years, 55.8 +/- 15 meters and 68.4 +/- 17 meters, and 86.7 +/- 19 meters and 103.9 +/- 27 meters, respectively. Both groups were equally matched for risk factors, including smoking, type II diabetes mellitus, and hypercholesterolemia. IPCFC was applied. The study protocol included follow-up visits at 1, 2, 3, 4, 6, and 12 months with the ABI, ICD and ACD being measured at every visit. The percent change from baseline for ICD and ACD for each patient visit and the mean +/- standard deviation (SD), standard error (SE), and median were calculated for the control and treatment groups. The percent change from baseline measurements (mean +/- SD) for ICD and ACD in the control group at 4, 6, and 12 months were 2.2 +/- 18 and 2.3 +/- 18, 2.9 +/- 17 and 5.2 +/- 20, and 3.6 +/- 18 and 5.8 +/- 20, respectively. In contrast, the changes in ICD and ACD at 4, 6, and 12 months in the treatment group were 137.1 +/- 128 (P < .01) and 84.3 +/- 82 (P < .01), 140.6 +/- 127 (P < .01) and 96.4 +/- 106 (P = .01), and 150.8 +/- 124 (P <0.01) and 101.2 +/- 104 (P <0.01), respectively. Although the ABI showed a slight increase in the treatment group, these differences were not statistically significant. The results of this pilot study show that IPCFC improves walking distance in patients with stable intermittent claudication. A significant increase in ICD and ACD was seen at 4 and 6 months of treatment, respectively, and the improvement was sustained at 1 year. The combination of IPCFC with other treatment such as risk-factor modification and daily exercise may prove useful in patients with peripheral arterial occlusive disease. It may be a useful first line of therapy in patients with disabling claudication who are unfit for major reconstructive surgery. Improved walking on long-term follow-up and experience from different centers may establish a role for this treatment modality in the future.