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.     

Relationship between free-living daily physical activity and peripheral circulation in patients with intermittent claudication

The purpose of this study was to determine the relationship between free-living daily physical activity and peripheral circulation under resting, reactive hyperemia, and maximal exercise conditions in peripheral arterial occlusive disease (PAOD) patients with intermittent claudication. Sixty-one PAOD patients (age = 70 +/- 6 years, ankle/brachial index [ABI] = 0.57 +/- 0.24) were recruited from the Vascular Clinic at the Baltimore Veterans Affairs Medical Center and from radio and newspaper advertisements. Free-living daily physical activity was measured as the energy expenditure of physical activity (EEPA), determined from doubly labeled water and indirect calorimetry. Patients also were characterized on ankle/brachial index, calf blood flow, calf transcutaneous oxygen tension (TcPO2), and calf transcutaneous heating power (TcHP). ABI and calf blood flow served as markers of the macrocirculation of the lower extremity, while TcPO2 and TcHP served as markers of the microcirculation. The claudication patients were sedentary, reflected by a mean EEPA value of 486 +/- 274 kcal/day. EEPA was related to calf TcHP at rest (282 +/- 24 mW; r = -0.413, p = 0.002), after postocclusion reactive hyperemia (275 +/- 22 mW; r = -0.381, p = 0.004), and after maximal exercise (276 +/- 20 mW; r = -0.461, p<0.001). ABI, calf blood flow, and calf TcPO2 were not related to EEPA under any condition. In conclusion, higher levels of free-living daily physical activity were associated with better microcirculation of the calf musculature in older PAOD patients with intermittent claudication.     

The association of acute exercise-induced ischaemia with systemic vasodilator function in patients with peripheral arterial disease

Patients with peripheral arterial disease (PAD) frequently experience ischaemic attacks of the affected tissues during exercise. The present study assesses the association of transient exercise-induced leg ischaemia with vasodilator function of the clinically unaffected brachial artery over the course of 4 hours. Thirty male patients with symptomatic PAD and 14 age- and sex-matched healthy controls were included in the study. They performed a treadmill exercise until intolerable exercise-induced ischaemic pain occurred in the affected lower extremity, or for at most 10 min. Flow-mediated dilation (FMD) of the brachial artery was measured at baseline, 30 minutes, 2 hours and 4 hours after exercise. Baseline FMD values were significantly diminished in patients (7.03 +/- 1.99% vs 8.22 +/- 1.60% in controls, p = 0.009). A significant decrease in FMD was observed in patients after exercise (at 30 minutes: 3.92 +/- 1.78% vs 7.03 +/- 1.99% at baseline, p < 0.001; at 2 hours: 6.36 +/- 2.12% vs 7.03 +/- 1.99% at baseline, p = 0.005), followed by a gradual return to its baseline value, whereas FMD in controls non-significantly increased after exercise. The difference in the pattern of FMD change over time between patients and controls was significant (p < 0.001). This study shows that in PAD patients ischaemia during intermittent claudication is related to a transitory functional deterioration of the distant arteries. This indicates the harmful systemic effects of repeated ischaemic attacks during exercise and might explain the generalized and advanced nature of atherosclerotic disease in PAD patients.     

Improved functional outcomes following exercise rehabilitation in patients with intermittent claudication

BACKGROUND: The purposes of this study were to identify predictors of increased claudication distances following exercise rehabilitation in peripheral arterial occlusive disease (PAOD) patients with intermittent claudication and determine whether improved claudication distances translated into increased free-living daily physical activity in the community setting. METHODS: Sixty-three patients were recruited (age, 68+/-1 years, mean +/- standard error). Patients were characterized on treadmill claudication distances, walking economy, peripheral circulation, cardiopulmonary function, self-perceived ambulatory function, body composition, baseline comorbidities, and free-living daily physical activity before and after a 6-month treadmill exercise program. RESULTS: Exercise rehabilitation increased distance to onset of claudication pain by 115% (178+/-22 m to 383+/-34 m; p < .001) and distance to maximal claudication pain by 65% (389+/-29 m to 641+/-34 m; p < .001). The increased distance to onset of pain was independently related to a 27% increase in calf blood flow (r = .42, p < .001) and to baseline age (r = -.26, p < .05), and the increased distance to maximal pain was predicted by a 10% increase in peak oxygen uptake (r = .41, p < .001) and by a 10% improvement in walking economy (r = -.34, p < .05). Free-living daily physical activity increased 31% (337+/-29 kcal/day to 443+/-37 kcal/day; p < .001) and was related to the increases in treadmill distances to onset (r = .24, p < .05) and to maximal pain (r = .45, p < .001). CONCLUSIONS: Increased claudication distances following exercise rehabilitation are mediated through improvements in peripheral circulation, walking economy, and cardiopulmonary function, with younger patients having the greatest absolute ambulatory gains. Furthermore, improved symptomatology translated into enhanced community-based ambulation.     

The effect of hypercholestrolemia on calf muscle hemoglobin oxygen saturation in patients with intermittent claudication

The purpose was to compare calf muscle hemoglobin oxygen saturation and exercise performance in hypercholesterolemic and normocholesterolemic patients with peripheral arterial disease. Hypercholesterolemic and normocholesterolemic patients had similar ankle/ brachial index (0.72 +/- 0.24 vs 0.79 +/- 0.28, [mean +/- SD]; P = .334). Hypercholesterolemic patients had shorter initial claudication distance (214 +/- 168 m vs 331 +/- 185 m, P = .026), absolute claudication distance (391 +/- 219 m vs 549 +/- 211 m, P = .035), and lower calf muscle hemoglobin oxygen saturation at the occurrence of initial claudication distance (27 +/- 21% vs 39 +/- 20%; P = .013), and absolute claudication distance (26 +/- 21% vs 36 +/- 21%; P = .021). Hypercholesterolemia is associated with shorter walking distances and calf muscle hemoglobin oxygen saturation during exercise in patients limited by intermittent claudication.     

Benefit of exercise conditioning for patients with peripheral arterial disease

Patients with atherosclerotic peripheral arterial disease (PAD) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the resultant pain of intermittent claudication. To evaluate the benefit of exercise training as a treatment for patients with PAD, as well as possible mechanisms associated with improvement, we randomly assigned 19 men with disabling claudication to treated and control groups. Treatment consisted of supervised treadmill walking (1 hr/day, 3 days/wk, for 12 weeks) with progressive increases in speed and grade as tolerated. Graded treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance. After 12 weeks, treated subjects had increased their peak walking time 123%, peak oxygen consumption 30%, and pain-free walking time 165% (all p less than 0.05). Control subjects had no change in peak oxygen consumption, but after 12 weeks, peak walking time increased 20% (p less than 0.05). In treated subjects, maximal calf blood flow (measured by a plethysmograph) increased 38 +/- 45% (p less than 0.05), but the change in flow was not correlated to the increase in peak walking time. Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle. In treated subjects, a 26% decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time (r = -0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Physical training for intermittent claudication: a comparison of structured rehabilitation versus home-based training

In a non-randomized, open-label study results after a structured institution-based peripheral arterial occlusive disease (PAD) rehabilitation program were compared with the results of training at home. Three groups were compared: group 1 (n = 19) PAD rehabilitation; group 2 (n = 19) PAD rehabilitation + clopidogrel 75 mg once daily; group 3 (n = 21) home-based training. The training period was 3 months for all groups, which was followed by a 3-month observation phase (without prescribed training). The rehabilitation program consisted of 3 training hours per week. Background variables, demographics, and baseline claudication distances were comparable between groups. After 3 months of training the absolute claudication distances (ACD) improved by 82.7%, 131.4%, and 5.4% for groups 1, 2 and 3. The initial claudication distances (ICD) changed by 163.8%, 200.6%, and 44.4%, respectively. All changes, except the ACD result for group 3, were statistically significant (p < or = 0.05). Structured training groups (1 and 2) performed significantly better than group 3 (p < or = 0.05). When results from groups 1 and 2 were pooled, ACDs changed from 493.3 +/- 218.1 to 1026.0 +/- 468.9 m, delta 546.0 +/- 378.8 m [95% CI 417.8-674.2 ml; p < or = 0.05. ICDs improved from 175.3 +/- 110.8 m to 493.1 +/- 326.7 m, delta 320.8 +/- 315.9 m [95% CI 213.9-427.7 m]; p < or = 0.05. The difference between the pooled mean results of the structured training groups and the results of group 3 amounted to 474.3 m [95% CI 270.2-678.4 m] and 242.4 m [95% CI 99.0-385.7 m], for ACD and ICD, respectively. Structured, supervised PAD rehabilitation is a highly efficacious treatment for intermittent claudication and may be regarded as the present gold standard among conservative treatment options.     

Exercise Rehabilitation Improves Functional Outcomes and Peripheral Circulation in Patients with Intermittent Claudication: A Randomized Controlled Trial

OBJECTIVE: To determine the effects of a 6-month exercise program on ambulatory function, free-living daily physical activity, peripheral circulation, and health-related quality of life (QOL) in disabled older patients with intermittent claudication. DESIGN: Prospective, randomized controlled trial. SETTING: University Medical (Center and Veterans Affairs Medical Center, Baltimore, Maryland. PARTICIPANTS: Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise rehabilitation and 30 to usual-care control. Three patients from the exercise group and six patients from the control group dropped out, leaving 28 and 24 patients, respectively, completing the study in each group. INTERVENTION: Six months of exercise rehabilitation. MEASUREMENTS: Treadmill distance walked to onset of claudication and to maximal claudication, ambulatory function, peripheral circulation, perceived QOL, and daily physical activity. RESULTS: Compliance with the exercise program was 73% of the possible sessions. Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134% (P < .001) and to maximal claudication by 77% (P < .001), walking economy by 12% (P = .003), 6-minute walk distance by 12% (P < .001), and maximal calf blood flow by 30% (P < .001). Changes in distance walked to maximal pain correlated with changes in walking economy (r = -.50, P = .013) and changes in maximal calf blood flow (r = .38, P = .047). Exercise rehabilitation increased accelerometer-derived daily physical activity by 38% (P < .001); this change correlated with the change in distance walked to maximal pain (r = .45, P = .020). These improvements were significantly better than the changes in the control group (P < .05). CONCLUSION: Improvements in claudication following exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy. Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community, which enabled the patients to become more functionally independent.     

Comorbidities and the entry of patients with peripheral arterial disease into an exercise rehabilitation program

BACKGROUND: Exercise rehabilitation is advocated to improve function in patients with peripheral arterial disease (PAD) who have intermittent claudication. Patients with PAD often have comorbid medical problems that may interfere with their ability to safely participate in exercise rehabilitation programs. There is a paucity of information regarding the medical comorbidities and the evaluation of PAD patients before their participation in exercise rehabilitation studies. The purpose of this study was to identify comorbidities that predicted exclusion of PAD patients from participation in an aerobic exercise rehabilitation clinical trial. METHODS: This was a prospective cohort study of 225 consecutive outpatient volunteers (mean age 68 +/- 8 years, SD) with a history of Fontaine Stage II PAD recruited for exercise rehabilitation. Patient eligibility was determined by a history and physical exam, blood chemistries, measurement of ankle to brachial index (ABI), and an exercise treadmill test. RESULTS: Seventy-nine volunteers (35%) were medically ineligible: 22 because of symptomatic coronary artery disease, 12 because of severe PAD, and the rest for a variety of medical problems. In stepwise logistic regression analyses, low ABI and use of insulin were predictors of exclusion, whereas peripheral revascularization was an indicator of inclusion. Age, a history of coronary artery disease, myocardial infarction, coronary bypass surgery, and hypertension were not independent determinants of eligibility. CONCLUSIONS: Insulin-requiring diabetes and a low ABI increase the likelihood that older patients with PAD will be ineligible to participate in a research exercise rehabilitation program, whereas peripheral revascularization was associated with inclusion. Whether intensive medical management and peripheral revascularization would enable the claudicants deemed ineligible for entry into the exercise rehabilitation program to safely exercise remains to be determined.     

Comorbidities and exercise capacity in older patients with intermittent claudication.

Patients with peripheral arterial disease (PAD) and intermittent claudication often have coronary artery disease (CAD) and other comorbid medical problems. There is a paucity of information on the impact of coexistent medical conditions on exercise capacity and functional status in patients with PAD. This study examined the impact of CAD, diabetes, cigarette smoking, prior peripheral surgical revascularization and other medical conditions on claudication pain times and peak oxygen capacity (VO2) during maximal effort treadmill testing in 119 male outpatient volunteers (ankle-brachial index (ABI) of 0.65 +/- 0.2, mean +/- SEM) with a history of Fontaine Stage II PAD. Smoking status was significantly related to ambulatory function. Current smokers had a lower peak VO2 expressed in l/min than either former or never smokers (ANCOVA adjusted for age, p = 0.003). However, after adjustment for body weight, there was only a trend for a difference in peak VO2 between current (13.2 +/- 0.5 ml/kg per min), former (14.2 +/- 0.4 ml/kg per min) and never (15.4 +/- 1.0 ml/kg per min) smokers (ANCOVA, p = 0.10). Current smokers had a shorter time to onset of claudication pain (p = 0.023) and shorter maximal claudication pain times (p = 0.029) than former or never smokers (p = 0.023). The ABI 1 min after cessation of exercise was also lower in smokers compared to former and never smokers (p = 0.018). There were no significant differences in functional performance measures or time to recovery from maximal claudication pain when patients were categorized on the presence or absence of CAD, diabetes, peripheral revascularization, arthritis, hypertension or dyslipidemia. Therefore, smoking adversely affected exercise capacity in these PAD patients, whereas the presence of CAD, diabetes and other medical problems had a relatively minor impact on exercise capacity. In conclusion, the relatively minor impact of comorbid medical conditions on walking ability in patients with PAD reflects the overwhelming limitation in ambulatory function due to the claudication pain.     

Characteristics of flow-mediated brachial artery vasodilation in human subjects

In an effort to determine whether arterial conductance vessels dilate in response to increased blood flow stimuli, brachial artery area (cm2) and diameter (cm) were derived by simultaneous measurement of forearm blood flow (ml/min.100 ml) and brachial artery blood flow velocity (cm/sec) following the release of arterial occlusion. Measurements were made at rest and at the time of maximal flow after the release of graded periods of forearm arterial occlusion (20 seconds to 10 minutes). These studies showed a graded large vessel dilation following occlusions of up to 1 minute (baseline diameter, 0.33 +/- 0.01; after 1 minute occlusion, 0.45 +/- 0.02 cm; p less than 0.05) after which time diameter plateaued (after 10 minutes of occlusion, 0.48 +/- 0.02 cm). In addition, the time course of diameter and flow changes after 3 minutes of arterial occlusion were examined. Flow was maximal at 5 seconds but diameter was maximal at 15-30 seconds after release. Furthermore, the half time for the return of diameter to baseline was longer than that for blood flow. We also measured the diameter after forearm heating (42 degrees C) and noted a substantial increase in diameter (before heating, 0.32 +/- 0.01; after heating, 0.39 +/- 0.02 cm; p less than 0.05). Finally, we applied pressure to the venous side of arteriovenous fistulae in five hemodialysis patients. This maneuver was associated with large reductions in forearm blood flow (baseline flow, 63.3 +/- 10.6; venous compression flow, 36.0 +/- 4.4 ml/min.100 ml; p less than 0.05) and a decrease in brachial artery size (baseline diameter, 0.63 +/- 0.07; venous compression diameter, 0.58 +/- 0.06 cm; p less than 0.05). We conclude that 1) the human brachial artery size changes in response to changes in blood flow, and 2) the maximal dilation occurs after maximal flow is noted. Although alternate explanations are possible for each of our observations, our results are most consistent with a flow-mediated, localized vasodilating process.     

The relationship between history of falling and physical function in subjects with peripheral arterial disease

The purpose of this study was to determine whether peripheral arterial disease (PAD) subjects with a history of falling had more impaired physical function than their non-falling counterparts. A total of 120 PAD subjects (26%) who had fallen over the past year and 346 PAD subjects (74%) who had not fallen were evaluated. Additionally, subjects were characterized on physical function, consisting of balance, strength, ambulatory function, and monitored physical activity, as well as PAD-specific measures of ankle/brachial pressure index (ABPI) and treadmill claudication distances. Full-tandem stance time was 19% shorter (p < 0.001) in the fallers than in the non-fallers (7.2 +/- 0.3 vs 8.9 +/- 0.1 s; mean +/- SEM), and the self-reported ability to climb stairs was 36% lower (27 +/- 4 vs 42 +/- 2%). Furthermore, the fallers were 126% more likely (p < 0.001) to report ambulatory stumbling and unsteadiness, took 14% longer (p = 0.022) to perform five sequential sit-to-stand transfers using an armless chair, covered 16% shorter distance (p < 0.001) during a 6-min walk test, and were 25% less physically active than the non-fallers. The groups had similar ABPI and treadmill claudication distances (p < 0.05). A history of falling was independently related to the self-reported ability to climb stairs, the full-tandem stance time, self-reported ambulatory stumbling and unsteadiness, and daily physical activity (multiple R = 0.47, p < 0.001). In conclusion, impairments in multiple domains of physical function were associated with a history of falling in PAD subjects with intermittent claudication. Furthermore, the link between poor physical function and falling was independent of PAD severity.     

Resting energy expenditure in subjects with and without intermittent claudication

Subjects with peripheral arterial disease and intermittent claudication have ischemia of the lower extremities, but little is known how this influences resting energy expenditure. The objective of the study was to compare the resting energy expenditure of subjects with and without intermittent claudication. One hundred six subjects limited by intermittent claudication and 77 controls who did not have peripheral arterial disease and intermittent claudication participated in this study. Subjects were assessed on resting energy expenditure, body composition, ankle/brachial index (ABI), and calf blood flow. Subjects with intermittent claudication had a lower resting energy expenditure (1585 ± 251 vs 1716 ± 277 kcal/d, P = .019), higher body fat percentage (33.4% ± 10.7% vs 29.6% ± 7.7%, P = .016), higher fat mass (29.6 ± 10.6 vs 24.2 ± 8.9 kg, P = .011), and lower ABI (0.66 ± 0.20 vs 1.19 ± 0.12, P < .001). Resting energy expenditure was predicted by fat-free mass (P < .001), ABI (P = .027), and calf blood flow (P = .040). Resting energy expenditure remained lower in the subjects with intermittent claudication after adjusting for clinical characteristics plus fat-free mass (1611 ± 171 vs 1685 ± 209 kcal/d, P = .035), but was no longer different between groups after further adjustment for ABI and calf blood flow (1622 ± 165 vs 1633 ± 185 kcal/d, P = .500). Subjects with intermittent claudication have lower resting energy expenditure than controls, which is partially explained by ABI and calf blood flow.     

Endothelial reactivity and cardiac risk factors in older patients with peripheral arterial disease

Peripheral arterial disease (PAD) is a major cause of morbidity and mortality. Endothelium-dependent vasoreactivity, which is advocated as a measure of vascular health, is impaired in persons with cardiac risk factors and coronary artery disease. Few studies have examined the degree of endothelial dysfunction in patients with PAD. Using high-resolution external vascular ultrasound, we measured brachial artery diameter and flow at rest, and in response to reactive hyperemia (flow-mediated dilation) in 50 older patients (age 69 +/- 1 year) with PAD (ankle-to-brachial artery index of 0.67 +/- 0.03), and 50 age-matched non-PAD patients. Coronary artery disease was more prevalent in PAD than in non-PAD patients (40% vs 4%, p <0.001). Systolic blood pressure (153 +/- 4 vs 141 +/- 3 mm Hg, p <0.01), fasting glucose (129 +/- 6 vs 109 +/- 5 mg/dl, p <0.001), and pack-years smoked (54 +/- 7 vs 25 +/- 3, p <0.01) were higher in the PAD than in non-PAD patients. There were no differences in baseline brachial artery diameter, blood velocity, or flow between the 2 groups. However, the 1-minute postocclusion percent change in diameter (6.5 +/- 0.7% vs 9.8 +/- 0.7%, p <0.001) and the change in diameter (0.22 +/- 0.02 vs 0.33 +/- 0.02 mm, p <0.001) were lower in PAD than in non-PAD patients, suggesting impaired endothelium-dependent dilation. The postocclusion hyperemic velocity and blood flow were also lower in PAD than in non-PAD patients. In multiple regression analyses the low-density lipoprotein-to-high-density lipoprotein cholesterol ratio, elevated fasting glucose, and high systolic blood pressure were independent predictors of percent change in brachial artery diameter (r2 = 0.37, p <0.001). Thus, older patients with PAD had impaired endothelial dependent vasodilation compared with controls that was associated with the presence of cardiac risk factors. The effect of cardiac risk factor intervention on endothelial function in patients with PAD remains to be determined.     

Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity

BACKGROUND: Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD. METHODS: We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD. RESULTS: Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014). CONCLUSION: We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.     

Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment

Simvastatin significantly increased treadmill exercise time until onset of intermittent claudication from baseline by 54 seconds (a 24% increase, p <0.0001) at 6 months after treatment and by 95 seconds (a 42% increase, p <0.0001) at 1 year after treatment. At 6 months and 1 year after treatment with placebo, treadmill exercise time until onset of intermittent claudication was not significantly different from baseline exercise time.     

Effects of long-term exercise rehabilitation on claudication distances in patients with peripheral arterial disease: a randomized controlled trial

PURPOSE: To determine if improvements in physical function and peripheral circulation after 6 months of exercise rehabilitation could be sustained over a subsequent 12-month maintenance exercise program in older patients with intermittent claudication. METHODS: Seventeen patients randomized to exercise rehabilitation and 14 patients randomized to usual care control completed this 18-month study. Patients exercised three times per week during the first 6 months of a progressive exercise program, followed by two times per week during the final 12 months of a maintenance program. Patients were studied at baseline, 6 months, and 18 months during the study. RESULTS: Eighteen months of exercise rehabilitation increased the initial claudication distance by 373 meters (189%) (P <.001), the absolute claudication distance by 358 meters (80%) (P <.001), walking economy by 11% (P <.001), 6-minute walk distance by 10% (P <.001), daily physical activity by 31%, and maximal calf blood flow by 18% (P <.001). These changes were similar to those found after 6 months of exercise rehabilitation (P = NS), and were significantly greater than the changes in the control group throughout the study (P <.05). CONCLUSION: Improvements in claudication distances, walking economy, 6-minute walk distance, physical activity level, and peripheral circulation after 6 months of exercise rehabilitation are sustained for an additional 12 months in older patients with intermittent claudication using a less frequent exercise maintenance program.     

Peripheral arterial disease

Peripheral arterial disease (PAD) in the elderly can be: 1) asymptomatic, 2) associated with intermittent claudication, or 3) cause critical limb ischemia. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease (CAD). Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism should be treated, and smoking should be stopped. Statins reduce the incidence of intermittent claudication and increase exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs (eg, aspirin, clopidogrel, angiotensin-converting enzyme [ACE] inhibitors, statins) should be given to all persons with PAD. Beta blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol lengthen exercise time until leg pain develops. Chelation therapy has no scientific basis and should be avoided. Revascularization or amputation may be indicated in some cases.     

The effect of six months intensive physical training on the circulation in the legs of patients with intermittend claudication

Out of 94 patients with intermittent claudication 65 completed a program of 6 months intensive physical training. Every 2 months the blood pressure indices at the thigh and at the ankle and the blood flow in the calf were measured at rest, after 5 min arterial occlusion and after exercise of the calf muscles until claudication. First the reproducibility of the blood pressure indices and the blood flow values was established. An increase of 15 in the pressure indices was considered to be substantial. An increase of 6.0 ml/100 ml/min in flow values was considered a substantial change. The blood pressure indices did not increase significantly during the training period, the blood flow values increased significantly. On the basis of the non-invasive tests no reliable statement can be made as to the expected result of the training.     

Management of peripheral arterial disease of the lower extremities in elderly patients

The prevalence of peripheral arterial disease (PAD) increases with age. PAD in elderly persons may be asymptomatic, may be associated with intermittent claudication, or may be associated with critical limb ischemia. Other atherosclerotic vascular disorders, especially coronary artery disease (CAD), may coexist with PAD. Elderly persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from CAD. Modifiable risk factors should be treated in persons with PAD such as cessation of cigarette smoking and control of hypertension, dyslipidemia, and diabetes. Statins have been shown to reduce the incidence of intermittent claudication and to improve treadmill exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, should be administered to all persons with PAD. Persons with PAD should be treated with angiotensin-converting enzyme inhibitors and also with beta blockers if CAD is present. Cilostazol should be given to persons with intermittent claudication to improve exercise capacity unless heart failure is present. Exercise rehabilitation programs improve exercise time until claudication. Indications for lower extremity angioplasty, preferably with stenting, or bypass surgery are 1) incapacitating claudication in persons interfering with work or lifestyle; 2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and 3) vasculogenic impotence. However, amputation should be performed if tissue loss has progressed beyond the point of salvage, if surgery is too risky, if life expectancy is very low, or if functional limitations obviate the benefit of limb salvage.