Peripheral arterial disease

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Peripheral arterial disease (PAD) is very common and increases with age. The main risk factors are similar to those for general cardiovascular disease. Both aerobic exercise (including various types of endurance training in addition to walking) and resistance-training appear to be useful methods of improving walking performance and reducing claudication symptoms in individuals with PAD.

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What is peripheral arterial disease?

Peripheral arterial disease (PAD) is the narrowing of the arteries in the legs as a result of atherosclerosis (Hirsch et al.) and it increases the risk of short-term cardiovascular events. It is most commonly measured using the ankle-brachial blood pressure index (ABI), which is a measurement of segmental blood pressure. The use of the ABI has been validated (Stoffers et al.) and researchers have recommended that PAD can be identified based on an ABI of <0.9 measured on 3 separate occasions (Stoffers et al.). The earliest and most frequent symptom of PAD is intermittent claudication, or pain in the leg muscles when walking. If PAD is allowed to continue unhindered, similar pains may develop in the legs at rest. While PAD is not as widely monitored as other aspects of cardiovascular disease, it is a serious health risk. Individuals with PAD display a 3.3 times greater rate of all-cause mortality (Criqui et al.), a 5.9 times greater rate of cardiovascular disease mortality and a 6.6 times greater rate of coronary heart disease mortality.


What is the prevalence of PAD?

Although PAD is less well-studied than other aspects of cardiovascular disease, it is perhaps the most prevalent element in the general population. However, not all studies have used the same methodology for assessing prevalence. While most use the ankle-brachial blood pressure index (ABI), the exact ratio is not standardized and there are variances, with some studies setting the cut-off ratio as 0.9 and others as 0.95. The following table shows the results of some of the larger studies:

Study Population Prevalence
Selvin and Erlinger United States adults aged >40 years 4.3%
Selvin and Erlinger United States adults aged >70 years 14.5%
Hirsch et al. United States primary care patients aged >50 years 29%
Stoffers et al. Dutch males aged 45 – 54 years 1.6%
Stoffers et al. Dutch males aged 55 – 64 years 7.7%
Stoffers et al. Dutch males aged 65 – 74 years 16.4%
Stoffers et al. Dutch females aged 45 – 54 years 3.1%
Stoffers et al. Dutch females aged 55 – 64 years 6.8%
Stoffers et al. Dutch females aged 65 – 74 years 11.2%
Fowkes et al. Scottish adults aged 55 – 74 years 9.0%
Meijer et al. Dutch males aged 55 years and over 16.9%
Meijer et al. Dutch females aged 55 years and over 20.5%
Murabito et al. United States males with a mean age of 59 years 3.9%
Murabito et al. United States females with a mean age of 59 years 3.3%
Coni et al. British elderly patients aged >65 years 18%
Fowler et al. Australian males aged 65 – 83 years 16.6%
Brevetti et al. Italian males aged 40 – 80 years 2.4%
Brevetti et al. Italian females aged 40 – 80 years 0.9%
Vogt et al. United States females aged 65 – 69 years 2.9%
Vogt et al. United States females aged >80 years 15.5%
Zheng et al. United States males aged 45 – 64 years 3.0%
Zheng et al. United States females aged 45 – 64 years 3.0%
Newman et al. United States males aged >65 years 13.8%
Newman et al. United States males aged >65 years 11.4%
Gofin et al. Israeli males aged 35 – 64 years 4.2%
Gofin et al. Israeli females aged 35 – 64 years 5.4%
Schroll and Munck Danish males aged 60 years 16%
Schroll and Munck Danish females aged 60 years 13%
Ostchega et al. United States adults aged 60 – 69 years 7.0%
Ostchega et al. United States adults aged >60 years 12.2%
Ostchega et al. United States adults aged >70 years 23.0%
Allison et al. United States adults aged >40 years 5.8%

Based on these studies, it appears that the prevalence of peripheral arterial disease increases rapidly with increasing age and can also vary extensively with gender, geography and type of population. The prevalence can therefore range from 0.9 – 29% with these variables.


What are the risk factors for PAD?

Although PAD is less well-studied than other aspects of cardiovascular disease, it is perhaps the most prevalent element in the general population. Additionally, since the mechanism by which PAD progresses is atherosclerosis, it is generally assumed that the risk factors that lead to atherosclerosis (i.e. smoking, type II diabetes, hypertension and hypercholesterolemia) will also be the key risk factors for PAD (Hirsch et al.). The following studies have identified some of the most common risk factors for developing PAD:

Study Method Finding
Ostchega et al. The researchers performed a cross-sectional, nationally representative health examination survey in the United States, in 3,947 men and women aged >60 years. The researchers found that non-Hispanic black men and women and Mexican-American women had a higher prevalence of PAD than non-Hispanic white men and women. They also noted that current smoking placed individuals at a 5.48 times greater risk of PAD, previous smoking placed individuals at a 1.94 times greater risk of PAD, diabetes mellitus placed individuals at a 1.81 times greater risk, low kidney function placed individuals at a 2.69 times greater risk of PAD, mildly decreased kidney function placed individuals at a 1.71 times greater risk of PAD, high-sensitivity C-reactive protein >3.0 mg/L placed individuals at a 2.69 times greater risk of PAD, treated but not controlled hypertension placed individuals at a 1.95 times greater risk of PAD, and untreated hypertension placed individuals at a 1.68 times greater risk of PAD.
Selvin and Erlinger The researchers analyzed data from 2,174 participants aged >40 years taken from the 1999 – 2000 National Health and Nutrition Examination (NHANES) Survey. The NHANES Survey is an ongoing cross- sectional survey of the civilian, non-institutionalized population of the United States (US). PAD was defined as an ankle-brachial index of <0.90 in either leg. The researchers reported that black race/ethnicity placed individuals at a 2.83 times greater risk of PAD, current smoking placed individuals at a 4.46 times greater risk of PAD, diabetes placed individuals at a 2.71 times greater risk of PAD, hypertension placed individuals at a 1.75 times greater risk of PAD, hypercholesterolemia placed individuals at a 1.68 times greater risk of PAD, and low kidney function placed individuals at a 2.0 times greater risk of PAD.
Murabito et al. The researchers assessed the risk factors for PAD in a population-based sample of 1,554 males and 1,759 females with a mean age of 59 years who attended a Framingham Offspring Study examination from 1995 – 1998. The researchers defined the presence of PAD as an ankle-brachial blood pressure index of <0.9. The researchers reported that each 10 years of age put individuals at a 2.6 times greater risk of PAD, hypertension placed individuals at a 2.2 times greater risk of PAD, and smoking put individuals at a 2.0 times greater risk of PAD.
Fowler et al. The researchers performed a cross-sectional survey of a randomly selected population of elderly males aged 65 – 83 years in the Metropolitan area of Perth, Western Australia in order to assess the risk factors for PAD. The researchers reported that current smoking status increased the risk of PAD 3.9 times, former smoking status increased the risk of having PAD 2.0 times, physical inactivity increased the risk of having PAD 1.4 times, a history of angina increased the risk of having PAD 2.2 times, and having diabetes mellitus increased the risk of having PAD 2.1 times.
Price et al. The researchers followed 1,592 men and women aged 55 – 74 years from 11 general practices in Edinburgh, Scotland for 5 years while tracking the incidences of PAD. The researchers reported that the risk of developing of PAD was 1.73 times greater in moderate-smokers (<25 pack-years) than in never-smokers and 3.8 times greater in heavy smokers (>25 pack-years).
Beks et al. The researchers performed a cross-sectional study in order to investigate the association between PAD and glycaemic level in a Caucasian population, aged 50 – 74 years. The subjects were stratified based on the results of 2 oral glucose tolerance tests (OGTTs) and categorized as having either normal, impaired, or a diabetic glucose tolerance. Subjects using medication were placed in a fourth category. The researchers reported that the prevalence of PAD in these subjects (as defined by an ankle-brachial pressure index of <0.90) were 7.0%, 9.5%, 15.1% and 20.9%, respectively. The researchers observed that parameters of glucose tolerance are independently associated with PAD.
Novo et al. The researchers assessed the risk factors in patients suffering from PAD in two clinical samples (102 patients with PAD matched for sex and age with 102 healthy volunteers; and 184 hospitalized patients with PAD) and in two epidemiological cohorts (the Trabia Study, with 835 subjects; and the Casteldaccia Study, with 723 subjects). In the first clinical study, the researchers observed a significantly greater prevalence of arterial hypertension (51.9 vs. 9.8%), hypercholesterolemia (48.2 vs. 21.6%), hypertriglyceridemia (53.7 vs. 26.1%), smoking (64.3 vs. 44.2%), and hyperglycemia (26 vs. 7.9%) in PAD patients in comparison to controls. In the second clinical study and in the epidemiological studies, the researchers found that the prevalence of PAD increases above all with aging, and more so in males. Additionally, in the Trabia Study the researchers observed that hypercholesterolemia, smoking and obesity were strongly associated with PAD in males, while hypertension, hypercholesterolemia and obesity were strongly associated with PAD in females. In the Casteldaccia Study, the researchers reported that smoking, hypercholesterolemia and hypertriglyceridemia were strongly associated with PAD in males in males, while obesity, hypercholesterolemia and diabetes were strongly associated with PAD in females.
Hooi et al. The researchers performed a cross-sectional survey in order to assess the risk factors for PAD in 3,650 subjects, aged 40 – 78 years. They defined PAD as an ankle-brachial pressure index of <0.95, measured on two consecutive occasions, without intermittent claudication. The researchers found that smoking and age were the most important risk factors for PAD. Being a current smoker was associated with a 3.2 times greater risk of having PAD, while being a former smoker was associated with a 1.9 times greater risk. They also found that hypertension and diabetes were also associated with PAD. Being hypertensive was associated with a 1.4 times greater risk of having PAD and having diabetes was associated with a 1.9 times greater risk of having PAD.
Garg et al. The researchers assessed whether higher levels of physical activity during daily life are associated with reduced functional decline in 203 subjects with PAD, who initially underwent vertical accelerometer-measured physical activity over a 7-day period and who were then followed annually for up to 4 years. The researchers found that higher baseline physical activity levels were associated with significantly lower annual decline in 6-minute walk performance, fast paced 4m-walking velocity and the short performance physical battery.

Based on these studies, the main risk factors for peripheral arterial disease (PAD) are current or previous smoking (in a dose-responsive relationship, with greater smoking being associated with a greater risk), physical inactivity, type II diabetes mellitus, hypertension, hypercholesterolemia and hypertriglyceridemia, and being older.


Can exercise help treat PAD?

The use of exercise for helping reduce the primary symptom of PAD, intermittent claudication, is well-recognized and is currently already a key recommendation for treatment in that “a program of supervised exercise training is recommended as an initial treatment modality for patients with intermittent claudication. Supervised exercise training should be performed for a minimum of 30 to 45 minutes, in sessions performed at least 3 times per week for a minimum of 12 weeks.” (Hirsch et al.). A number of studies and reviews have investigated the use of exercise interventions for the treatment of PAD, as follows:

Study Method Finding
Hiatt et al. The researchers compared the effectiveness of a resistance-training program and a walking program for relieving claudication in 29 patients with PAD. The researchers randomly allocated the subjects to 12 weeks of either supervised walking exercise on a treadmill (3 hours per week at a work intensity sufficient to produce claudication), the same period and duration of strength training or a non-exercising control group. The researchers reported that the patients in the supervised walking program displayed a greater increase in peak walking time in comparison to the strength-trained group had a (74 ± 58% vs. 36 ± 48%) while the control subjects displayed no changes.
Regensteiner et al. The researcher compared supervised, hospital-based and unsupervised, home-based exercise programs for improving treadmill exercise performance in 20 PAD patients with claudication. The researchers randomly allocated 10 subjects into a supervised, hospital-based program and 10 into an unsupervised, home-based program for a 3-month intervention. Both groups were intended to perform 1 hour of walking, 3 times per week. The researchers reported that the patients in the supervised group improved peak walking time by 137%, pain-free walking time by 150%, and VO2-max by 19%. However, the patients in the unsupervised group did not improve exercise performance on the treadmill.
Hiatt et al. The researchers assessed the benefits of exercise training in 19 male PAD patients with disabling claudication. The researchers randomly allocated the subjects to either intervention or control groups. The exercise group performed supervised treadmill walking for 1 hour per day, 3 days per week, for 12 weeks with progressive increases in speed and grade as tolerated. The researchers reported that the exercise intervention led to an increase in peak walking time of 123%, an increase in VO2-max of 30%, and an increase in pain-free walking time of 165% while there were no increases in the control group.
McDermott et al. The researchers performed a randomized controlled clinical trial in 156 patients with PAD to compare the ability of supervised treadmill exercise or lower body resistance-training for improving functional performance of PAD patients with and without claudication. The subjects were randomly assigned to supervised treadmill exercise, to lower extremity resistance training, or to a control group. The researchers reported that those subjects in the supervised treadmill exercise group increased their 6-minute distance walked by more than those in the resistance training group (35.9m vs. 12.4m) and both groups improved 6-minute distance walked than the control group. However, neither exercise group improved performance in the short physical performance battery. Additionally, both the supervised treadmill exercise and resistance training groups improved maximal treadmill walking time (3.44 vs. 1.90 minutes), walking impairment distance score (10.7 vs. 6.9), and 36-Item Short Form Health Survey physical functioning (SF-36 PF) score (7.5 vs.7.5) by more than the control group.
Zwierska et al. The researchers performed a randomized controlled clinical trial in 104 PAD patients with an average age of 69 years to compare the effects of upper- or lower-limb aerobic exercise training on pain-free walking distance. The subjects were randomly allocated into either an upper- or a lower-limb aerobic exercise training group or to a non-exercising control group. In the 2 training groups, exercise was performed 2 times weekly for 24 weeks. The researchers found that both the walking distance before claudication and the maximum walking distance increased in both the upper-limb (51% and 57%) and lower-limb (29% and 31%) groups. This indicates that both upper body and lower body aerobic exercise are useful in the treatment of claudication symptoms in individuals with PAD.
Walker et al. The researchers performed a randomized controlled clinical trial to assess the effects of upper-limb (arm cranking) and lower-limb (leg cranking) exercise training on walking distances in 67 PAD patients with intermittent claudication aged 33 – 82 years. The researchers randomly allocated the subjects to either an upper-limb training group or a lower-limb training group or a non-training control group. The training groups performed supervised exercise sessions, twice weekly for 6 weeks. The researchers found that both training groups displayed significant improvements in maximum power generated during incremental upper- and lower-limb ergometry tests, independently of the training mode, as well as significant improvements in pain-free and maximum walking distances. There were no significant differences in the improvements achieved by the two training groups.
Treat-Jacobson et al. The researchers explored the ability of upper-body aerobic exercise using arm-ergometry to improve pain-free walking distance and maximum walking distance in comparison to treadmill walking or no exercise in 41 subjects with claudication. The subjects were randomly allocated to either a control group or to 12 weeks of 3 hours per week of supervised exercise training using either arm-ergometry, treadmill walking, or a combination of the two. The researchers found that maximum walking distance increased significantly in the arm-ergometry (53%), treadmill (69%), and combination (68%) groups but did not increase in the control group. However, pain-free walking distance increased significantly in the arm-ergometry (82%) group but only trended towards significance in the treadmill (54%), and combination (60%) groups. This indicates that both upper body and lower body aerobic exercise are useful in the treatment of claudication symptoms in individuals with PAD.
Gardner et al. The researchers performed a prospective, randomized, controlled clinical trial to compare the effects of a home-based exercise program, a supervised exercise program, and usual-care control on exercise performance and walking activity in 119 PAD patients with intermittent claudication. The researchers reported that both exercise programs significantly increased claudication onset time and peak walking time but only home-based exercise increased daily average cadence.
Sanderson et al. The researchers compared the effects of cycle ergometer training with treadmill walking training in a group of 42 PAD patients (24 men and 18 women) with claudication. The subjects were randomly allocated into either treadmill, cycle or control groups. Both the treadmill and cycle groups trained 3 times a week for 6 weeks and the control group did not train. The researchers found that the treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance. In contrast, they found that cycle training significantly improved maximal cycle time but did not improve treadmill performance.
Tew et al. The researchers investigated the effects of arm-crank exercise training on lower-limb oxygen delivery in 57 elderly PAD patients (aged 70 ± 8 years) with intermittent claudication. The subjects were randomly allocated to either an arm-crank exercise group or a non-exercise control group. The exercise group trained twice weekly for 12 weeks. The researchers reported that the arm-crank exercise group displayed greater increases in maximum walking distances (from 496 ± 250 to 661 ± 324m) and VO2-max values (from 17.2 ± 2.7 to 18.2 ± 3.4ml/kg/min) than the control group. Using near-IR spectroscopy to determine changes in calf muscle tissue oxygen saturation, the researchers found that training also caused an increase in time to minimum muscle tissue oxygen saturation (from 268 ± 305 to 410 ± 366s), suggesting that the improvement in walking performance was at least partly attributable to improved lower-limb oxygen delivery.
Parr et al. The researchers compared the effects of different exercise protocols on functional walking performance in 30 PAD patients with intermittent claudication. The subjects were randomly allocated to either an upper body strength training program, a conventional exercise rehabilitation program (walking, cycling and circuit-training), or advice to 'walk as much as possible at home'. The researchers reported that maximum walking distance on the standard graded treadmill exercise test increased significantly in the conventional exercise rehabilitation program group compared with the control and upper body strength training program groups, respectively (93.9 ± 79% vs. 7.0 ± 19.8% vs. 7.3 ± 46%).
Wang et al. The researchers investigated the effects of maximal strength training on walking economy and walking performance in 10 PAD patients with mild-to-moderate-severe claudication. The subjects performed maximal strength training 3 times per week, involving 4 sets of 5 repetitions of the dynamic leg press at 85 – 90% of 1RM. The researchers observed that leg press 1RM significantly increased by 35.0 ± 10.8kg (i.e. 31.3%), rate of force development increased by 1424 ± 1217 N/s (i.e. 102.7%), walking economy increased by 9.7% and walking time-to-exhaustion increased by 13.6% on an incremental treadmill test. However, there were no changes in VO2-max.
Ritti-Dias et al. The researchers investigated the effects of resistance-training on walking capacity in 30 PAD patients with intermittent claudication in comparison with more typical walking training. The researchers randomly allocated the subjects into either resistance-training or walking groups, who both trained twice a week for 12 weeks at the same rate of perceived exertion. The resistance-training comprised 3 sets of 10 reps of whole body exercises and the walking comprised 15 sets of 2-minutes of walking. The researchers reported that the resistance-training group improved walking distance to claudication significantly (358 ± 224 to 504 ± 276m) and total walking distance (618 ± 282 to 775 ± 334m). However, there were no differences between the improvements achieved in either of the training groups.
Bronas et al. The researchers assessed the contribution of central cardiorespiratory function for improving the walking capacity of 28 PAD patients with claudication over 12 weeks of exercise training. The subjects were randomly allocated to either 3 hours per week of supervised arm-ergometry exercise training, or 3 hours per week of supervised treadmill-walking, or to a control group. The researchers found that improvements in cardiorespiratory function after both arm-ergometry and treadmill-training were significantly associated with improvements in both pain-free walking distance and maximum walking distance, indicating that central cardiorespiratory function does contribute to exercise training-related improvements in walking capacity seen in PAD patients with claudication.
Slørdahl et al. The researchers compared the effects of 8 weeks of either high- and low-intensity exercise in 16 PAD patients with claudication on VO2-max and walking performance. They also assessed the effects of each type of training on blood flow to the legs using ultrasound measurements to record popliteal blood flow during plantar-flexion exercise. The researchers randomly assigned the patients to train at either 60% or 80% of their VO2-max for 30 minutes, 3 times per week, respectively. The researchers found that both VO2-max and walking time-to-exhaustion increased by significantly more in the high-intensity group (by 9% and 16%, respectively) than in the low-intensity group. The researchers also reported that blood flow to the legs did not change after training in either of the groups. Since blood flow did not change, the researchers deduced that the improvements in VO2-max were likely caused by altered mitochondrial oxidative function and/or skeletal muscle diffusive capacity.
Gardner et al. The researchers performed a randomized trial to compare the effects of a low-intensity exercise rehabilitation program and a high-intensity rehabilitation program on physical function and health-related quality of life in 64 PAD patients with intermittent claudication. The researchers randomly allocated the subjects to either low-intensity or high-intensity exercise for a 6-month rehabilitation program. The exercise 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 was similar in both groups. The researchers reported that the patients in the two groups displayed similar improvements in initial claudication distance, which increased by 109% in both groups, and absolute claudication distance, which increased by 61% and 63% in the low-intensity and high-intensity groups, respectively. The researchers also observed that both groups displayed similar improvements in health-related quality of life.
Patterson et al. The researchers compared the effects of a supervised exercise program and a home-based exercise program on improving walking ability and quality of life in 47 PAD patients with claudication. The researchers randomly allocated the subjects to either a supervised exercise program or to a home-based exercise group for a 12-week period. The researchers found that both supervised and home-based groups significantly improved pain-free walking time (3.8 ± 2.74 to 11.2 ± 4.02 minutes vs. 3.6 ± 2.73 to 6.6 ± 3.17 minutes) and maximum walking time but the improvements in the supervised group were greater. Additionally, the researchers found that Short Form-36 (SF-36) outcomes on Physical Function Subscale, Bodily Pain Subscale, and Physical Composite Score were significantly improved in both groups with no significant differences between groups.
Clifford et al. The researchers assessed the effects of an exercise class in 18 PAD patients with intermittent claudication. The subjects attended a physiotherapy department for just 1 afternoon per week for an exercise training program lasting 1 month. The researchers performed a follow-up assessment at 6 months. The researchers found that the subjects walked 80% further and performed 75% more step-ups than at the baseline measurement.
Tsai et al. The researchers performed a prospective, randomized controlled trial in order to determine the effects of 12-week treadmill walking program on functional walking ability, free-living daily physical activity and health-related quality of life in 64 disabled older patients with PAD and intermittent claudication. The researchers randomly allocated the subjects to either an exercise training group or to a usual care control group. The researchers reported that the exercise training intervention led to an increase in treadmill walking time to onset of claudication pain of 88%, an increase in the time to maximal pain of 70% and an increase in 6-minute walk distance of 21%. The researchers also reported that perception of health-related quality of life improved from 12% to 178% in the exercise group and these improvements were significantly better than those observed in the control group.
Hiatt et al. The researchers investigated the effects of 12 weeks of exercise training on claudication-limited peak exercise performance and skeletal muscle metabolism in 26 PAD patients with claudication. The researchers randomly allocated the subjects into either a treadmill training group, a resistance-training group or a non-exercising control group. Before and after the training intervention, the researchers took gastrocnemius muscle biopsies. The researchers reported that only the treadmill training group displayed improved peak exercise performance and VO2-max. However, the treadmill training did not alter type I or type II muscle fiber area or citrate synthase activity (indicating no significant changes in mitochondrial function). On the other hand, the resistance-training group displayed a decrease in citrate synthase activity.
Langbein et al. The researchers performed a randomized clinical trial to assess the effects of a 24-week program of pole-striding exercise (walking with modified ski poles with a movement pattern similar to cross-country skiing) on exercise tolerance in 52 PAD patients with intermittent claudication pain. The researchers randomly allocated the subjects into either a pole-striding exercise group or non-exercise control group. The exercising group performed supervised training 3 times per week for 4 weeks, 2 times per week for 8 weeks, 1 time per week for 4 weeks, 1 time every other week for 4 weeks and unsupervised training for 4 weeks. Additionally, the were directed to perform unsupervised exercise sessions from week 5 onwards such that a total of four 30 – 45-minute poles0triding exercise sessions were performed in each week. The researchers reported that the pole-striding exercise led to significantly improved exercise tolerance on both constant work-rate and incremental treadmill tests and that ratings of perceived claudication pain were significantly reduced.
Collins et al. The researchers performed a randomized clinical trial to assess the effects of pole-striding exercise (walking with modified ski poles with a movement pattern similar to cross-country skiing) and vitamin E supplementation on walking ability and perceived quality of life in 52 PAD patients with claudication pain. The researchers randomly allocated the subjects into 4 groups: pole-striding + vitamin E, pole-striding with placebo, vitamin E without exercise, and placebo without exercise. The dose of vitamin E used was 400 IU daily. The pole-striding groups trained 3 times per week for 30 – 45 minutes. The researchers found that the pole-striding exercise led to significantly improved exercise tolerance on both constant work-rate and incremental treadmill tests and also led to reduced ratings of perceived claudication pain. However, they did not detect any significant effect of the vitamin E supplementation.
Pena et al. The researchers performed a randomized, controlled trial to assess the effects of a 6-week program of low-intensity, pain-free, low-intensity treadmill walking on the functional walking ability of 13 PAD patients with intermittent claudication. The researchers reported that the subjects displayed an average 148% improvement in distance, 34% in rate, and 94% in duration of walking.
Mika et al. The researchers performed a randomized, controlled trial to assess whether pain-free treadmill training at to 85% of the distance to onset of claudication pain can improve pain-free walking distance in 98 PAD patients aged 50 – 70 years. The researchers randomly allocated the subjects into either a supervised treadmill training group or a control group. The training group performed 12 weeks of supervised treadmill training. The researchers reported that the training group displayed a significantly increased distance to onset of claudication pain of 119.2%, from 87.4 ± 38 to 191.6 ± 94.8m. There were no significant changes in the control group.
Mika et al. The researchers performed a trial to assess whether pain-free treadmill training at to 85% of the distance to onset of claudication pain can improve pain-free walking distance in 60 PAD patients. The researchers randomly allocated the subjects into either a supervised treadmill training group or a control group. The training group performed 3 months of supervised treadmill training, exercising 3 times per week. The researchers reported that the training group displayed a significantly increased time to onset of claudication pain of 102% from 191 ± 34 to 386 ± 60 seconds and maximal walking time increased by 49% from 438 ± 62 to 656 ± 79 seconds. There were no significant changes in the control group.
Cachovan et al. The researchers performed a pilot study was to assess the increase in claudication walking distance following an intensive, 4-week long, supervised exercise program in 23 PAD patients with an average age of 62 years and intermittent claudication. The subjects participated in a standardized exercise program, 5 days a week including daily sessions of supervised gymnastics for 30 minutes, followed by 2 sessions of treadmill exercise each amounting to 66% of the absolute claudication distance. The researchers reported that initial claudication distance increased significantly from 83 to 134m (61%) and absolute claudication distance increased significantly from 127 to 222m (75%).
Regensteiner The reviewer performed a meta-analysis of walking trials for individuals with claudication brought about by PAD. They found that exercise training programs have a clinically important impact on functional capacity in individuals with claudication. In a meta-analysis, the reviewer found that pain-free walking time increased by an average of 180% and maximal walking time increased by an average of 120% in individuals with claudication who participated in an exercise program.
Gardner and Poehlman The reviewers performed a meta-analysis to identify the most effective components of exercise rehabilitation programs for reducing claudication pain symptoms in patients with PAD. The reviewers found 21 relevant studies that met the inclusion criteria. The reviewers reported that exercise programs were able to create a mean improvement in the distance walked to onset of claudication pain of 179% (from 125.9 ± 57.3m to 351.2 ± 188.7). The reviewers also reported that exercise programs were able to create an increase in distance to maximal claudication pain of 122% (from 325.8 ± 148.1m to 723.3 ± 591.5m). The reviewers reported that the characteristics of the most successful interventions were: walking interventions, a duration >30 minutes per session, a frequency of at >3 sessions per week, use of near-maximal pain during training, and program length of >6 months.
Leng et al. The reviewers performed a Cochrane review to assess the effects of exercise for exercise for leg pain (i.e. intermittent claudication). The reviewers initially identified 15 trials but subsequently excluded 5 of them because they did not meet the required quality standard. The reviewers found that exercise interventions led to significantly improved maximal walking times on average of 6.51 minutes and a proportional improvement of 150%. They reported that exercise led to significantly superior improvements in walking time in comparison to both angioplasty at 6 months and antiplatelet therapy and was not significantly different from surgical treatment.
Watson et al. The reviewers performed a Cochrane review to assess the effects of exercise for exercise for leg pain (i.e. intermittent claudication). The reviewers initially identified 22 trials. The reviewers found that exercise interventions led to significantly improved maximal walking time on average by 5.12 minutes and a proportional improvement of between 50 – 200%. The reviewers observed that pain‐free walking distance was improved on average by 82.19m and maximum walking distance was improved by 113.2m. However, the reviewers also noted that exercise did not affect the ankle brachial pressure index (ABI).
Bendermacher et al. The reviewers assessed the effects of supervised vs. non-supervised exercise therapy on maximal walking time or maximal walking distance for individuals suffering from PAD with intermittent claudication. The reviewers identified 8 trials in which the protocols generally performed 3 exercise sessions per week. The reviewers found that supervised exercise was significantly and clinically superior for increasing maximal treadmill walking distance compared with non-supervised exercise protocols. They noted that supervised exercise protocols were able to increase walking distance by an average of 150m more than non-supervised exercise protocols.
Parmenter et al. The reviewers performed a systematic review of the evidence for the effectiveness of all forms of exercise on claudication in PAD. The reviewers found 36 trials that reported on the effects of various exercise interventions on walking distance in patients with PAD, comprising 32 aerobic (including 20 walking) and 4 resistance-training. The reviewers found that most types of exercise program led to significant improvements in walking capability. They found that all modes of aerobic exercise appear equally beneficial for claudication. They noted that the benefits of resistance-training appear promising but there are few studies in that area.
Robeer et al. The reviewers performed a systematic review of randomised, clinical trials to evaluate the effects of exercise therapy in patients with intermittent claudication. The reviewers found that exercise therapy does in fact improve walking performance in patients with intermittent claudication. However, the reviewers were not able to identify any optimal exercise therapy, including questions around the optimal frequency, type, mode, intensity and duration of non- supervised or supervised programs.

Based on these studies and reviews, both aerobic exercise (including various types of aerobic training in addition to walking) and resistance-training appear to be useful methods of improving walking performance and reducing claudication symptoms in individuals with peripheral arterial disease.


Can plantar-flexion exercise help treat PAD?

While treadmill walking is the default option for most clinical interventions in PAD patients for helping to ease the symptoms of intermittent claudication, some researchers have investigated the very simple practice of plantar flexion for this purpose, as follows:

Study Method Finding
Wang et al. The researchers assessed whether a program of plantar flexion could reduce leg pain and increase functional walking performance in 27 PAD patients with claudication. The researchers randomly allocated the subjects to either a plantar flexion training group, who performed plantar flexion training in 4 sets of 4-minute intervals at 80% of maximal work rate, 3 times per week for 8 weeks or to a control group. The researchers reported that the training group displayed significantly increased plantar flexion power output (by 43.9%), treadmill walking-measured VO2-max (by 12.3%) and treadmill walking time-to-exhaustion (by 20.0%). The researchers therefore concluded that plantar flexion training is effective for increasing VO2-max and walking performance in patients with PAD.
Helgerud et al. The researchers investigated whether calf-muscle training immediately followed by whole body training would lead to improved aerobic power and cardiovascular function in PAD patients. The researchers randomly allocated the subjects to either a training group, who performed 8 weeks of high-intensity plantar-flexion interval training followed by 8 weeks of high-intensity treadmill training, or to a control group, who received advice according to exercise guidelines. The researchers reported that treadmill-measured VO2-max and time-to-exhaustion increased significantly (by 16.8 and 23.4%) during the plantar-flexion training period. Plantar-flexion peak power output also increased significantly from 7.1 ± 1.7 to 10.8 ± 1.9W (61.4%).The researchers also reported that after the treadmill training, treadmill-measured VO2-max and time-to-exhaustion increased significantly again (by 9.9 and 16.1%). The researchers therefore concluded that plantar-flexion training was effective for increasing treadmill-measured VO2-max and time-to-exhaustion in PAD patients.
Tebbutt et al. The researchers performed a 12-week prospective feasibility trial in order to determine whether the use of a plantar flexion device (Step It pedal) would be of benefit to 42 PAD patients. The subjects were randomly allocated to either a standard care group or a plantar-flexion resistance-training program, using the Step It pedal. The researchers observed improvements in walking distance to claudication symptoms and in maximum walking distance were observed in the intervention group but not in the control group.
Mosti et al. The researchers investigated the effects of 8 weeks of combined maximal strength training and plantar-flexion endurance training in 20 PAD patients. The researchers therefore randomly allocated the subjects into either a training group, who performed concurrent leg press maximal strength training and plantar-flexion endurance training, 3 times a week, or a control group, who received recommended exercise guidelines. The researchers found that the training group improved treadmill VO2-max and time-to-exhaustion by 12.7 ± 7.7% and 12.6 ± 13.2%, respectively, while leg press maximal strength and rate of force development improved by 38.3 ± 3.1% and 140.1 ± 40.3%, respectively. However, there were no changes in the control group.

Based on these studies and reviews, plantar flexion endurance training appears to be a promising method of improving walking performance and reducing claudication symptoms in individuals with peripheral arterial disease.


Evidence-based recommendations for exercise

Some reviews have made evidence-based recommendations for the treatment of PAD that include non-pharmacological treatments, as follows:

Study Recommendation
Hirsch et al. The reviewers recommend using a program of supervised exercise training as an initial treatment modality for patients with intermittent claudication. They suggest that supervised exercise training should be performed for a minimum of 30 – 45 minutes, at least 3 times per week for a minimum of 12 weeks.
Bulmer and Coombes The reviewers recommend that patients with PAD should partake in supervised treadmill walking 3 days per week for 45 minutes per session for approximately 20 weeks. They recommend that interval training should be performed with the intensity at the pain-free threshold.

Based on these guidelines, it appears that the general recommendation for patients with PAD is to perform supervised exercise training for a minimum of 30 – 45 minutes, at least 3 times per week for 12 – 20 weeks.


Conclusions

On the basis of these studies and reviews, the following conclusions might be drawn:

Area Conclusion
PAD is very common and increases with age The prevalence of peripheral arterial disease increases rapidly with increasing age and can also vary extensively with gender, geography and type of population. The prevalence can therefore range from 0.9 – 29% with these variables.
Risk factors for PAD are similar to those for general CVD The main risk factors for peripheral arterial disease (PAD) are current or previous smoking (in a dose-responsive relationship, with greater smoking being associated with a greater risk), physical inactivity, type II diabetes mellitus, hypertension, hypercholesterolemia and hypertriglyceridemia, and being older.
Aerobic exercise and resistance-training are effective Both aerobic exercise (including various types of aerobic training in addition to walking) and resistance-training appear to be useful methods of improving walking performance and reducing claudication symptoms in individuals with peripheral arterial disease.
Plantar flexion endurance training is effective Plantar flexion endurance training appears to be a promising method of improving walking performance and reducing claudication symptoms in individuals with peripheral arterial disease.
General recommendations are for regular walking The general recommendation for patients with PAD is to perform supervised exercise training for a minimum of 30 – 45 minutes, at least 3 times per week for 12 – 20 weeks.

In summary, exercise is effective for improving walking ability in individuals with peripheral arterial disease and the general recommendation is for supervised exercise training for a minimum of 30 – 45 minutes, at least 3 times per week for 12 – 20 weeks.


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