The prevalence of peripheral arterial disease (PAD) has risen dramatically in the last decade given the increasing age of the population, coupled with the escalating growth in the prevalence of diabetes mellitus, the most potent risk factor for PAD. Not coincidentally, the prevalence of PAD, which is present in 15% to 20% of individuals older than age 70, is rising in parallel with that of coronary artery disease (CAD). Most patients with PAD have coexisting CAD and its attendant cardiovascular disease (CVD) risk factors, such as hypertension and hyperlipidemia. Approximately one third of patients with PAD are asymptomatic, whereas the remainder present with intermittent claudication (IC), which is a progressive symptom of aching, cramping, or fatigue in the muscles of the lower extremity consistently reproducible by a certain magnitude of exercise (e.g., walking) and relieved by rest, typically within 10 minutes. IC is a marker for general atherosclerosis and predicts not only peripheral events such as ulceration and gangrene that can lead to limb loss, but also increased risk of major cardiovascular events. Because patients with PAD and IC have a greatly increased risk of mortality, it is important to recognize the magnitude of IC as a strong indicator of adverse health-related outcomes and impaired functional status.
Benefits of Exercise for Peripheral Arterial Disease
The benefits of exercise for Peripheral Artery Disease are assessed in terms of its effects on the damaged artery, occurring outside the limbs, and on the symptoms that result from the impaired blood flow to the limbs. The most direct way to impact arterial function with exercise is to work the specific muscles that are ischemic. This causes an increase in muscle blood flow, which occurs in healthy individuals as a result of an increased oxygen demand, and in PAD patients will increase the muscle pain-free walking time. More importantly, supervised exercise creates an opportunity for specific and aggressive exercise therapy of the legs. This can involve treadmill walking or the use of large muscle group exercise such as cycling. Such exhaustive exercise of the legs may result in temporary exacerbation of leg symptoms. However, it is known that exercise leads to a sustained increase in pain-free walking time within 6-10 weeks, and so the short-term consequences of the exercise can be considered extremely beneficial for an increase in long-term function. Supervised exercise has now been proved to be beneficial in randomized trials with improvement in exercise performance suggesting the possibility of change in underlying pathophysiology of PAD. Compressive u/s therapy by trained professionals, particularly for people with severe leg pain who cannot walk, is a viable option to consider to help increase time spent on feet and so increase long-term function in PAD.
Improved Blood Flow
First, we will take a look at improved blood flow and transport. During the onset and duration of exercise, there is an increase in oxygen demand and metabolism in working skeletal muscles. The vasodilatation that occurs in the muscle arterioles due to this activity is directly related to the increased blood flow to the muscles. This occurs in patients both with and without claudication. In normal muscles, the increased demand for blood flow and oxygen is easily met by increasing blood flow. However, in claudicating muscles, the reduced arterial supply prevents the increased demand for oxygen from being met due to the flow of blood being close to maximal already. This results in ischemia and exacerbates the claudication. Despite this, the regular occurrence of ischemia during exercise is known to stimulate angiogenesis, a process triggered by a chronic reduction in oxygen supply to tissues. This is important to patients with PAD and claudication, as an increase in the number of smaller vessels and capillaries in the muscles increases the blood flow that can be achieved, without causing ischemia. The increase in blood flow to muscles during exercise is also an effective way of training patients to walk further before the onset of claudication, and this too can help to increase angiogenesis and blood flow to ischemic muscles.
Increased Collateral Circulation
Functional collaterals add to the variety and extent of collateral networks available. Typically, there are alternative pathways of collateral circulation around an occluded vessel. Functional collaterals are those that can respond to changes in blood flow and can recruit a greater blood flow to compensate for acute ischemia. This ability to recruit blood flow can be very significant in reducing ischemic symptoms during and following exercise.
Arteriogenesis is the growth and remodeling of pre-existing arteriolar connections into larger conductance arteries. This is also stimulated by increased metabolic demand or ischemia, and the vessels involved in this process are typically downstream of an occlusion and represent an interconnection between the arterial trees on either side of the occlusion. Like angiogenesis, this process improves blood flow through ischemic areas and can also help to reduce ischemic symptoms.
Angiogenesis is the process of new capillary growth from existing vasculature. This can occur in response to tissue ischemia, during recovery from tissue ischemia (as occurs with intermittent claudication), or in response to an increase in metabolic demand. Angiogenesis is stimulated by hypoxia and some growth factors associated with exercise, such as vascular endothelial growth factor (VEGF). VEGF is a potent angiogenic growth factor that acts via stimulation of migration and proliferation of endothelial cells, and through increased production of nitric oxide (NO). This increased capillarity improves delivery of oxygen to ischemic tissues and can lead to a reduction in ischemic symptoms.
Collateral circulation is the alternative perfusion of tissues and organs through anastomoses between blood vessels. Exercise increases collateral circulation by the following mechanisms: angiogenesis, arteriogenesis, and development of functional collaterals.
Reduced Symptoms
Motor impairment during walking is the major symptom of leg ischemia, and regular exercise is often associated with worsening of these symptoms. However, supervised treadmill exercise can improve maximal and submaximal walking distances and walking speed in PAD patients. Flexibility exercise has been shown to increase the time to onset of claudication pain and increase walking distances before the onset of ischemic muscle pain. These improvements in walking ability are thought to be due to physiological adaptation in the skeletal muscle of the legs. Unfortunately, the competitive or recreational athlete with intermittent claudication is forced to curtail physical activity due to muscle discomfort. Many consider that exercise leads to worsening of leg symptoms, and exercise programs can be difficult to implement in this patient group. However, as the ability to walk an exercise therapy device at home for claudication is parallel to the amount of at-home prescription for either leg strength or locomotor exercise. Goal setting is a useful means of motivating patients, and recent work has shown that patients will walk a specifically defined distance for their post-revascularization procedure after instructions on the distance to be walked, conditioning, and pain relief exercise. This has been shown to be achievable with activity prompting strategies and is a safe and effective method in improving walking distance in patients with effort intermittent angina. Low-impact exercise such as cycling appears to improve pain-free and maximal walking distances. Intra-arterial PGE1 has been shown to increase walking distances in PAD patients, with a study of alternate-day stimulus of PGE1 and leg exercise having shown a significant increase in maximal walking time compared with exercise alone. Wider adoption of exercise therapy remains difficult despite the proven benefit, as even severe cases of PAD are spontaneously limiting in terms of exercise, thus it is difficult to separate the need for symptom relief and functional improvement at supervised exercise.
Considerations for Exercising with Peripheral Arterial Disease
Medical evaluation is the first step in developing an exercise prescription for patients with PAD. Before exercise training or testing is initiated, medical clearance should be obtained, particularly for patients with known cardiovascular, pulmonary, or other systemic diseases. The purpose of exercise testing in patients with PAD is to establish a baseline assessment of functional capacity and to assess for limitations to exercise and abnormal cardiovascular responses to exercise. If testing is done to assess claudication, a treadmill test using a standardized protocol and continuous monitoring of EKG, blood pressure and leg symptoms is preferred. Other forms of testing to assess general or specific cardiovascular fitness or to assess leg functional capacity and responses to exercise may also be appropriate in certain patients. Throughout testing and exercise training, pulse checks or Doppler blood pressure monitoring for the affected limb are useful for assessing the hemodynamic response in the limb and for correlating exercise intensity with the onset of ischemic symptoms. This information can help to determine whether it is safe to continue or increase exercise intensity or whether adjustments to the exercise prescription are needed.
Patients with PAD should be evaluated by a physician prior to starting an exercise program. The purpose of medical evaluation is to establish an accurate diagnosis of the severity of the disease and to identify and provide appropriate treatment for other coexisting conditions. The severity of claudication and functional limitations in patients with PAD can vary widely. Initial claudication work time should be assessed in patients who plan to undergo a formal exercise program. Patients with minimal claudication may require exercise testing to induce ischemic leg symptoms. Patients with more severe functional limitations may have too little ambulatory function to see significant improvement from exercise training and may require revascularization or medical therapy to improve their functional capacity. In special circumstances, such as patients with resting ischemic pain or those with limb-threatening ischemia, exercise testing may be needed to assess whether exercise may worsen limb ischemia. Although leg symptoms are the primary concern and target for improvement with exercise in patients with PAD, other cardiovascular or systemic limitations to exercise should also be assessed and addressed in developing an overall plan for physical fitness and activity. Once the exercise prescription is established, assessment of the response to exercise and clinical changes over time can help to guide progression or modification of the exercise program.
Medical Evaluation
Patients with PAD should undergo medical evaluation to confirm the diagnosis, assess functional limitations, cardiovascular and musculoskeletal fitness, and to determine the nature, location, and severity of atherosclerotic obstruction. Medical evaluation often requires several diagnostic tests to confirm the severity of the disease. Physicians will often start with a physical examination to evaluate signs of PAD such as weak or absent pulses in the legs, or other abnormal sounds such as bruits or whooshing sounds, that may indicate obstructed blood flow. The ankle brachial index (ABI) is a quick, non-invasive way to diagnose PAD. By taking the blood pressure in the arm and comparing it to the blood pressure in the leg, a ratio can be determined. A lower than normal ratio would indicate obstructed blood flow distal to the point of compression. An ABI of less than 0.90 is considered diagnostic of PAD. Additional vascular testing may include segmental blood pressure measurements or pulse volume recordings, which help to localize and determine the severity of the arterial obstructions. Blood tests such as a complete blood count (CBC), comprehensive metabolic panel (CMP), and testing cholesterol levels, can also be used to provide a clearer picture of the patient’s overall health and possibly identify other systemic issues related to the atherosclerosis. Finally, anatomical imaging tests can help to visualize the location and severity of the arterial obstructions. Duplex ultrasound uses sound waves to create images of the arteries and determine blood flow throughout the body. Other imaging tests such as computed tomography (CT) and magnetic resonance angiography (MRA) can also be used to visualize the arteries and identify any arterial lesions. While more invasive, an angiogram is considered the gold standard for diagnosing PAD. This test involves taking X-ray images of the arteries (angiography) to determine the location and severity of the arterial obstructions.
Exercise Prescription
Early trials of exercise training in patients with claudication were aimed at improving exercise duration by reducing ischemic leg symptoms. Results demonstrated that a supervised exercise training program which increases from a minimal level of 15 to 30 minutes of ambulation 3 times per week to at least 50 minutes of exercise 6-7 times per week will improve maximal and pain-free treadmill walking performance. A minimal threshold intensity of 60% VO2peak or heart rate reserve elicited the most consistent improvements in walking performance and is recommended. These results formed the basis of the 2000 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for exercise training for PAD. An update of these guidelines is in progress but has not yet been completed. For now, the ACC/AHA guidelines for cardiac patients should be applied for PAD patients. These guidelines recommend that exercise training programs for claudicants should include aerobic activities such as walking or treadmill walking with monitoring of heart rate, blood pressure, and claudication symptoms. However, patients with severe PAD and/or significant cardiac disease often lack the functional ability to walk consistently at a safe exercise intensity. These patients will require a more individually tailored program which intersperses a minimal amount of walk training with lower extremity strength training and short bouts of treadmill walking with less intensity and duration, but greater frequency. It is also important to provide these patients with education about methods to self-monitor exercise intensity through management of claudication symptoms. High intensity exercise bouts and activities which elicit ischemic leg symptoms should be avoided in all patients.
Monitoring Symptoms
3.3.2. Pedometers Pedometers are mechanical or electronic devices worn on the waist that count the number of steps taken or distance ambulated. They are easily used by elderly patients and provide an objective measure of gait and lower extremity function in the community setting. Changes in pedometer step counts and distance walked have been shown to be reliable for assessing the minimal clinically important difference in walking ability in patients with various chronic diseases. A pedometer may be used to monitor a patient’s response to an exercise intervention in terms of increased walking activity. Changes in claudication symptoms during a standardized pedometer walk test may also be assessed.
3.3.1. Discomfort Index This simple yet reliable method quantifies both the walking impairment and the intensity of leg symptoms. Patients are asked to walk on a treadmill at a constant 2 mph and 12% grade until they need to stop because of leg discomfort. The intermittent claudication distance (ICD) is calculated by subtracting the total walking time from the time at onset of pain. A maximal treadmill test is performed to determine the claudication onset distance (COD) and the peak walking time (PWT). These measures are used to calculate the WI, which is expressed as a percentage and is a functional impairment score. The intensity of ischemic leg symptoms at rest and during physical activity may be monitored by a visual analogue scale. Changes in symptoms in response to therapeutic intervention can be measured by calculating the difference in WI and/or the changes in ICD and PWT.
Claudication symptoms are closely associated with the location and severity of arterial occlusive disease. Descriptions of claudication symptoms vary greatly and are often ambiguous and unreliable. Moreover, these symptoms often fluctuate, and patients may have difficulty in recalling or quantifying their exercise-induced ischemic discomfort. An objective assessment of claudication symptoms is essential to monitor progression or improvement of the arterial occlusive disease and a response to medical or exercise therapy.
Safety Precautions
It is important to begin an exercise regimen for a patient with PAD, with an understanding that there is a higher risk of developing significant limb ischaemia. A sedentary patient who starts to exercise may experience discomfort in their legs. In patients with PAD, leg pain during walking may be due to intermittent claudication, a symptom of limb ischaemia caused by the obstruction of arterial blood flow. The patient may experience cramping, pain or tiredness in the leg muscles. When a patient experiences intermittent claudication during exercise, they often stop what they are doing and the symptoms will disappear quickly. It is well known that the painful symptoms of intermittent claudication cause patients to limit their activities in order to avoid pain. On the positive side, if a patient continues walking despite the pain, he or she is likely to increase the distance that they are able to walk. Although it is safe to continue walking through leg pain caused by intermittent claudication, in order to improve exercise capacity and quality of life, these patients need to be in a supervised exercise programme, where exercise can be continued safely.