The case for exercise testing as the optimal initial diagnostic approach to the patient with intermittent claudication is predicated on evidence that it provides superior diagnostic and prognostic information, is predictive of therapeutic response, affects patient management and clinical outcomes, and is safe and cost-effective. We will show that in comparison to exercise testing, the widely employed approach of traditional non-invasive testing (ankle brachial index, toe pressures, segmental pressures, pulse volume recordings, duplex ultrasonography) is often of limited diagnostic and predictive utility, and that these tests are more appropriately reserved for patients in whom the exercise testing is unsafe or equivocal. It is also relevant to the fact that we are at an exciting juncture in the fieldThe case for exercise testing as the optimal initial diagnostic approach to the patient with intermittent claudication is predicated on evidence that it provides superior diagnostic and prognostic information, is predictive of therapeutic response, affects patient management and clinical outcomes, and is safe and cost-effective. regarding novel interventions to our patients, many of which will affect functional status, and it is important that we are able to accurately assess and follow the response to these interventions. This will be explored in section five of the essay.
Understanding Peripheral Arterial Disease
PAD is a common yet serious disease that occurs when extra fat and cholesterol in the blood collect on the walls of the arteries that supply blood to the limbs. This buildup of fat is called plaque. Over time, the plaque can harden and narrow the arteries, limiting the flow of oxygen-rich blood to the organs and other parts of the body. In the same way that clogged arteries in the heart can cause a heart attack, in the arteries of the legs, it can cause a heart attack. The pain in the legs from this condition is called claudication. This is an indicator that a person has a higher risk of heart attack or stroke.
Early intervention in the management of Peripheral Arterial Disease (PAD) plays a critical role in altering the natural history of this disease. A large body of evidence suggests that early recognition and treatment of PAD can prevent unnecessary amputations and the progression of disease. Patient understanding and education about this disease is also an important first step in altering the course of PAD. This article provides an overview of the causes, risk factors, and symptoms of PAD to underscore the importance of early recognition and treatment.
Causes and Risk Factors
Less common risk factors include radiation injury, often to treat cancer in an area involving an artery; injury to the limbs; unusual anatomy of muscles or ligaments, which can compress an artery; and exposure to certain chemicals. Some persons have a genetic condition leading to a higher occurrence of early or severe atherosclerosis. This may lead to peripheral artery disease at a young age. Keep in mind that someone with a few risk factors can still develop the disease, while another person with many risk factors may never develop the disease.
Risk factors for peripheral artery disease are the same as those for atherosclerosis. The most important risk factor is smoking. Smokers may have 10 times the risk of developing peripheral artery disease as compared to nonsmokers. The more one smokes, the higher the risk. High blood levels of cholesterol and homocysteine are associated with a higher risk. High blood pressure is a risk factor. Persons with diabetes are at increased risk of developing peripheral artery disease. Sedentary lifestyle, with limited walking or exercise, is a risk factor. The older a person is, the higher the risk of peripheral artery disease, although one should not consider it a normal condition of aging.
Symptoms and Diagnosis
It is important to note that approximately half of all peripheral arterial disease is asymptomatic. In instances of symptomatic PAD, the severity of the symptoms can vary widely depending on the location and extent of the blockage. The classic symptom is claudication, or leg pain that occurs with activity such as walking and disappears with rest. This is generally a reliable indicator of PAD. However, even patients with more severe PAD can be entirely asymptomatic. Acute limb ischemia is a sudden worsening of limb ischemia which threatens the viability of the limb and is associated with severe pain, skin discoloration and coolness. If left untreated this can sometimes progress to chronic ischemia if there is revascularization through development of a chronic occlusion. This form of PAD with chronic ischemia carries the risk of chronic limb-threatening ischemia. CLTI is diagnosed by the presence of ischemic rest pain, non-healing ulcers or gangrene for 2 weeks. Patients with CLI are a particularly high-risk group and have the highest cardiovascular mortality. Other than typical claudication and CLI, the presence of atypical leg symptoms has been shown to be useful in identifying PAD. In patients with known cardiovascular disease, the absence of peripheral pulses in association with a history of claudication is predictive of symptomatic PAD and is increased in prevalence with age. An important principle in the diagnostic approach to PAD is therefore not to wait until severe symptoms develop to consider the diagnosis, particularly in patients with a history of cardiovascular disease. The presence of known PAD is also associated with a markedly increased prevalence of cerebrovascular and coronary artery disease.
The Significance of Early Intervention
Reducing the Risk of Complications Patients with ulcers or gangrene often suffer debilitating symptoms and have impaired quality of life. Often these patients will require repeat hospitalization and/or revascularization procedures and have a high risk of amputation. The prevention of amputation has been a major focus, as the prognosis for amputees is poor with 50% being dead within 5 years. The reduction of PAD disease progression and cardiovascular events is an important goal, leading to task force recommendations for secondary prevention of PAD. The prevention of complications and disease progression represents key aspects of secondary prevention and is important in improving patient outcomes. High-risk patients with severe claudication or those with CLI often have significant coexisting cardiovascular disease and are at risk of cardiovascular events as well as limb events. Improvement in global cardiovascular risk is paramount in these patients, often with aggressive management of risk factors. The ultimate goal is improvement in patient outcomes, with reduction in morbidity and mortality. Early intervention in PAD is important in achieving these goals.
Preventing Progression of the Disease Patients with PAD who have claudication have a 20% risk of developing severe claudication within 5 years and a 30% risk of developing CLI or acute limb ischemia within 10 years. Severe claudication and CLI are the result of chronic total occlusion of an arterial lumen, often with distal embolization or acute thrombosis. The result is ischemic pain at rest, ulcers, and gangrene. The prospect for limb salvage is poor with CLI as only 40% of patients will have resolution of their ulcers and symptoms, 30% will undergo amputation, and 10% will be dead within 1 year. Although acute limb ischemia is a treatable condition, the mortality rate within 30 days is still as high as 25% and amputation is still a frequent outcome. The reduction of cardiovascular events has been an important goal in recent years, also includes trying to prevent acute limb ischemia as the limb events are often as disabling as MACE.
Early intervention has a ubiquitous meaning to healthcare professionals as early detection of disease often leads to increased opportunity for intervention and prevention of progression. Timely interventions are important to improve patient outcomes. The progression of PAD is associated with significant morbidity and mortality. Development of claudication carries a 5-year mortality of 30% and those with critical limb ischemia (CLI) face a 50% mortality at 4 years. In addition to increasing mortality, CLI significantly increases the risk of amputation, major adverse cardiovascular events (MACE), and decreases overall quality of life. The prevention of progression to the point of severe claudication or CLI is therefore an important goal in those with early or intermittent claudication.
Preventing Progression of the Disease
Regular exercise has also been proven to be an effective way to prevent the progression of PAD. Supervised treadmill exercise improves treadmill walking performance and the 6-minute walk test in patients with PAD. It has also been shown to improve physical function and decrease the self-reported severity of PAD symptoms. Community-based exercise, such as the WISE program, has been shown to improve lower extremity physical activity in people with PAD. Unfortunately, despite the proven benefits of exercise, most patients with PAD do not exercise on a regular basis and some are unwilling to participate in any form of exercise. This is why it is crucial for health care professionals to stress the importance of risk factor modification and exercise to all patients with PAD.
To stop the progression of PAD, patients need to modify their risk factors and adhere to a structured exercise program. Evidence suggests that all patients with PAD should receive education on risk factor modification, which includes smoking cessation, lowering blood pressure and cholesterol to goal, and preventing or treating diabetes. Modification of these risk factors has been shown to not only prevent progression of the disease, but also to decrease the risk of development of other cardiovascular events. The Aggressive Risk Factor Lowering (ARF) Trial demonstrated that patients with coronary artery disease and PAD had a 25% reduction in the combined risk of myocardial infarction, stroke, and cardiovascular death for every 1mmol/L reduction in LDL cholesterol. This is a profound decrease in cardiovascular risk and must not be overlooked by patients or their physicians.
Reducing the Risk of Complications
Leg symptoms associated with P.A.D. can lead to a range of complications, the most severe being critical limb ischemia (C.L.I.). The cost of treating leg ulcers and non-healing sores can be substantial and can also impact on the emotional well-being of the patient. Patients who develop acute limb ischemia may require hospitalization and urgent revascularization or even amputation in severe cases. A British study found that the first-year healthcare costs for a patient with acute limb ischemia amounted to over £15,000 compared with peripheral vascular procedure costs of £2,500 for maintaining a patent vessel. These patients will also have a higher risk of myocardial infarction and stroke. Amputation of a limb can have devastating consequences for the patient and can sometimes be a continuing process whereby, following an initial limited amputation, further limb loss is required. Approximately half of these patients will be dead within 5 years. The common belief that life-threatening complications are confined to more advanced stages of disease underlies the finding that only 10% of intermittent claudicants are taking aspirin and little more than 10% are on lipid-lowering medication.
3.2.1 Spiraling costs of treatment 3.2.2 Overcoming the barriers to optimal care
Improving Quality of Life
The relatively subtle pain experienced in intermittent claudication can progress into a more serious limb-threatening event (LTE). LTE is a term used to describe a spectrum of acute ischemic states compromising limb viability, ranging from reversible ischemia to minor tissue loss (dry gangrene) and finally to frank gangrene with major tissue loss. Patients with PAD frequently have co-existent coronary and cerebrovascular disease. It is logical to assume that the disabling nature of claudication and the potential loss of independence in those who suffer from severe limb events can have a profound effect on health-related quality of life. Epidemiological studies have shown that the health-related quality of life (HRQOL) in patients with PAD is markedly lower than population norms and is comparable to that seen in patients with congestive cardiac failure and those with symptomatic treatment-resistant depression. Survey studies have shown that both patients and primary care physicians are often unaware that leg symptoms are due to PAD and frequently attribute them to musculoskeletal problems or aging. Ongoing patient education and the education of healthcare professionals are required to raise awareness of this often underdiagnosed condition. There is little information on the natural history of quality of life in PAD, a condition based on atherosclerosis. With medical and interventional treatments aimed at altering this disease process, it would, however, seem reasonable to envisage an improvement in HRQOL with effective treatment of the disease. Randomized clinical trials have traditionally assessed symptomatic improvement of claudication and effects of intervention on functional status in terms of treadmill walking performance or onset of claudication distance. These physiological measures may not always correlate to changes in HRQOL, and recent RCTs have included assessment of HRQOL as a primary endpoint with widely used validated questionnaires. Alteration of HRQOL as an endpoint can take a number of years to manifest, and thus identification of surrogate endpoints such as cardiovascular events and mortality, which frequently contribute to decline in HRQOL in PAD patients, would be an attractive proposition.
Available Treatment Options
When asked to write an essay on the importance of early intervention in peripheral arterial disease, at the very beginning of the section, the writer suggests that the goal of treatment for peripheral arterial disease is to control symptoms and halt progression of the disease, using exercise training, drug therapy, and endovascular or surgical revascularization. This sentence summarizes the whole of the following essay and shows the clear connection between the aims of treatment suggested by Norgren, writing in 2007. He also goes on to suggest that intermittent claudication is the most common symptomatic presentation of peripheral arterial disease and a major reason for intervention. It is characterized by pain, aching, cramping, numbness, or a sense of fatigue in the leg muscles that occurs during walking and is relieved by rest. The suggestion that this is the most common symptom and the fact that it is a major reason for intervention within the context of treatment can be seen to support the essay’s explanation on the use of exercise therapy within 4.1 of the essay. Also, Alam writing for the Cochrane database in 2016 suggests that a systematic review and his own clinical experience training muscle pain, which causes significant functional impairment, is best managed using supervised exercise training, which is of course elaborated by Regensteiner et al and Hiatt et al within their studies mentioned in the essay. This effectively again serves to support the essay’s content, with allopathy meta-analysis suggesting that treadmill training seems to be a more effective exercise modality for improving pain-free walking distance than just simple home-based exercise, and the most recent Cochrane review stating that exercise therapy has short-term clinical benefits on pain-free walking distance and patient-perceived walking duration. All of these sources further endorse the use of exercise training as a highly beneficial treatment to improve the quality of life and symptoms of PAD patients, and it is clear that the writer of the essay has selected these sources with the specific purpose of supporting the information that he is delivering to the reader.
Medications and Lifestyle Changes
There are two alternative treatments for intermittent claudication that are approved for use in some countries but not in the United States. Naftidrofuryl is given at a dose of 100 mg three times daily. It increases walking distance and improves quality of life. The drug is not available for use in the US. Pentoxifylline is a drug that decreases the viscosity (thickness) of the blood. It is given in a dose of 400 mg three times daily with meals. Pentoxifylline improves the maximum distance walked before the onset of leg pain, but it is not very effective in increasing muscle strength or the ability to climb stairs.
Medications that improve the distance patients can walk without pain and that reduce other symptoms are the first step in treating peripheral artery disease. Cilostazol increases blood flow to the legs, improves walking distance, and decreases the pain or cramping that occurs with activity. It is an antiplatelet drug (it reduces the ability of platelets to clump together and form blood clots). The dose is 100 mg twice daily. The combination of cilostazol with the antiplatelet drug clopidogrel may be more effective in improving walking performance than is either drug alone.
4.2 Surgical Interventions
Once the disease progresses to the point that medical management and/or lifestyle changes no longer adequately control the symptoms or improve the functional status, patients may require surgical intervention. At this point, it should be stressed that the goals of surgical intervention are to improve symptoms, quality of life, and functional status, and not to prolong life. Revascularization of the affected limb aims to achieve these goals by improving blood flow to ischemic tissues. However, before undergoing invasive procedures, it is important to identify patients who may be managed conservatively as these patients often have considerable comorbidities and a poor life expectancy. Patient selection for revascularization is therefore an important step. Currently available methods of revascularization are endovascular or open surgical techniques, with no one method being suitable for all patients. Nevertheless, revascularization has been shown to provide superior symptom relief and functional status compared to conservative measures and is therefore recommended for patients with lifestyle-limiting intermittent claudication. In those patients with critical limb ischemia, revascularization has been shown to improve both the amputation-free survival rate and overall survival compared to major amputation. As the vast majority of patients with PAD are affected by atherosclerosis, cessation of smoking, antiplatelet therapy, statins, and blood pressure control are important adjunctive measures to maintain the benefit from revascularization. How these medications might specifically be used to optimize antiplatelet and provide antithrombotic therapy in the prevention of ischemic events following revascularization is an area that warrants further research. For those patients who are not suitable for revascularization, or where revascularization has failed, major amputation may still be averted by performance of a distal bypass to improve blood flow to the affected limb. This, however, is usually with the aim of preventing progression to major amputation and does not significantly improve mortality rates in these patients. In recent years, major amputation has become less common due to improvement in both surgical and endovascular revascularization techniques and is now reserved as a last resort option in those patients with extremely poor functional status and a limited life expectancy.
4.3 Other Therapeutic Approaches
Angioplasty is used to dilate stenosed or occluded arteries and can be performed with or without stenting. The procedure is usually performed with the patient under local anesthesia. It involves the insertion of a catheter into the artery and the passage of a guidewire across the lesion. This is followed by advancement of the balloon catheter over the wire to the site of stenosis, where the balloon is inflated. Balloon angioplasty works by fracturing the plaque and stretching the arterial wall to increase lumen diameter. Although angioplasty initially results in high success rates, repeat intervention is often required because of elastic recoil of the artery, dissection of the arterial wall, or occlusion of the artery from distal embolization of plaque. This has led to the development of stents to provide more durable luminal support. Randomized trials comparing angioplasty and stent placement to surgical bypass have shown similar short and long-term clinical outcomes for both procedures in certain anatomic patterns of disease.
The development of new devices such as atherectomy and angioplasty catheters, and the refinement of surgical techniques, continues to offer benefits to patients with peripheral arterial disease. Atherectomy devices remove atherosclerotic plaque from the lumen of the artery. They rely on several different methods to remove the plaque, including the use of a rotating cutting blade, laser, directional coronary atherectomy, and ultrasonic vibrations. Several atherectomy devices have received FDA approval for use in the lower extremity arteries. In a randomized trial comparing atherectomy to angioplasty for the treatment of lower extremity atherosclerotic vascular disease, there was no difference in clinical outcomes during the subsequent year, although atherectomy was associated with reduced patient discomfort during the procedure.
