Functional impairment caused by PAD is of particular significance to the elderly, as it can lead to loss of independence and the need for institutionalization. Despite this, there is limited information regarding the natural history of PAD and its impact on elderly patients. This is an area in need of further research, which will be discussed later in our paper.
PAD is recognized as a disease of major arteries distal to the aortic arch. It is a widespread atheromatous process that affects the cardiovascular system, reducing blood flow to the legs, which can result in pain and ischemic ulcers. The severity of PAD is categorized by Fontaine classification or Rutherford classification in order to assess symptoms, functional impairment, and prognosis. A variety of non-invasive and invasive techniques can be used to diagnose PAD; however, elderly patients often have atypical presentations and multiple comorbid conditions that can make diagnosis more difficult.
The purpose of this paper is to provide a comprehensive review of PAD in the elderly. We will address the definition and diagnosis of PAD, functional impairment and quality of life, treatment options, and prognosis. Our aim is to present the current knowledge of PAD and identify areas in need of further research.
The elderly population is at an increased risk of developing peripheral arterial disease (PAD) due to the associated comorbid conditions of aging. Recent studies have shown that PAD is prevalent in 15% of persons older than 70 years, making it a major health concern for the elderly.
Overview of Peripheral Arterial Disease (PAD)
The ankle-brachial index (ABI) is a simple, noninvasive test for the diagnosis of PAD. A ratio of the systolic blood pressure in the posterior tibial or dorsal pedis artery divided by the systolic blood pressure in the brachial artery, the ABI has a sensitivity of about 95% and a specificity of about 99% for the diagnosis of PAD using angiography as the gold standard. An ABI value of less than 0.90 is abnormal and consistent with the presence of PAD. An ABI value of 1.30 or greater can occur in individuals with diabetes and severe medial artery calcification and is also consistent with the presence of PAD. The ABI is a useful test for the initial diagnosis of PAD, assessment of severity of the disease, and prognosis. An ABI value of less than 0.90 is associated with a four to fivefold increase in the risk of cardiovascular events and mortality. The major limitations of the ABI are that it can be unreliable in individuals with diabetes, and it may be unobtainable due to noncompressible arteries in individuals with severe PAD. A toe pressure can be done as an alternative in patients with noncompressible ABIs. Magnetic resonance angiography, computed tomographic angiography, and angiography are used in selective cases to further delineate the anatomy. However, the ABI remains the primary diagnostic test for PAD given its low cost and safety.
Peripheral artery disease (PAD) – symptomatic lower extremity arterial disease due to atherosclerosis – is a common, progressive condition associated with significant morbidity and mortality. Risk factors for PAD are the same as those for atherosclerosis, including diabetes, smoking, hypertension, and hyperlipidemia. Approximately one in every 20 Americans over age 50 has PAD, a prevalence of more than 12 million. PAD is associated with a marked impairment in functional status and is a predictor of future adverse cardiovascular events. Thus, PAD represents a major public health problem and is an important consideration in the care of the elderly.
Prevalence of PAD in the Elderly
Peripheral arterial disease (PAD) is a highly prevalent disease of the elderly, though few cases are diagnosed in the absence of symptoms. Noninvasive studies have provided an accurate measure of clinical disease prevalence. The Framingham Study was the first investigation to analyze the prevalence of intermittent claudication in a cohort of subjects. The study reported a crude prevalence rate of 4.5% for intermittent claudication among subjects 65 to 94 years of age. More recent epidemiological data suggests that PAD is highly prevalent in older adults. The Rotterdam Study reported a 9.7% prevalence rate of intermittent claudication among subjects 55 to 74 years old and 18.6% among subjects 75 to 84 years old. A recent analysis of NHANES data reported that 3.9% of all men and 3.3% of all women age 40 and older have PAD, with rates increasing to 11.7% in men and 9.9% in women age 65 to 74. PAD is a broad manifestation of atherosclerosis most commonly affecting the arterial circulation to the lower extremities. A variety of symptoms may result from lower extremity PAD, including intermittent claudication, atypical leg pain, or ischemic leg ulcers. The prevalence of classic intermittent claudication, pain in the lower extremities that occurs with exercise and is relieved by rest, increases with age, affecting 1% of those under 50 years of age and more than 5% of those over 70 years of age.
Risk Factors for Peripheral Arterial Disease
Aging is a non-modifiable risk factor for PAD. The results of the Framingham study indicate a steadily increasing incidence of claudication with each decade of life. Prevalence rates of claudication in the elderly population exceed 18%, with higher rates in men than in women. This gender difference narrows with advancing age. In general, PAD is underdiagnosed and undertreated in the elderly, in part due to decreased reporting of claudication by older patients and their physicians’ misconceptions about the natural history of PAD in the elderly. Even though PAD symptoms may not significantly alter function or quality of life in the elderly or may be attributed to other comorbid conditions, it is associated with a significantly higher cardiovascular event rate and mortality than the general population of the same age. This increased risk is independent of other risk factors and comorbid conditions. Data from the Cardiovascular Health Study indicates that elderly patients with PAD are twice as likely to have a cardiovascular event and three times as likely to die from a related event over a four-year period than those without PAD. These poor outcomes reinforce the importance of recognizing PAD in the elderly and vigorously managing its risk factors.
Age and Gender
Peripheral arterial disease (PAD) is an illness which is always related to elderly people, especially when they are in the most risky state in their life. Based on the research, PAD is an illness which commonly occurs because of the increasing age of someone. The risk level increases depending on the age and sex, but on the other hand, the patients don’t know that they have PAD because there is no significant difference between the risk level that they have and the patients that have other cardiovascular diseases such as stroke or heart attack. However, it is known that PAD is more common in male patients than in female patients. This is associated with the previous knowledge that cardiovascular diseases are more common in men than in women.
Smoking and Tobacco Use
Smoking is a major risk factor found in patients with PAD. It accelerates the progression of the disease, leading to potential limb loss. In fact, in patients who are heavy smokers, have a history of smoking or are exposed to environmental tobacco, the efficacy of both surgical and conservative treatments (exercise, pharmacological therapy) is greatly reduced. After 10 years of cessation, however, former smokers’ risk becomes the same as a person who never smoked. Tobacco has detrimental effects on the integrity and function of the arterial wall. Nicotine causes vasoconstriction, increases in blood pressure and heart rate, and has been found to increase the incidence of claudication in patients. Smoking causes an increase in oxidative stress, which impairs the endothelium’s ability to produce nitric oxide and increases the production of endothelin – a potent vasoconstrictor. These changes in the arterial tone increase the atherosclerotic process and can cause an acute thrombotic event. It is well documented that smokers have a higher incidence of both coronary and cerebral vascular disease.
Diabetes and Obesity
Obesity increases the risk of PAD in the presence or absence of other risk factors. For every unit increase in BMI, there is an associated increase in the incidence of PAD by one percent. Fat distribution also plays a role, with fat accumulation in the abdomen, rather than the hips and thighs, increasing risk. This is particularly relevant as central adiposity has been suggested as a contributing factor to the increased prevalence of PAD in women. Hyperlipidemia, hypertension, and insulin resistance are thought to mediate the effect of abdominal fat on exacerbating atherosclerosis. High cholesterol levels have long been known as a risk factor for coronary artery disease, and recent large-scale studies also support the association of hyperlipidemia with an increase in the risk of PAD.
According to the World Health Organization, diabetes mellitus (DM) and obesity, also considered a metabolic syndrome and a state of chronic inflammation, are significant and independent risk factors for the development of PAD. People with DM have a 3-fold higher risk of PAD compared with age-matched non-diabetics. The risk of developing PAD increases with the duration of DM and is higher in people with type 2 DM than those with type 1 DM. DM accelerates PAD, causing earlier symptoms and functional impairment. Atherosclerosis in diabetics tends to be more severe and extensive, and diabetics tend to have more widespread disease. Lower extremity bypass surgery does not improve survival compared to non-diabetics. There is evidence that statin therapy is effective in reducing the cardiovascular events associated with PAD in the diabetic population, and anti-platelet therapy for primary prevention of cardiovascular events and PAD in diabetics is recommended.
Hypertension and High Cholesterol
It is important to recognize that symptom-limited patients with hypertension may have difficulty with exercise tolerance due to leg pain from PAD. These patients may require longer warm-up periods and frequent rest intervals. It is crucial that they are not discouraged from exercise, as it is a key component in improving their PAD symptoms.
The recommendations include weight loss, adopting a DASH eating plan, increasing physical activity, moderating alcohol intake, and drug therapy. Pharmacologic treatment includes the use of thiazide diuretics, ACE inhibitors, calcium channel blockers, and angiotensin receptor blockers.
Approximately 80 million American adults have hypertension, and only 77.9% are aware of their condition. With the great prevalence of hypertension in PAD patients, it is important that healthcare providers are familiar with these guidelines and implement the recommendations into practice. Significant lifestyle modifications and drug therapy are necessary to control high blood pressure and prevent further cardiovascular complications.
In 1997, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure published the fifth report, which provided national standards and guidelines for detection, prevention, management, and treatment of hypertension. The guidelines were updated in 2002 with the publication of the sixth report and most recently in 2014 with the release of the eighth report.
Recognizing Symptoms and Diagnosis of PAD
Critical limb ischemia is the most severe form of limb ischemia. It is characterized by chronic ischemic rest pain (usually in the lower leg or foot) for more than 2 weeks, ulcers or gangrene in the extremities, and/or evidence of lower extremity ischemia by documenting low blood flow by Doppler ultrasound or lower pressures in the ankle compared to the arm (Ankle Brachial Index). Individuals with critical limb ischemia are at high risk of amputation and limb loss.
Symptoms of claudication are reproducible and are relieved by rest. The distance walked before onset of claudication symptoms may be used as a clinical measure of severity of the arterial disease. Individuals with intermittent claudication due to PAD usually stop walking when leg symptoms begin and then stand still to allow the leg muscles to “rest” and restore an adequate supply of oxygen. With rest, the muscle pain goes away. Resuming walking, the pain returns. This is the classic pattern of intermittent claudication. Pain at rest or at night involving the feet or toes is another type of ischemic pain also caused by PAD. This is because the oxygen demand of the nerve cells in the feet or toes is not being met.
Claudication – feelings of heaviness, fatigue, aching, and sometimes pain in the leg muscles that occur during walking – is a classic symptom of PAD. Patients may describe this pain as a muscle cramp, which occurs because the muscle is not getting enough oxygen when it is working. For some people, the muscle pain (or claudication) is the first and only symptom of PAD. Approximately 10 percent of individuals with PAD experience claudication. However, the absence of claudication does not rule out the presence of PAD. Up to 50 percent of people with PAD have no leg pain or intermittent claudication. In addition, it is a mistake to think that claudication is a minor problem. People with PAD and intermittent claudication are, in fact, at increased risk of heart attack, stroke, leg amputation, and death.
Claudication and Leg Pain
The following grades of claudication represent more severe disease and often times the patient’s ability to function is compromised. Grade III symptoms are considered severe and occur with less activity, such as walking short distances. Grade IV symptoms are also considered critical, and the patient may have pain at rest that prevents any walking. This is due to the development of ischemic rest pain, which is an indication of critical limb ischemia.
The first two grades of claudication are considered mild disease and the patient is usually still able to perform normal daily activities. Grade I symptoms are mild and occur only with vigorous exercise, such as walking a distance of greater than 2 blocks. The pain is not severe enough to alter the patient’s lifestyle. Grade II symptoms are moderate and usually occur with exercise, such as walking a distance of less than 2 blocks. This level of claudication prompts the patient to seek medical attention.
Intermittent claudication is the classic leg symptom of PAD. Claudication is described as a tired, aching, or cramping pain in the muscles of the leg that occurs during exercise and is relieved by rest. The location of the pain depends on the site of the arterial occlusive disease. The discomfort usually occurs in the calf muscles, but also may be felt in the thighs or buttocks. The severity of claudication can be graded on a scale devised by the Fontaine classification.
Non-Healing Wounds and Ulcers
It should be emphasized that up to 40% of patients with leg ulcers have evidence of PAD and the presence of an arterial pulse does not rule out PAD as the cause of the wound. These patients often have wounds that do not heal with standard treatment and it is important to conduct a thorough history and physical examination to assess for symptoms of claudication and to evaluate cardiovascular risk factors. Ankle-brachial index testing is a simple and non-invasive test that can be used to diagnose PAD in these patients.
The development of non-healing wounds and ulcers on the feet or legs is often a sign of critical limb ischemia, the most severe form of PAD. These wounds result from the lack of blood flow to an area and can have various appearances. The edges of the wound may be well defined with a pale base, the area may be yellow in color, and it may be dry or it may appear infected with redness and drainage. Ulcers often develop on the toes or areas of trauma, such as a bump or scratch, and are very painful. In severe cases, particularly in patients with diabetes, there can be such a severe lack of blood flow to the skin that an ulcer will develop without any trauma and may eventually lead to amputation of the foot or leg. Non-healing wounds and ulcers are a major source of morbidity for patients with PAD, particularly among the elderly, and can have a significant impact on physical functioning and quality of life.
Diagnostic Tests for PAD
When atherosclerotic peripheral arterial disease (PAD) is suspected, Doppler and blood pressure measurements before and after treadmill exercise testing should be the earliest non-invasive tests. Treadmill testing is preferred to Doppler segmental pressure measurements at rest for documenting claudication and determining distance walked till onset of pain, but in patients with severe limitation because of claudication, treadmill testing may not be feasible. Stored floppy Doppler audio signals may provide an inexpensive, semi-quantitative index of disease severity for purposes of follow-up in a standard clinical practice. High probe frequency and commercial devices that claim improved specificity for the detection of PAD in diabetics have not been proven better than the less expensive 8 MHz general purpose Doppler probes. If abnormal ABI and exercise tests suggest multi-segmental disease, MRA may be omitted in favor of more invasive angiography if percutaneous or surgical revascularization is contemplated.
Although the clinical features and history often provide adequate information for diagnosing PAD, sometimes more definitive diagnostic evidence is required. A variety of non-invasive and invasive studies are available for evaluating patients with PAD. Non-invasive testing may be performed in the physician’s office or in a hospital-based vascular laboratory. These tests are safe, have low morbidity, and are relatively inexpensive. The choice of a specific test or tests depends upon the arterial segment or segments being evaluated, the experience of the technologist, and the availability of specific equipment. Once the diagnosis of PAD is confirmed, further non-invasive testing of more distal segments may be appropriate.
Managing Risks and Treatment Options for PAD
Lifestyle modification is a cornerstone of the management of PAD and emphasizes the reduction of cardiovascular risk factors. Regular, supervised exercise programs such as walking to the point of intermittent claudication are beneficial. For those who are able, supervised exercise therapy has been shown to be a cost-effective and safe intervention. Smoking cessation represents one of the single most effective treatments to improve cardiovascular health. It is important to identify barriers to quitting and to provide the patient with counseling and pharmacotherapy to augment the likelihood of success. Additionally, the high risk of myocardial infarction and stroke in patients with PAD necessitates aggressive treatment of associated risk factors including hypertension, hyperlipidemia, and diabetes. Dietary counseling should focus on reducing calories, fat, and simple carbohydrates with the goal of weight reduction and lowering blood glucose and lipid levels. A single trial has demonstrated the benefit of lipid-lowering with a statin on walking performance and cardiovascular events in patients with PAD. High intake of fruits and vegetables has been associated with a lower incidence of PAD in some but not all studies. Finally, there are no specific recommendations for reducing sodium intake in PAD patients; however, given the high prevalence of concomitant hypertension, it seems reasonable to suggest a sodium-restricted diet.
Lifestyle Modifications
A supervised exercise program that monitors all patients for safety (adverse clinical events) and adverse limb events is a suitable method for those with claudication to improve their walking performance. Unfortunately, due to the lack of availability of supervised exercise programs and medical professionals trained to supervise such programs, this may not be a feasible option for many patients. At the least, patients should be advised to do a program of walking to the point of moderate claudication pain, resting, then resuming walking until the onset of pain. This type of program has been shown to initially increase symptoms of claudication; however, it ultimately results in improved pain-free walking time and total walking distance.
The patient’s pre-existing comorbidity of peripheral artery disease (PAD) adds further complications to the use of exercise as a means to improve health. Recommendations for exercise therapy to improve claudication symptoms have been advised based on the results of clinical trials. However, those with advanced disease that is symptomatic of potential limb loss, may be complicated by the presence of microvascular disease or other comorbidities, may put the patient at risk for adverse clinical events.
Just as with tobacco, it is important to aim for total cessation of alcohol consumption. This is due to the fact that drinking has been associated with the progression of the atherosclerotic process.
Also, all diabetic patients with PAD should be enrolled in a comprehensive foot care program. This is for the purpose of preventing complex foot ulcers, which may eventually lead to amputation. This program includes therapeutic footwear, with the goal of reducing the risk of pathology in the foot.
Healthcare providers should encourage all patients to avoid tobacco. It is important to ask about tobacco use and provide a strong message to encourage cessation, and offer assistance and follow-up.
Medications for PAD
To date, there is no medication solely FDA-labeled for the treatment of claudication. The most effective medical therapy for PAD symptom management is cilostazol. It is a phosphodiesterase III inhibitor that has been shown to be more effective than pentoxifylline and is on par with low to moderate intensity supervised exercise program. Unfortunately, many patients do not reach their best possible quality of life with cilostazol alone. Pentoxifylline or Trental is another medication option for PAD. This medication has been on the market for some time, but studies have not clearly shown a significant benefit in increasing pain-free walking distance. Aspirin and clopidogrel are antiplatelet agents that are used to prevent myocardial infarction, stroke, vascular death, and other vascular events. The use of these medications has been extrapolated to PAD patients as a means of secondary prevention for cardiovascular events. There is a growing body of evidence that suggests statins have a role in reducing cardiovascular events in PAD patients via plaque stabilization and reduction in inflammation. High-intensity statins have been shown to be more efficacious and should be considered for patients with symptomatic PAD in an effort to reduce future cardiovascular events. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are used to control blood pressure and offer organ protective benefits in patients with diabetes and kidney disease. This is essential for patients with PAD as tight blood pressure control can aid in the prevention of progression to other cardiovascular conditions and death. Although hypertension control is important in PAD patients, there is no evidence that beta blockers have a specific effect on increasing symptoms of claudication.
Interventional Procedures and Surgery
Atherectomy: Atherectomy involves the removal of atherosclerotic plaque from an artery. In contrast to PTA, it is a preferred technique for long segment occlusive disease and, in particular, for heavily calcified lesions. Due to the lack of distal embolization, it has a low incidence of complications and is an attractive option for patients with lesions that are at high risk for elastic recoil, such as the common femoral artery and the distal superficial femoral artery. There are several different types of atherectomy devices, but there is little evidence to suggest that one form of atherectomy is superior to another. Atherectomy has been proven to be more effective in improving limb blood flow and reducing the severity of claudication than PTA and may well become more popular.
Transluminal angioplasty: In younger healthy patients with focal stenotic lesions, the most beneficial treatment is percutaneous transluminal angioplasty (PTA) with or without stenting. This technique has had overwhelming success and has led to the procurement of a particular subset of equipment designed specifically for infrainguinal disease. PTA is less successful in long segment disease, in the presence of calcium and has unacceptably high complications in patients with infrapopliteal disease and those with long-standing diabetes. When treating stenotic lesions, it should be noted that a suboptimal result secondary to elastic recoil, although appearing initially successful, can be followed by a recurrence of the stenosis or occlusion within the subsequent few months. This can be obviated or minimized by the mechanical stabilization of the lumen with an endovascular stent. At first, stents were used only for iliac disease, but improvements in stent design and the efficacy of antiplatelet therapy now mean that PTA and stenting are being used more frequently in femoral popliteal disease, particularly in patients with claudication. Unfortunately, no randomized trials comparing PTA and stenting solely with PTA for below the knee lesions have been conducted, but stents have proven to be beneficial by allowing improved limb salvage rates, reduced need for acute surgery, and improved patency rates at 12 months in patients with a variety of below the knee lesions. In conclusion, the primary use of PTA and stenting is not an effective treatment for a large proportion of patients with symptomatic PAD, but rapid developments in technology and increased experience of the treating physician are likely to lead to an impending change in the paradigm of invasive management of PAD in the Western world.
