Peripheral Arterial Disease

Gregory S. Cherr

CLINICAL PEARLS

All patients with peripheral arterial disease (PAD) require atherosclerotic risk factor modification, antiplatelet therapy, and education regarding lifestyle modifications, including exercise therapy.
Consider revascularization for disabling claudication, ischemic rest pain, gangrene, or ulcers.
Below-knee amputation is recommended for ambulatory patients with adequate cognitive ability to participate in rehabilitation.
Bedridden patients and those with severe dementia will have fewer complications with an above-knee amputation.
Perioperative β-blockade is used to reduce the risk of coronary artery events.
Surgery has better long-term results but higher perioperative risks.
Technologic improvements in angioplasty/stenting have improved results and lowered the risk in patients.
Percutaneous intervention is performed with local anesthesia and sedation; therefore, cardiac stress testing is rarely required.
After surgery or angioplasty/stenting, surveillance vascular laboratory studies are used to monitor for progression of disease or graft/stent stenosis.

Peripheral arterial disease (PAD) is common among the elderly.¹,² PAD may be asymptomatic or cause symptoms ranging from mild (claudication) to disabling (lower extremity gangrene). Furthermore, PAD is associated with a high risk of subsequent cardiovascular events such as stroke and myocardial infarction (MI).²

Recently, remarkable technologic and medical advances have been made in the care of patients with PAD. These developments have led to improvements in functional status, quality of life and survival.² Furthermore, these advances may benefit the most sick and frail patients with PAD. Medical treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) has improved survival, and cilostazol has been shown to significantly improve claudication symptoms.³,⁴ Ongoing research is defining the role of medications such as clopidogrel and glycoprotein IIb-IIIa inhibitors. β-Blocker therapy has reduced the perioperative cardiac risk for surgical procedures.⁵ Advances in radiologic equipment have allowed sophisticated combined open/endovascular procedures to be performed in the operating room. Finally, improved outcomes may be realized with new medical devices such as cuffed prosthetic bypass grafts and tissueengineered bypass conduits.

Vascular surgery is undergoing rapid and profound changes involving minimally invasive endovascular procedures. Traditionally the purview of interventional radiologists, these procedures are increasingly being performed by both vascular surgeons and cardiologists. New therapies such as carotid angioplasty/stenting with distal protection devices and placement of covered stent grafts or drugeluting stents will likely become the standard of care in the future.

Care of the patient with PAD is stimulating and demanding. Recent advances have only made this field more challenging and rewarding. This chapter will present a broad understanding of the issues relevant to the care of the patient with PAD.

SIGNIFICANCE OF PERIPHERAL ARTERIAL DISEASE FOR THE OLDER PATIENT

PAD is frequently underdiagnosed and undertreated in the elderly.¹,² The incidence and prevalence of atherosclerotic occlusive disease (coronary, cerebrovascular, and PAD) increases with age. The survival of patients with atherosclerotic occlusive disease is increasing, although many patients live with significant (and possibly preventable) reductions in functional status and quality of life. The notion that atherosclerotic occlusive disease is a normal and untreatable part of aging is false. Quite the opposite, recognition and aggressive treatment of atherosclerotic occlusive disease and its associated risk factors have been shown to reduce the risk of primary or secondary ischemic events (such as MI, stroke, or PAD).²,³ Therefore, appropriate therapy (both medical and surgical) plays a significant role in prolonging both the length and quality of life for our aging population.

SYMPTOMS

Patients with PAD may have no complaints or severe symptoms, including claudication or pain at rest. Patients with claudication typically describe exercise-induced calf or thigh/buttock pain that is reproducible and relieved by rest. However, a significant proportion of patients with PAD will not describe typical symptoms. Some patients avoid the pain by avoiding exercise altogether. Others describe milder pain that does not cause them to stop walking.¹,⁶ With increasing recognition of the spectrum of symptoms of milder PAD, greater vigilance is required to identify patients who may benefit from medical therapy and possibly arterial revascularization.

The symptoms of patients with more severe PAD are easier to recognize. Patients with ischemic rest pain describe a constant, throbbing pain often located in the toes or the ball of the foot. The pain is usually worse with leg elevation and improves with leg dependency. Frequently, narcotics reduce pain but do not completely alleviate it. These patients also note worsening pain with ambulation and sometimes foot ulceration or gangrene. Topics associated with PAD are listed in Table 25.1.

TABLE 25.1 TOPICS ASSOCIATED WITH PERIPHERAL ARTERIAL DISEASE

Diagnosis	ICD-9 Code
Atherosclerosis of the extremities with intermittent claudication	440.21
Atherosclerosis of the extremities with rest pain	440.22
Atherosclerosis of the extremities with ulceration	440.23
Atherosclerosis of the extremities with gangrene	440.24
Coronary artery disease	414.01
Remote myocardial infarction	412
Angina pectoris	413
Carotid artery disease without cerebral infarction	433.10
Carotid artery disease with cerebral infarction	433.11
Tobacco use disorder	305.1
History of tobacco use	V15.82
Diabetes mellitus with neurologic manifestations	250.6
Diabetes mellitus with peripheral circulatory disorders	250.7
Pure hypercholesterolemia	272.0
Hypertension	401.1
Peripheral embolism to legs	444.2
Atherothrombotic microembolism	445.02
Popliteal artery entrapment syndrome	443.9
Popliteal artery adventitial cystic disease	443.9
Thromboangiitis obliterans (Buerger disease)	443.1
Popliteal artery aneurysm	442.3
Polyneuropathy in diabetes	357.2
Chronic venous insufficiency with pain	459.39
Venous claudication	459.19
Deep venous thrombosis of common femoral vein	451.11
Deep venous thrombosis of superficial femoral, popliteal, or tibial veins	451.19
Spinal stenosis, lumbar region	724.02
Lumbar spondylosis with myelopathy	721.42
Lumbar region intervertebral disc disorder with myelopathy	722.73
Osteoarthritis of the hip	715.15
Osteoarthritis of the knee	715.16

DISEASE BACKGROUND

CASE ONE

A 68-year-old woman presents to her new primary care physician for an initial evaluation and describes left calf claudication at approximately half a mile. Past medical history is significant for diabetes, tobacco abuse, hypertension, and a left iliac angioplasty 2 years earlier. Medications include a β-blocker, angiotensin-converting enzyme inhibitor, and an oral hypoglycemic. Physical examination confirms the presence of reduced peripheral pulses. She is started on aspirin, a statin (after a fasting lipid profile reveals dyslipidemia), and bupropion (for tobacco cessation). After 6 months, her symptoms have progressed to claudication at two blocks. She is started on cilostazol and again encouraged to quit smoking. Six months later, her symptoms have become disabling, with pain at less than one block. She is referred to a vascular surgeon who confirms significant infrainguinal arterial disease with a lower extremity arterial study (ultrasound) and then arteriography. Angiography/stenting is unsuccessful and bypass surgery is advised. She has a moderate functional status, intermediate clinical predictors of a perioperative cardiac event and will undergo a high-risk procedure (bypass surgery). She has a cardiac stress test that reveals no evidence of ischemia. Perioperative β-blockade is maximized and she undergoes an uneventful femoral-popliteal bypass. To reduce the risk of graft thrombosis, ultrasound graft surveillance is performed in the postoperative period, at 6 months, and then annually.

Pathophysiology of Peripheral Arterial Disease

Atherosclerosis results from a chronic inflammatory state. The final common pathway for the many known risk factors for atherosclerosis is injury to the artery wall. This injury causes chronic inflammation and the subsequent development of atherosclerotic plaques. Persistent inflammation leads to plaque progression or rupture (with a subsequent acute ischemic event). Atherosclerotic risk factor reduction aims to reduce the triggers for chronic inflammation and
the resulting plaque formation, progression, and eventual plaque instability.⁷

Incidence and Prevalence of Peripheral Arterial Disease

In community screening programs of older community-dwelling Americans, PAD has been found in 11% to 29% of subjects. In more than half of the subjects, PAD had not been previously diagnosed.¹,⁸ PAD was more prevalent in men than in women, but the ratio of men to women appears to be falling as more women develop cardiovascular diseases.⁸ PAD was diagnosed in similar proportions of elderly white, black, Hispanic, and “other” subjects.¹

Compared to coronary artery disease (CAD), patients with PAD receive less aggressive atherosclerotic risk factor modification and antiplatelet therapy.¹,⁸ Underdiagnosis and undertreatment of PAD likely represent a missed opportunity for treatment of claudication as well as secondary prevention of atherosclerotic events.¹,⁸

Impact of Peripheral Arterial Disease on Survival

Patients with PAD have a significantly increased risk of death over time. The 5-year survival for patients with claudication is approximately 65% (and is consistent among many population-based studies).² Most patients die from CAD. The survival rate is worse for patients with ischemic rest pain or gangrene. Even when controlled for atherosclerotic risk factors (diabetes, hypertension, tobacco abuse, dyslipidemia) and prevalent cardiovascular disease (such as CAD or cerebrovascular disease), patients with PAD have a significantly worse survival compared to patients without PAD.²

Impact of Peripheral Arterial Disease on Functional Status

Approximately 25% of patients will have worsening symptoms over time, although only a small proportion (<5%) will require surgery. Amputation is a great fear for patients with PAD. These patients are reassured to know that only 1% to 2% of those with claudication will eventually require a major amputation.

The clinician should be alert to the impact of lifestyle adaptation on symptom reporting. Many patients with PAD report that their symptoms are stable when in fact they have progressively reduced their activity level to avoid symptoms.⁹

The long-term functional status for older patients undergoing amputation is poor. Compared to younger patients, older patients undergoing major amputation are less likely to achieve full mobility. The prognosis is even worse for older women and bilateral amputees. Patients undergoing below-knee amputation are two to three times more likely to regain full mobility than those with above-knee amputations.²

Etiology of and Risk Factors for Peripheral Arterial Disease

In the overwhelming proportion of patients, PAD is a manifestation of atherosclerotic occlusive disease. Other less common etiologies of PAD include arterial embolism, popliteal artery entrapment syndrome, popliteal artery adventitial cystic disease, arterial dissection, trauma, thromboangiitis obliterans (Buerger disease), and popliteal artery aneurysm.

The predominant risk factors for atherosclerotic PAD include increasing age, preexisting cardiovascular disease (CAD, cerebrovascular disease), hypertension, tobacco abuse, dyslipidemia, and diabetes mellitus.

EVALUATION OF THE PATIENT WITH PERIPHERAL ARTERIAL DISEASE

Differential Diagnosis of the Patient with Exercise-Induced Leg Pain

There are many causes of exercise-associated leg pain or weakness (Table 25.2). It is important to differentiate intermittent claudication from the other causes of exercise-induced leg pain.

Nerve Root Compression

Compression of a nerve root may cause peripheral nerve dysfunction and associated leg pain with exercise. Compression of a peripheral nerve root is typically caused by a herniated disc or osteophyte formation. Patients note leg pain that usually starts soon after walking and is often present upon standing. Typically, the pain is experienced along the back of the leg, although occasionally it is present in only the calf or lower leg. For some patients, the pain may be present at rest and exacerbated by exercise. Patients may also note leg weakness, numbness, or paresthesias. Stopping does not relieve symptoms unless the patient also sits or bends forward. The onset of symptoms is gradual and the patient may note a history of back problems. Surgical decompression of the nerve root may be indicated for patients with severe symptoms.

Osteoarthritis

Osteoarthritis of the hip or knee may produce exercise-induced leg pain. The pain is often worse in the morning and when beginning movement. The severity of pain is variable from day to day. Arthritis-associated pain is not promptly relieved by cessation of exercise. Finally, many patients note exacerbation of the symptoms of arthritis with changes in the weather. Exercise programs, nonsteroidal anti-inflammatory medications, and, occasionally, surgery are indicated for the treatment of symptomatic osteoarthritis.

TABLE 25.2 DIFFERENTIAL DIAGNOSIS OF EXERCISE-INDUCED LEG PAIN

Disease	Symptoms	Diagnosis
Claudication	Exercise-induced buttock, thigh or calf pain; reproducible	Atherosclerotic risk factors, prevalent cardiovascular disease, vascular laboratory study, arteriogram
Popliteal artery entrapment syndrome	Exercise-induced calf pain; reproducible	Arteriogram, MRI, CT scan, absence of traditional atherosclerotic risk factors
Popliteal artery adventitial cystic disease	Exercise-induced calf pain; reproducible	Arteriogram, MRI, CT scan, absence of traditional atherosclerotic risk factors
Thromboangiitis obliterans (Buerger disease)	Exercise-induced foot pain, pain at rest, ulcers, gangrene	Young patient with tobacco abuse and absence of other traditional atherosclerotic risk factors, arteriogram
Diabetic peripheral neuropathy	Pain (shooting, burning); unrelated to exercise	History, physical examination, nerve-conduction studies
Venous claudication	Exercise-induced leg pain with bursting, tight sensation	History of deep venous thrombosis and chronic venous disease, ultrasound
Osteoarthritis	Exercise-induced aching pain (knee, hip)	History, physical examination, x-rays
Spinal stenosis	Pain/numbness of back and/or legs; leg cramping or weakness; symptoms worse with exercise or standing	History, MRI
MRI, magnetic resonance imaging; CT, computed tomography.

Popliteal Artery Entrapment Syndrome

Popliteal artery entrapment syndrome is caused by obstruction of the popliteal artery by an abnormally located portion of the gastrocnemius muscle. Patients note exercise-induced calf or foot pain that is relieved by rest. Physical examination is normal with palpable pedal pulses. While those affected are often young, the diagnosis should be considered in any patient without atherosclerotic risk factors. Surgery is indicated to correct the anatomic abnormality and alleviate symptoms.

Popliteal Artery Adventitial Cystic Disease

Popliteal artery adventitial cystic disease is a rare cause of stenosis or occlusion of the popliteal artery. An idiopathic cystic lesion develops in the wall of the popliteal artery and encroaches on the lumen of the artery. Patients may present with typical symptoms of intermittent claudication with arterial stenosis but others may have ischemic rest pain if the popliteal artery is occluded. The diagnosis may be suspected in older patients without typical atherosclerotic risk factors. The location of the arterial pathology (isolated to the popliteal artery) should also alert the clinician to the possibility of popliteal artery adventitial cystic disease. Surgical repair is indicated to alleviate symptoms and prevent progression of the lesion. Emergency surgery is necessary for limb salvage in patients presenting with acute popliteal artery thrombosis.

Chronic Venous Insufficiency

Chronic venous insufficiency is caused by venous hypertension. Leg pain is typically mild and associated with leg heaviness or tiredness. The symptoms are usually worse at the end of the day and relieved by leg elevation or recumbency. Although primarily caused by venous valvular incompetence, a minority of patients will be symptomatic secondary to remote deep venous thrombosis and resulting venous obstruction. Physical examination reveals chronic skin changes of the calf (brawny edema or lipodermatosclerosis) and occasionally varicose veins. Treatment includes graded compression stockings, leg elevation, and skin care to prevent infection/ulcers. A minority of patients will benefit from surgical treatment of varicose veins or incompetent superficial veins (such as the greater saphenous vein).

Venous Claudication

Venous claudication is caused by severe venous hypertension. Patients with this rare disease note exercise-induced leg pain most often in the hip and thigh. The pain is described as a tight or “bursting” sensation. Rest relieves the pain and recovery may be aided by leg elevation. The patients have a history of severe venous obstructive disease from prior iliofemoral deep venous thrombosis. Physical examination usually reveals leg edema and lipodermatosclerosis. Treatment is supportive and includes graded compression stockings, leg elevation, and skin care. Some patients may benefit from surgical therapy with venous bypass or venous valve replacement, although the results of these procedures are generally disappointing.

Differential Diagnosis of the Patient with Leg Pain at Rest

There are many causes of leg pain at rest (Table 25.3). Chronic lower extremity ischemia is a common cause of
leg pain at rest in the elderly. Patients note a gradual progression of symptoms from mild claudication to disabling claudication to pain at rest.

TABLE 25.3 DIFFERENTIAL DIAGNOSIS OF LEG PAIN AT REST

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