Online Medical Reference

Peripheral Arterial Disease

Amjad Al Mahameed

Published: January 2009


Peripheral arterial disease (PAD), cerebrovascular disease, and coronary artery disease (CAD) are the three major syndromes of atherothrombosis. Whereas luminal stenosis (or occlusion) and end-organ ischemia are late manifestations of this progressive process, the diagnosis of PAD is largely viewed as a measure of the individual's global systemic atherosclerotic burden. Thus, even the asymptomatic form of PAD is of great significance to both the patient and clinician. The discussion here will focus on lower extremity PAD.

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With an age-adjusted prevalence of approximately 12%, PAD affects at least 8 to 12 million Americans.1,2 The disease prevalence increases with age and 12% to 20% of Americans age 65 and older (4.5 to 7.6 million) have PAD. As the population ages, the prevalence could reach 9.6 to 16 million in those age 65 and older and 19 million overall by 2050 (Box 1 and Fig. 1).1 Although PAD affects men and women equally, worse outcomes have been observed in diabetic women compared with diabetic men. Studies have suggested a disproportionately higher PAD prevalence among African Americans compared with non-Hispanic whites (odds ratio [OR], 2.3).3 This ethnic propensity is independent of susceptibility to known cardiovascular risk factors such as diabetes, hypertension, and obesity.4,5 The major impediments to improving the care of patients with PAD are related to the lack of disease recognition, poor understanding of its impact on the patient, and the gross underuse of safe, effective, and widely available therapies. The PARTNERS (Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival) program has evaluated 7000 at-risk individuals seen in primary care practices.2 In this population, the program uncovered several important facts related to PAD epidemiology. First, PAD is common (prevalence, 29%) in high-risk individuals (age older than 70 years without additional risk factors, or age 50 to 69 years with a history of cigarette smoking or diabetes) in the primary care setting. Second, PAD is poorly recognized—44% of cases were diagnosed after enrollment in the program, only 83% of patients with a prior diagnosis of PAD were aware of it and, surprisingly, only 49% of their physicians knew about it, despite documentation in medical records. Third, patients who had both PAD and CAD were more likely to have been diagnosed than patients with PAD alone. Fourth, despite being an independent risk factor for cardiovascular morbidity and mortality, patients with PAD were less intensively managed.6,7 Hyperlipidemia, hypertension, and adequate antiplatelet therapy were less frequently prescribed compared with CAD patients.2,8

Box 1: Epidemiology of Peripheral Arterial Disease
Affects men and women equally
African Americans have higher incidence than whites
Highest risk for older adults, diabetics, and former smokers (present or remote)
High incidence in patients with chronic kidney disease
High incidence in transplant recipients
Poor public and physician awareness of the disease epidemiology
More than 90% of cases secondary to atherosclerosis

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Risk factors

The risk factors for PAD are similar to the risk factors for atherosclerosis elsewhere (Fig. 2). The three risk factors most strongly associated with PAD are advanced age (older than 60 years), cigarette smoking, and diabetes mellitus (DM). 2,4,5,9–11 PAD is more frequent in older adults, with a 1.5- to twofold increase in risk for every 10-year increase in age. 9–10 Smoking or DM increases the risk of PAD independently by approximately threefold. 9–11 In addition, smoking has a synergistic effect on other risk factors, and the number of pack/years is associated with disease severity. Smokers have at least double the risks of mortality, disease progression, and limb amputation rates compared with nonsmokers. 12–15 Although diabetics often have extensive involvement, diffuse and advanced PAD appear to be related to the duration of diabetes rather than glycemic control. 16 Other important risk factors include dyslipidemia (elevations of total cholesterol, low-density lipoprotein [LDL], triglyceride [TG], and lipoprotein(a) levels are all independent risk factors for PAD) and hypertension. 2,9,17

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Atherosclerosis accounts for more than 90% of cases of PAD in the United States, and uncommon vascular syndromes account for the remaining 10%. Atherosclerotic lesions are plaques composed of a central lipid core, connective tissue, inflammatory cells, and smooth muscle cells, all covered by a fibrous cap. Plaques tend to localize at the bifurcations or proximal segments of large and medium-size arteries. The femoral and popliteal arteries are affected in 80% to 90% of symptomatic PAD patients, the tibial and peroneal arteries in 40% to 50%, and the aortoiliac arteries in 30%.

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Signs and symptoms

Most patients with PAD are asymptomatic or present with atypical symptoms beyond those of classic intermittent claudication (IC; Box 2). As such, the diagnosis may be overlooked in up to 90% of patients if IC—and not an abnormal ankle-brachial index (ABI)—is used as the sole criterion for diagnosis. 18 In addition to leg symptoms, symptomatic patients often report poor quality of life related to their limited mobility and subsequent decline in overall functional capacity. 19,20

Box 2: Clinical Presentation of Peripheral Arterial Disease
Most cases are asymptomatic.
In symptomatic patients:
  • Most have atypical exertional leg pain.
  • Only 10% to 30% present with classic intermittent claudication.
  • Minority progress to rest pain or ischemic ulcers (critical limb ischemia).

Those with classic IC typically describe pain, ache, tightening, cramping, or sense of fatigue in one or more of the lower extremity muscle groups. The symptoms usually are triggered by ambulation and are relieved by rest. The site of claudication is distal to the diseased arterial segment. For example, buttock, hip, and thigh claudication are seen with aortoiliac disease and calf claudication with femoral-popliteal disease. With severe PAD, patients may present with signs and symptoms of critical limb ischemia. These include rest pain, cold, or numbness of the feet, with or without tissue loss (nonhealing ulcers or gangrene). Rest pain usually occurs at night (because of the horizontal position, which deprives the patient of the effect of gravity on blood flow through the tight lesions) and improves when the legs are in the dependent position. Subsequently, superimposed edema of the affected leg(s) occasionally may be seen in those who tend to dangle their legs overnight. Rest pain is a sign of more severe or multilevel arterial occlusions.

Physical examination should include evaluation of the entire vascular system. The intensity of peripheral pulses should be recorded numerically as follows: 0, absent; 1, diminished; 2, normal; 3, bounding. 21 The presence of bruits may reflect stenotic lesions in arteries that are not readily amenable to palpation (e.g., iliac, aorta, renal, and mesenteric arteries). Inspection of the lower extremities for skin lesions is also indicated. The clinical features of acute limb ischemia (commonly referred to as the “Ps”) include pain, pallor, pulselessness, paresthesia, paralysis, and poikilothermia (i.e., coldness; Box 3). Paresthesia and paralysis imply irreversible ischemia, and muscle rigidity is a sign of a nonsalvageable limb.

Box 3: Signs and Symptoms of Acute Limb Ischemia
Poikilothermia (“coldness”)

Laboratory studies are ordered to detect the presence of dyslipidemia, diabetes, and major metabolic derangement (e.g., renal or hepatic insufficiency). A baseline electrocardiogram (ECG) should be obtained at the time of diagnosis and, for select patients, cardiac stress testing may be indicated. Recommended strategies for subjects presenting with critical limb ischemia are presented in Box 4.

Box 4: Investigational Strategies for Evaluating Patients with Critical Limb Ischemia
Clinical history and physical examination, including the coronary and cerebral circulations
Hematologic and biochemical tests—complete blood count, platelet count, fasting blood glucose, hemoglobin Aκ, and creatinine levels, fasting lipid profile, and urinalysis (for glycosuria and proteinuria)
Resting electrocardiogram
Ankle or toe pressure measurement or other objective measures of severity of ischemia
Imaging of lower limb arteries in patients considered for endovascular or surgical intervention
Duplex scan of carotid arteries—should be considered for select patients at high risk (defined as those with cerebrovascular ischemic symptoms or in whom the risk of carotid revascularization is lower than the short-term risk of stroke)
A more detailed coronary assessment may be performed in select patients for whom coronary ischemic symptoms would otherwise merit such an assessment if CLI were not present (such coronary assessments should generally not impede associated CLI care).

CLI, critical limb ischemia. Adapted from Dormandy JA, Rutherford RB: Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Concensus (TASC). J Vasc Surg 2000;31(Suppl):S1-S296. © 2000, with permission from Elsevier.

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PAD can be easily and accurately diagnosed by calculating the ankle-brachial index (ABI). The ABI is the ratio of systolic blood pressure measured at the ankle by a Doppler ultrasound device to the higher systolic blood pressure at the brachial arteries (Fig. 3). The ABI test is helpful because of the following:

  1. Most PAD patients are asymptomatic or have atypical leg symptoms.
  2. Among symptomatic patients, 11% to 33% report classic intermittent claudication, and up to one third fail to communicate their symptoms to their health care provider.22
  3. Those with asymptomatic PAD have a risk of cardiovascular events (e.g., myocardial infarction, stroke, cardiovascular mortality) comparable with that of patients with symptomatic coronary artery disease.22–24
  4. The severity of PAD (as determined by a lower ABI value or presentation with symptomatic disease) predicts limb outcome and patient survival.25,26
  5. The ABI is an accurate measure (ABI less than 0.9 has a sensitivity of 95% and specificity of 100% in detecting PAD) that is noninvasive, inexpensive, office-based, and can be reliably performed by primary care providers and other health care personnel.2,6,21

Table 1 compares ABI values with the severity of PAD. Based on these characteristics, the most recent American College of Cardiology–American Heart Association (ACC/AHA) guidelines advocate ABI measurement for high-risk individuals (Box 5). 21 It is hoped that such strategy will facilitate early detection and institution of management strategies (e.g., risk factor modification, exercise rehabilitation, limb revascularization) that will help prevent disability, decrease cardiovascular events, and lower early mortality.

Table 1: Ankle-Brachial Index and Severity of Peripheral Arterial Disease
Ankle-Brachial Index Severity
>1.30 Noncompressible (calcific vessel; diabetes, chronic renal insufficiency, and older age)
0.91-1.30 Normal
0.71-0.90 Mild
0.41-0.70 Moderate
0-0.40 Severe


Box 5: Who Should Undergo Ankle-Brachial Index Testing?
Individuals with overt clinical lower extremity peripheral arterial disease who present with claudication or more severe limb ischemic symptom
Age ≥ 70 years or older
Age = 50-69 years with history of diabetes or smoking
Age < 49 years with diabetes and one additional risk factor (smoking, diabetes, hypertension, or elevated cholesterol levels)
Abnormal lower extremity pulse examination
Known atherosclerotic disease elsewhere (coronary, carotid, or renal arteries)

The shortcomings of the ABI test include the potential to miss mild proximal disease of the aorta and iliac arteries (also referred to as inflow disease) in those with well-developed collaterals and those with significant medial artery calcification. Thus, an exercise ABI should be determined when the resting ABI value is normal if the pretest probability of PAD is high. Other diagnostic tests (e.g., pulse volume recording, duplex ultrasonography, magnetic resonance imaging, and computed tomography angiography) are recommended for those with calcified vessels (e.g., older individuals, those with long-standing diabetes or end-stage renal disease) suspected of having PAD but with a resting ABI value of more than 1.3. Conventional contrast-mediated arteriography rarely is needed to establish the diagnosis of PAD; it is largely limited to patients being considered for revascularization procedures. Table 2 lists the recommended noninvasive vascular laboratory tests for lower extremity PAD by clinical presentation.

Table 2: Noninvasive Vascular Laboratory Tests for Lower Extremity Peripheral Arterial Disease (PAD) Patients by Clinical Presentation
Clinical Presentation Noninvasive Vascular Test
Asymptomatic lower extremity PAD ABI
Claudication ABI, PVR, or segmental pressures
Duplex ultrasound
Exercise test with ABI to assess functional status
Possible pseudoclaudication Exercise test with ABI
Postoperative vein graft follow-up Duplex ultrasound
Femoral pseudoaneurysm, iliac or popliteal aneurysm Duplex ultrasound
Suspected aortic aneurysm Abdominal ultrasound, serial AAA, follow-up CTA or MRA
Candidate for revascularization Duplex ultrasound, MRA, or CTA

AAA, indicates abdominal aortic aneurysm; ABI, ankle-brachial index; CTA, computed tomography angiography; MRA, magnetic resonance angiography; PAD, peripheral arterial disease; PVR, pulse volume recording.

Adapted from Hirsch AT: Recognition and management of peripheral arterial disease. In Braunwald E, Goldman L (eds): Primary Cardiology, 2nd ed. Philadelphia, WB Saunders, 2003, pp 659-671. © 2003, with permission from Elsevier.

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The goals of PAD management are limb salvage, symptom relief, improving functional status, and preventing cardiovascular events (acute myocardial infarction [MI], stroke, and vascular death). All PAD patients require intensive cardiovascular risk reduction and should be referred to a supervised exercise program. Limb revascularization procedures are offered to select patients. Table 3 summarizes the therapeutic interventions for patients with PAD.

Table 3: Therapeutic Interventions in Patients with Peripheral Arterial Disease
Therapy Intervention
Lifestyle changes Complete smoking cessation Supervised walking exercise program Weight loss (target BMI, 18.5-24.9 kg/m2) Healthy diet Foot and skin care, other protective measures
Pharmacotherapy Treat hyperlipidemia—use statin to target LDL < 100 mg/dL; if low HDL, high TG, add fibrate or niacin; if high Lp(a), add niacin.
Control HTN—ACEIs, ARBs, diuretics preferred; add medications as needed to achieve target BP < 140/90 mm Hg (<130/80 mm Hg for patients with diabetes or renal insufficiency); consider renal artery stenosis if uncontrolled HTN; beta blocker can be used especially if coexistent CAD; low-dose ACEI may be considered for normotensive patients.
Antiplatelet therapy—Use ASA (75-325 mg/day) or clopidogrel (75 mg/day).
Optimize diabetes management.
Treat claudication with cilostazol.
Limb revascularization Indicated for acute limb ischemia, critical limb ischemia, or lifestyle-limiting claudication; percutaneous or surgical

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ASA, acetylsalicylic acid; BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; HDL, high-density lipoprotein; HTN, hypertension; LDL, low-density lipoprotein; Lp(a), lipoprotein a; TG, triglyceride.

Adapted from Dormandy JA, Rutherford RB: Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Concensus (TASC). J Vasc Surg 2000;31(Suppl):S1-S296. © 2000, with permission from Elsevier.

Treatment of Underlying Conditions and Risk Factors

Smoking Cessation

Smoking is the most important preventable risk factor for PAD. Smoking cessation leads to improvement in leg symptoms, lowers the amputation risk, improves long-term patency after revascularization, and reduces the cardiovascular event rate.27,28 Nicotine is one of the most potent addictive substances known to humans (comparable with heroin). Data from the PARTNERS program has shown that only 50% of enrollees received advice on smoking cessation.2 Further analysis has revealed that PAD patients who are taught behavioral modification techniques and receive a physician's advice have a limited abstinence rate (15%/year).12,29 Thus, physicians should play an active and ongoing role in their patients' smoking cessation efforts; this can be achieved by repeated counseling, referral to a smoking cessation program, and pharmacotherapy.29 Nicotine replacement products—bupropion (Zyban), and the more recently FDA-approved smoking cessation product varenicline (Chantix)— are effective, but varenicline has shown more favorable results compared with placebo and bupropion.30

Managing Diabetes Mellitus

Current data regarding the benefit of aggressive diabetes management in PAD patients and its effect on morbidity or mortality are limited. Whereas aggressive diabetes control did not improve claudication symptoms or slow disease progression in the United Kingdom Prospective Diabetes Study (UKPDS), such a strategy reduced the rate of cardiovascular events and microvascular complications (e.g., retinopathy, neuropathy). 31 Therefore, strict diabetes control is advocated for this population.

Dyslipidemia Treatment

Lipid-lowering therapy reduces the risk of new or worsening symptoms of intermittent claudication. 32 The hyperlipidemia associated with PAD frequently is that of the metabolic syndrome (elevated TG [triglyceride], low high-density lipoprotein [HDL], and normal or slightly elevated LDL levels). The 2001 National Cholesterol Education Program Adult Treatment Panel (NCEP) III has identified PAD patients as being the highest risk group for future coronary events and recommended intensive lipid-lowering therapy to attain a target LDL level of lower than 100 mg/dL and a TG level of lower than 150 mg/day. 33 Statins should be the first-line lipid-lowering therapy. The evidence supporting statin use in PAD patients dates back to the Scandinavian Simvastatin Survival Study (4S), which documented a 38% reduction in new or worsening claudication in the simvastatin group. 32 More recently, the Heart Protection Study (HPS) has published evidence that supports the routine use of statins in patients with PAD regardless of their cholesterol levels. 34 In this study, simvastatin significantly reduced the cardiovascular ischemic event rate by 23%. Several reports have indicated that statins also improve pain-free walking distance and ambulatory activity in claudicants through a mechanism independent of their cholesterol-lowering properties. 35 Niacin or fibrate compounds may be considered for patients with elevated TG and low HDL levels once the target LDL level is reached.

Hypertension Treatment

The target blood pressure in hypertensive PAD patients is similar to that for patients who have CAD. 36 Special attention should be directed to hypertensive PAD patients who are also diabetic. The ABCD trial found a marked improvement in the risk of myocardial infarction, stroke, or vascular death in the group that received intensive blood pressure–lowering therapy; this benefit was independent of the ABI value. 37 The choice of antihypertensive agents should be individualized. Thiazide diuretics, beta blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and calcium channel blockers are all effective. The use of beta blockers is safe and effective; it reduces the incidence of new coronary events by 53% in those with a prior MI and concurrent symptomatic PAD. 38,39 The Heart Outcomes Prevention Evaluation (HOPE) trial documented a 22% reduction in the composite end points of MI, stroke, or cardiovascular death in patients with vascular disease or diabetes mellitus randomized to receive the ACEI ramipril compared with placebo. 40 A more recent analysis of this trial has concluded that the benefits of ramipril extend to symptomatic and asymptomatic PAD patients (the number needed to treat to prevent one ischemic event during the study treatment period of 4.5 years was 18 and 17 for symptomatic and asymptomatic patients, respectively). In addition to reducing the risk of fatal and nonfatal ischemic events, an ACEI may also increase peripheral perfusion and lead to improvement in walking distance. 41,42 Given the increased risk of renal artery stenosis in this population, renal function should be monitored closely when starting a PAD patient on an ACEI or ARB.

Antiplatelet Treatment

Given the proven benefit in reducing the risk of myocardial infarction, stroke, and vascular death in PAD patients, the ACC/AHA guidelines have given the strongest recommendation (IA) to the use of antiplatelet therapy (aspirin [ASA], 75 to 325 mg daily, or clopidogrel, 75 mg daily) in those with atherosclerotic lower extremity PAD. 21,42–44 The CAPRIE trial has compared clopidogrel (Plavix, 75 mg daily) with aspirin (325 mg daily) in a study of 19,185 patients with atherosclerotic vascular disease, more than 6,400 of whom were enrolled on the basis of symptomatic PAD (intermittent claudication with abnormal ABI or prior revascularization or amputation). 44 Clopidogrel provided a 8.7% reduction in the composite end points of fatal or nonfatal ischemic stroke, MI, or other vascular deaths compared with ASA. Importantly, patients in the PAD subgroup manifested a greater benefit from clopidogrel (relative risk reduction, 23.8%). Recent data have not supported the routine use of dual antiplatelet therapy in this population. 45 Ticlopidine (Ticlid) is another antiplatelet agent that received U.S. Food and Drug Administration (FDA) approval for use in PAD earlier than clopidogrel. Its use has declined markedly because of adverse hematologic effects (e.g., thrombocytopenia, neutropenia, thrombotic thrombocytopenic purpura), which occur in 2% to 3% of treated patients.

Treatment of Leg Symptoms and Improving Walking Distance

Exercise, pharmacotherapy, and invasive (surgical or percutaneous) procedures are strategies that relieve exertional leg symptoms, increase ambulatory distance, and improve quality of life. Revascularization procedures may also be required to prevent tissue loss, facilitate wound healing, and preserve the limb.

Supervised Exercise Rehabilitation Program.

A structured exercise rehabilitation program is one of the most effective strategies to improve claudication symptoms. This is recommended by the ACC/AHA guidelines as initial treatment for claudication (grade IA). 21,46–50 A meta-analysis of 21 published studies has shown that PAD rehabilitation programs increase pain-free walking time by 179% and maximal walking time by 122%. 46 The greatest benefit is obtained when the patient participates in three to five sessions/week, each lasting 30 to 45 minutes, for a minimum of 12 weeks. Maintenance of such a program should be considered indefinitely or the benefit may eventually be lost. The limitations of exercise rehabilitation programs are cost, lack of availability, and insurance coverage.


Cilostazol (Pletal), is a reversible phosphodiesterase inhibitor that inhibits platelet aggregation, thrombin formation, and vascular smooth muscle proliferation, promotes vasodilation, and increases HDL and lowers TG levels. 51–53 Cilostazol is the only FDA-approved medication to demonstrate consistent benefits on objective measures of exercise capacity and subjective measures of daily functioning and quality of life. In randomized placebo-controlled trials, cilostazol has been found to be superior to placebo and pentoxifylline (Trental), which is also an FDA-approved medication for relieving claudication and improving pain-free and maximal treadmill walking distance, community-based ambulation, and quality of life. 54 The ACC/AHA guidelines have given cilostazol a grade IA recommendation for patients with intermittent claudication. 21 A dose of 100 mg twice daily (taken on an empty stomach at least ½ hour before or 2 hours after breakfast and dinner) is recommended to ensure effectiveness. Common side effects of cilostazol include headache (30% of patients), diarrhea and gastric upset (15%), and palpitations (9%). Most of these side effects, however, are short lived and rarely require discontinuation of the medication. Given the increased incidence of sudden cardiac death with other phosphodiesterase inhibitors (e.g., milrinone, vesnarinone) cilostazol is contraindicated in patients with heart failure. 55,56

Pentoxifylline is a methylxanthine derivative that decreases blood viscosity and has hemorheologic (improves erythrocyte and leukocyte deformability), anti-inflammatory, and antiproliferative effects. Since its approval for intermittent claudication in 1984, two meta-analyses and two systematic reviews have concluded that its effect on improving walking capacity is small, if any. Thus, it has lost its status as a widely used medication for this indication. The ACC/AHA guidelines have given pentoxifylline a grade IIb recommendation. 21


At present, the absolute indications for lower extremity revascularization are acute limb ischemia, critical limb ischemia (usually manifested as rest pain, nonhealing lower extremity ulcers), and lifestyle, vocational, or economically limiting claudication.

Box 6 lists the accepted indications for revascularization in patients presenting with intermittent claudication. Box 7 shows factors that increase the risk of limb loss in patients with critical limb ischemia, and Table 4 lists the clinical categories of acute limb ischemia.

Box 6: Indications for Revascularization in Intermittent Claudication
Before a patient with intermittent claudication is offered the option of any invasive revascularization therapy, endovascular or surgical, the following considerations must be taken into account:
Predicted or observed lack of adequate response to exercise therapy and claudication pharmacotherapies
Presence of a severe disability, with the patient being unable to perform normal work or having very serious impairments of other activities important to the patient
Absence of other disease that would limit exercise even if the claudication was improved (e.g., angina or chronic respiratory disease)
Anticipated natural history and prognosis of the patient
Morphology of the lesion, which must be such that the appropriate intervention would have low risk and a high probability of initial and long-term success

Adapted from Dormandy JA, Rutherford RB: Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Concensus (TASC). J Vasc Surg 2000;31(Suppl):S1-S296. © 2000, with permission from Elsevier.

Box 7: Factors that Increase Risk of Limb Loss in Patients with Critical Limb Ischemia
Factors that reduce blood flow to the microvascular bed:
Severe renal failure
Severely decreased cardiac output (severe heart failure or shock)
Vasospastic diseases or concomitant conditions (e.g., Raynaud's phenomenon, prolonged cold exposure)
Smoking and tobacco use
Factors that increase demand for blood flow to the microvascular bed:
Infection (e.g., cellulitis, osteomyelitis)
Skin breakdown or traumatic injury

From Hirsch AT, Haskal ZJ, Hertzer NR, et al; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation: ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006;113:e463-e654.

Table 4: Clinical Categories of Acute Limb Ischemia
Category Description and Prognosis Sensory Loss Muscle Weakness Arterial Doppler Signals Venous Doppler Signals
Viable Not immediately threatened None None Audible Audible
Threatened marginally Salvageable if promptly treated Minimal (toes) or none None (Often) inaudible Audible
Threatened immediately Salvageable with immediate revascularization More than toes; associated with rest pain Mild, moderate (Usually) inaudible Audible
Irreversible Major tissue loss or permanent nerve damage Profound, anesthetic Profound paralysis (rigor) Inaudible Inaudible

Reprinted with permission from Katzen BT: Clinical diagnosis and prognosis of acute limb ischemia. Rev Cardiovase Med 2002;3(Suppl 2):S2-S6.

Endovascular Interventions

Short stenotic (or occlusive) lesions can generally be successfully treated percutaneously, whereas long lesions usually require surgical treatment. Percutaneous angioplasty carries a lower risk compared with surgical revascularization and can be performed on an outpatient basis. Proposed predictors of favorable long-term outcomes include the locations of treated lesions (better results with iliac artery angioplasty compared with femoropopliteal or infrapopliteal arteries), quality of the underlying vessels (better with preserved inflow and distal runoff arteries), patient's comorbid conditions (worse in those who fail to abstain from tobacco, diabetics, or when the risk factors are poorly controlled), indication for the procedure (claudication better than acute or critical limb ischemia), and immediate postprocedure outcome (return of ABI to normal postintervention value). Although primary stent placement in the iliac arteries appears to improve long-term patency rates, stent placement in the femoropopliteal area is reserved for special cases, such as suboptimal angioplasty result and flow-limiting dissection.

Catheter-Directed Thrombolysis

Catheter-directed thrombolytic therapy is an accepted initial treatment strategy for acute limb ischemia.57–60 It reduces the number of immediate surgical interventions required for acute limb ischemia and therefore markedly reduces perioperative risk. Thrombus resolution allows for better visualization of underlying atherosclerotic lesions and offers an opportunity for simultaneous treatment with percutaneous angioplasty. The ACC/AHA guidelines have given catheter-based thrombolysis a grade I recommendation for patients with acute limb ischemia (Rutherford categories I and IIa) of less than 14 days' duration and grade IIb for those presenting with a Rutherford category IIb of more than 14 days' duration.21

Careful patient selection and excluding patients with high bleeding risk are necessary to minimize hemorrhagic complications.

Surgical Procedures

Surgery is advocated for many patients presenting with acute or critical limb ischemia. Occasionally, it is used for individuals with lifestyle-limiting claudication. Endarterectomy and bypass grafting are the two most commonly used surgical techniques. Generally, endarterectomy is feasible and offers an excellent success rate when used for proximal arterial segments (aorta, iliac, common femoral or profunda arteries) and bypass grafting is preferable for distal, long, or diffuse disease. For infrainguinal bypass procedures, autogenous vein grafts have higher patency rates (70% to 80% at 5 years) compared with prosthetic grafts. 61,62 Operative complications include myocardial infarction and stroke, wound or graft infection, peripheral embolization, and sexual dysfunction secondary to autonomic nervous system injury. The operative mortality rate ranges from 1% to 3% and success rates depend on the lesion site and severity, anastomotic site, and status of the outflow system. Use of perioperative beta blockers is indicated because they significantly reduce the risk of cardiovascular complications (including MI and death). With the availability of percutaneous and surgical techniques, the types of revascularization procedures should be individualized depending on the lesion characteristics, the risks for perioperative complications, and patients' preference.

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PAD is a prevalent systemic atherosclerotic disease with associated high cardiovascular morbidity and mortality. Symptomatic PAD often impairs a patient's quality of life and untreated disease can lead to limb loss. Despite the fact that PAD can be noninvasively and accurately diagnosed with the ABI, it often remains underdiagnosed and undertreated. Health care providers must make every effort to detect the disease at an early stage, assess associated risk factors, and provide proper long-term care. Aggressive management of atherosclerotic risk factors, a structured exercise program, use of antiplatelet agents and, when indicated, percutaneous or surgical revascularization are the keys for successful management


  • PAD is a common but underrecognized cause of morbidity particularly in older adults, those with diabetes, and smokers.
  • The risk factors for PAD are similar to the risk factors of atherosclerosis elsewhere; risk factor modification is key to successful management and achieving favorable outcomes.
  • Although intermittent claudication is the classic symptom of PAD, the vast majority of those affected are asymptomatic and diagnosed by an abnormal ABI value.
  • Treatment of leg symptoms includes enrollment in a supervised walking program, use of cilostazol and, for select patients, percutaneous or surgical revascularization.
  • The primary care provider is expected to diagnose and manage most patients with PAD.

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  1. American Heart Association. Heart Disease and Stroke Statistics—2004. 2004; Dallas.
  2. The PARTNERS program: A national survey of peripheral arterial disease detection, awareness, and treatment. JAMA. 286: 2001; 1317-1324.
  3. Prevalence of and risk factors for peripheral arterial disease in the United States. Results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation. 110: 2004; 738-743.
  4. The prevalence of peripheral arterial disease in a defined population. Circulation. 71: 1985; 510-515.
  5. The epidemiology of peripheral arterial disease: Importance of identifying the population at risk. Vasc Med. 2: 1997; 221-226.
  6. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Circulation. 88: 1993; 837-845.
  7. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 326: 1992; 381-386.
  8. Atherosclerotic risk factors are less intensively treated in patients with peripheral arterial disease than in patients with coronary artery disease. J Gen Intern Med. 2: 1997; 209-215.
  9. Intermittent claudication. A risk profile from The Framingham Heart Study. Circulation. 96: 1997; 44-49.
  10. Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA. 270: 1993; 465-469.
  11. Lower extremity arterial disease in elderly subjects with systolic hypertension. J Clin Epidemiol. 44: 1991; 15-20.
  12. The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the treatment of peripheral arterial disease. Vasc Med. 2: 1997; 243-251.
  13. Cessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality. Acta Med Scand. 221: 1987; 253-260.
  14. The measured effect of stopping smoking on intermittent claudication. Br J Surg. 69: 1982; S24-S26.
  15. The influence of smoking on the level of lower limb amputation. Prosthet Orthot Int. 11: 1987; 113-116.
  16. Arteriosclerosis obliterans and associated risk factors in insulin-dependent and non–insulin-dependent diabetes. Diabetes. 29: 1980; 882-888.
  17. Serum lipoproteins and hemostatic function in intermittent claudication. Arterioscler Thromb. 3: 1993; 1441-1448.
  18. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. Circulation. 91: 1995; 1472-1479.
  19. Leg symptoms commonly reported by men and women with lower extremity peripheral arterial disease: Associated clinical characteristics and functional impairment. JAMA. 286: 2001; 1599-1606.
  20. Quality of life and peripheral obliterative arteriopathy. Perspective for the future. Drug. 56: 1998; 49-58.
  21. American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 113: 2006; e463-e654.
  22. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Concensus (TASC). J Vasc Surg. 31: 2000; S1-S296.
  23. Risk factors and cardiovascular diseases associated with asymptomatic peripheral arterial occlusive disease. The Limburg PAOD Study. Peripheral Arterial Occlusive Disease. Scand J Prim Health Care. 16: 1998; 177-182.
  24. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. Int J Epidemiol. 25: 1996; 1172-1178.
  25. The ratio of ankle and arm arterial pressure as an independent predictor of mortality. Atherosclerosis. 87: 1991; 119-128.
  26. The long-term prognostic value of the resting and postexercise ankle-brachial index. Arch Intern Med∼. 166: 2006; 529-535.
  27. The peripheral vascular consequences of smoking. Ann Vasc Surg. 5: 1991; 291-304.
  28. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: A meta-analysis. Arch Intern Med. 159: 1999; 337-345.
  29. Treating tobacco use and dependence: An evidence-based clinical practice guideline for tobacco cessation. Chest. 121: 2002; 932-941.
  30. U.S. Food and Drug Administration: FDA Approves Novel Medication for Smoking Cessation, 2006. Available at
  31. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 352: 1998; 837-853.
  32. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian simvastatin survival study (4S). Am J Cardiol. 81: 1998; 333-335.
  33. An evidence-based assessment of the NCEP Adult Treatment Panel II guidelines. National Cholesterol Education Program. JAMA. 282: 1999; 2051-2057.
  34. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet. 360: 2002; 7-22.
  35. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 108: 2003; 1481-1486.
  36. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 157: 1997; 2413-2446.
  37. Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. Circulation. 107: 2003; 753-756.
  38. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials. Arch Intern Med. 151: 1991; 1769-1776.
  39. Effect of beta blockers on incidence of new coronary events in older persons with prior myocardial infarction and symptomatic peripheral arterial disease. Am J Cardiol. 87: 2001; 1284-1286.
  40. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study investigators. N Engl J Med. 342: 2000; 145-153.
  41. Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease. Eur Heart J. 25: 2004; 17-24.
  42. Cardiovascular risk prevention in peripheral artery disease. J Vasc Surg. 41: 2005; 1070-1073.
  43. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 348: 1996; 1329-1339.
  44. Antiplatelet Trialists' Collaboration; Collaborative overview of randomised trials of antiplatelet therapy—I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ. 308: 1994; 81-106.
  45. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy—II: Maintenance of vascular graft or arterial patency by antiplatelet therapy. Antiplatelet Trialists' Collaboration. BMJ. 308: 1994; 159-168.
  46. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 354: 2006; 1706-1717.
  47. Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. JAMA. 274: 1995; 975-980.
  48. Exercise training for claudication. N Engl J Med. 347: 2002; 1941-1951.
  49. Exercise rehabilitation for the patient with intermittent claudication: A highly effective yet underutilized treatment. Curr Drug Targets Cardiovasc Haematol Disord. 4: 2004; 233-239.
  50. Exercise for intermittent claudication. Cochrane Database Syst Rev. 2000;
  51. Intermittent claudication—surgical reconstruction or physical training? A prospective randomized trial of treatment efficiency. Ann Surg. 209: 1989; 346-355.
  52. Effect of cilostazol, a phosphodiesterase III inhibitor, on experimental thrombosis in the porcine carotid artery. Thromb Res. 96: 1999; 261-268.
  53. Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells. Thromb Res. 57: 1990; 617-623.
  54. Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty. Circulation. 100: 1999; 21-26.
  55. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med. 109: 2000; 523-530.
  56. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 325: 1991; 1468-1475.
  57. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med. 339: 1998; 1810-1816.
  58. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg. 19: 1994; 1021-1030.
  59. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity. The STILE Trial. Ann Surg. 220: 1994; 251-266.
  60. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. N Engl J Med. 338: 1998; 1105-1111.
  61. Thrombolysis in the management of lower limb peripheral arterial occlusion—a consensus document. Working party on thrombolysis in the management of limb ischemia. Am J Cardiol. 81: 1998; 207-218.
  62. Six-year prospective multicenter randomized comparison of autologous saphenous vein and expanded polytetrafluoroethylene grafts in infrainguinal arterial reconstructions. J Vasc Surg. 3: 1986; 104-114.
  63. Present status of reversed vein bypass grafting: Five-year results of a modern series. J Vasc Surg. 11: 1990; 193-205.

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