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Peripheral arterial disease (PAD) is the result of atherosclerotic occlusive and thromboembolic pathophysiologic processes causing obstruction to blood circulation of the lower extremities, including the aortic, iliac, and lower limb arteries.1,2 Less commonly, the upper extremity can be affected (eg, left proximal subclavian artery).3


PAD primarily arises from insufficient tissue perfusion caused by atherosclerosis, which may be associated with emboli or thrombi. PAD may also be caused by thromboembolic, inflammatory, or aneurysmal disease caused by underlying hereditary or acquired (eg, smoking, trauma) causes.1

Epidemiology including risk factors and primary prevention

The worldwide prevalence of PAD is between 3% and 12%.4

Risk factors include the following3-5:

  1. Smoking
  2. Dyslipidemia
  3. Diabetes
  4. Obesity
  5. Hypertension
  6. Family history of PAD, heart disease, stroke, or atherosclerosis
  7. Inflammation
  8. High homocysteine level
  9. Age

The American College of Cardiology (ACC)/American Heart Association (AHA) classified the following groups at a higher risk1,4:

  1. Age 70 years or older
  2. Age 50 to 69 years with history of smoking and diabetes
  3. Age 40 to 49 with diabetes and at least 1 other risk factor for atherosclerosis

Primary prevention includes physical activity; blood pressure, cholesterol, and diabetes control; and tobacco avoidance.


Several pathologic processes can lead to arterial insufficiency as the result of obstruction of the vessels. PAD of the lower extremities predominantly results from atherosclerosis. Other reasons include degenerative diseases, dysplastic disorders, vascular inflammation, thrombosis, acute trauma, thromboembolism causing damage, inflammation, and blood vessel defects leading to inadequate blood flow to the limbs.

Arterial obstruction can lead to intermittent claudication. Blood flow is normative at rest but insufficient during exercise, causing pain. In contrast, critical ischemia is hemodynamic compromise leading to pain at rest, nonhealing ulcers, or gangrene in the lower extremities.4

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Clinical manifestations range from asymptomatic to critical limb ischemia. In patients who have diabetes, renal insufficiency, or who smoke, it could progress rapidly and unpredictably.

PAD has been categorized into the 4 following stages by the ACC/AHA1,6:

  1. Stage I (asymptomatic PAD): 20% to 50% of patients; no leg pain.
  2. Stage II (intermittent claudication): 10% to 35% of patients; mismatch between blood supply and activity-induced demand contribute to intermittent claudication and lead to atypical lower extremity pain in 40% to 50% of cases.
  3. Stage III (advanced ischemia with symptoms at rest): typically presents as pain.
  4. Stage IV (critical limb ischemia): 1% to 2% of patients; varying degrees of tissue loss or gangrenous ulcers in the lower extremities.

Specific secondary or associated conditions and complications

Ischemic ulcers (nonhealing wounds) occur as a result of insufficient blood supply from worsening PAD. Typically, the wound forms after local trauma and is painful. Necrotic tissue (dry gangrene) may be present around the ulcer. Wet gangrene happens when the ulcers are infected; it can quickly escalate to cellulitis.7



In early PAD, intermittent claudication with physical activity may be the only symptom. Leriche syndrome is a triad of symptoms consisting of intermittent claudication in the buttock and thigh, decreased or absent femoral pulses, and in men, erectile dysfunction. This syndrome could indicate aortoiliac occlusive disease. Pain that manifests in the calf could indicate femoral-popliteal disease. Chronic PAD may present with atrophic skin and muscles with hair loss, thickened toenails, and cool lower extremities.

Physical examination

Palpation of peripheral pulses (abdominal aorta to foot) and auscultation of bruits may help determine level of occlusion. Absence of pulse indicates obstruction proximal to the area palpated. Lower limb size, coloration, temperature, and hair distribution should be evaluated. Examination of upper extremities is important, and upper extremity occlusive disease may be present. Ambulation or toe raises can be used to reproduce symptoms. The ratio of ankle to brachial systolic pressure, ankle brachial index (ABI), should be obtained. Normative ABI is 0.9 to 1.1; it decreases with worsening PAD.

Functional assessment

Upper limb involvement may affect activities of daily living because of arm fatigue with exercise and, occasionally, embolization to the hands.Ambulation and gait examination is pertinent because it may be impaired as a result of pain and ischemic ulcers.

Laboratory studies

Laboratory studies are not used to diagnose PAD, but they are helpful to detect changes in renal function and elevated lipid profiles.


  1. Angiography is the standard arterial imaging study used prior to surgical intervention or percutaneous transluminal angioplasty.
  2. Arterial duplex imaging (Doppler) provides a direct anatomic and physiologic report. It can distinguish between occlusion and stenosis, length of disease, and patency of vessels. Additionally, doppler ultrasonography can be used with ABI measurements because pressure gradients and pulse volume waveforms can help distinguish isolated aortoiliac PAD from femoropopliteal PAD and below-the-knee PAD.7
  3. Magnetic resonance angiography is useful for large and small vessels.
  4. Computed tomography angiography can be used; however, it requires contrast dye.

Supplemental assessment tools

ABI is the standard noninvasive vascular evaluation prior to imaging. Bilateral arm and ankle systolic blood pressure is measured. An ABI of .90 or less signifies PAD with mild (.71-.90), moderate (.41-.70), or severe (≤.40). If ABI is normative, then patient should be asked to do exercise stress testing while assessing the ABI. A high index (>1.3) may mean noncompressible leg vessels beceause of arteriosclerosis with calcification of the wall.

If amputation of the lower extremity is indicated, transcutaneous oxygen pressure (TcPO) significantly predicts healing. It provides a way to evaluate skin perfusion and cutaneous healing at a specific level. An optimal value of TcPO 38 mm Hg while in a supine position had a sensitivity and specificity of 71% for predicting healing or failure. TcPO should be used to better accurately determine the correct amputation level; however, it should not be used in isolation.8

Early predictions of outcomes

Symptomatic large-vessel PAD has a very poor long-term prognosis, with 4 to 7 times the risk of mortality from all causes, and 15 times the risk of mortality from cardiovascular causes (eg, coronary artery disease, cerebrovascular disease) compared with people who do not have PAD.9


PAD is a chronic disease that is correlated with atherosclerotic disease. Therefore, extrinsic factors related to atherosclerosis (eg, smoking, obesity) can lead to PAD progression. Aggressive management of extrinsic risk factors is essential in PAD.

Social role and social support system

Intermittent claudication and ischemic ulcers can be very painful affecting quality of life, mobility, and level of independence. As patients become more debilitated, they will require assistance and support that may include social security disability insurance. PAD is listed under the Cardiovascular System Impairments Category (medical listing 4.12).

Professional Issues

Professional and work life may be impaired because of claudication pain and ischemic wounds. This leads to reduced walking capacity and impaired mobility leading to limited exercise and sedentary lifestyle. Asymptomatic patients or those with atypical symptoms also experience progressive functional impairment.10


Available or current treatment guidelines

Comprehensive prevention programs help reduce symptoms, improve exercise capacity, decrease physical disability, and prevent cardiovascular events.9 Aggressive risk factor modification should target obesity, smoking, diabetes, hypertension, hyperlipidemia, and homocysteinemia. A supervised exercise program should be started. For nighttime pain relief, the legs should be kept below the level of the heart, and the head of the bed should be elevated 10 to 15 cm.

Pharmacologic treatments include antiplatelet drugs (aspirin 81-162 mg orally daily or clopidogrel 75 mg orally daily).1,7 Claudication symptoms can be treated with cilostazol 100 mg orally twice daily in the absence of heart failure. Use of pentoxifylline has not been well established.1,7 Endovascular procedures and/or surgery are reserved for PAD that causes significant functional disability and has been unresponsive to conservative measures.1

At different disease stages

Acute PAD may result from acute compartment syndrome, rupture, thrombosis, or embolus of an atherosclerotic plaque. Immediate angiography to confirm location of occlusion and collateral flow is essential. Embolectomy, thrombolysis, and bypass surgery are options for treatment. Of the patients, 20% to 30% with acute arterial occlusion require amputation within the first 30 days.3

For chronic PAD, supervised claudication rehabilitation is recommended: 30 to 45 minutes of treadmill or track walking at least 3 times per week for 12 weeks. Initial workload is set to speeds that elicits claudication within 3 to 5 minutes followed by rest periods and is progressed to achieve an exercise-rest-exercise routine. It is expected to result in increased speed, duration, distance, and decreased claudication symptoms. If there are cardiac signs, exercise should stop.1,3

Cardiovascular risk reduction is as follows:

  1. Diabetes control and proper foot care.
  2. Hypertension: antihypertensives, specifically angiotensin-converting enzyme inhibitors and beta-blockers to achieve systolic blood pressure (SBP) less than 140 over diastolic blood pressure (DBP) less than 90 mm Hg (nondiabetics) or SBP less than 130 over DBP less than 80 mm Hg (diabetics).
  3. Hyperlipidemia: statin to achieve target low-density lipoprotein goal less than 70 mg/dL.
  4. Smoking cessation with behavior modification.
  5. Antiplatelets to reduce risk of future cardiovascular events (eg, myocardial infarction, stroke, vascular death in patients with atherosclerotic lower extremity PAD).

Individuals with professional and lifestyle limitations caused by PAD that are not responding to conservative treatments can be considered for endovascular interventions (eg, percutaneous transluminal angioplasty [PTA]). PTA with or without stent insertion is the primary nonsurgical method for dilating vascular occlusions.

Similarly, candidates for surgery have intermittent claudication that inhibits daily activities, rest pain, and gangrene. Surgery options include thromboendarterectomy, revascularization, and as a last resort, amputation.3

Coordination of care

A multidisciplinary approach with communication between the primary care physician, physiatrist, vascular surgeon, general surgeon (if amputation is a consideration), and the claudication rehabilitation program is essential. This should include addressing modifications for cardiovascular risk factors, pharmacologic and exercise claudication management, lifestyle modifications, and patient-family education.

Patient & family education

Patients and their family should be educated on PAD, importance of risk factor modification, lifestyle changes, and a rehabilitation exercise program. Referral to support group services should be offered.

Emerging/unique Interventions

Activity and treadmill walking distance should be measured in order to evaluate treatment outcomes. As patients are able to improve their exercise capability, the workload should be increased to ensure continued tolerance of exercise and pain-free walking distance. Range of motion and performance of activities of daily living or ambulation should be tracked as applicable.

Hemodynamic measurements, including ABI, can help in assessing patency of grafts, angioplasty, or stents.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Early detection and diagnosis of PAD is important for good prognosis. Diagnosis with history, physical examination, and ABI measurement is the standard of care. Treatment of mild PAD includes aggressive risk factor modification, an exercise rehabilitation program, antiplatelet drugs, and cilostazol as needed for claudication symptoms. PTA or surgical bypass are options in PAD that is not responsive to conservative measures with a possibility of amputation in necrotic, septic, or limb-threatening ischemia.




Gaps in the evidence-based knowledge

Improvement in walking distance, duration, and decrease of symptomatology of PAD with exercise has been established; the exact mechanism of improvement is not well understood. It is thought that muscles are conditioned to work by extracting more blood, which increases collateral vessel formation.


1. Hirsh AT, et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic).Circulation. 2006;113:1474-1547.

2. Graeme HJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006;295:547-553.

3. The Merck Manual for Health Care Professionals. Peripheral arterial disease. Available at: http://www.merck.com/mmpe/print/sec07/ch080/ch080f.html. Accessed December 11, 2013.

4. Harris L, Dryjski M. Epidemiology, risk factors, and natural history of peripheral artery disease. In: Basow DS, ed. Waltham, MA: UpToDate; 2013.

5. Centers for Disease Control and Prevention. Peripheral Arterial Disease (PAD) fact sheet. Available at: http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_pad.htm. Accessed December 11, 2013.

6. American College of Cardiology Foundation; American Heart Association Task Force; Society for Cardiovascular Angiography and Interventions; et al. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline).Vasc Med. 2011;16:452-476.

7. Casillas JM, Troisgros O, Hannequin A, et al. Rehabilitation in patients with peripheral arterial disease.Ann Phys Rehabil Med. 2011;54:443-461.

8. Andrews K, Dib M, Shives T, Hoskin T, Liedl D, Boon A. Noninvasive arterial studies including transcutaneous oxygen pressure measurements with the limbs elevated or dependent to predict healing after partial foot amputation.Am J Phys Med Rehabil.2013;92:385-392.

9. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease.N Engl J Med.1992;326:381-386.

10. Hamburg N, Balady G. Exercise rehabilitation in peripheral artery disease: functional impact and mechanisms of benefits.Circulation. 2011;123:87-97.


Aslam F, Haque A, Foody J, Lee LV. Peripheral arterial disease: current perspectives and new trends in management.South Med J. 2009;102:1141-1149.

Powell A. Office evaluation of leg pain.Semin Intervent Radiol. 2009;26:281-285.

Shammas NW, Dippel EJ. Evidence-based management of peripheral vascular disease.Curr Atheroscler Rep.2005;7:358-363.

Social Security. Disability evaluation under Social Security: 4.00-Cardiovascular System – Adult. 2008. Available at: http://www.ssa.gov/disability/professionals/bluebook/4.00-Cardiovascular-Adult.htm#4_12. Accessed January 1, 2014.

Author Disclosure

Marlis Gonzalez-Fernandez, MD, PhD
Nothing to Disclose

Tiffany Vu, DO
Nothing to Disclose