Peripheral Arterial Disease

I. What every physician needs to know.

Peripheral arterial disease (PAD) is a condition of blood vessels that result in narrowing of arteries and diminished perfusion to the tissues supplying the brain, visceral organs and limbs. This chapter primarily discusses lower extremity PAD. PAD and peripheral vascular disease are used interchangeably. PAD is predominantly the result of atherosclerosis. Risk factors for atherosclerosis increase the likelihood of developing lower extremity PAD. Other causes include trauma, infection, abnormal arterial anatomy from degenerative disorders, or vasculitis.

Initial clinical presentation can vary from asymptomatic PAD, claudication (the most common symptom of PAD), critical limb ischemia (usually chronic), or acute limb ischemia. Complications of PAD include limb loss, stroke, myocardial infarction (MI), infection, and restricted mobility. Individuals at risk for PAD should undergo a thorough vascular history and physical. Intermittent claudication presents as pain in the leg muscles with exercise that is relieved at rest; however, in severe cases, PAD can manifest with symptoms at rest.

Physical exam findings include abnormal pedal pulses, cool skin, abnormal skin color, femoral artery bruit and non-healing wounds. The ankle-brachial index (ABI) is a useful non-invasive test to diagnose lower extremity PAD. Contrast arteriography is used to identify PAD anatomy prior to intervention. Treatment options include lifestyle, medical and surgical therapies.

Continue Reading

II. Diagnostic Confirmation: Are you sure your patient has Peripheral Arterial Disease?


A. History Part I: Pattern Recognition:

Many patients present with asymptomatic PAD. Health care providers should be aware of atypical descriptions during the vascular history that describe muscle symptoms on exertion as well as symptoms from concomitant diseases that can conceal the description of lower extremity ischemia. Typical presentation of symptomatic chronic PAD, known as “claudication,” includes cramping pain in the buttock, thigh, calf or foot with ambulation which improves with rest. Other symptoms include leg weakness, erectile dysfunction, and cool extremities. When critical limb ischemia occurs, the major manifestations include rest pain, ischemic ulcers, and gangrene; these symptoms are subacute to chronic. Acute limb ischemia presents more abruptly with onset of the “5 P’s”: pain, paralysis, pallor, paresthesia, and pulselessness.

B. History Part 2: Prevalence:

PAD occurs in 5% of adults older than 50 and 20% of adults older than 70. Classic PAD risk factors include smoking, diabetes mellitus, hypertension, hyperlipidemia, increasing age (older than 50), family history of peripheral vascular disease, and coronary artery disease. New risk factors have emerged and they include elevated C-reactive protein levels, hyperhomocysteinemia, and chronic renal insufficiency.

C. History Part 3: Competing diagnoses that can mimic Peripheral Arterial Disease.

Differential diagnosis of PAD include neurologic, hematologic and musculoskeletal causes of claudication and they include:

a) Spinal stenosis – this can cause compression of the cauda equina and subsequent radiculopathy. The pain does not subside rapidly with rest as with claudication and there may be a history of back problems. Normal lower extremity pulses are present.

b) Deep vein thrombosis – symptoms include swelling and tenderness of the affected extremity at rest. Lower extremity pulses are present. There may be a history of prolonged periods of inactivity.

c) Hip arthritis – normal lower extremity pulses. No pallor present. Pain reproducible with motion of the hip joint.

d) Restless leg syndrome – sensations begin with periods of inactivity (primarily at night) and symptoms are lessened by movement. Lower extremity pulses are normal.

e) Chronic compartment syndrome – Unlike claudication, pain relief is accelerated by leg elevation.

f) Systemic vasculitides (e.g., Raynaud’s phenomenon) – commonly in young woman and manifested with exposure to cold or stressor.

Differential diagnosis for acute limb ischemia include:

a) Acute spinal cord compression – Unlike PAD, normal pulse and skin color will be present.

b) Acute Deep Vein Thrombosis – Normal pulses are predominantly present; pallor is not present.

D. Physical Examination Findings.

Physical exam can be normal but commonly reveals diminished pulses below the level of stenosis.

On inspection, physical findings may include shiny skin, hair loss, leg atrophy, ulcer on feet or toes, pallor on leg elevation and nail changes on the extremity with decreased perfusion.

On palpation there can be cool extremity unilaterally, delayed capillary refill, bruits, loss of sensations to light touch, vibration and proprioception.

The classic 5 P’s: pulselessness, pain, pallor, paresthesia and paralysis should trigger the possibility of acute limb ischemia.

E. What diagnostic tests should be performed?


1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

No single laboratory test will establish the diagnosis of PAD but labs that can assist at the time of diagnosis with managing risk factors or comorbidities include: complete blood count, hemoglobin A1C, fasting lipid profile, serum creatinine and urinalysis for proteinuria and glucosuria.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The Ankle-Brachial Index (ABI) is a non-invasive test to confirm the clinical diagnosis of PAD and should be performed in both legs. It is a ratio of the systolic blood pressure in the brachial artery compared to that of the ipsilateral ankle. The normal ABI value is 1.0-1.3, since ankle pressures are higher than arm pressures. An ABI below 0.9 is very specific for PAD; an ABI between 0.91-1.0 are considered “borderline”. An ABI below 0.4 is representative of advanced ischemia. Values above 1.3 suggest a calcified vessel that is non-compressible and may be a false-negative.

To further evaluate ABI above 1.3 which can be from non-compressible vessels as a result of age, long-standing diabetes or progressive renal disease, a toe-brachial index should be used to diagnose PAD.

Treadmill exercise testing with pre and post exercise ABI is useful for diagnosing lower extremity PAD when resting ABI values are borderline or normal with risk factors present.

Once PAD has been verified, further non-invasive testing to assess the level and extent of PAD include segmental pressure examination as well as duplex ultrasound.

Contrast angiography remains the gold standard for anatomic evaluation of PAD when revascularization is planned. CT angiography is often used for preoperative planning.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.


III. Default Management.


A. Immediate management.

Acute limb ischemia

Any individual who presents with symptoms and signs of acute limb ischemia should be evaluated promptly with initiation of treatments as early as possible to preserve the limb. The hallmark presentation of acute ischemia suggestive of limb jeopardy include the 5 P’s: pain, paralysis, pallor, paresthesia, and pulselessness. Once PAD is diagnosed via absent pedal pulses or if feasible with ABI, then immediate anticoagulation with unfractionated heparin or low molecular weight heparin should be started if no contraindications exist. Simultaneously a prompt vascular surgery consult should be obtained to collaboratively establish the diagnostic strategy to determine the site, type and extent of occlusion as well as the treatment plan.

The clinician should extract the following from the vascular history and physical:

a) Onset and duration of ischemia

b) History of bypass graft

c) Comorbidities

d) Viability of the limb based on sensory loss, muscle weakness and audible arterial and venous Doppler signals

e) Contraindication for thrombolytic therapy or surgery

Hemodynamic monitoring to avoid hypotension and maintain appropriate oxygen saturation is important.

Labwork should include CBC and Complete metabolic panel and coagulation profile.

Arterial embolus is a common etiology of acute limb ischemia, and optimizing rate control for a patient with atrial fibrillation and cardiac function is key.

A cardiac risk evaluation needs to be performed in individuals who have surgical revascularization planned.

Post-revascularization evaluation consists of:

a) Thorough vascular-focused physical exam examining for new or progressive ischemic symptoms.

b) Examining presence of femoral/pedal pulses.

c) Awareness of compartment syndrome which can develop following revascularization and manifests as painful, tense, and swollen limb. Pulses are usually present.

Critical limb ischemia (CLI)

CLI is chronic and is to be distinguished from acute limb ischemia. The diagnosis and management of CLI requires rapid evaluation to prevent limb loss. Common manifestations include severe rest pain in the limbs that is chronic, non-healing foot/toe ulcers or gangrene of foot.

The vascular history should assess comorbid risk factors that are present and the physical examination should evaluate lower extremity pulses and the presence of foot infection or ulcers and their precipitating factors.

Signs of chronic ischemia include: dependent rubor, pallor on elevation, reduced capillary refill. Signs of atheroemboli, such as livedo reticularis or elevated creatinine after recent endovascular catheter procedure, may be observed.

Particular attention should be paid to the timing and course of the ischemia to determine the urgency of revascularization.

An ABI should be performed and a value less than 0.4 and/or absent pedal flow demonstrates severe PAD.

A vascular surgery consult should be obtained promptly to define the medical care plan.

Non-invasive and/or angiographic testing will be necessary to evaluate the arterial anatomy and degree of ischemia.

Assessment of co-morbidities will determine if patient is a candidate for revascularization in addition to presence of a conduit on anatomy. The goal of surgical revascularization is the resolution of the clinical manifestations of CLI.

If medical therapy is the option, aggressive therapy to modify atherosclerotic risk factors is recommended. See treatment below.


Symptoms: Pain, cramping or discomfort in the leg muscles after exercise resulting from exercise-induced ischemia that is relieved with rest.

History and physical: Assess for atherosclerotic risk factors which include diabetes, hypertension, smoking, hyperlipidemia and family history of atherosclerotic disease.

Diminished pulses may exhibit in the femoral, popliteal, posterior tibial and dorsalis pedis arteries.

Systemic signs of atherosclerosis which may assist with vascular etiology of claudication include femoral bruits and carotid bruits.

Differential: See above

Diagnosis: All patients with claudication should have an ABI. An ABI less than or equal to 0.9 is abnormal and reflective of PAD.


Risk factor modification:

a. Smoking cessation – Complete abstinence is the single most important factor related to improved outcomes in patients with intermittent claudication.

b. HTN – Antihypertensive meds should be provided to achieve a BP of 140/90 mmHg or less, according to current guidelines. However, recent evidence from trials such as SPRINT may support lower BP targets in individuals at high risk of cardiovascular events without diabetes. It is likely that guideline-recommended BP targets will continue to change in the future to reflect these new data.

– Results of the HOPE trial showed ramipril, an ACE-inhibitor, reduced cardiovascular morbidity and mortality in patients with PAD by 25%.

– ACE-inhibitors should be considered in patients with PAD to reduce cardiovascular adverse events; however, physicians should monitor creatinine levels for deterioration and assess for renal artery stenosis if needed.

c. Diabetes – Treatment consists of diabetic medications and appropriate diet to achieve a HBAIC less than 7% to reduce the microvascular complications.

d. Hyperlipidemia – Lipid lowering therapy in conjunction with diet modification is recommended. Treatment with a HMG-CoA inhibitor (statin) at a high-intensity level (atorvastatin 40-80 mg daily or equivalent) is indicated for secondary prevention of cardiovascular disease.

Pharmacological risk reduction: Antiplatelet therapy is recommended for individuals with PAD to reduce the risk of serious vascular events.

a) Aspirin 75 mg to 325 mg po daily is recommended.

b) Clopidogrel 75 mg po daily is recommended as an alternative antiplatelet therapy to aspirin.

c) Presently there is no data indicating dual antiplatelet therapy with aspirin and clopidogrel versus a single antiplatelet medication in patients with PAD.

d) There is insufficient evidence to support oral anticoagulation in conjunction with antiplatelet therapy reduces the risk of cardiovascular events in individuals with PAD.

Individual risks for bleeding should be assessed before introducing antiplatelet agents for patients already taking warfarin for atrial fibrillation or mechanical heart valve.

If lifestyle limiting symptoms are present once PAD is confirmed:

Supervised exercise rehabilitation program. Several studies have shown its benefit to reduce symptoms of claudication. at least a 3-month trial with at least 3 sessions per week of 30-45 minutes each.

Pharmacologic therapy:

a) Cilostazol is a vasodilator with antiplatelet properties and has been shown to increase walking distance in many randomized studies of claudication caused by PAD.

– Dosage 100 mg orally twice daily.

– Cilostazol should not be used in individuals with heart failure!

b) Pentoxifylline is a rheologic modulator that has some antiplatelet effects. It is an alternative therapy to cilostazol to improve walking distance since the data has shown limited evidence of its effectiveness.

– Dosage is 400 mg orally three times daily.

If symptoms persist despite exercise and pharmacotherapy, should proceed to additional non-invasive or angiographic diagnostic testing to define vascular anatomy and the necessity for percutaneous interventional procedures or surgery.

Revascularization should be based on the severity of symptoms, lifestyle impairment, lack of comorbid conditions which would limit exercise if the claudication was improved, the vascular anatomy and the likelihood of long term success with limited risk.

Asymptomatic PAD

Defined as the absence of classic claudication symptoms. However, it is important to be aware that individuals with asymptomatic PAD have impairment of lower extremity function and increased cardiovascular ischemic risk. Many have systemic atherosclerotic disease. Manifestations include slower walking velocity, fewer distance walked over a course of time, slower time to rise from a seated position.

Diagnosis: The ABI allows for detection of PAD at all stages of the process. If ABI value is greater than 1.30, suggestive of non-compressible arteries, a toe-brachial index with pulse volume recording can help delineate lower extremity PAD. If ABI values are borderline or normal (0.91-1.30) in at risk individuals, an exercise ABI can help diagnose the presence of lower extremity PAD.

Treatment: see risk factor modification and pharmacological risk reduction above.

B. Physical Examination Tips to Guide Management.


C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.


D. Long-term management.


E. Common Pitfalls and Side-Effects of Management.


IV. Management with Co-Morbidities.


A. Renal Insufficiency.


B. Liver Insufficiency.


C. Systolic and Diastolic Heart Failure.


D. Coronary Artery Disease or Peripheral Vascular Disease.


E. Diabetes or other Endocrine issues.


F. Malignancy.


G. Immunosuppression (HIV, chronic steroids, etc).


H. Primary Lung Disease (COPD, Asthma, ILD).


I. Gastrointestinal or Nutrition Issues.


J. Hematologic or Coagulation Issues.


K. Dementia or Psychiatric Illness/Treatment.


V. Transitions of Care.

A. Sign-out considerations While Hospitalized.


B. Anticipated Length of Stay.


C. When is the Patient Ready for Discharge.


D. Arranging for Clinic Follow-up.


1. When should clinic follow up be arranged and with whom.

Patients who have undergone percutaneous and surgical revascularization should have regular surveillance follow up with the vascular specialist. The frequency of the follow-up will depend on the burden of disease and the specific procedure performed. At the minimum there should be a 1 month follow-up.

2. What tests should be conducted prior to discharge to enable best clinic first visit.


3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.


E. Placement Considerations.


F. Prognosis and Patient Counseling.


VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.


B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

The best way to prevent PAD is to reduce the risk factors. This includes lifestyle and medical therapy. See Treatment: Modification of risk factors above. Lifestyle changes should prioritize a healthy low cholesterol diet and engaging in physical activity for at least 30 minutes/day.

VII. What's the evidence?

Rooke, TW. “2011 ACCF/AHA Focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines”. J Am Coll Cardiol. vol. 58. 2011 Nov 1. pp. 2020

Hussein, AA, Uno, K, Wolski, K. “Peripheral arterial disease and progression of coronary atherosclerosis”. J Am Coll Cardiol. vol. 57. 2011 March 8. pp. 1220-5.

Anand, S, Yusuf, S, Xie, C. “Oral anticoagulant and antiplatelet therapy and peripheral arterial disease”. N Engl J Med. vol. 357. 2007. pp. 217-227.

Carter, SA, Tate, RB.. “Value of toe pulse waves in addition to systolic pressures in the assessment of the severity of peripheral arterial disease and critical limb ischemia”. J Vasc Surg. vol. 24. 1996. pp. 258-265.

Craft, LL, Guralnik, JM, Ferrucci, L. “Physical activity during daily life and circulating biomarker levels in patients with peripheral arterial disease”. Am J Cardiol. vol. 102. 2008 Nov 1. pp. 1263-8.

Hennrikus, D, Joseph, A, Lando, H. “Effectiveness of a smoking cessation program for peripheral artery disease patients: a randomized controlled trial”. J Am Coll Cardiol. vol. 25. 2010. pp. 2105-2112.

McDermott, MM, Liu, K, Ferrucci, L. “Circulating blood markers and functional impairment in peripheral arterial disease”. J Am Geriatr Soc. vol. 56. Aug 2008. pp. 1504-10.

Stone, NJ, Robinson, JG, Lichtenstein, AH. “2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines”. J Am Coll Cardiol.. vol. 63. 2014 Jul 1. pp. 2889-934.

James, PA, Oparil, S, Carter, BL. “2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)”. JAMA. vol. 311. 2014 Feb 5. pp. 507-20.

Wright, JT, Williamson, JD. “A Randomized Trial of Intensive versus Standard Blood-Pressure Control”. N Engl J Med.. vol. 373. 2015 Nov 26. pp. 2103-16.

Jump to Section