Peripheral arterial disease

Last updated: June 24, 2022

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Peripheral arterial disease (PAD) is a condition characterized by the atherosclerotic narrowing of peripheral arteries, most commonly of the lower extremities. Lower extremity PAD may be asymptomatic or manifest with intermittent claudication, critical limb ischemia (CLI), or acute limb ischemia (ALI), which is a surgical emergency that is described in a separate article. In the absence of acute ischemia, the first-line diagnostic test for PAD is the ankle-brachial index (ABI). Imaging, preferably via MR angiography, is indicated if revascularization is planned or if the diagnosis remains uncertain. Structured exercise therapy and modification of cardiovascular risk factors may improve intermittent claudication significantly; cilostazol, a vasodilator, may be considered for symptomatic relief. Revascularization is indicated in patients with limb ischemia and those with life-limiting claudication despite exercise therapy. Additionally, secondary prevention strategies for ASCVD should be initiated in all patients to minimize the risk of atherosclerotic cardiovascular disease.

Carotid artery stenosis and chronic mesenteric ischemia are less common types of peripheral arterial disease and are covered separately.

  • Prevalence: 8.5 million in the US
    • Prevalence increases with age, starting from the age of 40
    • US incidence rates are highest among African Americans, followed by Hispanics, who are at a slightly higher risk than non-hispanic whites.
  • Peak incidence: 60–80 years of age
  • Sex: = [1]

Peripheral arterial disease is equally common in women and men. [1]


Epidemiological data refers to the US, unless otherwise specified.

PAD usually coexists with coronary artery disease. Smoking is one of the most important risk factors for PAD!

Up to 20–50% of patients with PAD are asymptomatic.

Intermittent claudication

Rest pain

Rest pain occurs as disease progresses and indicates severe ischemia.

  • Typically occurs first in the toes and forefoot
  • Worsens with reclining (e.g., while sleeping)
  • Improves on hanging feet off the bed or on standing

Critical limb ischemia (CLI) [3]

  • Indicative of limb-threatening arterial occlusion
  • Characterized by the presence of any one of the following:

Examination findings

There are several classification systems for peripheral arterial disease, such as, the Rutherford classification, Global Limb Anatomic Staging System (GLASS), and the Trans-Atlantic Inter-Society Consensus (TASC). See “Overview of classification systems in peripheral artery disease” in the “Tips and Links” section below for details. [6]

Classification by clinical presentation [3][6]

Wound, Ischemia, and foot Infection (WIfI) classification [7][8]

  • Purpose
  • Description
    • The following factors are assigned values from 0 (normal) to 3 (severe abnormality):
      • Wound (W): depth and tissue involvement of existing ulcers
      • Ischemia (I): ankle systolic blood pressure and/or tissue oxygenation
      • Foot Infection (fI): local and systemic signs of infection
    • The benefit of revascularization and the risk of amputation can be estimated based on the three derived values.

Fontaine classification [6]

Approach [3][7]

ALI is an imminently limb-threatening emergency and treatment should not be delayed to investigate the underlying etiology. [10]

Ankle-brachial index (ABI) [7][10]

ABI is the ratio of systolic ankle blood pressure to systolic brachial blood pressure.

Resting ABI

  • Indications
  • Technique
    • Ask the patient to rest in the supine position for approx. 10 minutes.
    • Place the blood pressure cuffs on the ankles and the arms.
    • Locate the pulse using the Doppler.
    • Inflate the cuff until the pulse is no longer audible on the Doppler device, and then inflate the cuff by a further 20 mm Hg.
    • Deflate the cuff slowly, and note the pressure at which the pulse is audible again.
    • Calculate the ABI for each leg: Divide the highest ankle pressure by the highest brachial pressure.

Ankle–brachial index interpretation in patients with suspected PAD [7][10]
Resting ABI Interpretation Next steps
> 1.4
1–1.4 [14]
  • Normal
  • Borderline
≤ 0.9
  • Abnormal

A low ABI (≤ 0.9) and high ABI (> 1.4) are associated with an increased risk of all-cause and cardiovascular mortality! [15]

Exercise ABI [16]

  • Description: ABI testing following extended exercise of the lower extremity
  • Indication: suspicion of PAD in a patient with a normal or borderline ABI
  • Findings: Either of the following are consistent with PAD.
    • Post-exercise decrease in ABI by > 20%
    • Post-exercise decrease in ankle systolic blood pressure by > 30 mm Hg

Toe-brachial index [10][12][17]

  • Definition: the ratio of the systolic blood pressure of the first toe to the systolic brachial blood pressure
  • Indications
    • Suspicion of PAD in a patient with a normal or elevated ABI (i.e., ABI > 1.4)
    • Lower extremity wound suggestive of CLI
  • Findings: Toe-brachial index ≤ 0.70 is consistent with PAD.

Measures of tissue perfusion [13]

  • Examples: transcutaneous oximetry, fluorescent imaging of indocyanine green dye, skin perfusion pressure
  • Indication: nonhealing wounds or tissue loss suggestive of CLI

Imaging [7][18][19]

Differential diagnosis of claudication
Patient characteristics Clinical features
Arterial occlusion or narrowing Vasculitides Takayasu arteritis
  • Asian females
  • 15–45 years
Thromboangiitis obliterans
  • 20–40 years
  • More common in males before the age of 45 years [20]
  • Significant history of cigarette smoking
(Lower-extremity) fibromuscular dysplasia
  • Middle-aged women
Popliteal aneurysm
  • Chronic lower limb ischemia may manifest like PAD
  • ALI (6 Ps)
  • Blue toe syndrome: small vessel occlusion caused by embolus
Arterial embolism
  • Sudden onset of symptoms
  • 6 Ps
Popliteal entrapment syndrome
  • Most commonly affects young men < 30 years
Cystic adventitial disease
  • Generally affects men between 30–50 years
  • Foot pulses may be present during rest and absent following exercise [21]
Mimics of arterial occlusion Deep vein thrombosis
  • Swelling
  • Warmth
  • Erythema
  • Progressive tenderness
  • Dull pain: worsened by walking, improved by resting
Spinal stenosis
  • Middle-aged to older patients
Diabetic neuropathy
  • Middle-aged to older patients
  • High BMI
  • Progressive symmetrical loss of or abnormal sensation in the distal lower extremities (glove and stocking sensation)
  • Normal ABI
  • Neuropathic diabetic foot: warm, dry skin, palpable foot pulses

The differential diagnoses listed here are not exhaustive.

Overview [7][10][22]

Risk modification [3][25]

As patients with PAD are at an increased risk of atherosclerotic cardiovascular disease (ASCVD) events such as MI or stroke, secondary prevention strategies for ASCVD should be initiated in all patients.

Intensive treatment of atherosclerotic disease and its risk factors improves outcomes in PAD and prevents ischemic events in other arterial beds, including the coronary arteries. [10]

Structured exercise therapy [3][22]

Exercise therapy may improve claudication symptoms but not the ABI, as it primarily promotes collateral blood circulation. [30]

Vasodilators [3][7][28]

Cilostazol improves claudication symptoms and walking distance but has not been shown to decrease major cardiovascular events. [3][32]

Pentoxifylline is not effective for treating claudication. [3]

Revascularization [7][10][23]

The primary goal of revascularization is to improve blood flow in at least one artery to the foot to prevent pain and tissue loss.

  • Indications
    • CLI, if the limb is viable
    • Lifestyle-limiting claudication despite optimal medical therapy and exercise
  • Modalities [10][33][34]
    • Endovascular or surgical revascularization
    • The choice of procedure depends on the location and morphology of the arterial disease and the patient's comorbidities.
Revascularization procedures for peripheral arterial disease
Endovascular revascularization Surgical revascularization
  • Peripheral artery bypass surgery: Open surgical bypass of the vascular stenosis with an autologous vein or prosthetic material
  • Endarterectomy (may be combined with endovascular treatment)
Indications [10][33][34]
  • Consider in the following situations:
    • Short segment disease: stenosis < 10 cm or occlusion < 5 cm
    • Aortoiliac disease
    • High-risk patients [10][33][34]
  • Consider in low- and average-risk patients with any of the following: [10][33][34]
    • Extensive and complex disease: long segment lesions (> 10 cm); multifocal lesions
    • Lesions of the common femoral artery
    • Purely infrapopliteal disease
    • Chronic total occlusion
  • Unsuccessful endovascular revascularization [10][33][34]

Supportive care [3][7]

  • Foot care
    • All patients with PAD should be educated on self-foot examination and healthy foot care.
    • Any sign of foot infection in a patient with PAD should prompt referral to an interdisciplinary care team.
  • Analgesia
  • Wound management
    • Provide multidisciplinary wound care to all patients with tissue loss.
    • Consider adjunctive therapies (e.g., intermittent pneumatic compression) in patients unfit for revascularization. [3]

Amputation [7][10]

Apart from ALI, which is described in a separate article, the following complications can occur due to PAD.

Arterial ulcer

  • Definition: ulceration caused by impaired blood flow to the lower extremities
  • Clinical features
    • Punched-out ulcer with well-defined borders [35]
    • Usually involves the foot, particularly pressure points (e.g., lateral malleolus, tips of the toes)
    • Often causes severe pain
    • Infection of ulcerssepsis
  • Differential diagnosis: See “Differential diagnosis of leg ulcers.”

Dry gangrene

  • Definition: a type of gangrenous necrosis caused by ischemia that is characterized by coagulative necrosis on histopathologic examination
  • Clinical features
    • Areas with gray-black discoloration showing a clear demarcation between necrotic and viable tissue
    • Autoamputation is possible.
  • Diagnosis: based on clinical features
  • Management
  • Complications: wet gangrene

Wet gangrene

We list the most important complications. The selection is not exhaustive.

See “Prevention of atherosclerotic cardiovascular disease.”

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