Peripheral arterial disease includes a range of vascular syndromes caused by atherosclerosis and thromboembolic pathophysiological processes that alter the normal structure and function of the aorta, its visceral arterial branches and the arteries of the lower extremity.
Individuals at risk for lower extremity peripheral arterial disease should undergo review of vascular symptoms and comprehensive vascular examination to assess walking impairment, claudication, ischemic rest pain and/or the presence of nonhealing wounds.
Patients with peripheral arterial disease may be symptomatic or asymptomatic. Symptoms may range from claudication presenting as exertional leg pain to critical limb ischemia presenting as rest pain, ulceration or gangrene.


  • Peripheral arterial disease (PAD) includes a range of vascular syndromes caused by atherosclerosis and thrombolic pathophysiological processes that alter the normal structure and function of the aorta, its visceral arterial branches and the arteries of the lower extremity

Risk Factors

Individuals at Risk for Lower Extremity Peripheral Arterial Disease

  • Age <50 years old with diabetes mellitus (DM) and one of the following atherosclerotic risk factors:
    • Smoking
    • Dyslipidemia
    • Hypertension
    • Hyperhomocysteinemia
  • Age 50-64 years old with atherosclerotic risk factors or family history of PAD
  • Age ≥65 years old
  • Abnormal lower extremity pulse examination
  • Leg symptoms with exertion or ischemic pain at rest
  • Nonhealing wounds
  • Known atherosclerotic coronary, carotid, subclavian, mesenteric artery or renal artery disease
  • Previous claudication or arterial interventions
  • Chronic renal insufficiency
  • Increased homocysteine levels
  • Use of hormone replacement therapy and combined oral contraceptives may also increase risk for PAD

Signs and Symptoms

  • Patients with peripheral arterial disease (PAD) may be asymptomatic or symptomatic
    • Symptoms may range from claudication presenting as exertional leg pain to critical limb ischemia presenting as rest pain, ulceration, or gangrene

Asymptomatic or Atypical Leg Pain

  • Majority of individuals with lower extremity PAD do not experience recognizable limb ischemic symptoms or classic claudication symptoms but may have measurable limb dysfunction, decreased functional status, and increased cardiovascular ischemic risk
  • Individuals with PAD and no claudication may have subtle impairments of lower extremity dysfunction even after adjustments for age, sex, race, cigarette smoking and other comorbidities eg:
    • Poorer standing balance score
    • Slower time to rise from a seated position
    • Slower walking velocity
    • Shorter distance walked per week
  • Patients with asymptomatic lower extremity PAD have risk factor profiles comparable to those with symptomatic lower extremity PAD
  • Many PAD patients have leg symptoms that are not relieved promptly with rest (atypical leg pain) due to comorbid diseases
  • May also have other causes of leg pain (eg lumbar disk disease, spinal stenosis, sciatica, or radiculopathy), muscle strain, neuropathy, or compartment syndrome


  • Intermittent claudication (IC) is the most common symptom in patients with lower extremity PAD
  • Presents as fatigue, discomfort, cramping or pain that occurs in specific limb muscle groups due to ischemia induced during exertion
  • Many patients with PAD present with typical claudication
  • Sufficient blood flow is present to prevent ischemic symptoms at rest but impaired when increased metabolic demand of exercising muscles are not met
    • Typical claudication: Pain in one or both legs that occurs with walking and usually affects the calves
    • The pain does not go away with continued walking but subsides when at rest (within 10 minutes)
    • The location of pain and amount of exercise needed to create it suggests the level and extent of PAD
      • Iliac arteries: Hip, buttock, thigh, or calf pain
      • Femoral and popliteal arteries: Calf pain
      • Tibial arteries: Calf pain, foot pain or numbness
  • Diagnosis can be based mainly on history of IC but should be confirmed and localized with physical examination and ankle brachial pressure index (ABI)
    • If ABI is ≥1.40, confirm with a toe-brachial index
    • Risk factor assessment should also be undertaken
  • Rule out Takayasu’s Arteritis (Pulseless Disease), an inflammatory disorder affecting blood vessels, which may present with upper or lower extremity claudication, upper extremity deficit or unequal BP measurements of upper extremity

Critical Limb Ischemia (CLI)

  • Characterized as limb pain that occurs at rest or impending limb loss due to severe compromised blood flow to the affected extremity
  • Presents as limb pain at rest with or without trophic skin changes or tissue loss
    • Discomfort is often worse when the patient is supine and may lessen when the limb is maintained in the dependent position
    • Unlike claudication, perfusion during rest is inadequate to sustain viability in the distal tissue beds
  • Chronic ischemic rest pain, ulcers, or gangrene due to arterial occlusive disease that if left untreated may lead to major limb amputation within 6 months
  • Other signs of chronic ischemia:
    • Dependent rubor
    • Early pallor on elevation of the extremity
    • Reduced capillary refill

Acute Limb Ischemia

  • Hallmark clinical symptoms
    • Pain (may also be absent or diminished due to neurosensory loss)
    • Paralysis
    • Paresthesias
    • Pulselessness
    • Pallor
    • Polar (cold extremity)
  • A form of CLI that arises when a rapid or sudden decrease in limb perfusion threatens tissue viability
  • Sudden, severe, limb-threatening ischemia is more likely due to arterial embolism than arterial thrombosis
  • Pain may be as intense as the rest pain of severe CLI but is less often localized to the forefoot, often extends above the ankle, and is less influenced by positional changes
  • May be the first symptom of arterial disease in a previously asymptomatic patient
  • Persistent pain, sensory loss, and toe muscle weakness identify the patient with viable or threatened limb loss
    • Viable limb has no sensory loss or muscle weakness; Doppler arterial and venous signals audible
    • Marginal threatened limb is salvageable if treated immediately, has minimal or no sensory loss and without muscle weakness; Doppler arterial signal often inaudible, venous audible
    • Immediate threatened limb is salvageable with immediate revascularization, sensory loss is more than toes and associated with rest pain, mild to moderate muscle weakness; Doppler arterial signal usually inaudible, venous audible
    • Irreversible if with major loss of tissue or inevitable permanent nerve damage, profound sensory loss and muscle weakness; Doppler arterial and venous signals inaudible
  • Muscle rigor, tenderness, and pain on passive movement are associated with advanced ischemia predictive of tissue loss
  • May also occur as an acute event that causes symptomatic deterioration in a patient with known lower extremity PAD and intermittent claudication
  • Determine the cause of embolization and/or thrombosis in the patient’s history
  • Clinical diagnosis of arterial embolism:
    • Sudden onset or worsening of symptoms
    • Known embolic source (eg atrial fibrillation, severe dilated cardiomyopathy, left ventricular aneurysm, atheromatous plaque in the aorta or proximal limb arteries, or mural thrombus in the wall of an aortic or arterial aneurysm)
    • Absence of antecedent claudication or other manifestations of obstructive arterial disease
    • Normal arterial pulses and Doppler systolic blood pressures (SBP) in the contralateral limb
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