Peripheral Artery Diseases

Mark A. Creager, MD
Harvard Medical School

Definition/Etiology
Epidemiology/Prognosis
Clinical Presentation
Best Tests
Best Therapy
Best References


Definition/Etiology

• Perpheral artery diseases (PAD) include disorders that reduce blood flow to the limb
• Atherosclerosis is the most common cause of limb artery obstruction
• 80% of stenoses are in femoropopliteal artery, 30% in aorta or iliac arteries, 40% in tibioperoneal artery
• Most patients have multiple stenoses
• Other causes of PAD
• Thrombus
• Embolism
• Vasculitis
• Adventitial cysts
• Fibromuscular dysplasia
• Arterial dissection
• Trauma
• Vasospasm

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Epidemiology/Prognosis

• Prevalence increases with age, to > 20% at > 75 yr of age
• Risk of death increases twofold to fourfold
• Risk factors
  • Cigarette smoking
  • Diabetes mellitus
  • Dyslipidemia
  • Hypertension
  • Metabolic syndrome
  • Chronic renal insufficiency
  • Hyperhomocysteinemia
  • Low vitamin D levels
  • Elevated C-reactive protein

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Clinical Presentation

• Intermittent claudication: discomfort, pain, fatigue, or heaviness felt in the affected extremity during walking and resolving with rest
• Rest pain, typically in the toes or foot, initially worse at night
• Symptoms may be absent

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Best Tests

Physical Examination

• Palpate for decreased or absent pulses
  • Femoral
  • Popliteal
  • Posterior tibial
  • Dorsalis pedis
• Patterns of pulse abnormality may indicate sites of stenosis
• Auscultate for bruits, which may indicate arterial stenosis
  • Abdomen
  • Pelvis
  • Inguinal areas
• Check for foot pallor
  • At rest
  • With leg elevation
  • After exercise of the calf muscles
• Signs of chronic limb ischemia
  • Subcutaneous atrophy
  • Hair loss
  • Coolness
  • Pallor
  • Cyanosis, dependent rubor, or both
  • Petechiae, fissures, ulceration, and gangrene with critical limb ischemia

Noninvasive Tests

• Ankle:Brachial Index (ABI)
  • Sensitive indicator of peripheral artery disease
  • ABI ≤ 0.90 is abnormal
  • The lower the ankle:brachial ratio, the higher the risk of a cardiovascular event
  • Low ABI relates to decreased leg function
• Segmental pressure measurements
  • Determines systolic pressure in segments of the thigh, calf, and ankle
  • Pressure gradients between contiguous cuffs inidicates location of stenosis
• Pulse volume recordings
  • Utilizes plethysmography to measure change in limb volume that occurs with each pulse
  • Distal to the site of an arterial stenosis, the amplitude of the pulse volume waveform is diminished (may be absent in severe ischemia)
• Doppler ultrasonography
  • Can identify vessels with stenotic lesions
  • When stenosis is present, this triphasic waveform is altered distal to the stenosis
    • Amplitude is decreased
    • Rate of rise is delayed
    • Reverse-flow component disappears
• Duplex ultrasound scanning
  • B-mode ultrasonography plus pulsed Doppler ultrasonography
  • B-mode scan identifies areas of intimal thickening, plaque formation, and calcification
  • Color Doppler imaging detects blood-flow abnormalities caused by arterial stenoses
  • Increase > twofold in systolic velocity indicates a hemodynamically significant stenosis
• Transcutaneous oximetry
  • Assess severity of skin ischemia
  • Normal transcutaneous oxygen tension of the resting foot is ~ 60 mm Hg; often < 40 mm Hg in patients with ischemia

Angiography

• MR and CT computed angiography can be used to evaluate the location and severity of peripheral atherosclerosis To help determine appropriateness of endovascular intervention
• Each may help to determine appropriateness of endovascular intervention
• MR angiography more widely used than CT but slower
• May not be feasible in obese patients or those with pacemakers or defibrillators
• Gadolineum may causenephrogenic systemic fibrosis in patients with renal insufficiency
• CT angiography
  • Requires iodinated contrast and radiation exposure
  • Contraindicated for patients with renal insufficiency or contrast allergy
• Conventional cathter-based contrast angiography is used when diagnosis is in doubt or before endovascular interventions or surgical reconstruction

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Best Therapy

Risk-Factor Modification

• Smoking cessation
• Aggressive lipid-lowering therapy to achieve LDL cholesterol < 100 mg/dl
• Antihypertensive agents to achieve normotensive range
• Excessive reduction of blood pressure (> 20 mm Hg) may aggravate symptoms
• Beta blockers may exacerbate critical limb ischemia but do not worsen intermittent claudication
• Aggressive treatment of diabetes mellitus reduces microvascular comlications, but may not reduce risk of myocardial infarction or death
• ACE inhibitors may reduce risk of adverse cardiovascular events in patients with atherosclerosis

Antiplatelet Therapy

• May reduce risk of acute peripheral arterial occlusion
• Reduces risk of adverse cardiac events
  • Clopidogrel may be more effective than aspirin for patients with peripheral artery disease
• Reduces cardiovascular mortality in patients with atherosclerosis

Hygiene and Physical Therapy

• Prevent skin ulceration and foot infection
  • Keep feet clean and moisturized
  • Inspect frequently and treat minor abrasions promptly
  • Avoid elastic hose
  • Shoes should be carefully fitted
  • For patients with critical limb ischemia, maintain limbs in a dependent position below heart level to increase perfusion pressure
  • Use cotton wicks between the toes and sheepskin beneath the heels
  • Warm environment reduces vasoconstriction
  • Keep ulcerations and necrotic areas dry and covered
  • Drain infections
• Avoid local antibiotics
• Treat pain with analgesics
• Supervised exercise training
  • Improves walking capacity
  • Treadmill exercise for ~ 1 hr three times a week for at least 3 mo
  • Encourage walking outside the supervised program

Pharmacotherapy of Claudication and Critical Limb Ischemia

• Drug therapy has generally not successful in improving symptoms of claudication or reducing complications of critical limb ischemia
• Pentoxifylline, controlled release: improved exercise capacity in some but not all clinical trials
  • Reported to improve RBC flexibility and decrease blood viscosity
  • Dose: 400 mg t.i.d.
• Cilostazol: may increase distance walked before onset of claudication and also maximal walking distance
  • Vasodilator and antiplatelet properties, but mechanism of action in PAD is not known
  • Dose: 50–100 mg b.i.d.

Revascularization

• Indicated for patients with disabling claudication, ischemic rest pain, or impending limb loss
• Catheter-based revascularization
  • Percutaneous transluminal angioplasty (PTA)/stenting of iliac arteries
    • Initial success rate 90%
    • Patency rates after 4–5 yr ~ 60%–80%, higher with stents
  • PTA/stenting of femoral and popliteal arteries
    • Initial success rate < 90%
    • Patency rates: 1 yr, 60%; 3 yr, 50%; 5 yr, 45%
  • PTA of tibial and peroneal arteries
    • Poorer outcome than PTA of more proximal lesions
    • Limb salvage rates of 1–2 yr: 50%–75%
• Surgical reconstruction
  • Aortobifemoral bypass with a bifurcated Dacron or polytetrafluoroethylene prosthetic graft
    • Standard treatment for aortoiliac disease
    • Operative mortality 1%–3% at centers with expertise in this technique
    • Long-term patency and relief of symptoms > 80% over 10 yr
  • Intra-abdominal aortoiliac reconstructive surgery not feasible in patients whose comorbid conditions pose excessive surgical risk
  • Axillobifemoral bypass can circumvent the abdominal aorta and achieve revascularization of both legs
  • Femorofemoral bypass for unilateral iliac artery obstruction
    • Can be performed with regional anesthesia
  • Infrainguinal bypass
    • Femoropopliteal and femoral-tibioperoneal reconstruction
    • Femoropopliteal reconstruction most successful when the distal anastomosis is constructed proximal to the knee
    • 5-year patency rate ~ 75%–80% (higher in claudicants than in patients with critical limb ischemia; lower for synthetic grafts)
    • Operative mortality 1%–3%
  • Antiplatelet agents should be administered to maintain graft patency after bypass grafts

Amputation

• Alternative for advanced limb ischemia when revascularization is not possible or has failed
• Selection of amputation level requires assessment of perfusion
• Overall prognosis after major leg amputation is poor, usually because of coexisting coronary and cerebrovascular disease

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Best References

Norgren L, et al: J Vasc Surg 45 Suppl S:S5, 2007 [PMID 17223489]

Hirsch AT, et al: J Am Coll Cardiol 47:1239, 2006 [PMID 16545667]

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The author has received grant or research support from Sanofi-Aventis and Merck; he has served as a consultant for Biomarin, Genzyme, Sanofi-Aventis, and Sigma Tau.

December 2008