peripheral arterial disease; peripheral artery atherosclerosis (PAD)

Introduction

Also see

• internal carotid artery disease
• intermittent claudication

Etiology

• risk factors the same as for coronary artery disease
• in middle age & older men, major risk factors include:
  • smoking
  • hypertension
    • each 20 mm Hg increase in systolic BP & each 10 mm Hg increase in diastolic BP is associated with 63% & 35% higher risks for PAD
  • hypercholesterolemia
  • diabetes mellitus type 2
• less common causes include
  • adventitial cystic disease
  • arterial dissection
  • endofibrosis
  • fibromuscular dysplasia
  • popliteal artery aneurysm
  • popliteal entrapment syndrome
  • radiation arteritis
  • thromboembolism
  • vasculitis

Epidemiology

• 29% of patients who smoke or have diabetes (40% of these same patients had coronary artery disease)
• 9% of patients with PVD have symptomatic claudication
• 20% of patients > 70

Pathology

• most commonly involves the lower extremities
• part of a larger process involving atherosclerosis of the aorta & its branches
• patients appear to develop a metabolic myopathy & axonal polyneuropathy related to chronic lower extremity ischemia resulting in abnormal biomechanics prior to the onset of pain
• increased plasma levels of trimethylamine N-oxide increases mortality in patients with PAD

Genetics

• implicated genes
  • CHRNA3 (peripheral arterial occlusive disease type 2)

Clinical manifestations

• signs of asymptomatic disease
  • ankle to brachial index < 0.9 (lower extremity disease)
  • carotid bruit or diminished carotid pulse
  • femoral bruit
  • reduced exercise capacity
  • most patients are asymptomatic
• intermittent claudication is a sign of symptomatic disease
  • pain, paresthesias, pallor, paralysis, pulselessness
  • exertional leg pain that improves quickly (within 5 minutes) with rest (see intermittent claudication)
• abnormalities in torque & power at the hip, knee, & ankle immediately upon walking (before onset of pain)
• unequal brachial blood pressure
  • systolic blood pressure difference of >= 15 mm Hg between arms may be associated with PAD of subclavian artery
    • if occlusion occurs proximal to the origin of the vertebral artery, retrograde blood flow from the CNS to the arm results in subclavian steal syndrome
• abdominal pulse may be due to abdominal aortic aneurysm
• diminished peripheral pulses
• elevation pallor & dependent rubor
  • may be associated with mild dependent edema
• non-healing leg ulcers
• tendinous xanthoma

* also see carotid artery disease

Diagnostic procedures

• echocardiogram: embolic source of ischemia
• ankle/brachial index (ABI) of < 0.9 is diagnostic of PAD
  • ABI > 1.4 is uninterpretable, due to non-compressible arteries
    • obtain toe to brachial index
  • exercise ABI if resting ABI is equivocal
    • an ABI decrease of 20% after exercise suggests PAD
• bilateral brachial blood pressure for upper extremity PAD

* video

Radiology

• screening
  • ultrasound, ankle-brachial index
  • contrast-enhanced MRI best 95% sensitivity, 97% specificity
• CT angiography or MRI angiography
  • failure of medical therapy, including supervised exercise
  • identifies vascular pathology & aids in planning revascularization

* video

Complications

• acute limb ischemia
• chronic limb-threatening ischemia
• arterial ulcers*
  • often painful
  • frequently occur where collateral circulation is minimal
    • anterior lower leg, distal toes
• predictive of other comorbid cardiovascular disease
  • coronary artery disease
  • cerebrovascular disease
  • annual risk of cardiovascular event(s) is 5-7%*
  • 50% increase in risk of cardiovascular events*

* risk of myocardial infarction > arterial ulcers

Differential diagnosis

• lumbar spinal stenosis
• chronic exertional compartment syndrome
• also see intermittent claudication for distingushing features

Management

• acute arterial ischemia
  • start heparin
  • consult vascular surgery
• diet & life-style modification (see CAD)
  • exercise training & rehabilitation
    • structured, supervised exercise program most effective treatment
    • high-intensity walking therapy is the standard of care;
      • it is superior to low-intensity walking
    • a home-based exercise intervention consisting of a wearable activity monitor & telephone coaching, did not improve walking performance at 9-month follow-up
    • home-based, behavior-change program improved 6-minute walking distance by ~25 meters
  • smoking cessation
  • avoid second-hand smoke
  • fruits & vegetable consumption may lower risk
  • nut consumption may lower risk
• control blood pressure
  • target systolic BP of 135-145 mm Hg & diastolic BP of 60-90 mm Hg
• control diabetes mellitus
• pharmaceutical agents
  • treat dyslipidemia (see CAD)
    • high-intensity statin therapy
      • 40-80 mg atorvastatin QD or 20-40 mg rosuvastatin QD
    • 80 mg of atorvastatin may improve pain-free walking time (without effect on ankle to brachial index)
    • 40 mg simvastatin diminished risk of major vascular events in patients with peripheral arterial disease (5-6%)
    • target LDL < 70 mg/dL
    • statins reduce progression of arterial stiffness in Chinese as assessed by brachial-ankle pulse wave velocity
  • antiplatelet agents
    • monotherapy, no evidence to support dual anti-platelet therapy
    • recommended for all symptomatic patients
    • aspirin
      • of no benefit (statistically); uncertain benefit
      • preferred over clopidogrel
      • reduces risk for myocardial infarction, stroke, & acute limb ischemia
    • dipyridamole/aspirin (Aggrenox)
    • clopidogrel (Plavix) unless patient is taking aspirin
    • ticagrelor (Brilinta) no better than clopidogrel
    • no benefit of added warfarin; potential harm
    • rivaroxaban 2.5 mg BID + aspirin 100 mg/day decreases cardiovascular events (RR=0.72) at the cost of increased risk of bleeding (mostly GI bleeding) (RR=1.6)
      • recommended by AHA/ACC if not at increased bleeding risk
    • anticoagulation is not indicated in the absence of symptomatic limb ischemia
  • ACE inhibitors
    • reduce risk of myocardial infarction & stroke in patients with peripheral arterial disease
    • improve walking distance in patients with peripheral arterial disease
  • cilostazol rather than pentoxifylline for intermittent claudication
    • contraindicated in heart failure (HFrEF)
    • achieves benefits in walking distance sustained at 24 weeks
    • preferred option prior to referral to vascular surgery
  • in patients with type 2 diabetes GLP-1 agonists & SGLT-2 inhibitors reduce major cardiovascular events
  • beta-blockers are not contraindicated
  • Ginkgo biloba may be of benefit
  • GM-CSF of no benefit

see secondary prevention in patients with cardiovascular disease

• angioplasty or surgery (lower extremity revascularization)
  • failure of medical therapy, including supervised exercise & cilostazol
  • pain at rest
  • poorly healing ulcers
  • critical limb ischemia (urgent)
  • peripheral artery bypass
  • endovascular stenting for aortoiliac occlusion
    • conflicting data on mortality with use of paclitaxel-eluting stents
  • endarterectomy with passible surgical patch repair for common femoral artery occlusion
  • paclitaxel-coated angioplasty balloon catheter (Lutonix DCB) FDA-approved for superficial femoral artery & popliteal artery occlusion
    • apparent lack of benefit for women
  • 54-55% 3-year mortality in patients after endovascular revascularization
  • higher rates of adverse outomes with angioplasty, stenting, atherectomy ' within 6 months of diagnosis unless limb-threatening ischemia
• annual influenza vaccination
• screening for peripheral arterial disease (asymptomatic)
  • age >= 50 years & history of diabetes mellitus or smoking
  • age >= 65 years
  • evidence insufficient to support screening

Notes

• European Society of Cardiology guidelines

More general terms

• arterial occlusive disease
• peripheral vascular disease (PVD)

More specific terms

• atheroembolism; cholesterol embolism; aortic atheroembolism
• critical limb ischemia
• intermittent claudication; vascular claudication; Charcot's syndrome; myasthenia angiosclerotica

Additional terms

• ankle-brachial index (ABI) or ankle-arm index (AAI)
• arterial ulcer
• carotid artery disease
• coronary artery disease; coronary atherosclerosis (CAD)
• peripheral vascular system
• screening for peripheral arterial disease
• secondary prevention in patients with cardiovascular disease
• vertebrobasilar disease

Patient information

peripheral arterial disease patient information

Database

• OMIM: https://mirror.omim.org/entry/612052