Lower Extremity Peripheral Arterial Disease (PAD)

Resident Editor: Arvind Nishtala, MD

Faculty Editor: Atif Qasim, MD, MSCE

Background

• Disease that affects the lower extremity vessels by causing stenosis, occlusion, or aneurysmal dilation
• Most common cause is atherosclerosis. Can also be caused by vasculitis, vasculopathies, and fibromuscular dysplasia
• 2 broad subtypes: proximal disease (aortoiliac and femoropopliteal vessels) and distal disease (inferopopliteal vessels)
• Affects ~10% of adults over age 55, over 8.5 million adults in the US with PAD
• Risk factors – think about it the same way as CAD!
  • prior CAD or CVD, smoking, diabetes mellitus, HTN, HLD, CKD, age>70, hyperhomocysteinemia, men & post-menopausal women
• Prognosis – associated with several co-morbid conditions including CAD and CVD, higher all-cause and cardiovascular mortality in patients with PAD, ABI <0.9 associated with twice the mortality of ABI 1.11-1.40, higher risk of adverse limb outcomes
• USPSTF recommends against screening!
• Who to work up – evaluate patients at increased risk of PAD
  • Age ³ 65 
  • Age 50-64 with risk factors for atherosclerosis
  • Age <50 with DM and ³1 risk factor for atherosclerosis
  • Individuals with known atherosclerosis in another vascular bed
  • Symptoms/signs suggesting of PAD (intermittent claudication, non-healing ulcers)

Signs and Symptoms

• Patients can be asymptomatic (most common), have typical claudication symptoms, or have atypical leg symptoms (i.e. presentation is variable)
• Claudication: Exertional and reproducible cramp-like calf, thigh, or buttock pain relieved with rest (present in 10-35%)
• Atypical leg symptoms include leg fatigue, difficulty walking, leg pain not typical of claudication
• Some can present with advanced disease, including critical limb ischemia: night/rest pain, non-healing ulcers or gangrene, skin color changes
• Acute arterial occlusion is a different disease process that we will not discuss here. For that, think about the 6 P’s: pain, pallor, pulselessness, paralysis, parasthesias, poikilothermia!

Differential Diagnosis

• Vascular: Acute arterial embolism, DVT or venous outflow obstruction, chronic compartment syndrome
• Neurological: Compression neuropathy including spinal stenosis or herniated disc, peripheral neuropathy, restless leg syndrome
• Musculoskeletal: Arthritis, muscle/tendon strain, Baker’s cyst, stress fracture

Evaluation

• History – 
  • ask about typical/atypical claudication symptoms
  • location of pain can suggest level of occlusion
    • buttock/hip: aortoiliac
    • thigh: iliofemoral
    • upper calf: superficial femoral
    • lower calf: popliteal
    • foot: tibial or peroneal
  • ask about CAD risk factors (including family history and smoking history)
• Physical Exam (in addition to cardiac exam) –
  • Check for bruits (abdominal, femoral) and pulses (DP, PT, popliteal, femoral)
  • Assess skin for temperature (cool), appearance (shiny, hairless), color (dependent rubor, pallor with leg elevation), and for non-healing ulcers or gangrene
• Labs – CBC, HbA1c, lipid panel, creatinine, urinalysis (glucosuria, proteinuria)
• Non-invasive Arterial Testing – 
• Start with a resting ankle-brachial index (ABI)!
• Ankle-brachial index (ABI)*: ratio of ankle systolic BP (the higher of dorsalis pedis and posterior tibial) to the higher brachial systolic BP
  • ABI £ 0.90            Low (indicating diagnosis of PAD)
  • ABI 0.91 – 0.99    Borderline
  • ABI 1.00-1.40       Normal
  • ABI > 1.40            Non-compressible(stiff, calcified vessels)
• If ABI >1.40, check a toe-brachial index (TBI)
• If ABI borderline OR normal but high clinical suspicion, try checking after exercise (toe raises or walking on treadmill)
• Anatomic imaging assessment (Duplex ultrasound, CT angiography, MR angiography, or invasive angiography) is never first-line for stable PAD, should only be used when considering revascularization in symptomatic patients

Treatment

• Goals of treatment are to 1) reduce risk of adverse cardiovascular outcomes, 2) improve functional capacity, and 3) preserve limb viability
• Risk factor modification –
  • Smoking cessation – see “Smoking Cessation” chapter for recommendations (ACC/AHA Class I, Level A)
  • Treatment with a high-intensity statin (ACC/AHA Class I, Level A)
  • Anti-hypertensive therapy (ACC/AHA Class I, Level A) although target BP not established; consider ACE-inhibitors (ACC/AHA class IIa, Level A)
  • Treatment of diabetes mellitus and counsel patients on proper foot care and foot inspection (ACC/AHA Class I, Level C-EO)
• Improving functional capacity –  
  • Walking through the pain is not harmful – it allows muscles to adapt to anaerobic metabolism with repeated ischemia and increases available mitochondria
  • Supervised exercise therapy has the most evidence (ACC/AHA Class I, Level A). More recently, there is good evidence for structured community- or home-based exercise programs (ACC/AHA Class IIa, Level A). Providing general recommendations to walk more is NOT efficacious! 
  • Specific instructions: walk at least 3x/week for 30-45 minutes per session until near maximal claudication. Stop to rest until the pain subsides, then resume walking. May not notice benefits for 1-2 months. Should follow this program for at least 6 months.
• Medications –
  • Antiplatelet agents – the evidence is in favor of reducing cardiovascular outcomes, not claudication symptoms. ASA (75-325mg) or Clopidogrel (75mg). Not much evidence for DAPT, but can consider in symptomatic patients with low bleeding risk. 
  • Vorapaxar (PAR-1 antagonist) – approved for PAD in pts without h/o stroke, reduced risk of acute limb ischemia or peripheral revascularization events
  • No role for oral anticoagulation
  • Statins – improve pain-free walking time.
  • Cilostazol – PDE-3 inhibitor. May improve maximum walking distance/subjective symptoms. Contraindicatedin CHF (increased mortality).
• Surgical intervention in severe cases (see below)

When to refer

• Non-urgent referral to Vascular Surgery for patients with abnormal ABI (<0.9 or >1.4)
  • To predict location/severity by assessing segmental arterial pressures and pulse-volume recording
  • For consideration of additional imaging.
• Urgent referral to Vascular Surgery for revascularization if limiting symptoms despite medical and exercise therapy OR if critical limb ischemia

References

Solomon CG, Kullo IJ, Rooke TW. Peripheral Artery Disease. N Engl J Med. 2016;374(9):861-871.

Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FGR, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RAG, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;000:000-000.