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Peripheral Arterial Disease (PAD)

BASICS

  • Definition: Atherosclerotic occlusive disease of the peripheral arteries, mainly lower extremities.
  • Significance: 3rd leading atherosclerotic vascular disease after CAD and stroke.
  • Diagnosis: Resting ankle-brachial index (ABI) <0.90 is diagnostic.

EPIDEMIOLOGY

  • Risk Groups: ≥65 yrs, 50–64 yrs with risk factors (DM, HLD, HTN, smoking, family history), <50 yrs with DM + 1 other risk factor, and anyone with known atherosclerotic disease elsewhere.
  • Prevalence: ~6% of U.S. adults ≥40 yrs have ABI <0.9. ~238 million globally. >50% are asymptomatic.

ETIOLOGY & PATHOPHYSIOLOGY

  • Most Common Cause: Chronic atherosclerosis.
  • Others: Phlebitis, trauma, autoimmune/vasculitic diseases.
  • Pathophys: Arterial narrowing → ↓ oxygen delivery during exertion → claudication; resting reperfusion → inflammation, oxidative stress, endothelial & mitochondrial injury.
  • Genetics: Heritable risk factors; ongoing GWAS for PAD-specific SNPs.

RISK FACTORS

  • Older age
  • Atherosclerosis (any vascular bed)
  • Smoking (current/past)
  • DM, HTN, HLD, CKD
  • Heritable: chylomicronemia, hypercholesterolemia, hyperhomocysteinemia, pseudoxanthoma elasticum

PREVENTION

  • Regular aerobic exercise
  • Smoking cessation
  • BP & diabetes control
  • Statin therapy for secondary prevention

ASSOCIATED CONDITIONS

  • MI, TIA, CVA, other forms of atherosclerosis

DIAGNOSIS

History

  • 20–40% asymptomatic
  • 10–35% with intermittent claudication (IC): cramping, aching, or tired legs on walking, relieved by rest
  • 1–2% develop critical limb ischemia (CLI): nonhealing ulcers, rest pain, gangrene, acute limb ischemia
  • Skin discoloration, erectile dysfunction (Leriche syndrome), mesenteric ischemia (severe cases)

Physical Exam

  • Pallor with elevation, dependent rubor
  • Atrophic skin, hair loss, brittle nails
  • Reduced/absent distal pulses, cool extremities
  • Non-healing ulcers, gangrene (severe)
  • Acute ischemia: pulselessness, pallor, paresthesia, skin discoloration

Differential Diagnosis

  • DVT, aneurysm/dissection, Buerger disease, embolism, neuropathy, spinal stenosis (pseudoclaudication), popliteal entrapment

Diagnostic Tests

  • Screening: ABI for symptomatic patients; consider in high-risk asymptomatics
  • Initial: Fasting lipid panel, metabolic profile, exercise treadmill ABI (if normal ABI but symptoms)
  • Imaging (if revascularization considered): Duplex US, MRA, CTA; invasive angiography for CLI
  • ABI:
  • <0.9: PAD
  • <0.4: Severe PAD/CLI
  • 0.91–0.99: Borderline (consider further testing)
  • 1.0–1.4: Normal

  • 1.4: Noncompressible arteries (often DM)

TREATMENT

General Measures

  • Supervised exercise program: walk 30–45 min, 3x/week for 12 weeks
  • Cardiovascular risk factor modification (statins, BP control, DM, smoking cessation)
  • High-intensity statin for all PAD (LDL <100 goal)
  • ACE-I or ARB for CV event risk reduction
  • Behavioral + pharmacologic smoking cessation

Medication

First Line

  • Antiplatelet monotherapy: Aspirin 75–325 mg OR clopidogrel 75 mg (symptomatic PAD)
  • Reasonable in asymptomatics with ABI <0.9
  • Statins: Indicated for all with PAD
  • Cilostazol: 100 mg BID for claudication (improves walking distance)
  • DAPT (aspirin + clopidogrel): Only after endovascular intervention
  • Aspirin + low-dose rivaroxaban: In selected high-risk cases (balance bleeding risk)

Second Line

  • Pentoxifylline: Less evidence; rarely used
  • Vorapaxar: Emerging, not routine

Surgery/Procedures

  • Indication: Failed conservative therapy, lifestyle-limiting claudication, favorable risk-benefit
  • Percutaneous (endovascular): Angioplasty, possible stenting (best for aortoiliac; reasonable for femoropopliteal)
  • Surgical: Bypass graft for severe stenosis/occlusion
  • CLI: Urgent revascularization

COMPLEMENTARY & ALTERNATIVE MEDICINE

  • Not recommended: chelation, B vitamins, most supplements
  • Insufficient evidence: Ginkgo, L-arginine, carnitine, omega-3s, vitamin E

ONGOING CARE & FOLLOW-UP

  • Assess: Risk factor control, exercise compliance, symptoms, therapy effectiveness
  • After intervention: Regular resting/exercise ABIs

DIET

  • Heart-healthy/Mediterranean: Vegetables, fruits, nuts, healthy fats, protein

PROGNOSIS

  • 15–20%: Worsening claudication
  • 5–10%: Need for intervention
  • 2–5%: Amputation (esp. smokers, diabetics)
  • At 5 years: 20% nonfatal CV event, 15–20% die (CV disease most common)

ICD-10

  • I73.9 Peripheral vascular disease, unspecified
  • I70.209 Unspecified atherosclerosis, native arteries, unspecified extremity
  • I70.219 Atherosclerosis w/ intermittent claudication, unspecified extremity

CLINICAL PEARLS

  • ABI <0.9 = PAD; <0.4 = severe/CLI.
  • Most PAD patients are asymptomatic.
  • Cornerstones: Antiplatelet, statin, risk-factor management, supervised exercise, cilostazol.
  • Refer for vascular surgery if conservative therapy fails or if CLI develops.
  • No strong evidence for routine screening in asymptomatic adults.