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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Intermittent claudication: reproducible leg pain with walking, relieved by rest within minutes
- Diagnosis: ankle-brachial index (ABI) — <=0.9 is diagnostic; <0.4 = severe/critical
- Treat all PAD patients like CAD: aspirin or clopidogrel, high-intensity statin, BP control, smoking cessation
- Claudication treatment: supervised exercise therapy (first-line) + cilostazol 100 mg BID
- Critical limb ischemia (rest pain, tissue loss, gangrene): urgent vascular referral for revascularization (endovascular or surgical bypass)
Overview
Peripheral artery disease refers to atherosclerotic disease of the non-coronary and non-cerebral arteries, most commonly the lower extremities. The pathophysiology is identical to coronary atherosclerosis, and PAD is a strong marker of systemic atherosclerotic burden. Patients with PAD have a 2-3x increased risk of MI and stroke. The Fontaine classification stages disease severity: I = asymptomatic, II = intermittent claudication, III = rest pain, IV = tissue loss/gangrene. Stages III-IV constitute critical limb ischemia (CLI), which threatens limb viability.
Epidemiology
PAD affects ~8.5 million Americans, prevalence increasing sharply with age (~12-20% in those >65). The strongest modifiable risk factor is smoking (4x risk). Other risk factors: diabetes (2-4x risk), hypertension, hyperlipidemia, CKD, and family history. Up to 50% of patients with PAD are asymptomatic. African Americans have 2x the prevalence of whites. PAD is underdiagnosed — only ~25% receive appropriate treatment.
Clinical Features
Symptoms
Intermittent claudication: cramping, aching, or fatigue in calf (most common), thigh, or buttock with walking, relieved by rest within 2-5 minutes. Reproducible at same walking distance
Rest pain: severe ischemic pain in forefoot/toes at rest, worse at night, improved by dangling foot off bed (gravity-assisted perfusion)
Non-healing wounds or ulcers (usually distal: toes, heel, pressure points)
Erectile dysfunction (iliac artery disease — Leriche syndrome: buttock claudication + ED + absent femoral pulses)
Many patients (~50%) are asymptomatic or have atypical symptoms
Signs
Diminished or absent pedal pulses (dorsalis pedis, posterior tibial)
Femoral, popliteal, or pedal bruits
Cool, pale, or mottled skin; shiny atrophic skin; hair loss over dorsum of foot/toes
Delayed capillary refill (>3 seconds)
Arterial ulcers: punched-out, painful, distal (toes, heel), pale base — distinguish from venous ulcers (medial malleolus, irregular, shallow, hyperpigmented surrounding skin)
Gangrene (dry or wet) in critical limb ischemia
Buerger test (pallor on elevation, rubor on dependency)
Investigations
First-line
Ankle-brachial index (ABI)Ratio of ankle SBP to brachial SBP. Normal: 1.0-1.4. <=0.90 = PAD (sens ~95%, spec ~99%). 0.41-0.90 = mild-moderate. <=0.40 = severe. >1.40 = non-compressible calcified arteries (diabetes, CKD) — use toe-brachial index (TBI) instead (<=0.7 = abnormal)
Basic labsLipid panel, HbA1c, BMP (eGFR), CBC (anemia worsens claudication)
Second-line
Exercise ABIIf resting ABI is normal (0.91-1.40) but clinical suspicion is high: treadmill exercise then recheck ABI. Post-exercise ABI drop >=20% is diagnostic
Duplex ultrasoundNon-invasive anatomical assessment: localize stenosis, assess severity. First-line imaging for symptomatic PAD
CTA or MRA of lower extremitiesPre-revascularization planning: maps vascular anatomy, identifies stenosis/occlusion, assesses run-off vessels
Specialist
Invasive angiographyGold standard but reserved for when revascularization is planned (can intervene at the same time)
1
All PAD patients (cardiovascular risk reduction)
- Antiplatelet: aspirin 81 mg OR clopidogrel 75 mg (CAPRIE trial: clopidogrel marginally superior to aspirin in PAD)
- High-intensity statin: atorvastatin 40-80 mg or rosuvastatin 20-40 mg
- BP control <130/80; ACEi/ARB preferred (HOPE trial: ramipril reduced CV events in PAD)
- Diabetes control: SGLT2i or GLP-1 RA preferred for CV benefit
- Smoking cessation (single most important modifiable risk factor — improves claudication and reduces amputation risk)
2
Claudication management
- Supervised exercise therapy: first-line, 30-45 min sessions 3x/week for >=12 weeks — improves walking distance 50-200%
- Cilostazol 100 mg BID: phosphodiesterase-3 inhibitor, improves claudication symptoms + walking distance. CONTRAINDICATED in HF
- Avoid pentoxifylline — minimal efficacy, not recommended per guidelines
- Low-dose rivaroxaban 2.5 mg BID + aspirin 81 mg: COMPASS trial showed reduced MACE + limb events in stable PAD (but increased bleeding)
3
Critical limb ischemia (CLI)
- Urgent vascular surgery referral
- Revascularization: endovascular (angioplasty +/- stent) or surgical bypass — depends on anatomy, lesion pattern (TASC classification)
- Wound care for tissue loss, infection management
- Amputation if non-reconstructable disease or extensive tissue necrosis
4
Acute limb ischemia (6 P's)
- Emergency: Pain, Pallor, Pulselessness, Poikilothermia, Paresthesia, Paralysis
- IV heparin immediately (prevent thrombus propagation)
- Emergent revascularization: catheter-directed thrombolysis (if viable limb, <14 days), surgical thromboembolectomy (Fogarty catheter), or bypass
Complications
- Critical limb ischemia: Rest pain, non-healing ulcers, gangrene — 25% amputation rate at 1 year
- Acute limb ischemia: Embolic or thrombotic occlusion — limb-threatening emergency
- Cardiovascular events: PAD patients have 2-3x risk of MI, stroke — CV events are the leading cause of death in PAD
- Amputation: ~5% of claudicants progress to amputation over 5 years; much higher in CLI
USMLE Step 2 CK Exam Tips
- 1ABI <=0.9 = diagnostic of PAD. ABI >1.4 = non-compressible (diabetes/CKD) — use TBI instead
- 2Supervised exercise therapy is FIRST-LINE for claudication — always recommend before drugs or revascularization
- 3Cilostazol is the only drug proven to improve claudication. It is CONTRAINDICATED in heart failure
- 4Leriche syndrome: bilateral buttock/thigh claudication + ED + absent femoral pulses = aortoiliac occlusive disease
- 5Arterial ulcers: painful, distal, punched-out, pale base. Venous ulcers: medial malleolus, shallow, irregular, periulcer hyperpigmentation
- 6Acute limb ischemia 6 P's: emergent heparin + revascularization — time is tissue
- 7PAD is a coronary risk equivalent: treat with the same intensity as known CAD (statin, antiplatelet, BP control)
- 8Rest pain improved by hanging foot off bed (gravity) = critical limb ischemia — refer vascular surgery urgently
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