Peripheral Vascular Disease

Atherosclerotic (>90% of cases)

• Systemic atherosclerosis: the same lipid-driven, inflammatory intimal process that produces CAD and carotid disease; lesions favor the superficial femoral artery at the adductor canal, the aortoiliac segment, and the infrapopliteal (tibial) vessels in diabetics and CKD patients

Non-atherosclerotic mechanisms examiners use to break the pattern

• Thromboembolic: cardiac emboli from atrial fibrillation, post-MI mural thrombus, endocarditis vegetations, or a proximal aortic/popliteal aneurysm — abrupt onset, no prior claudication, normal contralateral pulses
• Inflammatory (vasculitis): thromboangiitis obliterans (Buerger disease) — segmental thrombosing vasculitis of small/medium distal vessels in a young male tobacco user; also Takayasu arteritis (upper extremity pulse deficit, young Asian women) and giant cell arteritis
• Vasospastic: Raynaud phenomenon — primary (idiopathic, symmetric, benign) versus secondary (scleroderma/CREST, SLE, cryoglobulinemia, vibration exposure, ergots, cocaine), where digital ulceration and abnormal nailfold capillaries appear
• Structural/mechanical: popliteal artery entrapment syndrome (young athlete, pulse lost on plantarflexion), cystic adventitial disease, fibromuscular dysplasia, external compression, trauma, and prior radiation

Modifiable risk factors

• Tobacco use: the strongest modifiable driver of PAD, more tightly linked to PAD than to CAD, and the dominant predictor of graft failure and amputation
• Diabetes mellitus: strongest predictor of critical limb ischemia and amputation; drives infrapopliteal, medially calcified disease
• Hypertension, dyslipidemia (high LDL, low HDL, elevated Lp(a)), chronic kidney disease, obesity/sedentary lifestyle, and hyperhomocysteinemia

Non-modifiable risk factors

• Age: risk rises steeply after 65; the 2016 AHA/ACC lower extremity PAD guideline considers patients ≥65, or 50–64 with risk factors, to be at increased risk and appropriate for history/pulse examination
• Male sex, Black race, family history of premature atherosclerosis, and established atherosclerotic disease in any other bed (CAD, carotid, aortic aneurysm)

• Atherosclerotic plaque formation: Endothelial injury from hypertension, smoking, hyperlipidemia, and diabetes initiates a cascade of LDL oxidation, macrophage infiltration, and smooth muscle proliferation, leading to progressive luminal narrowing of medium and large arteries
• Progressive stenosis and hemodynamic compromise: As plaque burden increases, arterial stenosis reduces blood flow; symptoms typically emerge when stenosis exceeds 50-70% of luminal diameter, preventing adequate blood supply during increased metabolic demand (claudication) or at rest (critical limb ischemia)
• Collateral vessel inadequacy: In acute occlusion or severe stenosis, inadequate development of collateral circulation prevents compensation, leading to acute or progressive tissue ischemia
• Endothelial dysfunction and thrombosis: Atherosclerotic plaques promote a prothrombotic state through tissue factor exposure and platelet activation, increasing risk of acute arterial thrombosis and occlusion
• Inflammation and plaque destabilization: Chronic inflammatory infiltrate (macrophages, T cells) and matrix metalloproteinase activity weaken the fibrous cap, predisposing to plaque rupture and acute arterial events

• Intermittent claudication (classic presentation): Reproducible cramping or burning pain in the calf, thigh, or buttock that develops with exertion and resolves within 10-15 minutes of rest; severity correlates with stenosis location (aortoiliac disease produces hip/buttock claudication; femoropopliteal disease produces calf claudication)
• Critical limb ischemia (CLI): Rest pain (often nocturnal, relieved by dependency), tissue ulceration, gangrene, or frank necrosis indicating severe arterial insufficiency with inadequate resting blood flow; requires urgent intervention to prevent limb loss
• Acute limb ischemia: Sudden onset of severe pain, pallor, pulselessness, paralysis, paresthesias, and poikilothermia ("6 P's") due to acute arterial thrombosis or embolism; constitutes a vascular emergency
• Atypical presentations: Exertional leg pain in atypical distributions, erectile dysfunction (aortoiliac disease), or asymptomatic arterial disease discovered incidentally on imaging
• Physical examination findings: Diminished or absent pulses, cool extremity (compare bilateral), pallor on elevation, rubor of dependency (reactive hyperemia), dependent edema, hair loss, thinned skin, brittle nails, and non-healing foot ulcers
• Important clinical pearl: Approximately 30% of patients with PVD are asymptomatic despite significant stenosis; diabetes blunts claudication symptoms due to neuropathy, making these patients at particularly high risk for silent ischemia progressing to CLI

• Ankle-Brachial Index (ABI): Gold standard screening test; normal ABI is 1.0-1.4; ABI 0.6-0.9 suggests mild-moderate disease, <0.6 indicates severe stenosis; performed at rest and after standardized treadmill exercise (claudication distance and time documented)
• Duplex ultrasound: First-line imaging modality; provides hemodynamic information (peak systolic velocity ratios) and anatomic localization of stenosis; non-invasive, no radiation, highly operator-dependent
• CT angiography (CTA) and MR angiography (MRA): CTA offers excellent spatial resolution and rapid acquisition but involves radiation and iodinated contrast; MRA is superior in renal insufficiency but may overestimate stenosis and contraindicated with ferromagnetic implants
• Digital subtraction angiography: Gold standard for anatomic definition and reserved for patients proceeding to intervention (endovascular or surgical); allows simultaneous therapeutic intervention
• Treadmill exercise testing: Establishes functional severity (claudication onset distance, maximum walking distance) and guides therapeutic decisions
• Important diagnostic considerations: Elevated creatinine warrants caution with contrast use; diabetes without claudication but with abnormal ABI increases risk and warrants preventive treatment; claudication-like pain from neurogenic claudication (spinal stenosis) typically worsens with prolonged standing regardless of rest position and improves with forward bending

• Lifestyle modification (foundation of all therapy): Smoking cessation (most impactful modifiable risk factor), supervised exercise programs (improve claudication distance by >50% through collateral development and improved muscle efficiency, 3x/week for ≥6 months), weight loss, and dietary modification (Mediterranean diet, reduced saturated fat)
• Antiplatelet therapy: Aspirin 81 mg daily as first-line (reduces CV events by ~10%) or clopidogrel 75 mg daily (superior in some trials, preferred if aspirin intolerant); dual antiplatelet therapy reserved for post-intervention period
• Risk factor modification: ACE inhibitors or ARBs (reduce CV events in PVD; benefit beyond blood pressure reduction), statins at high-intensity dosing (atorvastatin 80 mg or rosuvastatin 40 mg daily; reduce events by ~25%), aggressive blood pressure control (target <130/80 in most; individualize in elderly), tight glycemic control in diabetes (target HbA1c 7%)
• Cilostazol (phosphodiesterase-3 inhibitor): 100 mg twice daily; improves claudication distance by ~25-30%; contraindicated in heart failure with reduced ejection fraction; requires 2-4 weeks for full effect
• Endovascular intervention (percutaneous transluminal angioplasty ± stent): Indicated for symptom-limiting claudication refractory to medical therapy, acute limb ischemia, or CLI with anatomically suitable lesions; femoropopliteal lesions favor bare metal or drug-eluting stents; iliac lesions often respond well to PTA alone; restenosis rates 20-40% at 1 year depending on lesion characteristics
• Surgical revascularization (bypass grafting): Reserved for CLI, extensive multi-segment disease unsuitable for endovascular therapy, or endovascular failure; autologous saphenous vein preferred for patency; prosthetic grafts for upper extremity; perioperative morbidity higher but durable long-term patency
• Amputation: Considered when CLI is unsuitable for revascularization (no viable distal target, widespread tissue loss, or patient refusal); below-knee amputation preferred when anatomically feasible for better functional outcomes
• Special populations: Diabetics require more aggressive risk factor modification and lower threshold for intervention (microvascular disease increases CLI risk); elderly patients benefit from individualized approach balancing intervention risks against remaining life expectancy; chronic kidney disease requires careful contrast use and statin/antiplatelet consideration

• Acute limb ischemia: Sudden arterial thrombosis or embolism superimposed on chronic stenosis; leads to severe pain and rapid progression to tissue necrosis within hours if untreated; requires emergency angiography and intervention (thrombolysis, thrombectomy, or bypass)
• Critical limb ischemia and gangrene: Progressive arterial insufficiency inadequate for tissue viability at rest results in ischemic pain, ulceration, and gangrene; represents the most common reason for lower extremity amputation in developed countries; limb loss occurs in 5-10% of claudicants over 5 years if untreated
• Acute coronary syndrome and stroke: PVD is a marker of systemic atherosclerosis; patients with PVD have 4-6 fold increased risk of myocardial infarction and stroke, making cardiac risk stratification and stroke prevention essential
• Rest pain and functional limitation: Progressive stenosis leads to rest pain (especially nocturnal, relieved by dependency), severe functional impairment, and reduced quality of life
• Cardiovascular mortality: PVD patients have significantly higher mortality from cardiac and cerebrovascular causes; annual

• Single best next step for exertional leg pain with diminished pulses: resting ABI — cheap, noninvasive, and diagnostic at ≤0.90 per the AHA/ACC PAD guideline. Do not jump to CTA or angiography before an ABI. If resting ABI is normal but the history is classic, get an exercise ABI
• ABI >1.40 is not reassuring: it means noncompressible, medially calcified vessels (Mönckeberg sclerosis), classically in diabetes and ESRD. Next step is a toe-brachial index (abnormal <0.70) or pulse-volume/Doppler waveform analysis, since digital arteries are spared calcification
• Leriche syndrome is the association examiners love: aortoiliac occlusive disease producing buttock/thigh claudication + erectile dysfunction + absent femoral pulses
• Buerger disease buzzwords: young male heavy smoker, migratory superficial thrombophlebitis, digital ischemia/ulcers, Raynaud, and corkscrew collaterals on angiography. The only effective therapy is complete tobacco cessation — not revascularization, not steroids
• Statin for every patient with PAD, regardless of LDL — PAD is treated as clinical atherosclerotic cardiovascular disease under the 2018 AHA/ACC cholesterol guideline, warranting high-intensity statin. Say "ASCVD," not the retired ATP III phrase "CHD risk equivalent"
• Supervised exercise therapy beats revascularization as initial treatment for stable claudication (AHA/ACC Class I). Revascularization is for lifestyle-limiting symptoms refractory to therapy, or for critical/acute limb ischemia
• Common distractors to avoid: beta blockers are not contraindicated in PAD; cilostazol is contraindicated in HFrEF (PDE-3 inhibitor, like milrinone); and neurogenic claudication from spinal stenosis is relieved by lumbar flexion with normal pulses and normal ABI, not by simply standing still
• Acute limb ischemia (6 P's): immediate systemic anticoagulation with unfractionated heparin plus urgent vascular surgery consultation — imaging must not delay revascularization in a threatened limb