Clinical meaning
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis affecting the arteries supplying the lower extremities, most commonly the superficial femoral artery (most frequent site of stenosis), the aortoiliac segment, and the infrapopliteal (tibial) arteries. The pathogenesis mirrors coronary atherosclerosis: endothelial injury from hypertension, tobacco toxins, hyperglycemia, and dyslipidemia increases endothelial permeability, allowing LDL cholesterol to infiltrate the subintimal space. Oxidized LDL triggers monocyte recruitment and differentiation into macrophages that engulf lipid, becoming foam cells. Smooth muscle cell migration, proliferation, and extracellular matrix deposition create a fibrous cap over the growing lipid-rich necrotic core. Progressive plaque growth narrows the arterial lumen, reducing blood flow. During exercise, skeletal muscle oxygen demand increases 10-20 fold, but the stenotic artery cannot increase flow to match demand, producing the hallmark symptom of intermittent claudication -- reproducible cramping pain in the calves, thighs, or buttocks that occurs with walking and resolves within 2-5 minutes of rest. The Fontaine classification stages PAD progression: Stage I (asymptomatic), Stage II (intermittent claudication), Stage III (rest pain), and Stage IV (tissue loss/gangrene). The ankle-brachial index (ABI) is the cornerstone diagnostic tool: it compares systolic blood pressure at the ankle to the brachial artery, with a normal ratio of 1.0-1.3. An ABI below 0.9 is diagnostic for PAD with 95% sensitivity and 99% specificity. Critical limb ischemia (CLI) represents the most severe form, with ABI typically below 0.4, manifesting as rest pain (ischemic neuropathy causing severe forefoot burning at night, relieved by dependent positioning to augment gravity-assisted perfusion), non-healing ischemic ulcers, or gangrene. PAD is a coronary artery disease equivalent: patients have a 20-30% risk of myocardial infarction, stroke, or cardiovascular death within 5 years, making aggressive systemic atherosclerotic risk reduction (statin therapy, antiplatelet agents, smoking cessation, blood pressure control) as important as treating the limb symptoms.