Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) is an atherosclerotic disease causing progressive narrowing of arteries in the upper and lower extremities. It commonly affects the abdominal aorta, iliac, and femoral arteries, significantly reducing blood flow to the legs and, in rare cases, the arms.

Atherosclerosis begins with endothelial dysfunction, allowing low-density lipoprotein (LDL) to penetrate the arterial intima. LDL oxidizes into inflammatory oxidized LDL, attracting macrophages that engulf it and form foam cells. These accumulate into fatty streaks and eventually develop into atherosclerotic plaques comprising cholesterol, foam cells, calcium, and a fibrous cap.

Key risk factors include smoking, diabetes, high blood pressure, high cholesterol, obesity, aging, and family history. Smoking damages the arterial lining through oxidative stress and inflammation. Diabetes causes hyperglycemia-related vessel damage. These factors independently accelerate atherosclerosis and exacerbate PAD progression and severity.

When unstable plaques with thin caps and large necrotic cores rupture, they expose thrombogenic material, triggering clot formation. This can acutely block the artery, causing sudden, severe ischemia and potentially tissue death. However, the body may compensate by developing collateral circulation—new blood vessels forming around blockages to improve blood flow.

As atherosclerotic plaques enlarge and harden, they narrow the arterial lumen in a process called stenosis. This reduces blood flow and causes ischemia, where tissues receive insufficient oxygen. Initially, this may cause claudication—pain or cramping in the legs during exercise—as oxygen demand exceeds supply during activity.

Foam cells form when macrophages engulf oxidized LDL and accumulate within the arterial wall. These foam cells, along with accumulated lipids and migrating smooth muscle cells, contribute to plaque formation. The accumulation of foam cells represents an early sign of atherosclerosis and drives the progression toward stable or unstable plaque development.

Smoking introduces harmful chemicals that cause oxidative stress and inflammation, weakening endothelial cells and damaging the arterial lining. Diabetes causes hyperglycemia, which directly damages blood vessels. Both conditions contribute to endothelial dysfunction, increasing permeability and allowing LDL penetration into the arterial intima, initiating atherosclerotic disease.