Description

Peripheral arterial disease (PAD) represents an atherosclerotic occlusive disease of the peripheral arteries, most commonly in the lower extremities. Following coronary artery disease and cerebrovascular disease, PAD is the third leading source of atherosclerotic vascular morbidity. PAD manifests as intermittent claudication (IC) or atypical leg pain and is commonly diagnosed with a resting ankle-brachial index (ABI) of <0.90 (1).

Epidemiology

• Age: ≥65 years, 50 to 64 years with atherosclerosis risk factors (e.g., diabetes mellitus [DM], hyperlipedemia [HLD], hypertension [HTN], history of smoking) or family history of PAD, or <50 years, with DM and one additional atherosclerosis risk factor
• Individuals with known atherosclerotic disease in another vascular bed (e.g., coronary, carotid, subclavian, renal, mesenteric artery stenosis, or AAA)

Incidence
Incidence increases with age and the presence of cardiovascular risk factors.

Prevalence

• Data from the National Health and Nutrition Examination Survey (1999–2004) show that 5.9% of the U.S. population ≥40 years has a low ABI (<0.9) indicating the presence of PAD. In 2021, the American College of Cardiology estimated 238 million people are living with PAD worldwide.
• However, the true prevalence of PAD is difficult to establish because more than half of persons are asymptomatic.

Etiology and Pathophysiology

• In PAD, arterial occlusion is most commonly a result of underlying chronic atherosclerotic disease.
• The association between PAD and cardiovascular morbidity and mortality has been well established, with a lower ABI being an independent predictor.
• Other etiologies for PAD include phlebitis, trauma, or autoimmune/vasculitic diseases.
• Arterial narrowing results in insufficient oxygen delivery to the muscle during periods of increased demand (i.e., exercise), causing claudication and limiting exercise. Reperfusion at rest following ischemia can result in subsequent physiologic changes, including inflammation, oxidant stress, endothelial dysfunction, and mitochondrial injury.

Genetics
Several of the risk factors for PAD (as noted below) are heritable, and genome-wide association studies to isolate PAD-specific single nucleotide polymorphisms are being explored (2).

Risk Factors

• Older age, atherosclerotic disease of any vascular bed, current or history of smoking, DM, HTN, HLD, chronic kidney disease (CKD)
• Heritable conditions: chylomicronemia, hypercholesterolemia, hyperhomocysteinemia, and pseudoxanthoma elasticum

General Prevention

• Regular aerobic exercise program, smoking cessation, blood pressure (BP) and diabetes control
• Statin therapy is indicated in patients with clinical PAD for secondary prevention of atherosclerotic cardiovascular disease.

Commonly Associated Conditions

In addition to the aforementioned risk factors, PAD is associated with other forms of atherosclerotic disease including myocardial infarction (MI), transient ischemic attack (TIA), and cerebrovascular accident (CVA).