Peripheral Arterial Disease



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).


  • 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)
  • Impacts at least 7.1 million people in the United States

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


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

Etiology and Pathophysiology

  • In PAD, arterial occlusion is most commonly a result of underlying 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 multiple subsequent physiologic changes, including inflammation, oxidant stress, endothelial dysfunction, and mitochondrial injury.

Although several of the risk factors for PAD (as noted next) are heritable, genome-wide association studies isolating PAD-specific single nucleotide polymorphisms have not been as successful. This has been attributed to the increased clinical and genetic heterogeneity of PAD.

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).

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