Description

Peripheral arterial disease (PAD) represents 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.

Epidemiology

• Age: >65 years
  • Age: 50 to 64 years with risk factors for atherosclerosis or a family history of PAD
  • Age: <50 years in the presence of diabetes mellitus (DM) and one additional risk factor
• Sex: male > female (2:1)
• Impacts at least 8.5 million people in the United States
• Globally, an estimated 202 million people have PAD with increased prevalence in low- and middle-income countries.

• Annual incidence is 7.1/1,000 men and 3.6/1,000 women among all ages, per Framingham Heart Study.
• Incidence increases with age and the presence of cardiovascular risk factors.

• U.S. prevalence: 5.9% in adults >40 years
• Prevalence approaches 30% in high-risk populations.
• Higher prevalence and severity in African Americans and Hispanics

Etiology and Pathophysiology

• In PAD, arterial occlusion is most commonly a result of underlying atherosclerotic disease.
• 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.

Genetics
Although several of the risk factors for PAD (as noted below) 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

• Age >65 years
• Cigarette smoking
• DM
• Obesity
• Hypertension (HTN)
• Hyperlipidemia (HLD)
• Chronic kidney disease (CKD)
• Hyperviscosity
• 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).