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A systematic search of the medical literature was performed in January 2008. The search, limited to human subjects and English language journals, included the National Guideline Clearinghouse, the Cochrane database, PubMed, UpToDate®, and PIER®. The current American College of Cardiology/American Heart Association 2006 Guidelines for the management of patients with peripheral arterial disease can be found at

Peripheral arterial disease (PAD), the most common form of peripheral vascular disease, is a manifestation of progressive narrowing of arteries caused by atherosclerosis.1 PAD can be used to designate occlusive, stenotic, and aneurysmal diseases of the aorta and its branch arteries.2 This chapter will focus on lower extremity PAD. PAD is associated with elevated risk of cardiovascular disease (CVD) morbidity and mortality, even in the absence of prior history of acute myocardial infarction (AMI), stroke or other manifestations of CVD.1,3 Patients with PAD have approximately the same relative risk of death from CVD as do patients with a history of coronary or cerebrovascular disease and PAD should be considered a surrogate marker of subclinical coronary artery disease (CAD) and other vascular territories.1,4,5 The treatment of PAD focuses on decreasing the functional impairment caused by symptoms of intermittent claudication (IC) through nonpharmacologic and pharmacologic therapy and by minimizing the impact of other cardiovascular risk factors.6,7

PAD is most commonly a manifestation of systemic atherosclerosis in which the arterial lumen of the lower extremities becomes progressively occluded by atherosclerotic plaque.8 The major risk factors for the development of atherosclerosis are older age (greater than 70 years), cigarette smoking, diabetes mellitus, hypercholesterolemia, hypertension (HTN), and hyperhomocysteinemia.2,8,9 Additionally, patients less than 50 years of age are at risk if they have been diagnosed with diabetes and one additional atherosclerotic risk factor, as well as patients more than age 50 who have a history of diabetes or smoking.2 The arteries most commonly involved, in order of occurrence, are the femoropopliteral-tibial, aortoiliac, carotid and vertebral, splanchnic and renal, and brachiocephalic.10 Familial hypercholesterolemia (FH) leading to hypercholesterolemia and elevated low-density lipoprotein (LDL) levels is associated with accelerated development of atherosclerosis earlier and with more severe symptoms (e.g., IC) and abnormal blood flow studies compared to controls.11 Intima-media thickness can be used as a surrogate phenotype for cardiovascular risk in FH and carotid and/or femoral artery atherosclerosis results in increased intima-media thickness and it is correlated to cardiovascular risk in FH patients compared with normolipidemic individuals.7

The clinical presentation of PAD is variable and includes a range of symptoms from no symptoms at all (typically early in the disease, with 5% to 10% developing symptoms more than 5 years12,13) to pain and discomfort. The two most common characteristics of PAD are IC and pain at rest in the lower extremities.14–16 IC is ...

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