Genetics of Peripheral Artery Disease

Broadly defined, peripheral vascular disease refers to disease of the extracardiac blood vessels, including diseases of the arteries, veins, and lymphatics. Peripheral arterial disease (PAD) refers to disease affecting noncoronary arteries, but is most often used to describe disease of the arteries supplying the limbs. Peripheral arterial disease is most commonly due to atherosclerosis, but may also be secondary to cardiac or vascular embolism, vasculitis, hypercoagulopathy, vascular dissection, vascular compression syndromes, and other less common disorders. In addition, PADs include those characterized by fixed or dynamic stenoses, and aneurysmal disease such as abdominal aortic aneurysm, as well. In this review, we focus on atherosclerotic arterial occlusive disease affecting the vessels supplying blood flow to the lower extremities (PAD), and discuss our current understanding and the future directions of PAD genetics.PAD is a significant public health problem, and a major source of morbidity and mortality that affects ≈8 million Americans. PAD contributes to impaired quality of life (eg, intermittent claudication reducing mobility), morbidity (eg, nonhealing ulcers and ischemic rest pain), and mortality (generally owing to its association with coronary and carotid artery disease). PAD is responsible for approximately half a million hospitalizations and 100 000 angiograms annually.1,2 In part, because of a general unfamiliarity with these diseases among the primary care community, PAD patients receive suboptimal treatment in comparison with patients with coronary artery disease (CAD), being prescribed therapeutic doses of statins, antihypertensive medicines, and antiplatelet agents less commonly than patients with CAD.3–6 Much remains unknown about the biological origins of this disease and how to effectively identify and treat affected individuals.A greater understanding of how genetic variation influences susceptibility to PAD may inform the development of novel therapeutics. High-throughput, whole-genome technology efforts have recently made inroads toward these goals (Table). The advent …