Peripheral artery disease (PAD) is one of the most common cardiovascular diseases and is associated with high short-term morbidity and mortality. 1,2 It is the primary cause of lower extremity amputation throughout the world and is a powerful marker of advanced systemic atherosclerosis. Chronic critical limb ischemia (CLI) represents the most advanced clinical manifestation of PAD and is defined by the presence of ischemic rest pain, nonhealing wounds, or tissue loss (gangrene). CLI does not represent a single pathophysiologic process (ie, progressive leg arterial atherosclerosis), but is caused by multiple pathogenetic mechanisms, including native artery atherosclerosis, cardioembolic events, inflammatory arteritides (eg, thromboangiitis obliterans), hypercoagulable states, or leg bypass graft failure.
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Hirsch et al. (2013) studied this question.
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