Limb ischemia: cardiovascular diagnosis and management from head to toe.

Peripheral arterial disease (PAD) affects an estimated 27 million people in Europe and North America. Limb ischemia, defined as ischemic rest pain, ischemic ulcerations, or ischemic gangrene, represents the most severe manifestation of PAD and is associated with significant cardiovascular and limb morbidity and mortality. Critical limb ischemia (CLI), defined as limb ischemia symptoms for greater than 2 weeks, is characterized by a cascade of hemodynamically significant macrovascular atherosclerotic obstruction and microvascular changes culminating in decreased muscle perfusion, disrupted muscle energy metabolism, and inflammation. In contrast, acute limb ischemia (ALI) is defined as limb ischemia symptoms characterized by sudden onset of less than 2 weeks duration resulting in hemodynamically compromised limb perfusion. Diagnosis of both ALI and CLI is dependent on history, physical examination, and a combination of anatomic and hemodynamic assessment of the limb. Given that the risk factors for ALI and CLI overlap with risk factors for atherosclerotic coronary and neurovascular disease, the management of limb ischemia is focused on both endovascular or surgical limb salvage and cardiovascular risk factor control. Despite advancements in endovascular and surgical revascularization techniques, limb morbidity remains high; clinical trials of angiogenic and cell-based therapies are ongoing. Cardiovascular risk reduction in patients with limb ischemia also remains suboptimal and future studies will focus on novel antiplatelet agents.