Progression of Peripheral Artery Disease to Critical Limb Ischemia

Abstract

Critical limb ischemia (CLI), often considered the end stage of peripheral artery disease (PAD), is a tipping point in the balance between metabolic supply and demand of the lower extremity. This balance hinges on many factors, and the progression from stable PAD to CLI depends on the complex interplay of these variables. Despite the fact that PAD is classically categorized by disease severity, the natural history of PAD progression and general development of CLI does not follow a strictly linear path, a fact characterized by the often insidious clinical presentation of CLI. From a pathophysiologic perspective, CLI is the final result of the common atherogenic pathway that causes PAD. However, CLI manifests only in selected case largely due to a loss of compensatory mechanisms that leads to overt tissue ischemia. Many of the risk factors that contribute to the development of PAD are also responsible for its progression and ultimately for development of CLI, and important information can be gleaned from their modification both in PAD and CLI.