Inflammation in Peripheral Artery Disease

Peripheral artery disease (PAD), which consists of partial or complete obstruction of the arteries in the lower limbs, is one of the most common manifestations of atherosclerosis, affecting ≈27 million individuals in Europe and North America.1 Its main symptomatic expression, intermittent claudication, was first described by the French veterinarian Bouley2 in a horse affected by progressive limping and lameness consequent to a fibrous clot that occluded the femoral arteries of the posterior limbs. In humans, this condition was noted by Brodie3 in 1846, but it was Charcot4 who in 1858 clearly defined and described the syndrome (and used the term “intermittent claudication”).3,4 Reproducibly elicited by walking-induced muscle ischemia and consistently relieved by rest that allows reperfusion of the affected limb, intermittent claudication may be considered “leg effort angina.” Indeed, for a long time, treatment was aimed exclusively at relieving leg symptoms and improving the functional status of affected individuals. However, in the 1950s, Stammers5 and Allen et al6 independently observed that patients with claudication were at high mortality risk. Subsequent prospective studies confirmed that patients with PAD rarely progress to limb loss but that the presence of PAD is a powerful and independent predictor of cardiac and cerebral ischemic events.7,–,11 However, this increased risk appears to be poorly related to classic risk factors, suggesting that once PAD is established, subsequent cardiovascular risk is related to the severity and extent of the underlying atherosclerotic disease and possibly other factors.7,–,11It is well established that hypertension, smoking, diabetes mellitus, and hypercholesterolemia play a major role in the initiation and development of atherosclerosis and its clinical manifestations, although the prognostic potency of each of these factors in atherogenesis differs in the …