Peripheral arterial disease: A small and large vessel problem

Peripheral arterial disease (PAD) is one clinical manifestation of systemic atherosclerosis and is very common. Despite its prevalence, PAD remains underdiagnosed, undertreated, and understudied. The most common symptom in patients with PAD is intermittent claudication (IC), or pain in the lower extremities with walking or exertion, which is relieved after a short period of rest. Many patients with confirmed PAD are asymptomatic or have symptoms other than IC. Regardless of symptoms, patients with PAD have poor cardiovascular outcomes. PAD has largely been viewed a disease of large vessel atherosclerosis but what is becoming clear is that arterial plaques and occlusions are only one piece of the puzzle. Recent work has shown that abnormalities in the microvasculature contribute to the outcome of patients with PAD. From the perspective of the leg, limitation in blood flow is not the only problem as patients have a myriad of other problems, including muscle fibrosis, neuropathic changes, changes in the cellular respiration machinery and dysfunction of the small vessels that perfuse skeletal muscle and the supporting structures. Supervised exercise training remains one of the most effective tool to treat patients with PAD, however, the mechanisms behind its effectiveness are still being elucidated and use of structured exercise programs is not widespread. Medical therapy to treat systemic atherosclerosis is underutilized in patients with PAD. Invasive therapies are used only when patients with PAD have reached an advanced stage. While invasive strategies are effective in some patients with PAD, these strategies are costly, carry risk, and many patients are not amenable to invasive therapy. Appreciating the complex pathophysiology of PAD will hopefully spur new research and development of effective therapies for PAD.