Lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia

Circ Res. 2015 Apr 24;116(9):1540-50. doi: 10.1161/CIRCRESAHA.114.303517.


Lower extremity peripheral artery disease (PAD) is frequently underdiagnosed, in part because of the wide variety of leg symptoms manifested by patients with PAD and in part because of the high prevalence of asymptomatic PAD. In primary care medical practices, 30% to 60% of patients with PAD report no exertional leg symptoms and ≈45% to 50% report exertional leg symptoms that are not consistent with classic intermittent claudication. The prevalence and extent of functional impairment and functional decline in PAD may also be underappreciated. Functional impairment and functional decline are common in PAD, even among those who are asymptomatic. Lower extremity ischemia is also associated with pathophysiologic changes in calf skeletal muscle, including smaller calf muscle area, increased calf muscle fat content, impaired leg strength, and impaired metabolic function. People with severe PAD have poorer peroneal nerve conduction velocity compared with people with mild PAD or no PAD. The degree of ischemia-related pathophysiologic changes in lower extremity muscles and peripheral nerves of people with PAD are associated with the degree of functional impairment. New interventions are needed to improve functional performance and prevent mobility loss in the large number of patients with PAD, including in those who are asymptomatic or who have exertional leg symptoms other than claudication.

Keywords: intermittent claudication; peripheral arterial disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Exercise Test
  • Humans
  • Ischemia / physiopathology*
  • Leg / blood supply
  • Leg / physiopathology*
  • Lower Extremity / blood supply
  • Lower Extremity / physiopathology*
  • Models, Cardiovascular
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / physiopathology
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / physiopathology*
  • Walking / physiology