Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

Abstract

estimates a more than 30% increase in deaths and disability attributable to PAD between 2005 and 2015, which is largely determined by population aging. 3,12 PAD prevalence escalates with advancing age, affecting 1 in 10 adults older than 70 years. In addition to age, smoking and diabetes are the strongest risk factors for PAD across the world. A comprehensive global evaluation of PAD found that its prevalence and risk factors are similar in high-income countries to low-and middle-income countries. 2,13 Lower socioeconomic status is a newly recognized risk factor for PAD. 14 Importantly, there has been a greater increase in PAD prevalence in low-and middle-income countries, rising by 28.7% from 2000 to 2010 as compared with 13.1% in high-income countries. 2, 15 The changing burden of PAD is also greater in women as compared with men.The health implications of PAD derive from both its limb and cardiovascular manifestations. Consistent with the systemic nature of atherosclerosis, polyvascular disease is common in patients with PAD. 16 In the REACH registry, 61% of PAD patients had concomitant coronary artery disease (CAD) and/or cerebrovascular disease. 16 Thus, the presence of PAD portends a high risk for subsequent cardiovascular events. A meta-analysis of over 48,000 participants in population-based cohort studies demonstrated that a low ankle-brachial index (ABI) predicted a 2-fold risk of death, cardiovascular death, and major coronary events at all ranges of the Framingham Risk Score. 4 Further, the elevated risk of cardiovascular events is present in both symptomatic and asymptomatic patients. 17 Patients with atherosclerotic disease in more than 1 vascular territory have particularly poor outcomes. 6 In the over 5,000 Japanese T here is growing recognition of the effect of peripheral artery disease (PAD) on cardiovascular health. 1 Recent studies indicate that, globally, over 200 million adults have PAD, 2,3 which is an expression of systemic atherosclerosis and well-established as heightening the risk for cardiovascular events. 4-6 The limb manifestations of PAD induce considerable suffering. Patients with PAD experience intermittent claudication, characterized as exertional leg pain that limits walking ability, and often times, disability. 7-9 Current medical therapies to reduce the burden of lower extremity symptoms in patients with PAD are limited. Revascularization by endovascular intervention or surgical reconstruction is used to treat lifestyle-limiting claudication if patients do not respond adequately to medical therapy including exercise training. Indeed, lower extremity revascularization with endovascular approaches has undergone a dramatic increase in use. 10 Though endovascular therapy improves blood flow and function, there are significant associated risks, and durability may be limited, especially in infrainguinal disease. Abundant evidence demonstrates the benefits of exercise therapy in claudication, yet the mechanisms underlying the beneficial effects remain incompletely defined. 11 Thus, ...

Contrast-Enhanced Ultrasound Reveals Exercise-Induced Perfusion Deficits in Claudicants

“…The treadmill exercise therefore results in ischemia. An inability to compensate for increased demand during exercise results in unchanged perfusion and symptomatic ischemia [37]. Normal subjects, in comparison, show significant increases in perfusion intensity and decreases in time to peak.…”

Redox regulation of ischemic limb neovascularization – What we have learned from animal studies

“…Risk factors of PAD are age, smoking, and diabetes, and its pathogenesis is associated with atherosclerosis, endothelial dysfunction, and inflammation. Impaired angiogenesis and reduced microcirculation in the muscle of PAD patients potentiate limb ischemia [101]. Of interest critical limb ischemia patients have higher levels of plasma VEGF-A [102], indicating that VEGF downstream signaling may be affected in these patients.…”

Perfusion measures for symptom severity and differential outcome of revascularization in limb ischemia: Preliminary results with arterial spin labeling reactive hyperemia

“…Furthermore, measures of macrovascular resistance were found to be related to the manifested symptom severity, whereas microvascular function seemed to be related to prognosis following revascularization. 5,24 Therefore, although the relationship between macrovascular disease and symptom severity was established at a groupwise level, individual symptoms may be affected by other variables. ASL is advantageous primarily in that it offers temporally resolved absolute perfusion, which can be directly interpreted in the context of flow resistance and vascular reactivity.…”