Our research demonstrates that men and women with lower extremity peripheral arterial disease (PAD) have poorer functioning than men and women without PAD. Our preliminary data also indicate that more severe PAD at baseline, as measured by the ankle brachial index (ABI), is associated with a greater incidence of functional loss. However, the pathophysiologic mechanisms in the lower extremities responsible for PAD-related functional impairment and functional loss are not well defined. The purposes of this proposal are a) to define the pathophysiologic effects of arterial ischemia on lower extremity muscle and nerve and b) to identify the specific effects of ischemia-related pathophysiologic findings on lower extremity functioning in PAD. ? ? The study cohort will consist of 790 individuals identified from three Chicago-area medical centers, of whom 500 will have PAD. Participants will undergo a baseline and two annual follow-up visits. Pathophysiologic findings in the lower extremities refers to reduced muscle mass, reduced muscle quality, and reduced peripheral sensory and motor function. Quality of muscle tissue is defined as the ratio of muscle force to muscle mass. Muscle mass will be measured with Computed Tomography (CT). Peripheral nerve function will be determined using surface electroneurography (ENG). Lower extremity functional measures will consist of measures pertinent to functioning during daily living and include six minute walk distance, seven-day physical activity level (assessed by accelerometer), walking speed, balance tests, and lower extremity muscle power. ? ? In our primary cross-sectional aims, we will test the hypotheses that a) chronic lower extremity arterial ischemia is associated with specific pathophysiologic findings in lower extremity muscle and nerve and that b) these ischemia-related pathophysiologic findings are associated with lower extremity functional limitation. In our primary longitudinal aims we will test the hypotheses that a) greater baseline lower extremity arterial ischemia as measured by ABI is associated with greater progression of pathophysiologic findings over two year follow-up and that b) greater ischemia-related pathophysiologic findings in the legs at baseline is associated with greater functional decline over two year follow up. Results will be used to develop interventions designed to improve lower extremity functioning and prevent functional decline in persons with PAD.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Fabsitz, Richard
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Northwestern University at Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
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McDermott, Mary M; Polonsky, Tamar S; Kibbe, Melina R et al. (2017) Racial differences in functional decline in peripheral artery disease and associations with socioeconomic status and education. J Vasc Surg 66:826-834
McDermott, Mary M; Guralnik, Jack M; Tian, Lu et al. (2016) Incidence and Prognostic Significance of Depressive Symptoms in Peripheral Artery Disease. J Am Heart Assoc 5:e002959
McDermott, Mary M; Guralnik, Jack M; Ferrucci, Luigi et al. (2016) Community walking speed, sedentary or lying down time, and mortality in peripheral artery disease. Vasc Med 21:120-9
Forbang, Nketi I; McDermott, Mary M; Liao, Yihua et al. (2014) Associations of diabetes mellitus and other cardiovascular disease risk factors with decline in the ankle-brachial index. Vasc Med 19:465-72
McDermott, Mary M; Kibbe, Melina; Guralnik, Jack M et al. (2013) Comparative effectiveness study of self-directed walking exercise, lower extremity revascularization, and functional decline in peripheral artery disease. J Vasc Surg 57:990-996.e1
Huang, Chiang-Ching; McDermott, Mary M; Liu, Kiang et al. (2013) Plasma metabolomic profiles predict near-term death among individuals with lower extremity peripheral arterial disease. J Vasc Surg 58:989-96.e1
Jain, Atul; Liu, Kiang; Ferrucci, Luigi et al. (2013) Declining walking impairment questionnaire scores are associated with subsequent increased mortality in peripheral artery disease. J Am Coll Cardiol 61:1820-9
Raval, Zankhana; Liu, Kiang; Tian, Lu et al. (2012) Higher body mass index is associated with more adverse changes in calf muscle characteristics in peripheral arterial disease. J Vasc Surg 55:1015-24
Jain, Atul; Liu, Kiang; Ferrucci, Luigi et al. (2012) The Walking Impairment Questionnaire stair-climbing score predicts mortality in men and women with peripheral arterial disease. J Vasc Surg 55:1662-73.e2
McDermott, Mary M; Liu, Kiang; Tian, Lu et al. (2012) Calf muscle characteristics, strength measures, and mortality in peripheral arterial disease: a longitudinal study. J Am Coll Cardiol 59:1159-67

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