Our previous work shows that men and women with lower extremity peripheral arterial disease (PAD) have poorer lower extremity functioning, poorer leg strength, and greater functional decline than persons without PAD. However, pathophysiologic mechanisms underlying these relationships are not well understood. Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging. This study will build on our previous work by defining interrelationships between mediators of inflammation, D-dimer, C-reactive protein (CRP), homocysteine, and viscosity with pathophysiologic findings in calf skeletal muscle in persons with and without PAD. We will also study associations between inflammatory mediators, D-dimer, CRP, homocysteine and viscosity with functional decline. Inflammatory mediators will consist of interleukin-6 (IL-6), soluble vascular cell adhesion molecule (VCAM-1), and soluble intracellular adhesion molecule-1 (ICAM-1). This proposed study is ancillary to our ongoing NHLBI-funded study of functional outcomes among men and women with PAD, the Walking and Leg Circulation Study II (R01-HL71223). WALCS II is a prospective observational study of 500 men and women with PAD and 290 men and women without PAD that is identifying relationships between PAD, pathophysiologic findings in lower extremity skeletal muscle, and functional decline. WALCS II data collection includes measurement of lower extremity functional performance, calf skeletal muscle cross-sectional area, fat composition of calf skeletal muscle, leg strength, and leg power. We request additional funds to study associations between inflammatory factors, D-dimer, homocysteine, and viscosity with these important outcomes in PAD. In our cross-sectional aims, we will test the hypotheses that higher levels of inflammatory factors, D-dimer, homocysteine, and viscosity are associated with greater pathophysiologic impairments of lower extremity muscle and poorer lower extremity functioning. In our longitudinal aims, we will test the hypotheses that higher levels of the proposed blood factors and viscosity are associated with greater progression of skeletal muscle pathophysiologic findings and greater functional decline. Results will be used to develop interventions to improve functioning and prevent functional decline in PAD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL076298-01A1
Application #
6868415
Study Section
Special Emphasis Panel (ZRG1-HOP-L (02))
Program Officer
Ershow, Abby
Project Start
2005-01-01
Project End
2008-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$646,255
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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
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
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
McDermott, Mary M; Liu, Kiang; Ferrucci, Luigi et al. (2012) Vitamin D status and functional performance in peripheral artery disease. Vasc Med 17:294-302
McDermott, Mary M; Ferrucci, Luigi; Liu, Kiang et al. (2011) Women with peripheral arterial disease experience faster functional decline than men with peripheral arterial disease. J Am Coll Cardiol 57:707-14

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