High resolution magnetic resonance imaging (MRI) is emerging as the most promising modality for direct plaque imaging. Direct plaque imaging has substantially advanced our understanding of the pathophysiology of acute coronary syndromes and cerebrovascular events. For example, direct plaque imaging has identified that acute coronary events frequently result from rupture of lipid rich plaque in areas of coronary atherosclerosis that are either invisible or insignificant on angiography. However, little is known about the clinical significance, pathophysiology, or natural history of lower extremity atherosclerotic plaque characteristics and their association with lower extremity outcomes in patients with lower extremity peripheral arterial disease (PAD). Our prior work demonstrates that patients with PAD have increased functional impairment and increased rates of functional decline compared to persons without PAD. In this proposed study, we will use MRI to identify specific characteristics of lower extremity atherosclerotic plaque and changes in plaque characteristics that are associated with functional decline in PAD. We will also identify associations between lower extremity collateral vessels with functional impairment and decline in PAD. We will assemble a cohort of 500 men and women with PAD and follow them prospectively for two years. At baseline and two year follow-up we will obtain consecutive cross-sectional MR images of the superficial femoral artery (SFA). Atherosclerotic plaque characteristics we will study are measures of plaque quantity (mean total arterial wall area, maximum arterial wall area) and measures of lumen reduction (maximum percent lumen reduction and average percent lumen reduction). The primary aims of this study are 1) to determine whether greater MRI-measured atherosclerotic plaque characteristics (i.e. greater plaque quantity and greater lumen reduction) are associated with greater functional impairment and decline in persons with PAD;2) to determine whether greater progression of MRI-measured atherosclerotic plaque characteristics are associated with greater functional decline in PAD;3) to identify associations between lower extremity collateral vessels with functional impairment and functional decline in persons with PAD. Substantive pilot data collected for this application demonstrate the validity and reliability of our proposed MRI measures, including measures of plaque quantity, percent lumen reduction, and collateral vessels. Results are expected to increase our understanding of the pathophysiology of lower extremity atherosclerosis and mechanisms of functional impairment and decline in persons with PAD. This knowledge, in subsequent studies, is expected to lead to new therapies for PAD-related functional impairment and functional decline.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL083064-03
Application #
7649344
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Reid, Diane M
Project Start
2007-07-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2009
Total Cost
$736,869
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; Kramer, Christopher M; Tian, Lu et al. (2017) Plaque Composition in the Proximal Superficial Femoral Artery and Peripheral Artery Disease Events. JACC Cardiovasc Imaging 10:1003-1012
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; Carroll, Timothy; Carr, James et al. (2017) Femoral artery plaque characteristics, lower extremity collaterals, and mobility loss in peripheral artery disease. Vasc Med 22:473-481
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
White, Sarah H; McDermott, Mary M; Sufit, Robert L et al. (2016) Walking performance is positively correlated to calf muscle fiber size in peripheral artery disease subjects, but fibers show aberrant mitophagy: an observational study. J Transl Med 14:284
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; Carr, James; Liu, Kiang et al. (2014) Collateral vessel number, plaque burden, and functional decline in peripheral artery disease. Vasc Med 19:281-288
Galizia, Mauricio S; Barker, Alex; Liao, Yihua et al. (2014) Wall morphology, blood flow and wall shear stress: MR findings in patients with peripheral artery disease. Eur Radiol 24:850-6
Polonsky, Tamar S; Liu, Kiang; Tian, Lu et al. (2014) High-risk plaque in the superficial femoral artery of people with peripheral artery disease: prevalence and associated clinical characteristics. Atherosclerosis 237:169-76
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

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