Peripheral arterial disease (PAD) is characterized by lower limb arterial obstruction due to atherosclerosis. Most of the over 8 million in the U.S. with PAD are elderly and the prevalence is increasing. Patients with PAD are undertreated with life-saving risk factor modification including raising HDL cholesterol. Presently used diagnostic methods in PAD are limited and modalities that allow study of progression and regression of disease are clearly needed. Over the past 4+ years, our multi-disciplinary team from cardiology, radiology, vascular surgery, biomedical engineering, exercise science, biostatistics and clinical trials management has developed such techniques. These include magnetic resonance (MR) measures of atherosclerotic plaque volume and characteristics in the superficial femoral artery, phosphocreatine (PCr) recovery kinetics after exercise, and first pass contrast-enhanced measures of calf muscle perfusion at peak exercise. We are presently evaluating the mechanisms of benefit of LDL reduction in PAD with these methods. In the present proposal, we aim to improve and extend the application of these novel methodologies.
Aim 1 is to develop and test MR methods to quantify skeletal muscle blood flow at peak exercise in PAD without the need of a contrast agent. Twenty patients and 10 normal subjects will be studied with arterial spin labeling and blood oxygen level dependent MR and reproducibility will be determined and compared to contrast methods.
Aim 2 is to compare the previously developed MR methods at 1.5T and 3T in 30 patients and 20 normal subjects. Finally, we will use the most reproducible method for perfusion and the ideal field strength as determined in Aims 1 and 2 in a clinical trial.
Aim 3 is to use comprehensive MR to test the efficacy of raising HDL with a novel formulation of niacin with laropiprant that reduces flushing compared to placebo in mild to moderate PAD. Ninety patients with PAD and an ankle-brachial index between 0.4 and 0.9 will undergo comprehensive MR, exercise testing with respiratory gases, measurement of lipids and inflammatory markers at baseline and yearly for 2 years after randomization to active therapy or placebo. This study will establish the potential clinical benefit of raising HDL in PAD and will help to determine the mechanism of benefit, whether it be through macrovascular plaque regression or improved microvascular blood flow or muscle energetics. Improving the health outcomes and quality of life in patients with PAD is a major goal of this proposal.

Public Health Relevance

Peripheral arterial disease (PAD) affects over 8 million in the U.S. and techniques to evaluate potential benefits of new treatments are sorely lacking. This study aims to further develop and test new techniques using magnetic resonance imaging with the aim of identifying new therapies for PAD. One such therapy that will be tested is raising HDL cholesterol, so-called """"""""good"""""""" cholesterol, with a new formulation of niacin.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL075792-06
Application #
7525104
Study Section
Special Emphasis Panel (ZRG1-CVS-F (02))
Program Officer
Reid, Diane M
Project Start
2003-09-22
Project End
2011-06-30
Budget Start
2009-07-15
Budget End
2010-06-30
Support Year
6
Fiscal Year
2009
Total Cost
$673,798
Indirect Cost
Name
University of Virginia
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Mathew, Roshin C; Kramer, Christopher M (2018) Recent advances in magnetic resonance imaging for peripheral artery disease. Vasc Med 23:143-152
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; 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
Balfour Jr, Pelbreton C; Gonzalez, Jorge A; Kramer, Christopher M (2017) Non-invasive assessment of low- and intermediate-risk patients with chest pain. Trends Cardiovasc Med 27:182-189
Fielden, Samuel W; Meyer, Craig H (2015) A simple acquisition strategy to avoid off-resonance blurring in spiral imaging with redundant spiral-in/out k-space trajectories. Magn Reson Med 73:704-10
Lopez, David; Pollak, Amy W; Meyer, Craig H et al. (2015) Arterial spin labeling perfusion cardiovascular magnetic resonance of the calf in peripheral arterial disease: cuff occlusion hyperemia vs exercise. J Cardiovasc Magn Reson 17:23
Kramer, Christopher M (2015) Novel magnetic resonance imaging end points for physiologic studies in peripheral arterial disease: elegance versus practicality. Circ Cardiovasc Imaging 8:
Kramer, Christopher M (2015) Role of Cardiac MR Imaging in Cardiomyopathies. J Nucl Med 56 Suppl 4:39S-45S
Kramer, Christopher M; Chandrashekhar, Y; Narula, Jagat (2015) Is it T1me for tissue characterization in myocarditis? JACC Cardiovasc Imaging 8:115-7
Shaw, Peter W; Kramer, Christopher M (2015) The case for CMR. J Nucl Cardiol 22:968-70

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