This is an application for a collaboration between Wake Forest University School of Medicine (WFU, Dr. John Crouse) and the University of Washington (U Wash, Dr. Chun Yuan) - the Carotid Atherosclerosis Progression Study - to use Magnetic Resonance Imaging (MRI) to build on and expand WFU's longitudinal studies of non-invasive imaging of carotid arterial structure in patients with and with no coronary artery disease (CAD, NO CAD) (HL-35333:HL-63264). Dr. Yuan is at the forefront of carotid MRI (in Seattle HL-56874 is identifying vulnerable plaque and HL-61851 is quantifying progression in patients with carotid lesions). This new application will use MRI to test the hypothesis that extracranial carotid (EC) wall thickness:area:volume and plaque thickness:area:volume (ECMRI) are greater in CAD compared to NO CAD patients at baseline, progress faster over 2 years, and that risk factors (including inflammatory markers, genetic factors) impact more on progression in CAD cases and that fast progression relates to incident cardiovascular events. We propose that carotid plaque (defined by anatomic and morphologic characteristics) is the """"""""active progression site"""""""" and that walls not involved with plaque are less informative. In addition, we will use ECMRI to determine if """"""""vascular remodeling"""""""" in CAD patients is compromised compared to those with NO CAD. We will also directly compare ECMRI with EC intimal medial thickness (ECIMT) contemporaneously measured by B mode ultrasound (the current """"""""gold standard""""""""). Secondary aims are to evaluate plaque composition in CAD and NO CAD patients and to quantify dynamic enhancement in diabetics and matched controls. To test this we will evaluate 200 patients from HL-63264 equally divided between CAD and NO CAD, males and females. We will measure ECMRI and risk factors in them at baseline and ECMRI again after 2 years. We will use descriptive statistics, general mixed effects models, and random effects models to compare CAD and NO CAD patients for baseline correlates and for progression of ECMRI. We will relate ECMRI to contemporaneously measured ECIMT (B mode). We will relate ECMRI progression to incident events. Use of MRI overcomes pitfalls with B mode (operator dependence and limited ability to measure plaque) and CAC (limited ability to relate risk factors to progression). Proof that plaque progression relates to CAD status and risk factors will greatly increase the applicability of ECMRI for epidemiologic studies and clinical trials as well as increase our understanding of plaque pathogenesis in a highly informative population.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Epidemiology of Chronic Diseases Study Section (ECD)
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Srinivas, Pothur R
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Wake Forest University Health Sciences
Internal Medicine/Medicine
Schools of Medicine
United States
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Yuan, Chun; Wang, Jinnan; Balu, Niranjan (2012) High-field atherosclerotic plaque magnetic resonance imaging. Neuroimaging Clin N Am 22:271-84, xi
Wang, Jinnan; Gerretsen, Suzanne C; Maki, Jeffrey H et al. (2011) Time-efficient black blood RCA wall imaging at 3T using improved motion sensitized driven equilibrium (iMSDE): feasibility and reproducibility. PLoS One 6:e26567
Wang, Jinnan; Yarnykh, Vasily L; Yuan, Chun (2010) Enhanced image quality in black-blood MRI using the improved motion-sensitized driven-equilibrium (iMSDE) sequence. J Magn Reson Imaging 31:1256-63
Wang, Jinnan; Balu, Niranjan; Canton, Gador et al. (2010) Imaging biomarkers of cardiovascular disease. J Magn Reson Imaging 32:502-15
Underhill, Hunter R; Yuan, Chun; Terry, James G et al. (2008) Differences in carotid arterial morphology and composition between individuals with and without obstructive coronary artery disease: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 10:31