Magnetic Resonance Characterization of Carotid Atherosclerotic Plaque in Vivo: Effect of High-Density Lipoprotein Elevation on Plaque Morphology

Muredach P. Reilly, M.B.

University of Pennsylvania

Funded in December, 1999: $100000 for 3 years
LAY SUMMARY . BIOGRAPHY . HYPOTHESIS . SELECTED PUBLICATIONS .

INVESTIGATOR BIOGRAPHIES

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Muredach P. Reilly, M.B.

Cardiovascular Division
University of Pennsylvania

HYPOTHESIS

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Hypothesis:
The primary hypothesis of this randomized, double blind, controlled pilot study is to determine if therapies aimed at lowering LDL cholesterol (Simvastatin) or increasing HDL cholesterol (Niaspan) will induce regression of carotid atherosclerotic plaque in vivo using MRI imaging techniques.

Goals:
The effect of treatment with Simvastatin 10 mg (moderate LDL reduction), Simvastatin 80 mg (aggressive LDL reduction) and the combination of Simvastatin and Niaspan (aggressive LDL reduction and HDL elevation) on carotid MRI plaque characteristics will be compared. The primary end-point is the change in carotid plaque volume at MRI after 12 months of treatment. Secondary end-points include (1) change in carotid plaque lipid content at MRI after 12 months, (2) change in lipid parameters after 12 months, and (3) change in urinary isoprostane excretion after 12 months

Methods:
In the proposed clinical trial, patients (n=60) with carotid disease (>30% stenosis by ultrasound criteria) are being randomly assigned to one of three treatment arms: (1) Simvastatin 20 mg daily and placebo Niaspan (n=20), (2) Imvastatin 80 mg daily and placebo Niaspan (n=20), and (3) Simvastatin 20 mg daily and active Niaspan (n=20). Black blood imaging with oblique sagittal T1-weighted fast spin echo (FSE), axial proton density FSE through plaque, with and without fat saturation and axial T2-weighted FSE through plaque is used to quantify total plaque volume and percent of plaque occupied by lipid.

Follow-on Funding:
R01-HL/NS68908, Wehrli, Felix, Ph.D., 12/1/01 ? 11/30/04, $319,357 Structure-Function Assessment of Carotid Disease by MR To further develop and perfect the methodology developed in preliminary work for acquiring, processing and analyzing high-resolution MR images to measure plaque volume and architecture in vivo.

SELECTED PUBLICATIONS

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Reilly M.P., Wolf R., Mohler E.R. III, Wright A., Song H.K., Wehrli F., Rader D.J. (2001) Longitudinal study of lipid-modifying therapies on carotid atherosclerotic plaque morphology in vivo as assessed by magnetic resonance imaging. American Heart Journal.