The primary objective of this randomized, double blind, placebo controlled pilot study is to determine if therapies aimed at lowering LDL cholesterol (HMGCoA reductase inhibitor – simvastatin) or increasing HDL cholesterol (Niaspan) will induce regression of carotid atherosclerotic plaque in vivo using MRI imaging techniques. MR plaque morphology at baseline will be compared to that after 6 and 12 months of therapy and changes in MR characteristics will be compared to changes in lipoprotein parameters and urinary isoprostanes. The effect of moderate LDL reduction, aggressive LDL reduction and the combination of aggressive LDL reduction and HDL elevation on MRI plaque characteristics will be compared by randomly assigning subjects (n=69) with carotid disease (>30% stenosis by ultrasound criteria) to one of three treatment arms;

1. Simvastatin 20 mg daily and placebo Niaspan (n=23)
2. Simvastatin 80 mg daily and placebo Niaspan (n=23)
3. Simvastatin 20 mg daily and active Niaspan (n=23) Treatment group 2 and 3 will have roughly equivalent LDL lowering because of the synergistic LDL lowering effect of the combination of simvastatin and Niaspan.