Abstract 485: Effect of Intensive Lipid Therapy on Atherosclerotic Plaque Inflammation: Evaluation Using Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) in Carotid Disease
Background: As validated in human histology and animal models, the transfer constant (Ktrans) of contrast agent uptake in DCE-MRI reflects the increase in neovasculature and permeability associated with plaque inflammation, thus may be a surrogate marker of plaque inflammation. We investigated whether intensive lipid therapy with anti-inflammatory effect leads to measurable changes in Ktrans.
Methods: Subjects for this study were drawn from an ongoing investigation in which participants with established CAD or carotid stenosis ≥15% by ultrasound and with apolipoprotein B ≥120 mg/dl were randomized to one of three treatment groups:
atorvastatin (Atorva) (10 – 80 mg/day); or
Atorva plus extended release-niacin (ERN) (2 g/day); or
Atorva, ERN plus colesevelam (3.8 g/day) with appropriate placebos.
They received carotid MRI including morphological and DCE scans at baseline and one year after lipid therapy. Subjects who demonstrated measureable Ktrans [characterized by presence of a lipid-rich necrotic core (LRNC)] at baseline had significant HsCRP reduction by 39%. Ktrans images were analyzed using an established kinetic modeling algorithm programmed into custom-developed plaque analysis software. The differences between baseline and 1-yr follow-up in Ktrans and LRNC were compared using paired t-test.
Results: Of 36 subjects who had carotid plaques with LRNCs, 28 had acceptable DCE image quality at both baseline and 1-yr follow-up scans. After 1 yr of treatment, a statistically significant reduction compared to baseline was observed in Ktrans (0.067±0.028 vs. 0.085±0.037 min−1, p = 0.02); size of the lipid-rich necrotic core significantly regressed (57.2±57.2 vs. 64.3±59.4 mm3, p = 0.02).
Conclusion: The parameter Ktrans, as measured by DCE-MRI, is reduced after one year of intensive lipid therapy. The result suggests that DCE-MRI methodology may be a useful imaging marker for the assessment of therapeutic response to anti-inflammatory effect in patients with atherosclerotic plaque.