MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course

Abstract

Objectives: The purpose of this study was to test the lipid depletion hypothesis and to establish the time course of change in carotid plaque morphology and composition during lipid therapy using high-resolution magnetic resonance imaging (MRI).

Background: Lipid therapy is thought to improve plaque stability and reduce cardiovascular events by targeting the plaque rupture risk features such as large lipid core, thin fibrous cap, and high level of inflammatory infiltrates. However, the plaque stabilizing process during lipid therapy has not been clearly demonstrated in humans and in vivo.

Methods: Subjects with coronary or carotid artery disease, apolipoprotein B ≥120 mg/dl, and lipid treatment history <1 year, were randomly assigned to atorvastatin monotherapy or to atorvastatin-based combination therapies with appropriate placebos for 3 years. All subjects underwent high-resolution, multicontrast bilateral carotid MRI scans at baseline and annually for 3 years. All images were analyzed for quantification of wall area and plaque composition blinded to therapy, laboratory results, and clinical course.

Results: After 3 years of lipid therapy, the 33 subjects with measurable lipid-rich necrotic core (LRNC) at baseline had a significant reduction in plaque lipid content: LRNC volume decreased from 60.4 ± 59.5 mm(3) to 37.4 ± 69.5 mm(3) (p < 0.001) and %LRNC (LRNC area/wall area in the lipid-rich regions) from 14.2 ± 7.0% to 7.4 ± 8.2% (p < 0.001). The time course showed that %LRNC decreased by 3.2 (p < 0.001) in the first year, by 3.0 (p = 0.005) in the second year, and by 0.91 (p = 0.2) in the third year. Changes in LRNC volume followed the same pattern. Percent wall volume (100 × wall/outer wall, a ratio of volumes) in the lipid-rich regions significantly decreased from 52.3 ± 8.5% to 48.6 ± 9.7% (p = 0.002). Slices containing LRNC had significantly more percent wall volume reduction than those without (-4.7% vs. -1.4%, p = 0.02).

Conclusions: Intensive lipid therapy significantly depletes carotid plaque lipid. Statistically significant plaque lipid depletion is observed after 1 year of treatment and continues in the second year, and precedes plaque regression. (Using Magnetic Resonance Imaging to Evaluate Carotid Artery Plaque Composition in People Receiving Cholesterol-Lowering Medications [The CPC Study]; NCT00715273).

Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Example of Carotid Artery in Multicontrast MRI

Magnetic resonance imaging (MRI) example of 8 consecutive images of the common carotid artery (CCA) through bifurcation to the internal carotid arteries (ICA) from 5 contrast weightings: time of flight (TOF), proton density weighted (PDW), T2-weighted (T2W), T1-weighted (T1W), and post-contrast T1W. The lumen in red and outer wall boundary in blue of the carotid artery are identified and outlined. Plaque tissue components within the arterial wall are identified using an established algorithm and quantified (loose matrix in purple and lipid content in yellow). For example, lipid content in yellow appears isointense on the TOF and pre-contrast T1W images and hypointense on PDW and T2W images, and has no contrast enhancement compared with the surrounding tissue on post-contrast T1W images. Total lipid-rich necrotic core (LRNC) volume is calculated by multiplying the slice thickness (2 mm) by the sum of the areas circled in yellow color on the 8 consecutive images. Percent LRNC (%LRNC) is the proportion of the wall occupied by the LRNC only in the lipid-containing slices, from slice #2 to #7.

Figure 2. Carotid Plaque Lipid Depletion and Time Course During 3-Year Lipid Therapy

After 3 years of intensive lipid therapy, lipid-rich necrotic core volume (LRNC-V) (green squares) significantly decreased from 60.4 mm3 to 37.4 mm3. Percent LRNC (%LRNC) (pink circles) also significantly decreased from 14.2% to 7.4%. The plaque lipid depletion time course over 3 years showed that %LRNC for pooled slices containing lipid at any time point significantly decreased by 3.2% in the first year, significantly decreased by 3.0% in the second year, and decreased by 0.9% in the third year (the change from year 2 to 3 was not statistically significant). Bars around the estimates are standard error bars.

Figure 3. MRI Examples of Plaque Lipid Depletion and Time Course

(A) An example of significant lipid content reduction (yellow arrows) and plaque regression at 3 years compared to baseline in the left carotid artery. Overall, 11% of study subjects had completed plaque lipid depletion over 3 years. (B) Magnetic resonance imaging (MRI) example of the plaque lipid depletion time course. Regression in lipid-rich necrotic core (LRNC) size was notable between the baseline, 1-year, and 2-year MRI scans. Regression in plaque volume seemed to follow plaque lipid depletion and was most pronounced from years 1 to 3. CE = contrast enhanced; T1W = T1-weighted.

Figure 4. Carotid Plaque Tissue Composition Change Over 3-Year Lipid Therapy

Changes in plaque fibrous tissue (FT), calcium (CA), and loose matrix (LM), both volume (V) (green squares) and composition (pink circles), over 3 years. CA = calcium; FT = fibrous tissue; LM = loose matrix. Compared to baseline, volume of fibrous tissue decreased, but percent of fibrous tissue increased. These changes were significant at each of the first 2 years. Calcium and loose matrix did not change significantly over 3 years. Bars around the estimates are standard error bars.