Author + information
- Received December 15, 2010
- Revision received May 26, 2011
- Accepted June 8, 2011
- Published online September 1, 2011.
- Xue-Qiao Zhao, MD⁎,⁎ (, )
- Li Dong, MD†,
- Tom Hatsukami, MD‡,
- Binh An Phan, MD⁎,
- Baocheng Chu, MD, PhD†,
- Andrew Moore, BS⁎,
- Trevor Lane, BS⁎,
- Moni B. Neradilek, MS§,
- Nayak Polissar, PhD§,
- Duane Monick, MD∥,
- Colin Lee, MD¶,
- Hunter Underhill, MD† and
- Chun Yuan, PhD†
- ↵⁎Reprint requests and correspondence:
Dr. Xue-Qiao Zhao, University of Washington, Cardiology, Box 354800, 1107 Northeast 45th Street, Suite 114, Seattle, Washington 98105
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 mm3 to 37.4 ± 69.5 mm3 (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).
This research is supported by a National Institutes of Health grant (R01 HL63895) from the National Heart, Lung, and Blood Institute, and by Pfizer Inc. The study medications are provided by Pfizer Inc., Abbott Laboratories, and Daiichi Sankyo, Inc. The authors have reported they have no relationships relevant to the contents of this paper to disclose.
- Received December 15, 2010.
- Revision received May 26, 2011.
- Accepted June 8, 2011.
- American College of Cardiology Foundation