title: MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course.
abstract: OBJECTIVE
  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).
authors.affiliation: Department of Medicine, Division of Cardiology, University of Washington, Seattle, Washington, USA. xueqiao@u.washington.edu
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.forename: Tom
authors.initials: T
authors.lastname: Hatsukami
authors.forename: Binh An
authors.initials: BA
authors.lastname: Phan
authors.forename: Baocheng
authors.initials: B
authors.lastname: Chu
authors.forename: Andrew
authors.initials: A
authors.lastname: Moore
authors.forename: Trevor
authors.initials: T
authors.lastname: Lane
authors.forename: Moni B
authors.initials: MB
authors.lastname: Neradilek
authors.forename: Nayak
authors.initials: N
authors.lastname: Polissar
authors.forename: Duane
authors.initials: D
authors.lastname: Monick
authors.forename: Colin
authors.initials: C
authors.lastname: Lee
authors.forename: Hunter
authors.initials: H
authors.lastname: Underhill
authors.forename: Chun
authors.initials: C
authors.lastname: Yuan
mesh_terms: D001055:Apolipoproteins B / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007061:Idaho; D050356:Lipid Metabolism / Q000187:drug effects; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014861:Washington
chemical_list: D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D002118:Calcium