title: Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging.
abstract: OBJECTIVE
  Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease.
  
  
  METHODS
  98 participants from an AIM-HIGH sub-study underwent DCE-MRI of their carotid arteries. Expert readers who were blinded to all clinical variables analyzed the MR images to measure carotid plaque Vp in all participants. Associations between Vp and duration of statin therapy and other clinical risk factors were analyzed.
  
  
  RESULTS
  Prior duration of statin treatment at enrollment ranged from <1 year (21%) 1-5 years (40%) and >5 years (39%). In univariate analyses, shorter duration of statin therapy (P = 0.01), the presence of metabolic syndrome (P = 0.02), and higher body mass index (P = 0.01) and lipoprotein(a) (P = 0.01) were all significantly associated with higher baseline Vp values. In multivariate analyses, significant associations remained between shorter duration of statin therapy (P = 0.004) and lipoprotein(a) (P = 0.04).
  
  
  CONCLUSIONS
  These are the first human, in vivo findings suggesting a relationship between duration of statin therapy and regression of carotid plaque neovasculature. Future longitudinal studies are warranted both to confirm this finding and to address whether changes in neovasculature may translate into change in risk for plaque disruption. CLINICALTRIALS.
  NCT00880178, NCT01178320 and NCT00120289.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: cardiac@uw.edu.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Hippe
authors.affiliation: Center for Biomedical Imaging Research, Tsinghua University, Beijing, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Mountain-Whisper-Light Statistics, Seattle, WA, USA.
authors.forename: Moni B
authors.initials: MB
authors.lastname: Neradilek
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.affiliation: Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Peck
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Isquith
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA, USA.
authors.forename: Gador
authors.initials: G
authors.lastname: Canton
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Yuan
authors.affiliation: The Mountain-Whisper-Light Statistics, Seattle, WA, USA.
authors.forename: Nayak L
authors.initials: NL
authors.lastname: Polissar
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.affiliation: Presage Biosciences, Inc., Seattle, WA, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Kerwin
mesh_terms: D000328:Adult; D002339:Carotid Arteries / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Atherosclerosis; Lipoprotein(a); Magnetic resonance imaging; Neovasculature; Statin