title: The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease.
abstract: OBJECTIVE
  The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy.
  
  
  BACKGROUND
  Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation.
  
  
  METHODS
  Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (DeltaSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks.
  
  
  RESULTS
  Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (DeltaSI 0.13; p = 0.0003) and at 12 weeks (DeltaSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks.
  
  
  CONCLUSIONS
  Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589).
authors.affiliation: University Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Tjun Y
authors.initials: TY
authors.lastname: Tang
authors.forename: Simon P S
authors.initials: SP
authors.lastname: Howarth
authors.forename: Sam R
authors.initials: SR
authors.lastname: Miller
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Graves
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Patterson
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: U-King-Im
authors.forename: Zhi Y
authors.initials: ZY
authors.lastname: Li
authors.forename: Stewart R
authors.initials: SR
authors.lastname: Walsh
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Brown
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kirkpatrick
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Warburton
authors.forename: Paul D
authors.initials: PD
authors.lastname: Hayes
authors.forename: Kevin
authors.initials: K
authors.lastname: Varty
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Boyle
authors.forename: Michael E
authors.initials: ME
authors.lastname: Gaunt
authors.forename: Andrew
authors.initials: A
authors.lastname: Zalewski
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gillard
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069059:Atorvastatin; D015415:Biomarkers; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D016893:Carotid Stenosis / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D003287:Contrast Media; D003911:Dextrans; D004311:Double-Blind Method; D005260:Female; D052203:Ferrosoferric Oxide; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D007501:Iron; D008264:Macrophages / Q000187:drug effects*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D058185:Magnetite Nanoparticles; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D010087:Oxides; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D003287:Contrast Media; D003911:Dextrans; D006538:Heptanoic Acids; D058185:Magnetite Nanoparticles; D010087:Oxides; D011758:Pyrroles; C097921:ferumoxtran-10; D000069059:Atorvastatin; D007501:Iron; D052203:Ferrosoferric Oxide