title: Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study.
abstract: OBJECTIVE
  The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT).
  
  
  BACKGROUND
  Intensification of statin therapy reduces major cardiovascular events.
  
  
  METHODS
  Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment.
  
  
  RESULTS
  Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p < 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [-2.3% to 10.4%]; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes.
  
  
  CONCLUSIONS
  Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, MA, USA. atawakol@partners.org
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Robin
authors.initials: R
authors.lastname: Mogg
authors.forename: Achilles
authors.initials: A
authors.lastname: Alon
authors.forename: Michael T
authors.initials: MT
authors.lastname: Klimas
authors.forename: Hayes
authors.initials: H
authors.lastname: Dansky
authors.forename: Sharath S
authors.initials: SS
authors.lastname: Subramanian
authors.forename: Amr
authors.initials: A
authors.lastname: Abdelbaky
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
authors.forename: Michael E
authors.initials: ME
authors.lastname: Farkouh
authors.forename: Irene O
authors.initials: IO
authors.lastname: Nunes
authors.forename: Chan R
authors.initials: CR
authors.lastname: Beals
authors.forename: Sudha S
authors.initials: SS
authors.lastname: Shankar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging* / Q000473:pathology; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000473:pathology; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000188:drug therapy*; D049268:Positron-Emission Tomography / Q000379:methods; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D019788:Fluorodeoxyglucose F18; D000069059:Atorvastatin
keywords: 2-18F-fluoro-2-deoxy-D-glucose; AC; C-reactive protein; CRP; FDG; LDL; MDS; PET/CT; SUV; TBR; atherosclerosis; atorvastatin; attenuation correction; inflammation; low-density lipoprotein; most diseased segment; plaque; positron emission tomography-computed tomographic imaging; standardized uptake value; statins; target-to-background ratio