title: Effect of intensive atorvastatin therapy on coronary atherosclerosis progression, composition, arterial remodeling, and microvascular function.
abstract: BACKGROUND
  There is a discrepancy between the marked reduction in adverse events with statins and their modest effect on atheroma regression. We hypothesized that, in a Western population, high-dose atorvastatin will result in alterations in coronary atheroma composition, phenotype, and microvascular function.
  
  
  METHODS
  Serial coronary radiofrequency intravascular ultrasound (VH-IVUS), coronary flow reserve (CFR), and hyperemic microvascular resistance (HMR) were performed at baseline and after 6 months of treatment with 80 mg atorvastatin in 20 patients with moderate coronary artery disease (CAD). For each VH-IVUS frame (n = 2249), changes in total plaque atheroma, composition, and phenotype (pathological intimal thickening, fibrotic plaque, fibroatheroma), and serial remodeling were assessed.
  
  
  RESULTS
  Total serum cholesterol decreased from 186.0 mg/dL (interquartile range [IQR], 168.0 to 212.5 mg/dL) to 139.0 mg/dL (IQR, 124.3 to 151.3 mg/dL). Percent atheroma volume did not change significantly (-0.5% [IQR, -2.8% to 3.7%]; P=.90) and serial remodeling analysis demonstrated 40% constrictive, 24% incomplete, and 36% expansive patterns. There was a trend toward lower percent fibrous tissue (-3.47 ± 1.78%; P=.07) and percent fibro-fatty tissue (-2.52 ± 1.24%; P=.06) and increase in percent necrotic core (+2.74 ± 1.65%; P=.11) and percent dense calcium (+1.99 ± 0.81; P=.02), which translated into significantly less pathological intimal thickening (4% vs 12%; P<.0001) and more fibroatheromas (67% vs 57%; P<.0001) at follow-up compared to baseline. There were modest non-significant improvements in CFR (+0.26 [IQR, -0.37 to 0.76]; P=.23) and HMR (-0.22 [IQR, -0.56 to 0.28]; P=.12).
  
  
  CONCLUSIONS
  In this pilot study of Western patients with moderate CAD, high-dose atorvastatin resulted in alterations in coronary atheroma composition with corresponding changes in plaque phenotype and modest improvement in coronary microvascular function.
authors.affiliation: Interventional Cardiology, Emory University School of Medicine, 1365 Clifton Road, Suite F606, Atlanta, GA 30322, USA.
authors.forename: Parham
authors.initials: P
authors.lastname: Eshtehardi
authors.forename: Michael C
authors.initials: MC
authors.lastname: McDaniel
authors.forename: Saurabh S
authors.initials: SS
authors.lastname: Dhawan
authors.forename: José Nilo G
authors.initials: JN
authors.lastname: Binongo
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Krishnan
authors.forename: Lucas
authors.initials: L
authors.lastname: Golub
authors.forename: Michel T
authors.initials: MT
authors.lastname: Corban
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D055806:Microvessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012189:Retrospective Studies; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin