title: Determinants of arterial wall remodeling during lipid-lowering therapy: serial intravascular ultrasound observations from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial.
abstract: BACKGROUND
  Coronary plaque progression and instability are associated with expansive remodeling of the arterial wall. However, the remodeling response during plaque-stabilizing therapy and its relationship to markers of lipid metabolism and inflammation are incompletely understood.
  
  
  RESULTS
  Serial intravascular ultrasound (IVUS) data from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial were obtained during 18 months of intensive versus moderate lipid-lowering therapy. In a subgroup of 210 patients, focal coronary lesions with mild luminal narrowing were identified. Lumen area, external elastic membrane (EEM) area, and plaque area were determined at the lesion and proximal reference sites at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing the lesion EEM area by the reference EEM area. The relationship between the change in remodeling, change in plaque area, lipid profile, and inflammatory markers was examined. At the lesion site, a progression in plaque area (8.9+/-25.7%) and a decrease in the RR (-3.0+/-11.2%) occurred during follow-up. In multivariable analyses, the percentage change in plaque area (P<0.0001), baseline RR (P<0.0001), baseline lesion lumen area (0.019), logarithmic value of the change in high-sensitivity C-reactive protein (P=0.027), and hypertension at baseline (P=0.014) showed a significant, direct relation with the RR at follow-up. Lesion location in the right coronary artery (P=0.006), percentage change in triglyceride levels (P=0.049), and age (P=0.037) demonstrated a significant, inverse relation with the RR at follow-up. Changes in LDL cholesterol, HDL cholesterol, and treatment group demonstrated no significant associations.
  
  
  CONCLUSIONS
  Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.
authors.affiliation: FAHA, Department of Cardiovascular Medicine, Cardiovascular Imaging, The Cleveland Clinic Foundation, HB-6, 9500 Euclid Ave, Cleveland OH 44195, USA. schoenp1@ccf.org
authors.forename: Paul
authors.initials: P
authors.lastname: Schoenhagen
authors.forename: E Murat
authors.initials: EM
authors.lastname: Tuzcu
authors.forename: Carolyn
authors.initials: C
authors.lastname: Apperson-Hansen
authors.forename: Chaohui
authors.initials: C
authors.lastname: Wang
authors.forename: Kathy
authors.initials: K
authors.lastname: Wolski
authors.forename: Songhua
authors.initials: S
authors.lastname: Lin
authors.forename: Ilke
authors.initials: I
authors.lastname: Sipahi
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: William A
authors.initials: WA
authors.lastname: Magyar
authors.forename: Aaron
authors.initials: A
authors.lastname: Loyd
authors.forename: Tammy
authors.initials: T
authors.lastname: Churchill
authors.forename: Tim
authors.initials: T
authors.lastname: Crowe
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000032:analysis; D006328:Cardiac Catheterization; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D012307:Risk Factors; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood; D018084:Ultrasonography, Interventional; D014657:Vasculitis / Q000209:etiology / Q000503:physiopathology
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin; D017035:Pravastatin