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

Circulation. 2006 Jun 20;113(24):2826-34. doi: 10.1161/CIRCULATIONAHA.105.585703. Epub 2006 Jun 12.

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.

Methods and 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / drug effects
  • Adult
  • Aged
  • Atorvastatin
  • C-Reactive Protein / analysis
  • Cardiac Catheterization
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Coronary Angiography
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / physiopathology*
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / physiopathology*
  • Female
  • Follow-Up Studies
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / blood
  • Hyperlipidemias / complications
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / physiopathology
  • Male
  • Middle Aged
  • Models, Cardiovascular
  • Pravastatin / therapeutic use*
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Risk Factors
  • Single-Blind Method
  • Triglycerides / blood
  • Ultrasonography, Interventional*
  • Vasculitis / etiology
  • Vasculitis / physiopathology

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Triglycerides
  • C-Reactive Protein
  • Cholesterol
  • Atorvastatin
  • Pravastatin