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.
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.
Schoenhagen
Paul
P
FAHA, Department of Cardiovascular Medicine, Cardiovascular Imaging, The Cleveland Clinic Foundation, HB-6, 9500 Euclid Ave, Cleveland OH 44195, USA. schoenp1@ccf.org
Tuzcu
E Murat
EM
Apperson-Hansen
Carolyn
C
Wang
Chaohui
C
Wolski
Kathy
K
Lin
Songhua
S
Sipahi
Ilke
I
Nicholls
Stephen J
SJ
Magyar
William A
WA
Loyd
Aaron
A
Churchill
Tammy
T
Crowe
Tim
T
Nissen
Steven E
SE
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
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