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(Circulation. 2006;113:2826-2834.)
© 2006 American Heart Association, Inc.

Interventional Cardiology

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

Paul Schoenhagen, MD; E. Murat Tuzcu, MD; Carolyn Apperson-Hansen, MStat; Chaohui Wang, MS; Kathy Wolski, MPH; Songhua Lin, MS; Ilke Sipahi, MD; Stephen J. Nicholls, MD, PhD; William A. Magyar, BS; Aaron Loyd, BS; Tammy Churchill, BS; Tim Crowe, BS; Steven E. Nissen, MD

From the Departments of Cardiovascular Medicine (P.S., E.M.T., K.W., I.S., S.J.N., W.A.M., A.L., T.C., T.C., S.E.N.), Radiology (P.S.), and Quantitative Health Sciences (C.A.-H., C.W., S.L.), The Cleveland Clinic Foundation, Cleveland, Ohio.

Correspondence to Paul Schoenhagen, MD, FAHA, Departments of Cardiovascular Medicine and Radiology, Cardiovascular Imaging, The Cleveland Clinic Foundation, HB-6, 9500 Euclid Ave, Cleveland OH 44195. E-mail schoenp1{at}ccf.org

Received November 22, 2005; revision received April 8, 2006; accepted April 14, 2006.

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.

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