Relationship Between Atheroma Regression and Change in Lumen Size After Infusion of Apolipoprotein A-I Milano

• Published in: Journal of the American College of Cardiology 2006-03, Vol.47 (5), p.992-997
• Main Authors: Nicholls, Stephen J., Tuzcu, E. Murat, Sipahi, Ilke, Schoenhagen, Paul, Crowe, Tim, Kapadia, Samir, Nissen, Steven E.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angina pectoris; Apolipoprotein A-I - administration & dosage; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Cholesterol; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - drug therapy; Coronary Vessels - diagnostic imaging; Coronary Vessels - pathology; Heart attacks; Humans; Infusions, Intravenous; Male; Medical sciences; Middle Aged; Phosphatidylcholines - administration & dosage; Remission Induction; Ultrasonography, Interventional
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2005.11.040

Relationship Between Atheroma Regression and Change in Lumen Size After Infusion of Apolipoprotein A-I Milano Stephen J. Nicholls, E. Murat Tuzcu, Ilke Sipahi, Paul Schoenhagen, Tim Crowe, Samir Kapadia, Steven E. Nissen This study defined the changes in the arterial wall that accompanied atheroma regression after five weekly infusions of reconstituted high-density lipoprotein cholesterol containing recombinant apolipoprotein A-I Milano. Regression was associated with a reduction in external elastic membrane (EEM) but no change in lumen volumes. This occurred in the 10-mm subsegments with the greatest baseline plaque burden but not in subsegments that contained the least amount of plaque. Changes in plaque volume correlated with changes in EEM but not lumen. These findings suggest that the arterial wall undergoes focal reverse remodeling in association with plaque regression, which involves changes in the EEM but not the lumen. The aim of this study was to determine the relationship between atheroma regression and arterial wall remodeling. Infusion of reconstituted high-density lipoprotein (rHDL) containing recombinant apolipoprotein A-I Milano (AIM) has been reported to promote rapid regression of coronary atherosclerosis. The current study analyzed intravascular ultrasound (IVUS) to define the changes that take place in the arterial wall that accompanied atheroma regression in this study. Forty-seven patients, ages 30 to 75 years, after an acute coronary syndrome were randomized to receive five weekly infusions of placebo or rHDL containing either low- or high-dose AIM. External elastic membrane (EEM) and lumen volumes were compared between coronary IVUS studies at baseline and follow-up. In comparison with baseline, infusion of rHDL was associated with a 4.6% reduction in EEM volume. Lumen volume did not change. In 10-mm arterial subsegments with the greatest plaque burden at baseline, atheroma volume regressed by 10.9% with a similar reduction in EEM volume but with no change in lumen size. In contrast, EEM and atheroma volume did not change in the 10-mm segments containing the least plaque burden. The reduction in EEM in the most diseased segments was only apparent in subjects who underwent plaque regression. Reduction in EEM volume correlated with the decreased atheroma volume (r = 0.62), but there was no correlation between change in lumen size and change in plaque volume. Remodeling of the arterial wall is a focal and heterogeneous process. After i