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March 17, 2004

ApoA-1 Milano and Regression of Atherosclerosis

Author Affiliations

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2004;291(11):1319-1320. doi:10.1001/jama.291.11.1319-a

To the Editor: Dr Nissen and colleagues1 reported that 5 weeks of treatment with intravenous recombinant ApoA-I Milano–phospholipid complexes (ETC-216) resulted in an average of 4.2% reduction in the volume of coronary atheroma. We disagree, however, with their speculation that this benefit is related to dimerization of high-density lipoprotein (HDL) and improved reverse cholesterol transport. In fact, the HDL pattern of individuals with the ApoA-I Milano variant has been shown to consist primarily of the smaller HDL-3 particles with a nearly total absence of the larger HDL-2 particles.2 Consequently, the infusion of ApoA-I Milano is likely to generate HDL-3 rather than HDL-2 particles. The misconception regarding the term dimerization may originate from the finding that ApoA-I Milano is indeed capable of giving rise to ApoA-I dimers while the size of the resultant HDL particles on lipidation remains small.1

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