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
It is also of interest that individuals with another cardioprotective isoform, ApoA-I Paris, also show an HDL pattern that consists primarily of HDL-3 particles.3 A recent epidemiologic study4 found that HDL-3, but not HDL-2, was associated with a reduced risk of progression of coronary artery disease (CAD). Furthermore, the ability of HDL-3 particles to prevent and/or release oxidative damage to LDL offers a potentially important mechanism of cardioprotection while HDL-2 particles show little activity in this regard.5 Both ApoA-I Milano and ApoA-I Paris also have been reported to exhibit more potent antioxidant activity than wild type ApoA-I.6 Taken together, the emerging evidence suggests small HDL particles are antiatherogenic, and this concept appears to be supported by the findings of Nissen et al.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
Instructions
Comments are moderated and will appear on the site at the discretion of the Journal of American Medical Association editors. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest* Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Customize your page view by dragging & repositioning the boxes below.
and access these and other features:
Register Now
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.