Robert Harrington, MD; Renu Virmani, MD; Stephen Nicholls, MBBS, PhD


October 16, 2013

This feature requires the newest version of Flash. You can download it here.


Robert Harrington, MD: Hi. I'm Bob Harrington from Stanford University. I'm here at the European Society of Cardiology (ESC) meetings in Amsterdam and have had an opportunity to talk with a few colleagues about some of the hot, breaking science at these meetings. Joining me today is Renu Virmani, pathologist from Washington, DC. Welcome, Renu.

Renu Virmani, MD: Thank you.

Dr. Harrington: And Steve Nicholls, cardiologist from Adelaide, Australia, also joining us.

Stephen Nicholls, MBBS, PhD: Thank you.

Dr. Harrington: Now, we are having this discussion because while we were sitting out there in the lunch room, there was a bit of argument going around about whether raising HDL is going to help our patients.

You presented a trial this morning, Steve, about inducing ApoA. There are a number of phase 2-type trials going on with direct infusion of ApoA1 or the prime constituent protein of HDL. None of it has looked good so far, and that is where the context of the argument would be.

Biologics of Plaque

Dr. Harrington: So, Renu, I will ask you first. You are skeptical that giving people back HDL is going to help from a cardiovascular perspective.

Dr. Virmani: For me, what really matters is in the arterial wall, the lipid that gets in.

Dr. Harrington: Don't we think about ApoA as a molecule that can suck out LDL from the plaque? I am an interventional cardiologist. I like the visual of sucking out the plaque.

Dr. Virmani: I think it sounds attractive. In vitro you can do macrophages and you can see it suck out, but macrophages have to travel to that necrotic core to be able to suck out. And, you know, that surface is very rich in type 1 collagen; to break that is not that easy. I'm not convinced that we can get macrophages there, pick it out, and then take it back into the circulation.

Dr. Harrington: Interesting hypothesis, but you believe there might be biologic mechanisms that prevent it from working?

Dr. Virmani: Absolutely. I think biologics of the plaque itself prevent it.

Why HDL?

Dr. Harrington: Steve, you probably have a little bit of a different perspective. Before you tell us where you think the field is going, review for our audience what has been studied so far -- mechanisms -- and what have been the results.

Dr. Nicholls: We could ask ourselves why we are interested in HDL in the first place.

Dr. Harrington: Let's start there.

Dr. Nicholls: The reality is that in large populations, if you've got low levels of HDL cholesterol, you have got a high risk. We know that in animal studies, if you do something to HDL -- you infuse it, you turn on one of its major proteins using transgenic studies -- favorable things happen to plaque models of atherosclerosis. It has a range of biological activities which, in theory, could have a favorable effect on the arterial wall: lipid mobilization, anti-inflammatory effects, antithrombotic effects. We don't know which of them occur in vivo and whether that will translate to a favorable effect. We have seen, if you look at established medical therapies, that even small increases in HDL cholesterol predict the benefits of the fibrate studies when they worked. We have seen it associate with the benefit of statins.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: