The confusion around HDL and its link to cardiovascular disease | Dan Rader, M.D.

**Peter Attia, MD** (0:11)
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Now, without further delay, here's today's episode.
I guess this week is Dan Rader. Dan is a professor of molecular medicine at the Perelman School of Medicine at the University of Pennsylvania, where he conducts translational research on lipoprotein metabolism and atherosclerosis, with a particular focus on the metabolism, and most importantly, the function of high density lipoproteins, HDLs.
Dan has received numerous awards and has been elected to the American Society of Clinical Investigation, the Association of American Physicians and the National Academy of Medicine. He also currently serves on the Board of Directors of the International Society of Atherosclerosis, the Board of External Experts at the National Heart, Lung and Blood Institute, and the Advisory Board for the Clinical Research of the NIH.
In this episode, we focus our entire conversation around high-density lipoproteins or HDLs. Now, as any listener of this podcast will know, we have no shortage of content around lipids. And we focus a lot of that energy on the APOB side of the family. That is, to some extent, VLDLs, and of course, Lp little a, which is a subset of LDL. However, this is the first time we're doing a dedicated podcast on HDLs.
Now, the reason for that, in other words, the reason for that disparity, is largely because HDL biology is so much more complex and we know so much less. I mean, at the highest level, I think people generally think of HDL as quote unquote, the good cholesterol, but you've no doubt heard me rail on the stupidity of such a designation. But there is clearly something good about HDLs, as in the lipoproteins, not the cholesterol. And in this discussion, we really talk about everything from the biology of the HDL, its genesis, its origin, its metabolism, its life cycle, and of course, its function. And we also talk about why it has been so complicated to use pharmacologic interventions on the HDL side of the equation to impact atherosclerosis. Conversely, of course, it's been the easiest thing, I would say, in medicine. And perhaps the greatest success of modern medicine, especially as it comes to cardiovascular disease, has been our ability to manipulate the APO-B side of the equation, as opposed to the APO-A side of the equation. That's one thing that's going to be important here when we get into the terminology. When we talk about APO-A in the context of HDLs, we're talking about APO-A as in a big A, which has no bearing whatsoever to APO-a, the thing that of course defines an LP-a. But I digress, that is simply one of the many details we get into. So, as I said, we're going to talk here about the genesis of the HDL, the structure, its metabolism. We talk about the differences between HDLs, LDLs, the difference between the HDL measurements. So what exactly is HDL cholesterol versus APO-A concentration versus HDL particle number? Talk about the idea that having a high HDL means you don't need to worry about cardiovascular disease and how that's obviously going to be bunk. I'm just going to let the cat out of the bag on that one. We speak about CTEP inhibitors, which are a class of drug that have been repeatedly used to try to increase HDL cholesterol with the hopes that that would reduce cardiovascular disease. And finally, we end the conversation around some of the new thinking around HDL and neurodegenerative disease, something again I learned a lot about. So without further delay, please enjoy my conversation with Dan Rader.

**Dan Rader, MD** (4:04)
Hey!

**Peter Attia, MD** (4:04)
Well, Dan, thank you so much for making time to join us on the podcast today. Tom Dayspring really recommended you highly. And anytime Tom Dayspring says to me, you should have so-and-so on the podcast to talk about anything that has to do with lipids, I immediately pay attention.

**Dan Rader, MD** (4:20)
Tom's an amazing guy.

**Peter Attia, MD** (4:21)
Now in particular, the subject matter I want to explore with you today is probably the area of lipidology that I personally am the least familiar with. And that has to do with kind of one half of the lipid family. I explain this to patients as they're broadly speaking two families, the ApoB family and the ApoA family. We spend obviously so much more time talking about the ApoB family based on I think two things. One is our clearer understanding of it, and two, the direct and causal relationship to pathology.