Lp(a) and its impact on heart disease | Benoît Arsenault, Ph.D.

**Peter Attia** (0:11)
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Now, without further delay, here's today's episode. My guest this week is Benoît Arsenault. Benoît is an associate professor at the University Institute of Cardiology and Pulmonology of Quebec at Laval University.
He's also a research scientist in the cardiology excess at the Quebec Heart and Lung Institute in Canada.
His research background is in understanding the risk of cardiovascular disease, such as atherosclerosis and aortic stenosis in relation to lifestyle and inherited risk factors. This includes extensive research in the unraveling of the role of LP little a, HDL metabolism, PCSK9 and lipid lowering therapies. In this episode, we really dedicate our focus to that of LP little a, something that many of you are aware of, especially if you've been listening to this podcast for some period of time. This is a subject, of course, that we've gone into great detail, but we haven't had a dedicated podcast on this subject matter since I did an AMA on it many years, and a lot has changed since then. So you may be asking, why should I care about this? Well, as Benoît points out in the podcast, while it varies by race, about 20% of the world's population is in a high-risk category of LP little a. This is actually higher than I thought. I had always cited the number of somewhere between 8 and 12%. On top of that, most doctors aren't checking LP little a with their patients. And I see a lot of my patients who show up who have never heard of this or had it tested. So that means there's going to be some of you listening to this who may not realize they have a high LP little a. And of course, that means you're at risk. In fact, LP little a is the single highest genetically inherited trait that confers high risk of ASCVD.
All of this is to say, this is a very important topic for everyone to understand, because even if you don't have an elevated LP little a, chances are you know somebody who does. Now in this discussion, we talk about a bunch of things. Of course, we go back to the basics. What is LP little a? We talk about the epidemiology of it, the basic biology of it. How is it inherited? How is it measured? How does it impact things besides ASCVD, such as aortic stenosis, and of course, ultimately myocardial infarction. We talk about the importance of measuring it in order to get the risk factors, how to manage lipids around it, et cetera. We also talk about what we know about the possible current therapies and treatments for LP little a, including niacin, statins, PCSK9 inhibitors, as well as the possibility on the horizon for things called antisense oligonucleotides. So without further delay, please enjoy my conversation with Benoit Arsenault.
Hey, Benoit, wonderful to sit with you today and talk about a subject matter that, you know, honestly, I think five, certainly 10 years ago, nobody would have a clue what we were talking about. And yet today we get so many requests to go back and revisit this subject matter.
So again, delighted to have you here and look forward to talking about something that probably impacts a lot more people than most might appreciate. So let's take a step back and give me a sense of where your interest in this little lipoprotein, Lp little a, came from.

**Benoît Arsenault** (3:50)
So first, Peter, thank you so much for the wonderful invitation. I'm really excited about our discussion today. So I got involved in LPA research actually during my postdoc years.
I trained here at Laval University in Quebec City, did some work in the field of lipids, looking at LDL particle size, triglycerides, ApoB, et cetera, on cardiovascular outcomes. So that was in 2006 to 2009, and that was really at a point where not that many people talked about Lp little a, because there had been so many negative studies on LPA and the risk of cardiovascular disease, like MIs and stroke and so on. And it's really the genetic association studies that have kind of resurrected the field of LPA, and these were published in 2009 to 2011 And that was during the time I was a postdoc in Amsterdam, and I was working over there with John Castellane. And he was working on the treating to new targets trial, the TNT trial, which is one of the first trial that showed that if you reduce low density lipoprotein, protein levels by increasing the statin dose, you'll get an incremental benefit in cardiovascular outcomes. So we were working on a bunch of sub-analyses in that trial, and they had just measured a whole panel of emerging biomarkers that could be associated with cardiovascular events like CRP, antiprobian P, other markers, inflammatory markers, other biomarkers of insulin sensitivity and LPH.