Qualy #106 - Does LDL cause heart disease?

**Peter Attia** (0:11)
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Without further delay, I hope you enjoy today's Qualy.
Let's talk a little bit about a paper that you were an author on this year. It was the European Atherosclerosis Society consensus statement. Now, you and I were joking about this a while ago that you almost couldn't believe this paper needed to be written, but sometimes there's a benefit in writing it. And what was the conclusion of that paper? Or more to the point, consensus statement. It was more than just a paper. I mean, it was really a tour de force.

**Ron Krauss** (1:01)
So this paper assembled multiple lines of evidence addressing the question, does LDL cause heart disease? Is LDL a causal factor for heart disease?

**Peter Attia** (1:12)
And just to be clear, the counter argument is, sure people with high LDL are more likely to get heart disease. That can't be disputed. The epidemiology is clear.
The counter argument is, but LDL is not a causal role.

**Ron Krauss** (1:26)
That's right. And it's associated with that. Efforts to lower LDL cholesterol are not fully justified as a means of attacking the cause. I don't want to be responsible for having stated that incorrectly, because I still can't quite believe anybody would hold that opinion.
But that was my understanding that led to the group coming together to counteract that perception that lowering LDL was not beneficial.

**Peter Attia** (1:51)
But there are many people. I mean, not that I spend terrible amounts of time on Twitter, but it's a pretty commonly held view, at least in the vocal minority that love to write about this and talk about this, that, hey, LDL cholesterol is a myth. Like, heart disease has nothing to do with this.

**Ron Krauss** (2:06)
And the problem is, and it did come out in the paper to some extent, but I'll tell you, there is a second component to that effort that is still being written.
It was planned and will be a two-part series. The first part is assembling all the evidence from epidemiology, clinical trials, genetics, et cetera, that speak to the causality. And the second component was really relating all of this information to the role of LDL in the pathophysiology of atherosclerosis. And that paper is a work in progress, but it collectively, those two papers, assemble just about all the evidence one needs to support the use of LDL cholesterol.

**Peter Attia** (2:44)
And when will that second paper be out?

**Ron Krauss** (2:46)
I can't tell you. We don't even know yet. It has taken longer than we thought.

**Peter Attia** (2:49)
Well, we'll certainly link to the first one in the show notes because that was published in early 2018

**Ron Krauss** (2:54)
Yeah, yeah, we expect it in the next year or so. But one thing I do want to say, because there's a caveat, and part of my life as a researcher, as well as a clinician, is recognizing the complexity of what we're dealing with. In discussions such as this, it's important to keep the concepts straightforward and understandable to the best degree possible. But the flip side of that is the risk of oversimplifying a complex situation.
So when I just said that the evidence is that lowering LDL cholesterol is beneficial, that's not always true.
And so one can point if one is so inclined to the evidence that under certain conditions in certain populations with certain approaches, lowering LDL cholesterol does not result in reduced heart disease risk. And to the extent that you consider that to be a fatal flaw in the argument, that can be, I think, very misleading because it's not. The fact is that LDL is causal, but there are other circumstances that modify that causality to the extent that some forms of LDL under certain conditions, and this may not be uncommon, can be elevated without pathologic consequences. And so lowering LDL in those cases may not give benefit in that we know there is heterogeneity in the clinical response when one looks at cardiovascular protection with LDL lowering treatment. So I have to absolutely extend the simple notion of LDL causality to saying that one has to look very carefully at the arguments against LDL causality because they latch on to pieces of information that are really misleading. Just because lowering LDL cholesterol is not always beneficial doesn't mean that LDL is not pathological. And the second component of that is the focus on LDL cholesterol that goes back to our initial discussion here today as a marker for a causal mechanism, but it's the particles that are causal. And LDL cholesterol, as we just talked about, does not always mirror the number of LDL particles.