Hey everyone, welcome to the drive podcast. I'm your host Peter Atia, this podcast, my website and My Weekly Newsletter, all focus on the goal of translating, the science of longevity into something, accessible for everyone. Our goal is to provide the best content in health and wellness. And we've assembled a great team of analysts to make this happen. If you enjoyed
This podcast, we created a membership program that brings you far more in-depth content if you want to take your knowledge of the space to the next level. At the end of this episode, I'll explain what those benefits are or if you want to learn more now, head over to Peter attea, m.com forward, slash subscribe. Now, without further delay, here's today's episode, welcome to another special episode of the drive as the podcast is. Now over four years old, we realize we've covered certain Topics in a variety of ways across multiple episodes. We
Of course, at times it can be hard to piece together this information. And it's also difficult for new listeners to be able to go back and keep track of information that's been covered in great depth in previous episodes. As a result, we wanted to release another episode. That is kind of a compilation of clips from previous episode. We did this before and it was a huge success. So for this one, we want to focus on atherosclerosis, cardiovascular disease, ascd, cholesterol, and apob. This episode includes Clips on why it is so important to care about ASC video.
D, the role of cholesterol in a SCV D, and why, I don't think anyone should refer to cholesterol is good or bad. And finally, we look at why a poby is an important metric to track. When looking at your lipids, put these clips in order of what we think, is the best way to listen to them, from top to bottom, and also provide some commentary in between Clips to give you a little bit of context. Our hope, is that not only will you understand this topic better, but you will also be able to identify some past episodes. You may want to go back to and listen, more deeply
Final thing, is that some of these clips are taken from AMA? So if you're not a subscriber, we hope this gives you a little bit of a sneak peek of what's covered in those episodes. This is still a fairly New Concept, we've only done this once before we got great feedback on that which is why we're doing it again. So, if you continue to like this, please tell us, and if you don't tell us why. So, without further delay, I hope you enjoy this special episode of the drive. What we thought would be important is just answering the first question, which is why
Would someone care about this? It's such a complex topic. Why is it important for people to put the time in to really think through and understand it? It really starts with the ubiquity of this disease and its assault on human longevity. People probably heard me say this before. But after sclerosis is really the only inevitable disease of our species cancer while prevalent with aging and dementia. Well, prevalent with aging do not appear inevitable.
Atherosclerosis does. So not everybody dies from atherosclerosis but I think to my knowledge everybody dies with it assuming they live long enough so you have a condition that as I said is inevitable is ubiquitous also I think based on what you're going to hear me talk about today, we know a lot about this condition and we really have tools to mitigate it to me that's the reason you want to really understand this the
The impact is huge and the tools that we have are also huge. So again we talk about longevity, longevity has two parts, healthspan lifespan, the lifespan part comes down to delaying the onset of chronic disease of which this is the most common chronic disease so you can think of a couple of different paths to get there but really the two biggest risk factors. I'm putting smoking aside for a moment which is a very straightforward behavioral risk factor in terms of less.
Our behavioral risk factors. The two biggest art, clearly hypertension, high blood pressure, and lipid abnormalities. And that's the one we're going to focus on here. So asterisk, erotic cardiovascular disease, will just abbreviate. A s cvd, for short is really what we're here to talk about. As we get started on this topic, Peter, I think we have people who listen to this podcast of all ages, young old everywhere in between and I think it's a common thought for people under 30 40, even
When some people under 50 where they're just like, this is something that only affects old people all think about this when I'm older. But right now, it doesn't really affect me. How would you answer the question in its basic form of? Isn't this just a disease of old age? And why should those people who think that not just shut off the podcast at this point? And instead continue to listen and continue to put in the effort probably have told this story before and if not were folks haven't heard anything that's worth hearing again, right? I remember in sort of my first year,
G lecture in medical school, that pathologist said, what's the most common presentation for a first heart attack. So if a person is having their first heart attack, what is the most common thing that they will present with? That's the terminology we use in medicine. And of course, the hands shot up, chest pain, being the obvious. Nope, that's not it. Nausea. Nope, that's not it. Left arm pain. No, that's not it. It was a trick question. Of course, the answer was sudden death, the answer, was that over 50% of people's first
First heart attack is fatal. Now, the good news is today, that number is a little bit less, it's probably slightly below 50%, but that's still a staggering number. Now, another way to think about this is through the lens of understanding the age distribution of people who have their first major adverse cardiac event. So that is a heart attack stroke or sudden death due to one of those if you don't mind Nick pull up Figure 1, this graph shows
The age distribution for both male and female in the United States in terms of these incidents. I think the easiest graph for me to look at here is the one on the right total annual events and what you can focus on is the first two bars. That is the bars that are for people up to the age of 65. So if you look at the
Male bars which are the darker bars. You can see that the sum total of those two bars. Slightly below 25%, slightly above 25%, the implication of that is over. 50% of men who are going to have a cardiac event in their life will have it before the age of 65. And for women, you do the same exercise, you can see that it's one-third of women. So it's clear that there's a shift in time and that
While subject to the exact same burden of disease, seem to experience it about a decade. Later still, fully one-third of women are going to have their first cardiac event. Which is going to be heart attack stroke or death, as a result of those things before the age of 65 and a little over. 50% of men will be in that camp. So as we're going to talk about in this episode that's not the whole story. It's even more compelling to care about this when you're young when you understand how long it takes for this disease to take.
Hold and the implications. Therefore for prevention, the most stubborn and thing for me when you look at this as it's not even the 50% under 65. It's almost the especially for males, the almost 25% under 54 and especially when we get to what we get to later, which is for that to happen to someone who's 4550, it doesn't mean it started two years earlier, right? And so, I think it's pretty crazy. When you see these type of stats, laid out how it creates that
Shift in your mind around. Why you should care about this.
What we need to do
is first almost step back and look at what exactly is a SCV D. I think people have to understand what it is to then really understand how it comes about how to think about prevention. So what do you think the best way to walk people through in a relatively simple?
I'm what this disease is. I'll explain it at a high level now and I think we should go through it in some detail, in a moment. But the precis on this would be the ASC. Biddies disease State characterized by the deposition for the build-up of cholesterol. More clearly or more rigorously sterols which include cholesterol. And phytosterols in the artery wall. Initially starts his something called a fatty streak which I'll explain in a little bit more detail later and then it later consolidates into things called plaque.
And these can ultimately lead to a reduction in blood flow and of course it's this reduction in blood flow that leads to what's called ischemia ischemia is the reduction in blood flow and therefore the resulting tissue damage that occurs to the heart is what results in a heart attack which can be fatal. Depending on the amount of the cardiac tissue. That is impeded from appropriate amount of oxygenation, to have this disease, you don't have to be obese, you don't have to have high blood pressure.
Or things of that nature. It's really a question of the cholesterol in your blood. That's really what defines the disease. So the essential condition of atherosclerosis is the presence of cholesterol. In the artery wall, which by the way, is not necessarily related to the measure of cholesterol in circulation, which we will talk about in great length. And although these often coexist patients with cholesterol in their arteries, do not necessarily have to have Co aggravating factors such as high blood pressure, diabetes, obesity
History, smoking. All these things that exacerbate it. You mentioned cholesterol a few times and obviously it's a topic that's been talked about on more podcasts and I can even counter recall right now. But for this conversation, can you define cholesterol just in its simplest form? So everyone's aware of exactly what we're talking about. As we're going to get into kind of the more nitty-gritty cholesterol is an organic molecule that resides in the lipid family. So we typically characterized these molecules by
Their solubility in water and this is a not soluble in water molecule. So it is a hydrophobic molecule and I think the easiest way to sort of picture those things is to think about oils. So if you took an oil like olive oil and you poured, some of it into a cup of water, you would immediately see what it means to have a hydrophobic substance in contact with something, which is the ultimate hydrophilic substance water, right? So they repel each other. Now, of course, class.
Is about one of the most important molecules in the body to be clear. If we didn't have the ability to make cholesterol, we would cease to exist. In fact, you couldn't be born without the ability to do this. There are rare genetic conditions that impair the ability to make cholesterol and these are uniformly. Fatal, why do we need cholesterol? There are broadly, two things that cholesterol is essential for. The first is that they contribute heavily to
To the cell membrane of virtually every cell in the body. So cells are actually kind of fluid things, spherical things. And what allows them to have that fluidity and what allows them to have membrane channels that allow things in and out of them is the cholesterol layer that forms the membrane and secondly, cholesterol is an essential substrate for the production of some of the most important hormones in the body, cortisol, estrogen testosterone, it's also essential for the creation
Bile acids which are necessary to be able to digest food. So, the Mantra that I like to say, is no cholesterol, no life, period. You should put that on a bumper sticker on your car. Just roll around, Texas with that guy. No, I think that's great. Why don't we look at and discuss Peter? How does a s CB D come about? So before I jump to the figures, I want to make one other point that I should have made a moment ago, and that is the necessity of the body to make cholesterol.
After all. So I think most people when they think of cholesterol will probably first think of what it is that's floating around in their bloodstream, but will very quickly turn to cholesterol within food because it turns out that when you eat certain foods, you can also eat cholesterol. Everybody knows for example, eating eggs means eating cholesterol and a natural question is what is the relationship between the food that I eat? That contains cholesterol and cholesterol, you're measuring in my bloodstream. And the short answer is very little. And the reason for that
Is the cholesterol that we eat is in a form that the fancy term for it is called its esterified. So it has a chemical bond that swings between an intermediary oxygen and then another side chain from just a straight mechanical problem that is too large for The receptors in our gut to absorb. So most of the cholesterol that we eat is, in fact, excreted, out of our backside, we don't bring it into our body.
And therefore, most of the cholesterol that we are going to talk about today is actually cholesterol that we have made and it's transported between cells through these things called lipoproteins one of the things I remembered from pathology a, so it's the first of the three major classes you take in pathology with something that the professor said, which is he said, no doctor has more experience.
Experience with what it is to have heart attacks than Pathologists because 50% of the people who have a heart attack died on their first heart attack. So he said I'm seeing 50 percent of the people who have a heart attack and their first presentation is death. So I kind of remember that and it's a very sobering fact to think that half the time and again I don't think
That's true today but I think 25 years ago that was the case. The numbers are probably a bit better today. It might be a third of first events or fatal but nevertheless it was sobering. So you have this sort of weird factoid that's again off in the recesses of my brain somewhere and then you hand me this textbook and it actually made sense with what he said because in addition to going through in great detail the pathological staging of atherosclerosis it was littered with
Topsy sections of coronary, arteries of people who had died for other reasons and notably, they were quite young. So here's a 26 year, old male victim of a gunshot wound. Here's a 27 year, old female who died in a motor vehicle accident. Here's a so, and so, and so, and so, then when you look at their coronary arteries, you realize they already have atherosclerosis.
They already have oxidized they poby bearing particles, engulfed by macrophages and thickened intima. And while they may not have calcification in their arteries yet, or the types of plaque that would rupture within the ensuing weeks or days or months. They nevertheless had atherosclerosis and they were in their 20s and in their 30s. So, all of a sudden, what this professor said, 20 some odd years earlier,
Made sense which is this was now an explanation. This was a bridge to explain what otherwise seemed hard to
understand atherosclerosis. It's a disease in the tissue and almost everything that lipid people talk about is in plasma. And if we don't understand the natural history of the disease, how can we construct a strategy to prevent it? And although, much of my work has been on a poby
The more important part I think has been on understanding how the natural history of atherosclerosis should direct our prevention strategy. What that leads to is that every major guideline in the world bases, their selection of subjects for Statin prevention on the 10-year risk of disease and that was a huge step.
Forward in 1980 and 1990, but it totally are not totally but it very fundamental. He makes prevention of premature disease, almost impossible. When you plug in the numbers to calculate somebody's risk for any of the risk algorithms that American College of Cardiology 2019 aha multi Society you plug in numbers.
That belong to the that particular patient. And what comes out is what you think is the risk for that particular patient. It actually isn't. But what drives that calculation is the age and the sex of that patient things, like cholesterol blood pressure, they contribute minimally to the actual calculation of ten year risk. So what that?
Means is if you're 35, but there is a real risk calculator for you. But if you get to 40 almost everybody's risk is low at age 40 and it is until you get to about 55, 60, that risk, gets you over the threshold for the American prevention, guideline treatment. So, prevention, really starts at 55 to 60, but half almost half of all in,
If arcs and strokes occur before the age of 16. So how can that be? What's Terry? And his colleagues established was for the first three decades or so of Life. The disease begins gets a foothold in the artery but it's only in the fourth decade that you start to develop the lesions that can actually precipitate a clinical event, but risk is low and yet the event rate is high. How can that
Possibly be. Well, the answer is stunningly obvious which we published there are a ton more people under 60 than over 60. So the rate of events is low but the absolute number of events is high. That's problem. Number one. Problem number two is say you get to 60 and you didn't have an event. Well, the disease was developing
And extending during your 30s 40s and 50s. So by the time we start to try and prevent an event, the disease is well, advanced in the arteries that to me are the two fatal flaws in the 10-year risk approach and we published a paper pointing this out in Jama. Cardiology a few years ago, born or discarding. His colleagues have done exactly the same thing with European guidelines.
Can't beat these numbers. So rather than what's Terry taught me. And it took some years before we could develop the methodology. Of course risk is a good concept. Of course it is, but we should be selecting people. Also based on causes, I can measure your a Kobe pretty precisely. I could measure your non HDL, cholesterol.
A little less precisely, but pretty well. And I know it's yours when I calculate the risk. If I said, okay, Peter, you're my patient. You're a healthy guy. Hi, calculate. Your risk is 4.1%. Now, what does that number mean? Is that your risk, though? It means that out of 100 people at 4.1%. Four point. One of them will have an infarct, but we know that with
In that category, there's a tremendous variance in real risk, not everybody's at 4.1, some are higher, some are lower, some are dead on.
So, if I had to risk algorithms, the Philosopher's a.j. are the English, The Logical positive, he was actually darn good on probability. There's a real challenge, predicting singular events. I'm either going to have an infarct in the next year or not, it's not really a probability. So, either I am or I'm not, if one algorithm said, I had a 10% risk. And another one said, I had a 15%
And or 20% whether I have an infarct or not both of them were right. Because they said there was sort of a chance you could and there was a far larger chance you wouldn't when we say people should be treated with a risk above 7.5 percent that means 92.5 percent of the time nothing will happen. Well, that's not a great incentive. I think for helping people understand what's truly going to happen. So the way
We can deal with this and what we've done is develop, what's called a causal benefit model, we measure non HL, or apob, and we can project the risk over 20 or 30 years. If you're 30 years old, the period of time, you should care about, is up to age at least 60. And so, if you were in a group, let's say and let's say, I make it 35 again and I say your chances of having an infarct.
Or a stroke before you're 65 or 30%. Now, that's a number. You can deal with that's a number that has meaning. And we could also calculate how much the risk can be reduced by starting at age, 35, or how much you lose by starting at age, 45 or how much more you lose by starting at age 55?
This next set of Clips is a
A deeper dive into cholesterol, the limitations of the standard cholesterol, blood panel, and an important segment on why, I think no one should ever refer to cholesterol as good or bad. So, I recently posted something on social media about my frustration with the way that the crest and frankly, even sometimes the medical establishment writes about cholesterol, referring to good cholesterol, and bad cholesterol. Now, if you've ever listened to me on podcasts, you understand that
Talk about this in great detail, but a number of the comments suggested that there are a lot of people that are kind of new to this discussion. They haven't necessarily followed me. They certainly haven't heard the, I don't know. Literally 25 hours worth of content on cholesterol over the last four years on my podcast and they were kind of looking for a little bit of call it the tldr version of cholesterol and I thought this would be great excuse to do it. So if you want to understand why I whale on people when they say bad cholesterol and good cholesterol,
All you have to really understand what cholesterol is and why that type of imprecise language is unhelpful to put it mildly. Okay, so let's take a step back. What is cholesterol? So, cholesterol is a lipid. It is synthesized by every cell in our body. That means every cell in our body makes cholesterol. Okay, so why do we make this stuff? Well, this stuff is super important for every cell in our body wouldn't make it. It's essential
Or the creation of a cell. So, a cell, when you look at a picture of a cell in a Booker online or something, they look like two dimensional structures right there sort of these flat things but really that's not what cells look like. That's kind of a cut open cell projected onto 2D the reality of your cells are three-dimensional and they are fluid. They have to be able to be more than just perfectly open spheres. So what gives them that fluidity is their membranes and it's the cholesterol within the membrane.
Rain that provides that fluidity. It's also, what allows Transporters to go across the surface of cells. These Transporters are what allow various things like glucose ions, hormones, Etc, to Traverse cell membranes. So, compared to understand that. If we didn't have cholesterol, we wouldn't have cells. If we didn't have cells. Wouldn't be making this video and you would be here to watch this video. No, cholesterol equals, no life. There are things that are almost
Essential for life, that go beyond that cholesterol is the precursor to some of the most important hormones in our body, which ranges for things like vitamin D2, cortisol to estrogen testosterone, progesterone, Etc, also essential for bile acids. We wouldn't be able to digest most of our food without bile acids, especially fatty foods. So, the list goes on and on, as to why cholesterol is essential.
So why does the story not end there? Why are we having this discussion? Well, when it comes to something, as essential as cholesterol, not every cell in the body is capable of making enough cholesterol to meet its individual needs. So the body has to be able to traffic cholesterol. So there are certain cells the tend to be net exporters of cholesterol. The liver for example, as a general rule deliver makes more cholesterol than it needs, whereas, through parts of the body that need
More cholesterol than they are typically capable of making especially during periods of high stress. So those parts of the body need to receive cholesterol and this poses a little bit of a problem because the main channel that we like to use in the body to transport things back and forth is of course the circulatory system. It is not the only system we have a lymphatic system but the circulatory system is the system that we tend to use most to transport things like this. Now there are lots of things we transport in the circulatory system and we do
Without any difficulty, we transport glucose about any difficulty, we transport electrolytes, without any difficulty, we transport lactate without any difficulty. Why? Because all of those things that I just stated are water-soluble and of course the circulatory system is made up of plasma and proteins. That's what your blood is the plasma being basically the water of the cell. And so things that are water soluble like all of the proteins hemoglobin and things like that, things that I already stated glucose electrolytes.
They are soluble in water and therefore, they transport easily. But as I said at the very outset cholesterol is a lipid. And if you remember a little bit from chemistry class, you'll know that a lipid is not water soluble. It is hydrophobic as opposed to what we say is hydrophilic. So things that are hydrophobic can't move in water, just as you would olive oil into a glass of water, you would quickly realize how much they repel each other.
So we have this totally essential thing that we have to move around the circulatory system otherwise we would die and we can't do it directly because the medium through which we need to transport it repels. The thing we're trying to transport. Aha there's a solution. We need to create a vehicle that we can transport this in and that vehicle is called A lipoprotein. And as its name suggests,
Lipo and protein its part, lipid, part protein and it's engineered in a way that the lipid part is on the inside the protein part is on the outside, protein is water soluble. So now you create this spherical molecule which on the inside you can package the cargo that is hydrophobic repels water and on the outside, you have a coating that is hydrophilic, it is attracted to water and moves.
Mostly through the water, and that's how we transport cholesterol. Now, broadly speaking, these lipoproteins traffic in two types of families, a family that is defined by a Toby which is lipoprotein that wraps around it or an ape, A lipoprotein that wraps around the spherical larger lipoprotein and a Poe a there's an echo, a family, there's an 80 be fit technically there's two apob families. There's
An APO be 100 and an APO be 48. I'm going to ignore the apob 48 right now that just exists on chylomicrons. And we could do another class on that and another day. But for now, we're going to focus on a bow. Be 100, which defines the lineage of lipo proteins that are terms. You've probably heard of vldl Ideal LDL, LP little a and the, a Poe, a lipoproteins Define, a totally different class of these called hdls. So what are those
Names mean anyway vldl IBL LDL HDL. They all refer to another feature of the life of proteins that is distinct from the ape of lipoprotein that wraps around them which is their density. So if you think about a high school experiment where you take various different substances and you put them into water, you might notice that you can separate how they would float. Now water is kind of a bad example of how that works because things are
Eclis binary behaving and water either sink or they're going to float, but I think that gives you a conceptual understanding of the difference in density density is mass over volume and a higher density. Object relative to a lower density, object will sink versus float. So if you take all of those lipoproteins that I mentioned, all of the apob ones, all bapa ones, and you put them in a certain type of gel in the lab. You can see a separation of them.
Their density and the highest density ones of those, we just call the high-density lipoproteins, the hdls. You have more than one a Poe, a on an HDL and you have different subclasses of hdls. Make shells are really complicated and we don't even come close to understanding all the ins and outs of them. Which, by the way, is why I get really annoyed. When people say having a high good cholesterol is good again, what they really mean to be saying is having a high HDL cholesterol is good. And while it's true,
That on average higher HDL, cholesterol is associated with and traffic's with metabolic Health in a way that low HDL cholesterol, tends to traffic with bad, metabolic Health. You can absolutely not tell by looking at an individual based on how high their HDL cholesterol is if they're in good shape or not because that single snapshot of how much cholesterol is in the HDL. Tells you nothing about the functionality of the
It's the functionality of the HDL that matters my going to talk anymore about that because I have an entire podcast coming out on HDL, biology, where we'll go into that in great detail, but it should be stated that efforts to raise HDL cholesterol. Pharmacologically have by and large mostly not exclusively but mostly failed in improving outcomes. Okay. So over on the LDL paper beside the most abundant 80 be 100 or 80 be for sure.
Short lipoprotein is the low density lipoprotein. That's the one that gets called bad cholesterol and again on the APA side we have HDL which is called good cholesterol. So couple things I want to say on this one. If you're talking LDL, you are referring to the low density lipoprotein. If you say HDL, you are referring to the high-density lipoprotein. But if someone says, what is your HDL? What is your LDL? They're asking for a laboratory.
Rick, they are asking incorrectly, there is no laboratory metric called LDL or HDL. There is HDL cholesterol, LDL cholesterol abbreviated ldl-c and hdl-c there's L DL P and H DL P, which is the particle number of LDL, which can be counted via electrophoresis or NMR course. My preferred way to count the number of these particles is to look at a pub. Be the apob concentration to me is the most important.
Number you want to understand to predict from a biomarker standpoint, your cardio metabolic risk, a, a cvd risk, because it captures all of the, after genic particles, so apob counts, the total of the ldls inclusive of the LT. Malaise, the ideals will go, they virtually never exist. They have such a short residence time and the vldls which can become problematic in people with metabolic syndrome and high triglycerides. So a Kobe gives you the total after genic burden of those lipoproteins and therefore I think it's the preferred met
By which we want to assess risk, but if you want to look at LDL, you have to look at ldl-c, LDL cholesterol and HDL. You look at HDL cholesterol now is the cholesterol in the HDL. Any different from the cholesterol in the LDL. No, of course not. Therefore, it is totally erroneous to say HDL is good cholesterol and LDL is bad cholesterol. Now, instead, what is true, is that ldls themselves as lipoproteins are
Are Bad actors because of what they do, what they do is they go into artery walls, where they get oxidized and they basically dump their oxidized sterile contents into the sub endothelial space, which elicits an immune response and a whole bunch of other things that lead to atherosclerosis, which I'm not going to get into now. But the point of this discussion that I want people to understand that LDL and HDL Sr lipoproteins. If you want to talk about the cholesterol, you talk about LDL
HDL cholesterol. But the cholesterol in them, is the exact same. And there is no such thing as good cholesterol or bad cholesterol. And so, you just have to be careful. When you see, things written that are written through that lens. Because what it tells you is the person writing, this doesn't understand the basics of lipids and lipoproteins. And if they don't understand the basics of lipids and lipoproteins, because what I just told you guys is, literally the 101 on this subject, we didn't get to the senior level
Class, let alone, The Graduate level class. And this is complicated stuff once you get into that level. So if someone writing to me is butchering, the 101, you can stop reading because whatever else they're saying, they're undoubtedly, screwing it up. So there it is. There's the tldr on lipids,
if a doctor gets a report, now, he gets total cholesterol triglyceride.
Non hdl-c, ldl-c hdl-c, five numbers. Do you think he actually looks at any of those numbers? He's trying to do a good job. He does. But let's say the triglycerides are high. Can he do anything with that? Nope. Because everything is based on ldl-c. So he's got in reality for numbers that are doing nothing.
Let's explain that to people Alan because you, and I know the ins and outs of that very well, but I think most people,
I'll here don't understand the difference between the calculated and measured LDL. So let's start with that and then let's talk about how vldl has been estimated and let's bring this all back in terms of some other work you've done, which is understanding the role of triglyceride in a bow be. So let's start with the basic you go to the doctor, you get a set of labs done and the LDL number comes back at 140 milligrams per deciliter. Is that actually what it is or is that an estimation?
Destination is almost always a calculation. And there are at least eight different methods to calculate LDL cholesterol. So if there are eight different methods, they don't all give the same answer or you wouldn't have eight different methods. LDL cholesterol can also be measured directly that assay has never been validated in disease. Patients, and no one has ever published a paper. Showing that it's more accurate in terms of disease identification.
In then, calculated LDL cholesterol. And yet people have paid good money for that lab test. There's no question that the number of LDL particles is a more accurate index of risk than the LDL cholesterol. The V LDL cholesterol is a cholesterol. It's in the Via very low density lipoprotein, particles particles that come out of the liver. That cholesterol is atherogenic.
There's a lot of triglyceride in that particle. So the people who measure triglyceride say, well, the triglycerides are high, that must be the problem. And there's no question that people with high triglycerides are at increased risk of heart disease. But the people with the high triglycerides who are at increased risk of heart disease, have a higher number of LDL particles and vldl particles. It's the particle and when you're measuring the triglyceride, you're just measuring a blob.
Of liquid in a bunch of particles and you need to know the number of them. So it's an important number in the sense of, If You're A lipoprotein guy, trying to figure things out. If it's extremely high, it increases the risk of pancreatitis. But I haven't seen any solid evidence. That's triglyceride itself is pro atherogenic. What's atherogenic is the cholesterol. Inside the V LDL particles. It's the number of those particles that get into the wall. Now, there's
A complicating reality because in general all I need to know is the apob but there is a disorder called Remnant type 3des lipoprotein emia and that's a very specific highly atherogenic condition that manifests with Hydro glycerides, high cholesterol. But get this, you know, low a probie. So when I measure my lipids in apob, I can recognize that
But if you don't measure the apob and this applies to most of the people who are listening to this podcast, if they go to see their doctors, that condition can't be diagnosed.
A lesson, Eclipse will focus on why I think apob is a superior lipid metric to LDL cholesterol or even on HDL cholesterol when trying to predict risk,
Are you optimistic? I mean is this just a question of time? I mean in 10 years will kids in med school be learning about apob instead of LDL?
I'm pessimistic Europe, the 2019 guidelines, were very Pro able to be the evidence from mendelian randomization like the newer Technologies mendelian randomization they've just been slammed on. Freebo be
what's explain that to folks? Because I want to talk about the causality of this and this might be the perfect way.
Way to actually explain the causality of a poby in the context of this tool. So can you explain to folks what a mendelian randomization is were people see this all the time in studies but I don't think it's entirely clear for the average person. What it
means. I'll try. Okay? It's not my expertise, but I'll try the conventional ways of taking things apart with prospective observational studies like Framingham, there's a limited amount of the certainty of York.
Inclusions because of confounding, you can't deal with. You take measurements at age 20, and you follow someone for the next 30 Years. Well, a lot of things change in the next 30 years that you don't have a handle on your inference is our probable, but not causal. What mandelian randomization allows you to do is to come a lot closer to causality because, for example, you can identify
Defy groups of genes that are associated, where changes in the gene are associated with the little lower cholesterol or little higher cholesterol. And when you lump together a bunch of those different genes that can have different makeups because you can change the makeup of a gene pretty easily. You can see fairly substantial differences in cholesterol. So what you've got is information on somebody that's fixed at Birth and you
Is that associated with a difference in outcome? You've gotten rid of a lot of stuff in the middle and what a number of been Delian. Randomizations have shown, is that a poby includes all the information in triglycerides? LDL cholesterol, and even HDL cholesterol, it sums them which in a sense of vldl and LDL makes perfect sense. So, there are caveats in mendelian randomization
You can't just push a button and say give me the answer but George Davey Smith. Really arguably one of the founders have been dealing randomization or not arguably was he's the author of a number of them in dealing. Randomization say apob incorporates and therefore, beats triglycerides in LDL cholesterol. So that's a huge level of information.
That isn't even mentioned in almost any of the
guidelines. Yeah, so let's make sure people understand everything. You just said because you said a lot of things in there when you prospectively follow a cohort. The way the Framingham cohort was followed or the Framingham Offspring, or the Mesa cohort, or any of these cohorts have been followed, you can take a bunch of people and you could measure their a poby or their ldl-c or whatever metric, it is that you are trying to determine if it. In fact, has a causal relationship to the
disease of interest. You can follow them over decades and you would demonstrate as has been demonstrated that the people with higher be higher, ldl-c higher non hdl-c and lower hdl-c. All have a higher risk of developing atherosclerosis over time but it's hard to say that that's causal just based on that information because over the ensuing 20 years that you follow them, they are free to make other choices.
May impact those variables of interest and other variables. So the mendelian randomization attempts to get around that by saying, at the time of, I was going to say birth. But really, at the time of conception, we all get randomized to a set of genes. We get assigned a set of genes, I guess they're not perfectly random because they come from our parents, but for the purpose of not changing, they are indeed a random assignment. That is fixed. If we,
Can identify which genes map to which phenotype and we can figure out the genes that map to the phenotype of our interest namely driving up, or down a variable of interest such as a poby. Then we don't really have to worry about the confounders that occur in between because the genes can't change just to put a bow on that. Basically. Now, when you see a difference in outcome,
It's much more likely to be causally related to the phenotype of interest because the gene has not changed that underlies. It. Now, what are some of the ways that we can get tripped up with mendelian randomization? I mean, there's some pretty big ones.
Yeah, before we get there HDL cholesterol was the rage, okay? The total rage because the epidemiological evidence couldn't be clearer.
In fact, it was four times more clear my recollection.
Action. Was that Framingham? Demonstrated low
hdl-c was four times more
predictive of cardiac events than high ldl-c am. I remembering that correctly?
Not sure. It's that mobile. Yeah, but it's multiples and it turns out as we know now, at least in the CTP Inhibitors that you can't manipulate HDL and change outcomes. And that's one of the elements of demonstrating, an overall, causal relationship, and the mendelian randomization.
And show HDL is not cause we're as they show a bobi is and cholesterol is too. By the way,
those are two very important studies, Alan. I mean, and both of those have been in the last 10 years.
Yeah, it's a incredible technical advance in being able to examine questions and look at numbers of people that are would be unimaginable in conventional studies. The mendelian ran out there.
He's talking hundreds of thousands of people because they've got these huge data banks with jeans. And those numbers get you around the confounding of things you have huge numbers, but it's like any methodology. No method is perfect. This one can mislead you too, particularly when you've got a sequence of associated variables, for example, people show using Mr. That triglycerides were quote, causing or
And with increased risk, but when you took into account that not HDL cholesterol or the apob disappears, so when you've got a linked metabolic chain, you've got to be careful that you've gone to the end of it. You've got the real actor, not act, one leading to the you've got the real drag Persona dramatis,
which is why it's surprising that HDL didn't, at least at the first order demonstrate causality because there's no doubt that
Eclis the high triglyceride. Low HDL phenotype is so associated with metabolic syndrome, but it makes up two of the five
criteria. That's an incomplete description, that's like you. Describing your self as six feet tall. I wish, and not giving your wait. Let me guess your BMI. You cannot characterize any phenotype without the apob it
Dries me around the bend when people speak saying I got somebody because I got their triglycerides HDL. Well, I say okay, what's their apob how can you pretend you've evaluated the system when you haven't counted the number of atherogenic particles because they could be normal. They could be high or you can have a type 3. They don't know and it's not a phenotype. There is no.
Type without putting any booby in there. There lipoprotein particles there, disorders of lipoprotein, particle metabolism, of course, the triglycerides, and cholesterol are important, but my analogy, I didn't do a good analogy there but it's so fundamental that it drives me to distraction as to why you wouldn't want to know a core element of knowledge.
But it doesn't seem to bother many of my friends.
He walked through the pathophysiology of how the apob bearing particle wreaks, havoc in the artery wall, many, many years, before we see clinical events. And you also mentioned that there are other factors that can amplify or exacerbate that I can remember exactly how you said it, but that was the gist of it. Well, two of those things that are widely accepted to exacerbate risk are smoking and hypertension.
Ian in fact, smoking and hypertension probably carry a greater risk for atherosclerosis than apob or is that not the
case. It all depends the way you think about it because if you just say what's the risk somebody with hypertension phases, they have high risk. I know question. But then you say what is hypertension the last 30 or 40 years. There have been almost an infinite number of basic science studies on hypertension.
And when you were in medical school and even before that, when I was in medical school, we talked about pathophysiology of hypertension. And what strikes me is, we don't talk about the pathophysiology of hypertension anymore, but the basic science goes on in rats does healthier than ever. And there isn't anything. I know of that's come out of that basic science. That's been clinically useful in the last 30 years. The drugs we use, we use
Use them because they work. So what is hypertension. It's a higher blood pressure than we should have. And where is the disease that produces that higher blood pressure. Is it resistant? We don't have a clue. Okay, we don't have a clue and it strikes me. It's the same thing as much of the debate and lipids about a bow b or the drunk looking for the key under the light. Because this is where the light is not where you lost it everybody, who's anybody?
Has the same Viewpoint. My bet is, it's in the proximal aorta, my bed is that it isn't that complicated? We lose elastance in the proximal aorta and that's just all like hypertension. Thank you very much. What could accelerate that process?
What's the mainstream view that this is
renal? When I read hypertension, I get lost. Because I get page after page after page of Peripheral arterial alert own and very complex
Malik studies and very sophisticated animal models. And there's some renal left. It's a miasma for me, an absolutely asthma.
I hadn't heard about the proximal aorta. So say a bit more about that. Well,
I'd say, this is me, the approximately order is elastic. And if you look at it flow curve, hydrostatic pressure curve, when were young, it's rounded because as the left ventricle ejects blood rapidly into the aorta, the aortic spans
So it absorbs, some of that energy, you know, that wind Castle, but they mentioned in school, it's not that big a deal. But the energy is, partially captured partially regained, but the wall isn't bad. The wall, can give way me personally, just in the middle of my brain. Imagine that. If those elastic fibers start to go, then the wall stiff. So now, when the left ventricle ejects blood,
The pressure goes up more rapidly and it falls more rapidly in diastole and that's why you get systolic hypertension with normal diastolic pressures. So my bet would be if I was not the age I am I would be looking at factors like cardiac output again which used to be way back when or factors that alter the behavior of the proximal aorta as much as something. That's to me pathophysiological e much more likely to
To be involved. So once I got hypertension, okay, then I've got a driving force to push particles into the wall,
and so you think it's the actual increase in the pressure of the
plasma and the response of the wall. I think there are responses of the wall. The wall, thickens up. It gets harder for particles to go through. Does it also damaged the endothelium? Do you think that plays a role? That's right. I don't understand into thelia dysfunction. It's more a language thing to me than it is a reality.
I know the endothelium is critically important, it functions abnormally and that's endothelial dysfunction how that fits into the overall thing. I don't know. My bet is April be particles are part of the process of inducing endothelial dysfunction, but I don't know that clearly experimentally
so going back then to the question at the top. Does it make sense to even compare hypertension to apob? They both seem to play a causal role.
Is one more causal than the other. Or is that a silly question because they're not binary and
static? I think that's not the right question. I think our blood pressure goes up as we age. I mean, hypertension involves so much of the population. That's not clear to me what the word disease needs, the prevalence. As we age is so high that to me, it becoming almost a aging process because we're lasting a lot longer than we were probably designed to go.
Go. So you have this repetitive injury to the proximal, aorta, it gets a little progressively, less able to deal with it. So the time were 50 what percent 60 percent have higher blood pressure between the figures are staggering. Is it really that high? I'm not sure. Don't don't quote me on that, but it's hi. Hi. Hi.
But doesn't apob also rise with age.
It does rise with age, but not that much. When we look at people at age, 35, we can
Pretty accurately, categorize the group they belong to at age. 35 not that they won't change somewhat. So if you're high at age 35 you got about a 95 percent chance of staying high, five percent will go out of the high Zone. They won't go low low. So if you're high at age 35 I wouldn't bet. Anything is going to move you down. That's why I think it's such a good signal for when we should start thinking about treating people.
And if you're low, some people go from low towards high but the majority don't and we keep following them. But if you're high no we've published a fair amount of this. If you're high, it's not 100% but it's about 90%. If you're going to be high,
is there a gender difference at least? Clinically I seem to see women as they go through menopause experience dyslipidemia. That men wouldn't experience over that same decade or even five year transition,
I think there are changes in paper will be goes up with menopause. I'd like there to be more data. Think part of the reason it's held a bow be back, is that people didn't measure it. So they were sort of. Well what I measured has to be important because I can't answer your question. Hopefully, more data will be coming but I agree with you. People can change at the menopause. So I'm not saying we don't keep looking at people, but when you have somebody at age 35 to 40 whose High, the odds are high that they're going to stay high.
Hi,
are we doing a better job treating hypertension than this lipid emia
have no idea. The incidence of coronary disease is going up in the last five years and that's despite Statin therapy and that's the Obesity diabetes. So I think we've been too quick to congratulate ourselves at how. Well we're doing there are many reasons that treatment is not succeeding as well as it should. And I think the complexity of the
Phenotype of the lipid model is part of the answer. It's easy for me. I get the apob where I want it to go.
Yeah, I mean, an explanation for your observation would be if in the last 5 to 10 years, the incidence of atherosclerosis or major adverse. Cardiac events is rising despite the advances we have. You would argue or could argue that if we're measuring ldl-c and that's our proxy for treatment. But as dyslipidemia is
Growing in the metabolic context. Meaning, if you have more medicine and more insulin resistance and more type 2 diabetes. We know that those phenotypes are associated with greater discordance between apob and ldl-c suggesting that you have a greater and greater portion of the population that is being undiagnosed, or being under diagnosed because you're treating their ldl-c and you believe that it's lower than their risk actually is because they're able B is higher. I know, you know what I just said. I hope the listener understands what I just
said
Yeah, what you just said was important. It's another example and unfortunate sad example. The trying to quantify lipoproteins based just on lipids is not adequate. You're not capturing, all the information that you should.
Let's go back to Canada macro Point here around a bow B, which is a greater coalescing around. The idea that
That apob concentration matters. So I think it's very well understood that two of the biggest risk factors for cardiovascular. Disease are smoking and hypertension. I don't think there is any ambiguity that cigarette smoking and high blood pressure. Increase the risk of cardiovascular disease and they both appeared to do so through a mechanism that weakens the endothelium or creates an injury to the endothelium,
The question now becomes as you put it Tom how Ironclad is the story that it's the, a poby bearing particle in the presence of injured endothelium that is. The Trojan Horse that begins. This destructive trajectory of taking that cholesterol into the sub, endothelial space becoming retained undergoing, this chemical oxidation process, which then kicks
Off an inflammatory response that paradoxically as an attempt to repair the damage results in what can be a fatal injury. There are other hypotheses. For example, there are people who note and we have, I mean, look, I have a patient in our practice time. You've weighed in, on her case, walks around with a total cholesterol of 300 and something and LDL cholesterol of 220 milligrams per deciliter and apob of 170.
My grams per deciliter, she's in her late 60's, and her coronary artery calcium score is zero. We have elected to not treat her with any lipid-lowering therapy. In other words, there are exceptions to this. How do we reconcile
that? Well, let's the human body and medicine. As you know, not all smokers are going to come down with lung cancer or chronic obstructive lung disease. Why not? If that's such a horrible risk factor, I try to explain this a color and
Certainly seen cases like you say where oh my God if I was just going to say give me your April be or whatever cholesterol metric. You're going on three drugs right now you got no choice and maybe the old days. We approach people that way but no more. I think you have to individualize your whatever risk factors. You discover that might wind up causing a thorough Genesis and then figure it out. So particle. Number is certainly a major factor that might force it in but not always
And that the allele function although you can certainly if you review the history this and how do you really determine endothelial function. Not everybody has serious endothelial dysfunction, who winds up with a sirs car. So particle number itself in. Some people can just make the particles go in. I think if you would take most adults, who's not going to have a little bit of endothelial dysfunction. So I agree with you. It's a combination of something about atherogenic, particles be it their number, and that
You'll dysfunction but I'm talking more and more. Now when I discuss any type of lipoprotein, I don't care which subgroup you want to talk about. I think we certainly have to know it's particle concentration but I like to talk about particle quality. So what are the other attributes of any lipoprotein that might contribute to its Etheridge Anissa t or in some perhaps not understood, meaning red make it relatively. It's not going to generate atherosclerosis in are certainly have to be
Things like that going on. So as we're getting smarter, we're looking at other components of the lipoproteins, that could be other proteins that are on them, that could be their complex lipid ohm and trying to see. Aha. Can that help us discern whether in you a given particle? Concentration is more worrisome than it is in the next and the next person. So there's a lot going on and also from the gist of this conversation, listeners will know atherosclerosis
After a Genesis is a multi complex multifactorial disease and that's why even when Peter and I if we consult on a case and we realize in this person we have to beat up apob and get their particle numbers to more physiologic range. We don't stop. Once we do that, we examine in great detail, for other things. That might be injuring the endothelium or the arterial wall and C are any of those treatable or so. So we're getting a little bit smarter on lipoproteins but there's
Certainly is more to it than just particle number.
Do we think that there's a limit to where the benefit of reduction becomes diminishing, or even J Curves in the other direction. So we discussed it in the first episode significantly, we did. So again, with Ron Krauss, it wouldn't be, you know, the worst idea in the world, a couple of years from now to sit down, and do it again and re-examine the data. But again, I think the causal relationship between apob and atherosclerosis.
Is as strong as virtually anything we see in medicine for which you can't do the perfect experiment where you have to rely on natural experiments. Nevertheless. Maybe it's not entirely clear with the dose response looks like. So if you have somebody who's a poby is 160 milligrams per deciliter, there's a risk reduction that comes to lowering it from 160 to 110, oring it from 100 to 80 and lowering it from 80 to 60.
What do we know about the risk reduction in lowering it say, from 60 to 40, to 20? And I asked both what we could infer pharmacologically and non-pharmacological E. In other words from the mendelian, randomization versus the pharmacologic.
Well even using pharmacologic trials. In mendelian randomization. You're going to the concept. You're going to come across with his lower is better. And with the pharmacologic thing, we're modulating things that either have clinical trial proof that. If you lower them, it's good or the mendelian. Randomization looking at Gene's, where that drug might be doing something it works. Now, you do need a few April, be containing lipoproteins, they do traffic other lipids, they traffic fat soluble.
I'll lipo proteins but we must never confuse a beta lipoprotein emia where nobody ever that person can't make them or hypo beta lipoprotein email, where they make a few enough to traffic. Those other things that are lipoprotein might have to traffic, but even the guidelines where they examine people base looking at their Baseline April, be your LDL cholesterol. The first thing they suggest at least in the higher risk people is try and get a 50% reduction and that's where most
Said a bang for the buck is going to be. Now if you still have options that you can lower it further. Yeah, the trial show. Yeah, there is incremental reduction events but it's a much smaller absolute risk reduction and dropping it. The 50% or so. So I don't know if that answers your question. So, most people don't have the type of levels where with modern Therapeutics with modern lifestyle, we can more often than not.
Attain physiologic concentrations. And if I want to talk about apob that's probably under 50 milligrams per deciliter. If we can get there, that's what the newborns have. That's when you go and clinical trials, if you take it down that low you see your most risk reduction and so far at least with pharmacologic lowering of apob with the currently FDA approved. Drugs there is no signal of harm.
Yeah, again, it's fun of you because I was just about to say, with the current crop of drugs, specifically, the pcsk9 Inhibitors. We are routinely seeing patients who easily can get an ape OB into the 20, to 40 mg per deciliter range. You and I actually sat down a couple of months ago, and did a calculation to estimate, how much cholesterol is actually contained in the circulating. Light Beam.
The proteins versus that, which is in cell membranes. Remember doing this with
me now per say, and where we're developing equations. You're the master of that. Well, it was one of these things, right? It was, it was
sort of like, look, you know, when you look at a person's plasma, glucose level, you realize pretty quickly. It represents a tiny fraction of total body glucose. And similarly, there's such a concern about plasma cholesterol level, but, you know,
Given how essential cholesterol is, it's understandable. Why people would be concerned that low cholesterol could be problematic. But once you do the calculation and realize virtually, all of the cholesterol in the body is contained within the cell membrane or within the steroidal producing tissue, the circulating amount is a very narrow window into the total amount of cholesterol and therefore a reduction of say 60 milligrams per deciliter.
DL 250 milligrams per deciliter of a poby or even something more extreme like a full. 50% reduction of total cholesterol, 200 milligrams per deciliter to 100 milligrams. Per deciliter does not represent a significant reduction in total body. Cholesterol is a very important Point. All right. Let me repeat it. You have a total body cholesterol that you measure in the plasma. That says, oh, it's 200 milligrams per deciliter that goes down to 100 milligrams.
DL. Let's say the LDL fraction reduced from 100 and 50 to 75 or something. Someone might say God, you just cut cholesterol in half that can't be good for you given the importance of cholesterol, but my point is no, you simply, cut the amount of cholesterol being carried by the lipoproteins, in the plasma in half that doesn't capture the majority of the cholesterol.
Yes, thanks for refreshing. My memory. What you're talking about? Now it's really pools of cholesterol throughout the body.
D. And I think I'm so glad you brought this up, because this is just not even understood, even in the lipid ology Community. We have a total body cholesterol. They're basically three pools. There's your brain and nothing were talking about today has anything to do with brain cholesterol to separate system. It doesn't interact with the other cells in your body are certainly with the cholesterol in your plasma. So if it's not in your brain, where is cholesterol in your body? Well, it's either in all your peripheral see
All's perhaps some more than others, or it's circulating in your plasma and if it's in the plasma, where is it? There's a eat seaweed. See amount bound to albumin. There's more bound within all of the Lipo proteins that are trafficking in your body. Meaning you are able be and you're a bow, a one particles but believe it or not. If I wanted to search down blood cholesterol for you, I would suck out your red blood cells and extract cholesterol from them, red blood cells, carry
Far, far more cholesterol than you, all of your life, o proteins, put together and the other crucial point you made subtle and I hope everybody understood you the amount of cholesterol within your lipoproteins has no correlation with your cellular cholesterol or even your red blood cell cholesterol. So whatever. However your modulating some LDL total cholesterol, HDL cholesterol metric that tells you nothing about what might you be doing to the
Stroll content of your cells. So don't have a panic attack if you're making LDL cholesterol, 30 because I can assure you virtually every cell in your body. Even if that's your plasma LDL cholesterol, has more than enough cholesterol because it can de novo synthesize it. It can put it in its cell membranes or other organelles that require cholesterol. If it's a stereogenic destroyed. Genic tissue can produce a little more, or perhaps the lipid ate, some like so there's no cell it's being
Deprived of cholesterol in the periphery when you are modulating lipids, through lifestyle or drugs.
So what is CBD? I've also become far more aggressive on the timing and magnitude of a poby reduction. So, take a step back and ask what are the leading causes or modifiable?
Is of a SCV d. The Big Three are pretty, unambiguously smoking hypertension and Hyper beta lipoprotein emia, which is just a really fancy word for saying too many lipo proteins that have a poby on them. So that's LDL IDL. Vldl LP little, a by measuring a poby why I'm such a fan of measuring a poby as opposed to just measuring LP LDL particle number or LDL
All number is, we have one single number that captures, the total concentration of a poby. And while that's pretty well, associated with non HDL cholesterol, which is a far better surrogate than LDL cholesterol, it's still better. And that's been demonstrated that I think we even covered that in a previous podcast where we went over the discordance between non HDL cholesterol and a poby. So now the question becomes well, when should you start a Kobe reduction and how much should
You lower it and I'll tell you, I used to take a point of view that if a 40 year old had an elevated apob, let's just put some numbers to this, right? So the 20th percentile of a poby is about 80 milligrams per deciliter. I used to say that let's say somebody was at the 50th percentile. They're 40 years old, their calcium score is zero and they were ambivalent about lipid-lowering therapy and let's assume that they're not insulin resistant and UV.
Done all of the things that you can do reasonably with nutrition. I wouldn't push that hard. I've now taken a very different stand, which is, I've basically taken the stand with others that I've taken with myself, which is the evidence is overwhelming that infantile levels of a poby are not dilatory Us in any way. Meaning an APO be of 30 to 40 milligrams per deciliter which is the level that children would have poses. Not only no risk to children as evidenced by the fact that
I mean that doesn't require an explanation. But as evidenced by what we see in the literature, on adults with levels that have been pharmacologically reduced tells me that we need to be lower. And the amount of time, it takes to see a benefit tells me, we don't want to wait until there's an issue. In other words, if the reason we begin therapy is because somebody has a positive calcium score, which again, we covered this in great detail. So, for people listening, we have a dedicated
Added a SCV, D AMA which goes into heavy detail for about 90 minutes on all this stuff where if this is of Interest, that's a great AMA. That goes super deep on, basically, all of the reasons why I think my point of view now is treat early and treat aggressively and I will now also make a very bold statement. Again it's let's start with the thought experiment, right? If the thought experiment for colon cancer was do a colonoscopy every day on a
Wife starting at the age of 30. Would you eliminate colon cancer deaths. I think the answer is yes. And similarly, I would say, pharmacologically lower apob to somewhere in the 20, to 30 milligrams per deciliter range for everybody in the population while someone is in their 20s. Can you eliminate a SCV D? And I think the answer is probably yes. In other words, I think what you're basically going to do is eliminate
Death from a thorough squatted causes and that would need to be started in 20s. I think so yeah. Very early on. Yeah. So again, how do you take that? Thought experiment, and turn it into a practical implication because I don't think it's practical to take every 20, year-old and obliterate their a poby. Although, it's clearly something we do in the subset of patients who have significant genetic abnormalities such as the cluster of genetic abnormalities that coalesced.
Around a condition called familial hypercholesterolemia. We certainly do medicate. Those patients, usually as teenagers. So, this is not some completely crazy idea, but I think practically what it means is basically, by the time you're in your late 30s or early 40s. If you have any measure of apob, that's even north of the 20th percentile. That should be completely lowered. So in some ways I would do in a poby ceiling of 60 as the limit and that's probably at about the
Fifth percentile, you sort of want everybody to be below the fifth percentile. Hope you enjoyed this special episode of the drive. This is one of the most talked about topics, not only on previous podcast but also one that we write about frequently in our newsletter, if you want to dive deeper there's no shortage of content and we'll link to it all in the show notes. However, we hope this provided you with a little more understanding of ascd cholesterol and a poby. Thank you for listening.
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