#203 - AMA #34: What Causes Heart Disease?

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Ask Me Anything episode. Welcome to Ask Me Anything episode number 34. I'm once again joined by Nick Stenson. In today's episode, we do a super deep dive, answering a lot of questions that have been accumulating around atherosclerotic cardiovascular disease. Now, atherosclerosis, of course, is the number one killer in the developed world. It affects basically everybody. So you undoubtedly know somebody who's affected by this, if not you. So we thought it was really time to kind of focus deep on this. So for this reason, we combined a lot of previous questions that have come in into this episode. And so we discuss a lot of things here. We discuss why everybody should care about atherosclerosis. We talk about exactly what it is and try to explain how it comes about. Now, it's important to spend a lot of time on this because if you want to understand how to prevent it, you really need to understand how it's caused, and then that'll give you some sense of what the markers are and what the markers don't tell you and what they do tell you. So we look at why it's not a disease that only affects old people, but why it really takes hold at an early age. And you need to be aware of this if, of course, you want to present it. We talk about cholesterol, blood work, what these numbers mean, what's typically run, what's not run, what metrics I like to look at and what you should be concerned over. We also get into a question that comes up a lot, which is can cholesterol levels be too low? So if you're taking medications to lower cholesterol or what happens if your cholesterol levels get really no, what are the risks of that? From there, we answer questions around coronary artery calcium scores or CACS, CIMT, CT angiogram, and a whole bunch of other things along that. So if you're a subscriber and you want to watch the full episode of this in video, you can do so on the Show Notes page. And of course, we'll have the show notes that include a whole Bunch of details worth pointing out here. Before I start, this is an episode where I probably have more figures than any other episode I've done. So even if you're not someone who likes to look at the graphics, I think this is the one time you probably want to make an exception and watch the video. If you're not a subscriber, you can still catch a sneak peek of this on our YouTube page. So without further delay. Hope you enjoy. AMA number 34. Hey, Nick, how you doing?

I'm not doing too bad. How are you doing?

I'm good. We got a doozy today.

More so than usual.

I know. I'm bracing myself for the intensity of this discussion. We've accumulated, I don't know, almost an endless supply of questions on heart disease in one format or another. The specifics around lipids, atherosclerosis in general, these things like that. And so, as is often the case, I think we've accumulated a critical mass of questions that we can now organize them into a coherent and thoughtful discussion around all things related to atherosclerosis. So I know you've done an amazing job taking these questions and organizing them in a way that makes for, hopefully, a logical discussion. So let's take it away.

The hope is a lot of this stuff we're gonna talk about today, we could dive in so deep, so many of these questions could be their own ama. But what we thought as a team was it'd be just much better to touch on all these aspects so people who listen top to bottom can just get a really good understanding of what this is, why they should care about it, how they should think about it. On that note, what we thought would be important is just answering the first question, which is, why should 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 have probably heard me say this before, but atherosclerosis is really the only inevitable disease of our species. Cancer, while prevalent with aging, and dementia, while prevalent with aging, do not appear inevitable the way 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 impact is huge, and the tools that we have are also huge. So again, we talk about longevity. Longevity has 2 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 am putting smoking aside for a moment, which is a very straightforward behavioral risk factor. In terms of less clear behavioral risk factors, the two biggest are clearly hypertension, high blood pressure and lipid abnormalities. And that's the one we're going to focus on here. So atherosclerotic cardiovascular disease, we'll just abbreviate. ASCVD 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 some people under 50, where they're just like, this is something that only affects old people. I'll 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, or if folks haven't heard it, I think it's worth hearing again. Right. I remember in sort of my first year pathology lecture in medical school, the 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. And it was a trick question. Of course. The answer was sudden death. The answer was that over 50% of people's 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 women, 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 sobering thing for me when you look at this is 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 45, 50, 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. I think what we need to do is first almost step back and look at what exactly is ascvd. 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 form, what this disease is?

I'll explain it at a high level now and then. I think we should go through it in some detail in a moment. But the precis on this would be that ascvd is a disease state characterized by the deposition or the buildup of cholesterol. More clearly, or more rigorously, sterols, which include cholesterol and phytosterol in the artery wall. It initially starts as something called a fatty streak, which I'll explain in a little bit more detail later, and then it later consolidates into things called plaques. 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, family 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 than I can even count or 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 characterize 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, cholesterol 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 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 of 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. The next section we're going to go through, which has the potential to be a little deeper than a lot of what this conversation is, which is how this all comes about and luckily and a quick shout out to Tom Dayspring who created a bunch of images that we're going to look at. This kind of allows us to dive into this. And so for people who are listening to this, if you can watch a video, it's probably going to be really helpful, but otherwise the show notes will also have all these images. But why don't we look at and discuss Peter, how does as CVD come about?

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