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I'm William Callahan, and today we're gonna be talking about hyperlipidemia and recognizing high-risk patients for ASCBD. I have no disclosures Uh, so today, we're going to describe the clinical significance of cumulative LDL exposure and its relationship to ASCBD, and we're also going to identify and certify those patients at elevated risk for ASCVD. So, ASCBD, leading cause of death worldwide, causing about a third of all deaths across the globe. Now, if we were to, instead of saying a third of all deaths across the globe instead of 32% of all deaths across the globe, we could break it down into those who die of ischemic heart disease, which would be close to 16% of all death across the globe. Or we could say close to 12% are dying of strokes across the globe. So, these are things we see fairly commonly in practice, and, you know, if there's anything we can do to prevent those from happening, it's something that we do need to pursue. When we talk about cholesterol, which we know is the basis of plaque, there's endogenous in dietary. Endogenous is made in the liver and it requires HMGCA reductase, which we're all familiar with due to the medications we use to treat cholesterol. Looking at cholesterol and the way it comes into our blood. So we eat something that has fat. Right, it's broken down, becomes triglycerides, and chylomicrons take that to the cells who want it. So think muscle cells, think fat cells, they will take it there, they will transport it there, and then the chylomicron remnants will then make their way to the liver, where the liver will then make it into a very low density lipoprotein, or they will discard it. Either way. But if they make it into a very low density lipoprotein that now has cholesterol particles attached to it, they will then leave the liver and make their way around the cells that want cholesterol. So cholesterol in and of itself is not necessarily a bad thing. You know, cells do need it. So if we think of our cell membranes, they do require cholesterols. It's more just that in overabundance, it becomes a problem. So very low density lipoprotein, VLDL will start dispersing its, its cholesterol particles, and as it does that, it becomes an intermediate density lipoprotein and ultimately ends as a low density lipoprotein. Which will go around and disperse cholesterol particles. HDL does the opposite and binds cholesterol that really is somewhere it shouldn't be and brings it back to the liver. A few things to know about cholesterol. So, these lipoprotein products do contain AOB 100. It's found in all LDL particles, and this really becomes important because it allows LDL to bind in the body. We're able to measure AOB 100, and that allows for us to say, is an LDL particle dense or is it fluffy? Think of it this way. Think of a suitcase, right? You have one suitcase, that's your LDL, your, your low density lipoprotein. Um, is it really crammed with clothes, right? You really densely packed it, or did you pack just one or two outfits and it's fairly light? That's how we can look at our LDL and our AOV 100, because each cholesterol particle carried by that LDL will have its own AOV 100. So if it's densely packed with cholesterol particles, it's going to have more AOB 100 than if it's. Not densely packed. If it's quote unquote fluffy, then it's only going to have, you know, a few AOB 100s because there's not many cholesterol particles to that low density lipoprotein. And then there's lipoprotein A. So lipoprotein A is LDL-like, but it is separate. This is not really affected by lifestyle. This is something more genetic, and it is something that increases risk for heart disease. So this is something that we should pay attention to, particularly when we are risk stratifying patients. If you do have a lipoprotein A level, this is something that we should be discussing with patients, assuming we have that information. So, LDL flows in the blood, but in overabundance where we have more LDL than necessary, it can start becoming trapped in blood vessel walls. Now, the immune system recognizes this, recognizes it shouldn't be there, and macrophages then engulf the cholesterol. This, of course, then really bloats the macrophages. They become fatty and foamy, and they then are known as foam cells. And this is the quote unquote, bad cholesterol because this is the basis for plaque. HDL does the opposite. HDL recognizes this and starts taking this back to the liver. So HDL, that's why it's known as good cholesterol, because HDL is taking it back to the liver and away from areas where it could really cause some trouble. When it comes to plaque, so these foam cells and plaque is starting to build up, it's not uniform across a blood vessel. It's like looking out at a mountain range. You have peaks and you have valleys. So, you know, when I'm describing this to patients, I'll say, look, you, you look at a blood vessel, you might have a lot of plaque in this one, and you might not have so much plaque in this one, and we know this. We do imaging studies, calcium scores, ultrasounds, and we can see which arteries are more affected than others. The problem really becomes that when plaque is disrupted and it breaks away, the body then responds in any way that you would expect. It tries to clot it off to stop any further damage, and that clotting it off can then lead to ischemia. Here's a clinical scenario. So, Mr. Smith, a 45 year old male, presents for his annual physical. On family history, he says that his father died of an MI at 52. Um, when you take a social history, he works a high-stress job, often eating fast food, and he's a former smoker. He quit five years ago, and you applaud him on this, of course. Um, he did do blood work. LDL is 165, and then he tells you that he, he can't remember the last time he had blood work. It's been at least 20 years. So Given Mr. Smith's family history of premature ASCVD, what is the most significant clinical implication of his high LDL level being present for an unknown but likely extended period of time? A, his current LDL of 165 is his primary risk factor. B, his high stress lifestyle is the only factor requiring immediate intervention. C. He has accumulated a high lifetime burden of LDL exposure, which is a major driver of atherosclerotic plaque progression. D. His risk is likely to decrease because he quit smoking five years ago. Or E, a single measurement of LDL is sufficient to determine his long-term risk. So just get, get everyone a little bit of time here to, to answer. OK, great. So the answer here. You see, he has accumulated a high lifetime burden from his most likely regular LDL level, and I say regular in the sense of it likely hasn't changed. He's not giving us any reason to believe that his current period in life is very different than it's been in the recent history. So, his level of 165 is likely where it's been hanging for most of his adult life, and that's a problem because it's elevated, and that elevated LDL is most likely causing trouble. Studies do show that if we address the LDL, if we can drop it by about 40 points, we can decrease the risk of major adverse cardiovascular events by upwards of 22%. So it's really important for us to know because when we're sitting with patients and talking with them, We can discuss this and we can say this is why you might wanna consider medication because your risk is high of developing an event, and we can lower that. But it also leads to the idea that LDL, if we can lower it at all or even earlier, we can help decrease the likelihood of these events. So, again, atherosclerosis is the buildup of plaque. And as LDL becomes trapped in the blood vessel walls and it starts building up, this is what creates a problem. And then again, as that plaque breaks off and then the body tries to clot off the remnant of that plaque, this can lead to ischemia. So it's, it's really problematic that this is occurring. Further complicating this is that there is a long asymptomatic period, and the studies bear this out, where atherosclerosis is building up, and we're most likely not doing a great job of addressing it. When we think that we're talking to patients and we're talking to them about, you know, their cholesterol, generally starting at least after the age of 30, if not 40, where we're checking these levels and we're talking to them about how to lower it. We're often not considering that plaque is building up in those years, and it's not until later in life that it becomes much more clinically significant. And this is just an example, right? The plaque starts building up. It's not at all blocking blood flow, but over time, it starts to decrease the amount of blood that can go by, and then once you have an event where the plaque ruptures, the body tries to clot it off, that's where you run into trouble. So here's a few studies.