- What if the bad cholesterol you've been told to fear your whole life isn't the whole story? What if there's a different test that could offer a clear, more accurate way to assess your true risk for cardiovascular disease? Well, we have a test and today we're talking all about it. Welcome back everybody to the Building Life on Godthies podcast, thanks so much for stopping by. For those of you who haven't met me, my name is Jordan Reinke, I'm a dual board certified physician in family and sports medicine. And the goal of this podcast is to keep you active and healthy for life through actionable evidence informed education. And today we're talking about a popular topic of APOB or Apolipoprotein B. It's all over the health YouTube and podcast scene. And today we're talking all about it, teaching why it's important, you know, what you should do, what you should look for, how to interpret it. And so really all those basic things, so let's get started today. So first and foremost, APOB, it's, this is really evolving, right? The understanding of heart disease and cardiovascular disease is moving much more beyond just simple cholesterol, right? Everyone thinks they hate, get your cholesterol levels checked, you're good to go. Well, APOB is now a different way, different measure to get something that we're looking at in those labs. So you get your traditional, you know, lipid panel, and then APOB is an additional test you can get. And APOB, we're gonna call it, so Apolipoprotein B or APOB, it's a crucial protein in lipid metabolism and a key structural component of atherogenic lipoproteins. When I mean atherogenic lipoproteins, what I mean are the things that get into your wall and cause heart disease, that's what that means by atherogenic lipoproteins. So APOB plays a big role in those. And traditionally lipid panels have had limitations, right? So we all know there's multiple values in there and they mean different things, they can fluctuate a lot. And we're starting to learn APOB might be a better indicator of what the actual risk is going on there. APOB is, yeah, gives a clearer picture of what's going on. And the goal here of this talk is to educate both, you know, the general public and healthy providers that haven't heard about this before, all about the significance of APOB. And so we're gonna talk about the structure of it, its role on atherosclerosis, might maybe be a better test than LDL, how to apply it, all that stuff. So we're gonna continue to go with that. So first APOB is a large protein and it's essential for the assembly and secretion of atherogenic lipoproteins. Once again, like I said, atherogenic lipoproteins are the ones that we care about a lot 'cause they're the ones that cause atherosclerosis. There's two major forms of APOB protein though, essentially there's APOB. So if we're gonna talk about APOB, there's two big forms. There's APOA, those are attached on HDLs, but APOBs, there's APOB48 and APOB100. APOB48s are only found on chylomicrons, which is a different type of a carrier protein and molecule, whereas APOB100s are on the VLDL, IDL, and LDL. And those are the ones we really care about. So APOB100s are typically the ones we care about 'cause those are the ones that are predominantly the ones that are getting into the wall and causing them. And so the big takeaway for this was that each lipoprotein particle contains only one molecule APOB. So once again, each lipoprotein particle has one molecule APOB. So when we're measuring APOB, APOB is providing a direct count on the total number of atrogenic lipoproteins around. Typically your traditional lipid panel, what you do is you get a cholesterol. And the cholesterol is actually like a volume. Essentially it's how much is on them. These carriers, lipoproteins, carry around cholesterol into the bloodstream 'cause cholesterol can't dissolve into the blood and transport. Normally it needs a transport protein. So these lipoproteins carry cholesterol. Our traditional cholesterol measurements are just measuring the amount of cholesterol that's on those carriers. But you could have a huge amount of cholesterol or a small amount, and we don't know about how many carriers there are. And this is giving us a direct number. So there's a one-to-one ratio. So we know exactly how many carrier proteins we have. And that's important spoiler 'cause we find that that's actually a good correlation to heart disease. And as I mentioned before, the APOB containing lipoproteins are chylomicrons, VLDL or very low density lipoproteins, IDL intermediate density, and LDL low density lipoproteins. And these are transport lipids. And yeah, they have, these are the ones that cause atherosclerosis, like I said before. They enter into the wall, accumulate into that arterial wall and lead to the development of atherosclerosis. And just a little side note as well, sometimes people get APOB and lipoprotein A confused a little bit. I'm gonna step back. They're both really important topics that people are talking more and more about, but lipoprotein little A or LP little A is kind of, it's another APOB containing lipoprotein that is also a big risk factor for cardiovascular disease, but they are separate indeed in terms of, the way I think about it is there's an APOB on an LP little A and LP little A is a higher risk form of a atherogenic lipoprotein. So step back there, you're like, dude, I've turned off, 'cause you said lipoprotein and atherogenic so many times. APOB, it's given us a one-to-one indicator how many carrier proteins there are. LP little A is a specialized carrier protein that's specifically bad for the heart and gives us heart disease. So that's what we're talking about with that. But as I talked about before, APOB, there are physiologic roles of what's going on there. So it does facilitate the transport of lipids from the liver to peripheral tissues. And it is regulated by multiple mechanisms, so it's a little complex. This is a cool illustration here. Thomas Daystream is someone who's a really big lipoprotein world lipidologist, and this is kind of an article. This is one of his big illustrations kind of showing the different atherogenic lipoproteins as they are. It's a little complex, but I wanted to show it, 'cause I thought it was really cool. But moving on here, atherosclerosis and APOB, I just wanna talk a little bit about this. So the trapping of those APOB-containing lipoproteins in the arterial wall is the fundamental cause of atherosclerosis. So getting in there, that causes it. If you don't get any APOB particles into the arterial wall, then we can't have atherosclerosis. The APOB particles in and of themselves are thought to be able to trigger inflammation, leading to formation of oxidation and inflammation, and leading to these atherosclerotic plaques. So essentially we can get them in there, cause that, and these oxidized phospholipids and oxidized APOB can further exacerbate this inflammatory process. So we stop and think about it as we have this process, something gets in the wall. Somehow, something gets in. These atherogenic lipoproteins get into the wall, starts triggering a little bit of inflammation, and that triggers an immune response, and it gets bigger and bigger, and this plaque grows. That's what it is. So APOB is important, because these are the ones that are measuring how many particles get into that wall and start leading to that. It's simplified a little bit, but that's the big thing that we're looking at there. And why is APOB potentially superior to LDL? There's a lot of people in the world say like, "Hey, APOB is all that matters. LDL doesn't matter." It's not quite that simple, but I think it might be a better marker, and I've started to transition a little bit more in my practice as well. And APOB seems to be a little bit more superior to LDL and non-HDL. So as I mentioned before, LDL-C measures the mass of the cholesterol on these particles, right? And it's variable. It may not accurately reflect the number of atherogenic particles. And that's the big thing with APOB. We know how many particles we have, 'cause it's one-to-one, whereas LDL, you could have a very low LDL, but have a ton of different particles, a ton of carriers, and we know that's actually bad. And so that's why we care about that. So people can have that normal LDL, but can have elevated APOB, meaning they have an increased risk due to a high number of these cholesterol-depleted particles. So what we're saying here is the total number of carriers seems to be a big indicator of risk. And if you have a, quote, low LDL, but have lots of carriers, you're still at a higher risk pattern, but the tests don't pick up on it. And so that's a big problem where, hey, you look good, things look good, but you're still at high risk, but we wouldn't catch it with traditional tests. That's what we're looking at. And as I mentioned before, APOB represents all the atherogenic particles, including VLDL, IDL, LDL, all that stuff, and it kind of provides a more comprehensive view of risk. And the number of APOB particles is more directly linked to the risk of cardiovascular disease than the amount of cholesterol within them. And that's a big, big thing. Time and time again, we see that, and the studies show that if you look at LDL versus APOB, APOB seems to be a better marker and predictor of cardiovascular disease than just LDL cholesterol. So that's why we care about it. And it's also repeatable. It can be measured accurately, relatively inexpensively, and there are standardized processes to do this. So it's starting to become more and more common. And I think as we learn more and more, we'll start to see it become more and more common in all the kind of cholesterol testing. So moving on to the atherogenic lipoprotein particle paradigm, which is a mouthful. This paradigm is based on multiple studies showing the importance of the number of APOB particles as the driver of atherosclerosis. So the core idea in this whole thing is that the total number of atherogenic lipoprotein particles is more critical for predicting vascular disease or cardiovascular disease than traditional cholesterol measures, as I mentioned before, as we think about it. APOB is that direct measure of the particle number. So we're counting how many VLDLs, IDLs, LDLs, LP little A, all those contain one APOB. So we're measuring all of them when we get our APOB test, as opposed to if we just do LDL as just a segment of it. In LDL-C, like we've mentioned before, that's a big one everyone knows about, I quote bad cholesterol. It's not that simple. Cholesterol isn't good or bad, it's just cholesterol. But traditional proxies used to be LDL or non-HDL. So non-HDL is just that. So essentially you get all your cholesterol, subtract your HDL, and then that's non-HDL. And that's a better marker than LDL probably, 'cause what's happening there is it's including the LDLs and the VLDLs that aren't captured necessarily. So that's what we're looking at. But once again, those are looking at the mass of the cholesterol from the particles and not the number of particles. But if we think about it, LDL can be useful. Non-HDL probably more useful, and then APOB even more useful. And once again, particle number is something we talk about there. The number of APOB-containing particles in the blood kind of determine how many enter into the artery. 'Cause a lot of times I think about it as kind of a gradient. So if you have a ton of APOB, just swimming in the bloodstream, if there's any sort of opening or issue with the endothelium or lining of the blood vessel, you can go in, right? Just 'cause there's more numbers there. If you have fewer particles, there's fewer chances of them getting in there. So direct particle number seems to have a direct correlation with the risk of developing cardiovascular disease. And APOB proteins in general are equally atherogenic. Most APOB particles are equally atherogenic, except for necessarily Lp(a), which seem to be a little higher risk. But overall, that's why we want to know all of them, 'cause they all can go in there and cause that. And once these APOB particles get into the arterial wall, then these APOB particles are modified, oxidized, inflammation starts, and then we start to form that plaque, and that's the big thing. And once again, we've shown also that the main therapeutic strategy for decreasing cardiovascular disease, we think comes down to reducing the number of APOB particles. Obviously, take a step back. If we can stop all the bad stuff in terms of, hey, how do we stop? It's not just lowering necessarily, by all means, pharmacologically, if we go lifestyle and can lower it through that. We want to see exercise, and we want to have good blood sugars, and we have good blood pressure. All those things are still very important. But currently, the main strategy, other than those things from a lipid perspective, is trying to lower APOB through different, either pharmacologic or lifestyle interventions. But that's the focus on reducing the APOB particles. And yeah, I think it's overall where we're heading, 'cause I think it also helps integrate information from the standard lipid panel, and it simplifies the understanding of the role of lipoproteins, where, yeah, we're moving the paradigm from just focusing on cholesterol mass, right? And it kind of highlights the importance of these specific atherogenic lipoproteins. And this kind of new view suggests that atherosclerosis, the risk is primarily related to the level and duration of exposure to APOB lipoproteins. And what I mean by duration of exposures, it's kind of a lifelong thing, right? If you think you had a high cholesterol for four days, it's not gonna do anything. I'm not worried about that at all. But it's a lifetime exposure. It's the same thing with, if your blood pressure's high for a little bit, I'm not too worried about that. Over time, I worry blood sugar, it's really that lifelong exposure, right? 'Cause that's what happens, is we have lifelong exposure to high blood pressure, high blood sugar, elevated APOB particles. All those things, over a long run, seem to cause issues. And so that's what we care about. And so, in essence, the atherogenic lipoprotein particle paradigm suggests that maybe we should be treating the atherogenic particles as measured by APOB, instead of just looking at the general cholesterol numbers. That's kind of where we're moving them. That's what we're generally thinking. And so what about these actually in practice? Well, in practice, the measurement is simple, standardized, and cost-effective. When I went online, it's about 20 to $100, depending on the thing. Obviously, I'm not saying $100 is nothing, but if this gives you a better understanding of your cardiovascular risk, then it may be worth it. The one cool thing is APOB testing does not require fasting. A lot of times, you're fasting before your cholesterol panel, and that's actually important. And this is a side note. You don't necessarily have to be fasting. You can still make decisions based off of a lipid panel that's not fasting. That's in the guidelines. You can do that. But to get a better view, specifically where those triglycerides are, we like to have people fasting. But one thing on APOB that's nice is you don't have to be fasting at all. Just go get it, and that's what it is. And when should we measure it? Well, a lot of times it could be kind of part of the normal lipid panel, right? So it can be that initial lipid evaluation also can be used when assessing the effectiveness of lipid-lowering therapies. I think I'll probably talk about this a lot, but this is starting to change as well. We basically have LDL goals, and right now that's what everything and all the guidelines are based off of, but I would not be shocked. In the near future, we have APOB goals specifically, and there's different societies who have different recommendations. They're very much not clear, and they're kind of all over the place. We'll talk about those in a little bit, but that's just something worth mentioning that eventually we're gonna use it for a target as well. And it's also really important to test an APOB in specific environments. So specifically patients with high triglycerides, that can sometimes throw off the regular lipid panel. So your LDL might not be as accurate with traditionally high triglycerides, so APOB is more important. Those who have insulin resistance, diabetes, obesity, and/or metabolic syndrome, once again, can have a profile that doesn't look as risky as it truly is. That's why APOB became helpful with that. Individuals with very low LDL-C, we can help determine if that's actually true, and those with a family history of cardiovascular disease, it may give us a clearer picture. And so this is clinically why we do it. It can be very helpful in numerous situations. And overall, this is just a table for those watching the video version. I'll kind of walk through it in the audio version. Here are the averages of LDL, non-HDL, APOB for Americans in the NHANES from, so to say, the National Libinan Association came out with this big study in NHANES, this big database, and they're kind of saying, what are the averages here? And so for a, specifically when we're looking at averages of LDL, non-HDL, and APOB, for Americans, about 50 percentile is 112 for LDL, 135 for non-HDL, and then 84 for APOB. And kind of my quick and dirty way I think about like LDL and non-HDL is, whatever LDL is, usually add 30. That's generally-ish, kind of where the ballpark of what we expected to see, but here you can say 50% is about 112 for LDL, 135 for non-HDL, and 84 for APOB. So that's like just average American. I think for the 20th percentile of Americans for APOB, it's 70, whereas the 80th percentile is 113. So you can see the range they're going from, 70 at the 20th percentile, and then up to 113th or 80th percentile. That's kind of what we're looking at there. And so this is just general averages, right? I'm just including these so we understand what is their baseline? 'Cause I think most people know the cholesterol numbers, or at least familiar with them, they've seen them and they say, okay, what should be a cholesterol number? And then APOB be like, I have no idea what it is. So overall 50 percentile, chilling out around 84. So that's like an average person, that's what it is. So the American Association for Clinical Chemistry, it's a working group that they kind of looked at a bunch of different lab values and said, hey, what is the average APOB? They thought overall looking at kind of different cohorts and whatnot, APOB of 80 was equivalent to about an LDL of 100 and APOB of 100 was similar to LDL-C of 130. And so that's kind of overall what they're looking at there and saying, hey, we're generally in the ballpark and it's just generally good information to know. It's not game changing by any means, but understand that 80 LDL, or I'm sorry, 80 of APOB is about 100. So that's kind of where we're at sitting there. And then do we actually have targets? So this is a really kind of hotly debated. There's no one unifying guideline, like the ACCHA or anything like that, but APOB targets vary depending on the goals of the guideline and source of the guidelines and the patient's risk. So overall general recommendations and considerations that APOB levels reflect the number of pathogenic particles like we talked about, making them a direct target for reducing cardiovascular resist. So some say the APOB target should be in line with the LDL targets for simplicity and consistency in clinical practice. So you mentioned before how I mentioned that, 80 of APOB was about 100 LDL. Some people were saying, hey, what are the LDL goals? Just use that for APOB. There are a bunch of different societies who talk about different things though. Specifically the Canadian Cardiovascular Society, their guideline uses percentile equivalents APOB based on LDL-C data. And for low risk patients, statin threshold or treatment for them would be, but APOB when they said are greater than 145, which is pretty darn high, I think most people would not be okay with that. Intermediate risk they said if APOB is over 105, and then if you're a high risk patient, APOB is over 70 would be indicating treatment. So that's kind of where it is. Whereas also have the European Society of Cardiology and the European Atherosclerosis Society. For here they say typically target treatment goals, patients who are at very, very high risk should be less than 65, high risk should be less than 80, and moderate risk less than 100, that's for APOB. And then we had in 2019 ACC AHA, they kind of consider APOB levels greater than 130 as a risk enhancing factor for whether you should initiate treatment. And then in 2020, we had the AACE and ACEE, the American College of Clinical Endocrinologists and American College of Endocrinology. It's just that APOB goals should be based on risk factors, which yeah, spoiler there, everything should be based on individual risk factors. But they said, hey, if you're at extremely high risk, get it lower than 70, very high risk, lower than 80, and national, kind of national average, higher moderate risk, less than 90. And then 2024, the National Lipid Association came out, recommends APOBs for high risk patients less than 70, very high risk patients less than 60, and borderline to intermediate less than 90. And so that was a lot of words, a lot of numbers, what's going on, that's just to say that we don't have a consensus on like, this is what it is. But generally what we're seeing, once again, we know that they kind of tie up where that 100 LDL is about 80. And so what they're saying is a lot of times we wanna keep that APOB less than 80 for pretty much anyone who's like borderline to intermediate risk, which will be pretty much anybody as they age. 'Cause as you age, spoiler, that's a risk factor for cardiovascular disease. And so as we get there, that's probably gonna be general target, this can happen through diet and nutrition, like in lifestyle. And I'm not saying you have to start a medication, but that's our general goal. And then we see also for high risk patients, like really high risk are people who've already had heart attacks. So they're gonna be once again, less than 70, which are kind of the guidelines for LDL as well. And we just know that if we're getting less than 70 with LDL and APOB, we're probably decreasing the chance we have of, yeah, having further cardiac problems. But as you can see that kind of 70 to 90 range is where we're shown. And there are a couple societies that say, oh, greater than 130. I think that's probably a little passive for me personally. I'm not comfortable with that. I feel like, yeah, as we know, the average is not 130 and that's putting someone at the way above the 50th percentile in terms of the average person. So, you know, if we're looking at the average person, their LDL, you know, chilling around a little over a hundred or APOB is maybe in the 85 or whatnot. Getting up to the 130 is giving me a lot more. And so we're not going there. But so overall that's what the general kind of consensus is just kind of interesting. And as I mentioned before treatment options, we do have treatment options. Lifestyles always gonna be first, right? Always, always, always. Diet, exercise, weight management, soaking sensations, all those things are so important because once again, it's not an isolation, right? I'm not saying that just having an elevated APOB is gonna guarantee you have heart disease. 'Cause we know it's not necessarily the truth. We see tons of people who've had elevated LDL, no issues, others have normal and have heart attacks. It's not simple, but one's gonna take a risk factor for you. So we wanna keep that in mind. So lifestyle first, always diet, exercise, control the other things, blood pressure, your blood sugars. We, yeah, good sleep, don't smoke, please don't smoke. All those things. And you can definitely do a lot of this through dietary interventions. Eating lots and lots of fiber, lower saturated fat intake. Specifically those can decrease LDL and APOB and can be very potent and powerful. But some people that doesn't work for them. So sometimes we have to talk about medications and here we have our classic ones, right? So we think about our statins. Everyone knows those, very controversial, but that's the mainstay treatment. They're very effective in lowering APOB. Other options that we have are Azetimibe. So the way I think about this is statins inhibit production of cholesterol, whereas Azetimibe inhibits absorption of it. So that is another one to use. A lot of times you use those in dual therapy. We also have the PCSK9 inhibitors, which are fancy and really do a good job of lowering it. So we have lots of other things that we can do. And there are emerging therapies like antisense oleonucleotide therapy for lowering Lp(a), but we're not quite there yet. And what are the reasons? Some people say, well, this is all, I think, worthless. We don't need this and I think APOB is overkill and it doesn't actually matter. This is kind of a couple of things that I just looked at. I kind of went on the internet, watched a couple of videos and see, hey, why are some people against APOB? Seems like most people I'm bored for, but this is what I saw. Some people thought that there's a lot of cholesterol content variation. So the cholesterol per mass of LDL particle varies leading to cholesterol depleted and cholesterol enriched lipoprotein, saying that, hey, if you have lots of cholesterol on a lipoprotein, that's less risky than someone who has a cholesterol depleted and I think overall, that's generally true to some extent and there's kind of some nuance there, but yeah, it can also be the opposite too, where we have high cholesterol depleted lipoprotein. So you're not having a lot of cholesterol on there and it can lead to a lower LDL, but you still have a higher ASCVD. So some people say, from just using LDL, that can be an issue, but APOB kind of eliminates that, but some people also say like, well, it's not necessarily the number and so whatever. Either way, some people say that the content of the particles is much, much, much more important than the actual number of particles. So that's what they're saying is like, it doesn't matter for APOB is up, 'cause if those particles are big and fluffy or like that, they're not as risky. I'm not super convinced on that yet, but that's one argument people do say. They also say that there's no studies that really show a huge improvement over short-term risk prediction. They're saying that APOB may not significantly reduce short-term cardiovascular risk prediction compared to LDL or other measures. So they're saying, why would I do it? It's not necessarily better. I think that is starting to parse out that it is better when we look at it, but there's not a robust, yeah, there's not a huge base saying that this is definitively has to be true. It's more a lot of observational studies. People have had our attacks looking at it there, but we also have seen observational, I'm sorry, clinical ones where they've done RCTs and lower their APOB and gotten improvements there. So I'm not sure on that. Others have cost concerns, meaning measuring APOB adds a cost to a standard lipid panel, which is very true. And a lot of times, when I talk with my residents and we're asked like, do you wanna get APOB? Well, sometimes it does treat and change things. Sometimes it doesn't. If you have a floridly high triglycerides and LDL and cholesterol, will an APOB definitively change things? Not necessarily in the interim. Target goals for APOB that may challenge things. But if it's floridly high, like an APOB may be an unnecessary expense. 'Cause you say, okay, I know this person needs to treat it anyways. So, but that is something, and it has to be conscious of that, that this does add additional costs if you think about it. Also people have mentioned that, well, there's no guideline, like definitive guidelines. So therefore we shouldn't use it yet. There's a lack of consistent guidance on interpreting and applying APOB results. So we say, until we get better guidance, we shouldn't use it. And then other people will say that ultimately, atherogen and lipoproteins are just something we see with heart disease and not necessarily a huge player or cause, it's more mechanical damage, inflammation and immune dysfunction are the big factors of atherosclerosis. And I would say this is kind of the, a lot of times we see this view from people who don't think that LDL plays a role in cardiovascular disease. And it is something we see on the internet quite frequently and it's predominantly in like the lower carb carnivore communities. And this is the whole talk, I have other podcasts talking about that. But for me, this is why some people say APOB doesn't matter because LDL doesn't matter, it's the same logic. And once again, for me, I'm just not willing to risk, I'm just not willing to risk it. I think they say that as long as you're metabolic healthy, meaning you're insulin resistance, you don't have any resistance, you're very insulin sensitive, the inflammation, your blood pressure is good, all those things are good, then you can't get atherosclerosis. And I just am not willing to bet the house on that yet. I wanna control all the risk factors I can. And so, but that's what people say. Sometimes APOB, like we just use LDL, use the standard, it's not validated yet, we don't have a one set guideline, it costs something. It may not be that give us the whole picture. Once again, I never said it's giving us the whole picture, it's just giving us a better piece and a more clear picture potentially. And what's the evidence that supports this? And well, overall, there's multiple different types of evidence. I won't go into detail, I have other podcasts all about this, I have a whole playlist on YouTube about cholesterol, but there's different lines of evidence saying, hey, this is why we think APOB matters and why we think APOB is important for helping us predict and treat cardiovascular disease. So the first one are epidemiologic studies. So we have lots of studies that show APOB is a more accurate marker of cardiovascular than total cholesterol or LDL. We found that elevated APOB levels are associated with an increased risk of future coronary heart disease events. APOB is identified as an independent risk factor for atherosclerosis and specifically irrespective of LDL. So once again, LDL could look normal, but APOB is high. And so lots of these epidemiologic studies show that APOB levels are more stronger correlate with ASCVD. And then we also have cross-sectional studies, right? Where initial studies suggested that APOB was better marker for cardiovascular disease than either total cholesterol or LDL. And yeah, they've consistently studies have shown a strong correlation to an APOB. We also have discordance analysis where discordance analysis has shown that APOB improves the risk prediction of atherosclerosis, especially among individuals with discordant APOB, LDL or non-HCC levels. So once again, as I'm talking before discordance means that, hey, my LDL was relatively low, but I still have like a heart attack or I still had lots of particles. And so like there's that discordance where you can look at stone cold normal, but still be a high risk, or you can look quote more high risk, but be less at actual risk. And that's kind of discordance. And individuals with discordantly high APOB relative to LDL and non-HCL have a greater risk of atherosclerosis. We've seen that as well. It's also been some genetic evidence where in Mendelian randomization studies, they've demonstrated that APOB is a better predictor of coronary artery disease rather than serum LDL or triglycerides. And overall, these studies reveal that the net absolute change in the number of APOB particles rather than the cholesterol content determines the cardiovascular disease. Yeah, and Mendelian randomization, just to take a step back for people who aren't sure what they do is they essentially look at people prospectively saying, hey, you have this gene that elevates your cholesterol versus these people who do not. And they're saying, so they're kind of taking everything out saying those people who have higher cholesterol genetically based on this gene, what happens to them and it seems like, they have a higher cardiovascular disease and APOB they tie with that. I don't need to bore you with all that stuff. They've done that. They've done additional genome-wide associated studies. They've also done actual like in-depth clinical trial evidence where every time you lower APOB with medication or lifestyle, you tend to have an increased, or I'm sorry, you tend to improve your chances of developing or having cardiovascular disease, all those things. And there's lots and lots of different studies. We can talk all about that. There's clinical trials, all those things. But this is really just a step back, say like this is why overall we think APOB is better. 'Cause we've done a lot of the studies that kind of determined LDL. That was the start, right? Cholesterol and then LDL and now we're refining it. Kind of thinking of the funnel, right? You start here as we're narrowing things down, we're starting to find better and better tests. And that's what I think we're finding here. And so this is just a lot of nerdy stuff. I have lots of resources here. If you wanna talk to me about it or need more resources, but it's just to show that we have multiple lines of evidence that indicate APOB is probably starting to become a little bit better of a resource for that. So the guidelines are increasingly recommending APOB measurements, specifically in populations with elevated triglycerides, diabetes, obesity, or low LDL. And some guidelines recommend APOB measurement as an alternative to LDL-C. And yeah, a lot of people are saying this is what we're using. It's what we're going towards. And yeah, this is the reason why we have just multiple lines of evidence for that and specifically. And overall the conclusion here, like you're, all right, Jordan, you just blabbed on for 30 minutes. And what do I do about this? Well, overall, I think it's worthwhile to get, but not absolutely necessary necessarily. You can still get a approximation with LDL, specifically non-HDL, probably even better, but APOB is probably the best. If I had to say, hey, you had your lipid panel, that's great, you can get your non-HDL from there. Let's use that, probably better than just the LDL, but APOB is probably the best. And yeah, that's what we think of, but we wanna be price conscious, right? So you're locked in and you're doing everything perfectly and you've gotten your APOB before or something like that, or you've had all your cholesterol levels, your everything looks good, your triglycerides are on HDL, your ratio, everything looks fine and great. Will APOB add a lot to that? I'm not sure, and we kind of have to have that discussion as a patient and physician, you kind of have the discussion, hey, is it worth it? What do we do? And so that's kind of where I think about, it can give you additional information, can be helpful. I have gotten that on myself and I like it 'cause it's kind of helpful to guide. I'm a nerd though, that's like what I do. I've seen him producing podcasts on cholesterol, so I understand that, but not entirely necessary for everyone. I think we'll start getting there hopefully and start to be covered more by insurance. We'll get there, but right now can be useful to help illustrate and get a clearer picture of a risk. There are variable targets though, which is challenging. And I think at minimum we should match LDL recommendations. So as we talked about, if you're just hanging out with an LDL greater than 100 and you're relatively healthy, we tend to think, okay, we want to be less than 100. So APOB, we definitely want to do that. I think probably getting down to less than 80. If you have known cardiovascular disease, it needs to be low, like low, low, low. I think it's pretty common. If you have no cardiovascular disease, then it's gonna be more variable. And I think like 80 is probably reasonable, certainly not 100 like they've said, or 120, 130 that other society said. I think 80 is kind of where we go. That's looking at more like 50th percentile. But as you get lower and lower, there's kind of the idea that if you get it below 70, below 60, there's a much greater decreased chance of having cardiovascular disease. But overall, if you're a relatively healthy person, at minimum line up with our LDL guidelines, but otherwise I think like lower than 80 for a very lowest person is probably reasonable. And then decreasing that to 70 or 60 depending on your risk. But really the whole goal of these tests is to help give you more data to make decisions and decide what is important for you. So no single test is perfect. No single test is gonna cure everything or tell you that you can't get cardiovascular disease. I mean, sometimes bad stuff just happens. Genes or environmental, who knows what. It's out of your control. And so in this space on the internet, a lot of people try to think that they can perfectly seal their fate by doing the right things. They have no chance of having risk. Well, guess what? Life has lots of risks and bad things happen sometimes. And so I don't want you to get caught up in this to be worried about this. If it's something that produces anxiety in you, and then maybe it's something that we don't necessarily have to do. Doing this on your own can also produce anxiety. So do it with someone who understands this and can talk about it and kind of walk you through the risks and options. But that's just something you'll think about. Overall, I think it's helpful, a helpful tool on your path to health. But once again, I'm all about trying to simplify things. And for me, it does help simplify things 'cause some people recommend like, just get this. You can get this in triglycerides and that's all you need. I don't know if it's necessarily true. It's nice to have more information, but always put it through the lens of someone who can interpret it for you rather than just having this and worrying about it. So work with someone if you need to. But overall, I think kind of helpful, kind of cool. Hopefully you'll understand a little bit more about APOE-B now. But that is it for today. Thank you so much for stopping by. I really appreciate it. And if you did enjoy this, it would mean the world to me. If you liked the video on YouTube, subscribe to your podcast platform of choice, or if you share it with a friend, that'd be like the greatest compliment you can give. Now, get off your phone, get outside, have a great rest of your day. We'll see you next time. Disclaimer, this podcast is for entertainment, education and informational purposes only. The topics discussed should not solely be used to diagnose, treat or prevent any condition. The information presented here was created with an evidence-based approach, but please keep in mind that science is always changing. And at the time of listing this, there may be some new data that makes this information incomplete or inaccurate. Always seek the advice of your personal physician or qualified healthcare provider for questions regarding any medical condition.
