High LDL. Normal ApoB. Now What??

What do you do when your "bad cholesterol" (LDL) flags high, but your other metabolic markers look great? In this video, I’m sharing my personal lab results to explain why standard lipid panels only tell part of the story.

We’ll dive deep into the world of lipoproteins, exploring why ApoB is a more precise measure of cardiovascular risk than LDL-C alone. Using a highway analogy, I’ll show you why the number of "cars on the road" (particles) matters far more for plaque formation than the "cargo" (cholesterol) they carry.

In this video, we cover:

Standard vs. Advanced Testing: Why I look at the Triglyceride/HDL ratio and ApoB.
The Concept of Discordance: What it means when your LDL and ApoB numbers don't track together.
Metabolic Health: How inflammation and insulin resistance act like "potholes" on your arterial highway.
The 2026 Guidelines: How to put your numbers into the context of your overall risk.
Beyond the Lab: Why I’m prioritizing imaging (CIMT) over blood work to decide my next steps.
🔬 JOIN THE EXPERIMENT! I’m going to run a 90-day experiment to see how different interventions affect my numbers, and I want YOU to choose the path. Vote in the comments:

Dihydroberberine: A supplement known for lipid and glucose support.
Ezetimibe (Zetia) Monotherapy: A medication that targets cholesterol absorption.
Drop your questions about lipids below—I’ll be answering as many as I can in an upcoming Q&A!

#Cholesterol #ApoB #HeartHealth #MetabolicHealth #LDL #VascularHealth #PreventativeMedicine

Chapters:
00:00 – Introduction: My cholesterol results are in 
00:24 – The standard lipid panel: Total cholesterol vs. Triglycerides 
01:22 – Why the Triglyceride to HDL ratio matters for metabolic health 
02:11 – The myth of raising HDL: Trials and outcomes 
03:08 – Understanding LDL calculations and limitations 
04:18 – The deep dive into ApoB: Why lipoproteins matter more than cholesterol 
06:02 – The highway analogy: Particles vs. cargo 
07:49 – Two types of ApoB (100 vs. 48) and their roles 
10:20 – Road conditions: The role of the endothelium and inflammation 
11:32 – 2026 ACC/AHA lipid guidelines and risk assessment 
13:41 – Understanding discordance: Why my LDL is high but ApoB is normal 
16:56 – Advanced testing: NMR particle count breakdown 
21:09 – LPIR: Assessing insulin resistance through lipids 
22:38 – Why numbers aren't enough: The importance of imaging (CIMT) 
24:38 – The Experiment: Help me choose between Berberine and Ezetimibe

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🧬 About Dr. Lily Johnston
  
Dr. Johnston is a double board-certified vascular and general surgeon in San Diego, specializing in metabolic and cardiovascular prevention. She practices at Scripps Clinic and is also the founder of CorSight Health, where she is a passionate advocate for reimagining how medicine approaches chronic disease.

Transcript

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I checked my cholesterol and my LDL is high. Let's get into it and please stick around for the end and hear what I am going to do about it. If you are new here, I am Dr. Lily Johnston. I am a board-certified vascular surgeon, but I specialize in cardiometabolic prevention. So hopefully you will never need me as a surgeon. So let's just start with the classic fasted lipid panel, which all of you, I'm sure, have had done and seen before. So total cholesterol is the first number that always shows up, and it's sometimes the most alarming and honestly kind of the least relevant. My total cholesterol flags high at 209. Now, again, I have not captured the units here, but I'm gonna do my best to say them as we go through this. This is all gonna be in milligrams per deciliter for the standard lipid panel. So again, total cholesterol 209. It's high, but again, I don't care that much about total cholesterol. We want to know the different components. So, next up, the thing I personally find most helpful in a classic lipid panel are the triglycerides and the HDL. So my triglycerides are 45 milligrams per deciliter, my HDL is 79 milligrams per deciliter, and that gives me a triglyceride to HDL ratio of less than one. I would say less than two is good, less than one is optimal, right? That means your triglycerides are lower than your HDL. Why is this important? This tells us about your metabolic health in general. When triglycerides are high and HDL cholesterol is low, that is indicative of metabolic syndrome. In fact, they are two out of the five criteria to diagnose metabolic syndrome. Now, it doesn't mean that raising HDL is automatically a good thing. This is a myth that we've talked about in other videos. If your HDL goes up as the result of good lifestyle changes and improved metabolic health, we believe, yes, of course, that represents an improvement in your health and a reduction in your cardiovascular risk. But there have been a number of molecules that have been trialed to improve HDL cholesterol. And while some of them in fact did raise the HDL cholesterol number, none of them, not one, improved outcomes enough to make it a true therapeutic target that we use today. Now, there's a whole other story here about another CTEP inhibitor. This was the class of medications, by the way, that was used to try and raise HDL. Niacin is another one. That's a separate talk for another day. The CTEP inhibitors, we thought was a story that just died a sad, tragic Shakespearean death. However, there is a new one, Obacetrapiv, that is in trials and is looking very promising for a lot of things. If you haven't seen the ApoE4 video where we talk about it, I'll link that for you in the description below. Okay, so my HDL is great, my triglycerides are fine. Now, LDL calculation. So LDL is not typically measured directly unless it says direct LDL. And usually there is a calculation that is done messing with your triglycerides. The old Friedwald equation was to multiply it by five and subtract, and this, that, and the other thing. Suffice it to say, the LDL is a derived number. And if your triglycerides are reasonably normal, that is acceptable most of the time. We get into trouble with calculated LDL cholesterol when patients' triglycerides are very elevated: 400s, 500s, 600s. That's a problem. Even over 300, I would say I would be a little bit suspicious about a calculated LDL cholesterol under those conditions. But the equations have changed, and it's worth knowing which of the equations have been used for you. Again, I don't actually display that here, and that's a little unfortunate for us in this conversation. Um, but that is a limitation of this conversation that we're having today. Next is apolipoprotein B. So we need to back up because we've been talking about cholesterol. And cholesterol is interesting, and it was great because it was what was originally measured when we started thinking about lipids in the bloodstream 50 years ago. The easiest thing for us to be able to measure was just the cholesterol. But we know, right, that our bodies are mostly water. Cholesterol is a fatty, waxy molecule. It does not get to travel in our bodies all by itself. It needs a partner, it needs something to allow it to mix in the watery environment of our body, and those are the lipoproteins. It is, in fact, the proteins, the lipoproteins, that impact how cholesterol functions or behaves in our body, not the cholesterol itself. The cholesterol is the same, the exact same molecule that is on HDL cholesterol, is on LDL cholesterol, is on VLDL cholesterol, all of these cholesterol molecules are the same. And they are the things in our cell membranes and found throughout our body. Absolutely, cholesterol is an essential molecule, but when it's attached to these lipoproteins, it can behave in ways that we don't always like. So as our ability to measure things got better, as our understanding of the biology got better, we began to realize that it's not so much the cholesterol component that's relevant, it's the lipoproteins. And the ones that behave badly all actually have this same signature of an APOB molecule. So think about an analogy. Your blood vessels are a highway system. And the cars and trucks and motorcycles that are moving things around in your highway system are all the lipoproteins. The stuff in their cargo holds or in the trunk is the cholesterol that they carry. So when we were just measuring cholesterol, like in this classic lipid panel, all you knew was the cargo. And you could maybe make some uh some generalizations about which things came with which based on, you know, where they could park, right? How big the parking spot was for all these things. And that's the high density versus the low density component of this. You know, sure, a motorcycle parking space is different than a semi-truck parking space. And so maybe you can inverse some things about kinds of cargo and how they're going to behave, but it's very much a proxy measure. It's not that informative. And when you think about the formation of plaque, this is like getting in an accident on the freeway. Your likelihood of getting into an accident has a lot to do with how many cars and trucks are on the road and not so much to do with how much is in the trunk, right? So when we think about how to interpret lipid panels, we need to really understand, especially in terms of cardiac risk and the formation of plaque, which is what we're here to talk about. We want to know how many cars and trucks are on the road and how many of those are likely bad actors, how many of those have had revoked licenses? Are they going to contribute to the formation of plaque? Particles that contribute to the formation of plaque all have this APOB molecule. Okay, the story gets a little bit more complicated here. There are actually, in fact, two types of APOB. There is the full APOB protein, which is called APOB100 for 100% or full length. There is also an APOB48. In my recent Ask Me Anything, somebody actually brought this up as a question, and I thought I knew the answer. I looked it up later, and it turns out I was a little incorrect. The commenter said that their lab only checks APOB100, and I said, I thought that was probably true. In fact, most of the immunoassays or the antibody tests in the lab that we use to measure APOB will actually detect both. Both APOB48 and APOB100. It's probably actually not that relevant because far and away, the majority of the particles contributing to plaque formation are APOB100. And it's probably well over 90, maybe 95% of the Apo B that's captured in this assay would be the ApoB100 particles. The 48s are both smaller by mass and also much less relevant. The APOB48s are the ones that come from our intestine and help us manage the dietary fats and cholesterol that we eat and bring that into the body's circulation and energy system. Okay, so those are the chylomicrons, the little tiny soap bubbles of dietary fats and cholesterol that we eat. Those are carrying that APOB48. Some of those will be captured in a complete serum APOB assay. If you're fasted, which you probably should be for a fasting lipid panel and your APOB at the same time, that will be a very small proportion of what's captured in APOB. Also, in terms of atherogenic particles, total sum, very small component. APOB100 is what is on your LDL particles. It is also on all of the what we call remnant particles or the things that are highly volatile in their circulation and are getting trafficked a lot, like very low density lipoprotein or VLDL, the intermediate density lipoproteins like IDL. All of these particles carry this ApoB100 molecule, and it is the ApoB100 particles that are creating plaque or at least contributing to the formation of plaque. Some of you will quibble with that language, but that are involved in the plaque formation process in the artery wall. Okay. Also, the pavement on the highway impacts our ability to get into an accident. And this is going to come back to the triglyceride HDL piece of this puzzle. There are places in the world, or in your town perhaps, like I live in a place where there are enormous potholes, right? And if you have irregular or unpaved streets or you have big tree roots or debris in the middle of the highway, obviously that is going to participate in your inability to control your vehicle and potentially get into an accident. So metabolic health, all of the other things we talk about are how healthy the road surface is. And the road surface is like our endothelium, the lining of our blood vessels. So high insulin, high blood sugar, high inflammation, all of these things contribute to a bumpy potholed, debris-filled road surface that is highly problematic and also related to how these particles interact and create traffic, create accidents. Okay, so my APOB is 86 milligrams per deciliter. If we go look at the new 2026 American College of Cardiology, American Heart Association lipid guidelines, what it says, what they say is that we need to first understand a patient's baseline risk. So based on my age, my normal blood pressure, never smoking history, and these numbers, I have a low 10 and even a low 30-year risk of cardiovascular disease. Incidentally, I don't have a strong family history of cardiovascular disease. That's considered a risk-enhancing factor, but it's something that I, as a physician, in my practice, take very seriously when I'm talking to patients about their numbers and how to put them in context. The other piece of this is, you know, the thresholds will change. So for me, again, at low risk, my target LDL cholesterol would be less than 100 milligrams per deciliter. My target APOB would be less than 90 milligrams per deciliter. These new guidelines do lean more into APOB than they ever have before. At least it's come up, right? It never used to even be mentioned. Now, today in 2026, we do have a suggestion that for some people, they're still not recommending it for everybody. For some people, APOB is worth considering. And who would those people be? The people in whom, and we're about to talk about this, we're likely to see discordant results. Okay, I just told you that APOB captures all of the particles that are likely to get into an accident or form plaque. The vast majority of those are low density lipoprotein particles, LDL particles. So for most people, LDL cholesterol and APOB track together. Those numbers should be very, very similar. And if one goes up, the other should go up with it. If one goes down, the other should go down with it. So for the vast majority of people, APOB doesn't provide a huge amount of additional information. However, sometimes there is discordance. One number is high and the other number is disproportionately lower. So I have discordance with lower APOB and higher LDLC. What does that mean? That means that I have a lot of big semi-trucks carrying a lot of cargo, right? I don't have small little scooters carrying little bits of packages here and there. I have big semi-trucks that are chock a block full of cholesterol, but relatively few of them. Okay. So I have fewer LDL particles. Each of those is carrying more cholesterol. Incidentally, that's gonna mean my particle sizes are gonna be higher. We'll see that in a minute. And so therefore, APOB, which reflects the total particle count, total number of cars and trucks on the road is gonna be lower. This is a favorable discordance profile, right? This is a good thing. You want fewer cars and trucks on the road, period the end. But discordance the other way is a problem. And this is the circumstance in which the ACC AHA is recommending looking for this. And these are people with metabolic syndrome or these other things that will cause them to have lots and lots of cars and trucks, but proportionally, each of them carrying a small amount of cargo. So this is, for example, what happens if somebody has an LDL cholesterol of 100 but an APOB of 120. Okay, that is discordantly high APOB relative to the LDLC. Again, this means there are more cars and trucks, more particles on the road, but they're not very full. They're only carrying one or two boxes a piece. And again, it's the number of particles that is contributing to the likelihood of getting in that accident. So the people who are most likely to be discordant, people with elevated triglycerides, people with diabetes or prediabetes or insulin resistance, and people with genetic lipid problems. Some of those patients, again, will have very elevated triglycerides or hyperkylomicronemia. There are a bunch of sort of esoteric things that may be impactful here. When in doubt, APOB is a pretty cheap test. Ask your doctor or your clinician to order it for you. If you can't get them to do it, go out and do it yourself through Ulta Labs, through Own Your Labs. There are a bunch of places where you can get this done yourself. If you are concordant and your health is about the same, you probably don't have to check it again, right? If your LDLC and your APOB are about the same, you're in the 85% of the population for whom numbers will track together. You can just keep checking your regular lipid panel. If you are metabolically well and are showing high levels of LDLC but normal APOB, like me, then you may want to be following APOB. If you are discordant in the other direction, your LDL is normal or low, but your APOB is high, then you've got some metabolic work to do. And again, I would keep tracking both. All right, let's get into the particle counts and see what else we can learn about advanced lipid testing here. So, APOB is all of the different particles on the road that could cause trouble, but the NMR or nuclear magnetic resonance spectroscopy, this is the fancy way that we're looking at all of these different cars and trucks now. We're gonna break these down one at a time. So my LDL particle number is 874. This I think is in either nanomoles or micromoles per liter. Sorry, the units, I apologize. Under a thousand would be optimal. Okay. So again, it's light traffic, not rush hour. We don't have a huge number of cars and trucks on the road. And this was predictable from the discordant low APOB relative to my LDL cholesterol, right? I could have told you that my LDL particle number was almost certainly going to be in an optimal or very good range based on that discordance. And the small LDL particle number, this is maybe less predictable, but also fits with this story, right? Again, I have fewer particles that are bigger and track a block full of cholesterol. So I'm not surprised to see that my small LDL particle number is again optimal at less than 90. My LDL sized, 21.7. This is gonna be, I think 21.5 is the cutoff for here, but again, all of this predictable based on just the standard lipid panel and my Apo B. And my HDL total particle number flags slightly low at 27.6, but my HDL cholesterol is pretty high. Again, the HDL story is much, much more complicated than the LDL cholesterol or LDL particle story because HDL these particles engage in reverse cholesterol transport. They actually bring cholesterol out of the plaque and away from even LDL particles and into other places in the body where it can be used. So this is a functional capacity, and we cannot tell most of the time with any of our lipid measures, whether it's NMR, classic lipid panels, whether HDL is functional. There are some very advanced panels that are available now where people are measuring different components of the HDL lipoproteins and making some inferences about functionality based on that. I don't think those are ready for prime time. I am not using them in my practice. That actually also came up in a very early Ask Me Anything, I think one or two. And we went through that a little bit. Again, I don't use them yet in my practice because I don't believe they're actionable. It means I don't know what to do with them, right? I can't, even if I knew your HDL was not that functional, what can I do about it other than not be falsely reassured by a normal to high level of HDL cholesterol? I tend not to be super reassured by those lump numbers anyway. So yet I am not measuring that. I am not following that for patients. Uh, I'm not even sure how reliable and valid those tests are clinically. So stay tuned on this. The function of HDL is really important, but most of our tests don't measure it. Therefore, I am not gonna get overly excited about the fact that my total HDL particle count flags a little bit on the low side. Clearly, my HDL cholesterol values are on the high side. Nobody knows what that means right now. There's nothing I'm gonna do about it. My metabolic health is pretty decent. So I am not losing sleep over this and I don't know what to do to fix it. So we're not gonna worry about it. We're gonna move on. And HDL size is 10.8. My large VLDL particle number less than 0.8. My VLDL size is 38.5. And the last piece of this, probably the most helpful piece of the NMR testing that I use these days in practice, the first would be small LDL particle number. If that is optimal, then I feel pretty good about that. And then the LPIR or LP insulin resistance score. This is a calculation that is done and it combines the LDL particles, the VLDL particles, and the HDLs, as well as their sizes, to help generate an understanding of whether there's any evidence of insulin resistance in the lipid panel. And I mentioned this uh in the first video. There are times where this actually also tracks with HOMA IR, which is a measure of your fasting insulin and fasting glucose ratio, but not always. There are times where I will see an elevated fasting insulin, but a normal LPIR. And there are times where I see a normal LPIR or an elevated LPIR, excuse me, and a low fasting insulin and fasting glucose. So I think that. These are different measures, but additive and helpful in understanding a complete metabolic picture and which tissues and which pathways we might be seeing insulin resistance early. But there's absolutely some clinical data that low LPIR scores are associated with protectin from cardiac events. Elevated LPIR scores are associated with increased risk for major adverse cardiac events. So again, my LPIR score is great, less than 25, even less than 30 would be pretty good for age and gender. That's very, very reassuring. However, we spend a lot of time on this channel discussing that numbers alone are not adequate. If you want to know what the very first thing I did when I saw these lab results for myself was, it was to make sure that my imaging was up to date. Because I am never going to rely on my lab values or my prevent calculation or my family history to determine what I should do about these test results. Just because the guidelines say that my APOB of 89, which is less than 90, which should be okay for my level of risk, is fine, does not mean I'm not going to dive a little deeper and figure out what to do about this. So, what did I do? I got my next CIMT test done, carotid intimal medial thickness. My results are still pending. This is a second test for me. So when I have them back, you bet we will be back here to review my first test, what that showed, and what has changed since then. Because my inflammation has gone down, my lipids have always been kind of like this. My Apo B was a little bit higher the last time I had it done. And my LDLC has always been in the sort of 120 to 130 range, and at least in the last few years. So what I need to know is what is happening to my arteries. So what I'm gonna do about this has very little to do with the guidelines and everything to do with what is happening on the inside. So if you have not hit that subscribe button yet and you want to be here for when we drop my CIMT video, please hit that now and we will get to that as soon as those results come back, which I expect to be in the next week or two. However, I love you guys. You guys are awesome and you have supported this channel. We are growing, and you will have questions. You have wanted to know about things like zetamide monotherapy. You've wanted to know about things like berberine and what that might do for a lipid panel. And even though my decision for me personally about what I should do for my lipid panel rests on the imaging, we're gonna go ahead and do an experiment anyway, because it's gonna be fun and you guys wanna know. So as a patient, the decision about whether I need to treat my lipid numbers, that's an imaging-based decision. For the sake of experimentation and science and having some fun with you all, we're gonna do an experiment. We're gonna pick one of these things. You have to help me pick. I need you in the comments below to vote. We have two options, and I've decided that these are my two options. Option number one, dihydroberberine for 90 days. Dihydroberberine is the active and better absorbed version of berberine. It has some excellent evidence for lipid lowering as well as improved glycemic control. And I have a feeling you guys are gonna like that one because it's a supplement, not a drug, but uh I'm open to your perspectives. That's the first option. Option number two, which many of my patients in clinical practice are opting for, but for which we don't have a huge amount of data, is Zetamib monotherapy, or Zetia. Zetia is a very interesting molecule that prevents reabsorption and absorption of cholesterol and bile salts from the intestine. So it doesn't work in the liver, it doesn't impact the muscle, it really has some GI side effects, but by and large, it's very well tolerated. And there is some evidence that in leaner individuals, much of the impact on LDLC is actually from absorption and reabsorption. And you get a disproportionate LDLC lowering from azetomide in that group of people. So I'm curious because the average advertised LDLC lowering from azetomide is about 10 to 15% of total. But I have some patients who see 30% lowering on azetomide monotherapy only. Now, neither of these interventions is associated or has been described in the literature as having reduction in cardiac events or certainly in all-cause mortality. We are just here for the data, for the experimentation, and to see what happens. So let me know in the comments below which one you want to see, berberine or azetomide, and we'll make it happen. Also, whatever questions you have about lipids, and there will be a bunch, please, please drop them down below. We'll do a comment response and get to as many as we can. Until then, take really good care.