Welcome to Dr. Warrick's podcast channel. Warrick is a practicing cardiologist and author with a passion for improving care by helping patients understand their heart health through education. Warrick believes educated patients get the best health care. Discover and understand the latest approaches and technology in heart care and how this might apply to you or someone you love. Hi, my name is Dr Warrick Bishop and I'd like to welcome you to my podcast and videocast station. Today I have the opportunity to have with me Dr Karam Kostner, a friend and a colleague and a leading lipidologist. Hi Karam, how are you? Hi Warrick, good to speak to you. Today we've decided to put LDL particle size on the menu. LDL is this so-called bad cholesterol, and it can come in different sizes and people talk about it. Would you like to give us just a little bit of a definition or a description of LDL particle size and what that really means so that the people listening know what we're talking about today, Karim? Very happy to, Warrick. So when we talk about lipoproteins, just to recap, and we've mentioned it in different other podcasts, lipoproteins are proteins that carry lipids. They carry them through the bloodstream and deliver them to various tissues in the body. Unfortunately, also arteries. Now, when it comes to lipoproteins, they were initially classified by their density and particle size by ultracentrification. And the largest lipoproteins are chylomicrons, followed by very low density lipoproteins, intermediate density lipoproteins. low-density lipoproteins, LDL, which we are talking about now, and high-density lipoproteins, such as HDL, which we often refer to as the good cholesterol. So that's how it all started. Before you go too far, Karim, just for the ease of the people listening, this concept of lipoproteins is that they're almost a carrier, if you like a little capsule, carrying... cholesterol around the body so if you imagine in a really simple term cholesterol a family of cholesterol say five or six cholesterol particles you could put them in a bus in which case that's a large particle with a low density because there's five people in a large bus or you could cram those five or six people in a small sedan and that'd be a high density particle driving or moving that cholesterol family around I just want people to get there idea of what a lipoprotein is and how it's literally a carrier or transport mechanism for the cholesterol that we're discussing. Great analogy. So I interrupted. A thousand apologies. You were talking about particle size and density and I jumped in. I'm sorry. That is a very important thing to make people understand. So we talked about the density of different lipoproteins, and you're absolutely right. Small, dense LDL are in everybody's mind, simply because several studies have shown that not all LDL is as arthrogenic as we think. But I would like to say that I'm of the opinion that 99% of LDL is bad, whether it's small, dense LDL or slightly larger LDL. So what we have found in clinical trials, and you've participated in many of them, is that LDL is the bad guy. It ends up in arteries, it clogs arteries, it is calcified in arteries, no matter whether it's small, dense or not. So that's the first thing I would like to state. So when people do talk about particle size, because this pops up a fair bit in social media and on different blogs that people advocate. particularly on some of the diets which are perhaps more inclined to reduce carbohydrates or perhaps more ketogenic. People talk about these particle sizes. What are they actually saying? Are they saying that bigger particles, less dense particles are less problematic? Exactly. And the analogy here is HDL, you know, and in HDL, it's actually much more pronounced. Not every HDL. high-density lipoprotein, good cholesterol, is as protective as we think. And I think particle size is probably more important for HDL, but we still don't recommend to measure it unless you're doing research trials. To give you an example, the most effective HDL in removing cholesterol from arteries is the very small, lipid-poor HDL, discoidal small HDL particles. The larger HDL becomes, the less effective it often is in this reverse cholesterol transport. Now, with LDL, some of the trials that I mentioned have shown that the smaller, more dense LDL particles that have a different composition in cholesterol ester, triglycerides, phospholipids, and cholesterol than other LDL particles are even more arthrogenic. But in my opinion, it does not make sense to measure that for clinical purposes. Because there is much better things we can do. We can measure LP little a, which we've touched on in other podcasts. You can do imaging, which you're an expert in. You can look at coronary calcium and plaque burden. In clinical practice for our patients, it does really not make sense to measure different LDL particles because all LDL is basically bad. So when we look at these different... sizes for the LDL particle, the so-called bad cholesterol particle, are we born with a pre-set genetic LDL particle size or can we vary that? Does it vary through different foods or diets or exercise or conditions like diabetes? It's a very important question and it's quite complicated because there is a lot of genetic predisposition for all major lipoprotein particles. And there is genetic defects. Again, we've talked about them in other podcasts that predispose you to a very high LDL, such as infamilial hypercholesterolemia, or to a very low HDL, such as in L-cut deficiency. So to a certain degree, we are born with it. But then as our diet changes, as our fat content in the body changes, as we maybe develop diabetes, particle sizes change dramatically again. And then as we give our patients or prescribe our patients medication, particle size changes again, because if you're on a fibrate or if you're on a statin or esotrol, your particle size will change accordingly as well. So these are the major determinants, genetics, diet and medical therapy. So one of the things that I thought might impact particles is diabetes. One of the things that we know about diabetes is your triglyceride levels can go up, those so-called free fats. So my understanding to a degree, and I'm keen to be educated here, is that as the triglycerides go up, we might see a change in the LDL cholesterol and may get smaller particle size, smaller, denser particles. Can you speak to that? Is that the case? No, that's absolutely the case. So as you become a diabetic or as you develop metabolic syndrome, usually your triglycerides go up, your HDL goes down, your HDL may become a bit more dysfunctional, and your LDL particles may be a bit more arthrogenic. But again, you know, if we measure LDL as we do in clinical practice every day, that tells us all about our patient's risk, even in diabetes. We don't need to measure small dense LDL particles. All the trials in diabetics and non-diabetics have shown that if you reduce LDL, independent whether it's small dense LDL or not, you reduce cardiovascular risk. And that's why I think it is confusing if patients want to measure their small dense LDL, because independent what the small dense LDL are, we are going to try to reduce their overall LDL with effective therapies, diet and lifestyle, etc. So what I'm hearing from you is that LDL is the problem and that not necessarily do we make a distinction in terms of potential deposition of cholesterol in the arteries between small or larger LDL particles. Look, my own experience with this was I got a chance to speak with one of the researchers. who was in a lab where they measured these particle sizes. This is one of the fantastic opportunities. You were there as well at the European Cardiology Society Atherosclerosis meeting. And look, I put this question about particle size to one of these people who ran this lab. And as far as I understood, he was talking about a... pore or an opening in the vessel wall which might be 50 microns in size. The large fluffy particles were say 30 microns in diameter and the small dense were 20 microns in diameter and you can quickly imagine that if you've got a hole that's 50 microns wide then something that's 30 or 20 or fall through pretty easily and that the difference in density was so apparent because density is radius to the power of three so that difference in diameter is exaggerated by the density so are you aware of um you're obviously aware of the study and the research has gone into that has there been any trials that have specifically looked at particle size to try and See if it's more atherogenic that you're aware of, Cairo? There have, but they're not very well-conducted, randomized clinical trials. You know, for example, with interventions, as we see with statins, ezetrol, PCSK9 inhibitors, et cetera. There's many trials that look at the biochemical composition of lipoproteins. But that doesn't necessarily mean that it's clinically important for our patients to measure these particles. So again, for research purposes, this is very interesting. And some of it is important, but not for clinical purposes and not for risk assessment. It would be more important to measure HDL particles and see how effective a patient's HDL is in reverse cholesterol transport. But again, we're not going to change our clinical management if we know that, because we're still trying to get the LDL cholesterol to the lowest possible level with the therapies we have available. So again, it's very interesting for research purposes. And you can look at reverse cholesterol transport with various means, but it's clinically not very relevant at this stage. That may change in the future. And there's obviously companies that make some money with this. You know, if you have a company that measures this small, dense LDL, Of course, you're going to want to sell the essays. And, you know, again, for research, this is fantastic and we all utilise it. But for clinical purposes in our patients or for clinical practice, in my opinion, it is not very useful at this stage. In fact, you've answered a question I was just about to ask you because I've had a number of people, some of my patients have turned up with these beautiful profiles of lipid particle size, which they've paid for over and above. standard costs to get exactly this sort of breakdown. And I guess what you're saying is at this stage, they're really interesting, but really don't necessarily guide us. That's correct. And in fact, the danger that I see is a similar danger that we see with HDL. You know, we all see patients who have high HDL, but still develop coronary disease that you see on cardiac CT, for example. And if these patients think they don't need to lower their LDL just because their HDL is high, Unfortunately, that can be dangerous. Yeah. Okay. Well, I'm going to offer you the chance to wrap up with any final points, and then I think we might close it up. But it's been a fantastic and interesting discussion for me. These particle size questions come up with some regularity, and I'm delighted to have the chance to speak about them. Would you like to finish off with a comment? Just very briefly. So lipoproteins come in different sizes. They come in different densities. This is very interesting for research and very interesting for biochemical research trials. But at this stage, the clinical utility is not very high. And what people need to realize is that LDL is bad and we try everything to lower LDL to the lowest possible level in high-risk patients. But the particle size at this stage is mainly a research tool. That's my take on it anyway. Karam, thanks so much. I really do appreciate your time. Great to catch up. I'm going to wrap it up there. I hope those who are listening really got something out of it as I did. If you have any queries or questions, please drop myself or Karim a message at info at drwaribishop.online. Thank you for joining us. Thank you for your attention. Till next time, I wish you the very best and please don't die from a heart attack. Goodbye. You have been listening to another podcast from Dr. Warrick. Visit his website at drWarrickbishop.com for the latest news on heart disease. If you love this podcast, feel free to leave us a review.
