Welcome, my name is Dr Warrick Bishop. I'm a cardiologist, an author and a keynote speaker. I'm CEO of the Healthy Heart Network. I'm all about trying to help people live as well as possible for as long as possible. Heart disease is huge in Australia. Every 20 minutes someone suffers a heart attack. Most of these could probably have been avoided if only we knew what to do. This podcast is all about helping you understand blood pressure, weight, cholesterol for better health. If you enjoy this podcast, I would be honored for a five-star review. You can share it with your family and friends. It may well save someone you love. Hi, my name is Dr. Warrick Bishop and welcome to my podcast and videocast station. Today, I have the absolute pleasure of interviewing and communicating. conversing and chatting with two of my colleagues, Dr. Karam Kostner, who you've met before, and Dr. Tony Sangster, who's Zooming in all the way from Adelaide. Karam, in fact, is Zooming in all the way from Austria. So first of all, good day, Karam. Good day. Thank you for having me again. Absolute pleasure. Now, Tony, who we haven't had on the podcast series before. Thank you so much for joining us. Thank you, Warrick. It's a pleasure to be here. And thank you so much for making the time to join us. But just so that the people listening and if we've got people watching, just for their background, what's your history? I understand you've been in general practice. You've also had diabetes and a significant interest in diet. reduced carbohydrate eating and sugar control. Just speak to that for us as a way of background. Okay. Thank you, Warrick. Yep. Well, I guess my story really begins when I was 13 and I developed type 1 diabetes. And back then we had rudimentary or relatively rudimentary type insulins compared to today. And we didn't have any blood sugar testing. It was all done with urine testing. and the diet was a high-carbohydrate diet. And I somehow, I'm now 70, so that's nearly 57, oh, sorry, I'm nearly 70, so nearly 57 to six years of diabetes. And it's really only been through looking during my professional life as a doctor, and I retired from being a general practitioner back in 2014. And it was through looking more and saying, can I do any better with my diabetes? And what about these, you know, the statins and the other agents that the doctors are saying, yes, you need to be on these, you're diabetic, it's very important. And it was only through looking at a lot of this and having more time to read that I came to realise that there was more detail and... aspects involved than I had ever thought possible during my professional life. So there is absolutely nothing like having a condition yourself to drive you to a deep dive on it so that you have a better understanding. The other thing that you touched on is there is an enormous complexity to that. whole complex axis of diabetes, coronary artery disease and diet. And to a large degree, that's what I was hoping we could discuss over the next couple of podcasts. And we might kick off this particular podcast speaking about LDL cholesterol, the so-called bad cholesterol and coronary artery disease, because there is. Still in the community, mixed opinion about this, although in the medical community, we would be pretty comfortable to think that there's a close link. Would you like to speak? Actually, I might give Karim a chance to speak on that. Karim, just in a couple of words or a couple of sentences, where would you say that LDL story fits when it comes to coronary artery disease and risk? Look, for us as cardiologists, we recognize that there is several risk factors that can progress plaque in coronary arteries. And I'm a bit more biased towards lipids because I run a big lipid clinic, as you know, and primary prevention clinic in Queensland. But there's no doubt in 99% of cardiologists' mind that high LDL cholesterol is one of the main drivers of coronary plaque, which then leads to coronary syndromes. acute coronary syndromes, and all the complications that we're all very well aware of. There's also no doubt in my mind that there is a lot of people who have high LDL cholesterol who will not get coronary artery disease. So it's more complicated than it seems at first. But for us, LDL is one of the main risk factors for heart disease. And the only example I would like to give is that people who are born with very high LDL, which is a condition called familial hypercholesterolemia, very often end up with cardiac complications, coronary disease at an early age, et cetera. So for me, there's certainly a strong link there. Thanks, Karim. Look, Tony, I'm sure you've done some reading around LDL cholesterol, coronary artery disease, risk of developing disease. Would your reading and the sort of view you have on LDL match up with CARM or are there some points of difference between how you would see it and how would you articulate that? Okay. I mean, certainly I've read a lot about that a high LDL can correlate well with coronary artery disease. I think what really made me think further about it, though, was seeing some... paper and research by a professor Ronald Krauss from the US. And he was the one that took all the fractions of the HDL cholesterol. So we're talking about, it's like a bus in the blood that carries a blob of cholesterol around, just to give an idea. And what he found was that that these low-density cholesterol, this combination of the bus and the passenger, had a number of smaller divisions. They weren't all the same. And that he was the one that started to divide these out. And what he found was that there was a group who had... DL cholesterol, it may well be raised cholesterol, who had what he called these larger particle size. And then there was another group that had these smaller particle size. And we're only talking about a very small fraction. And there seemed to be a strong correlation between the large particle size having very little heart problems compared to the, which is called the A pattern. And then there was the B pattern with a slightly smaller HDL cholesterol that had much greater incidence of heart disease. So, and of course, I mean, there was a bit of overlap. It wasn't sort of two absolutely distinct groups, but they were there. And that led to a number of investigations he then did, including looking at what effect saturated fat and cholesterol and carbohydrates, sorry, had on these. these two particular groupings so really a very important point tony you're talking about all cholesterol not being the same yes um cholesterol maybe being more problematic than others before we um really tease that out a bit more and i might even get calm to con uh comment on this one of the things that i've always found needs to be well articulated in that LDL or so-called bad cholesterol and coronary artery disease conversation is, as both you and Karam said, not everyone ends up with problems. So if we try and use the cholesterol level of its own to predict who's going to have a problem, we get a bit confused. As Karam and you, in your own clinical practice, you will have seen people with high cholesterol. bad arteries, high cholesterol, but good arteries. But you equally have seen people with low cholesterol, good arteries, low cholesterol and bad arteries. So when we use cholesterol to predict, it's just not accurate. And that throws a bit of doubt over the whole conversation. The bit that is... robust is when we know someone's got significant plaque in their arteries, when we know someone's got bad plaque. These are people who've had a heart attack or a stroke or a bypass. These people have defined themselves regardless of whether their cholesterol is high or low as someone who put cholesterol in their arteries. And in those people, correct me if I'm wrong, Karim, but we've got over 25 years of robust. vast research that tells us as we lower cholesterol in those high-risk individuals, when we identify them, we can reduce their relative risk into the future. Would that be how you would describe it, Karim? Look, I think it was a very good comparison. And I also agree with what Tony said, that not every cholesterol particle is the same. You know, we have good, we have bad, and we have ugly. For years, we've seen LDL is a negative predictor. And LP little A is very ugly. LP little A. Exactly. Well, that's the ugly, you know. But I think it's not as easy as it seems at first look. But for most people, it is important to realize that most LDL is actually a risk factor, you know. So whether it's small dense LDL, large dense LDL, whether it's LDL within LP little A, because every LP little A particle contains an LDL. They are the things that unfortunately often end up in arteries. But I think Tony made a very important point, and also you, Warrick, that not everybody really ends up with bad coronary disease just because their LDL is a little bit elevated. So I think we're all on the same line there. So my own... approach to this as both you gentlemen know is to say well we can't predict very well who's going to run into strife unless we wait for people to have a problem in my opinion that's just a little bit too late my my own approach is to say well look why don't we image the arteries or image the carotid arteries whether it's in the neck or in the heart and see for that individual what their cholesterol is doing to their arteries is that sort of the approach you would have been taking in your clinical practice tony yeah i think it it was certainly back then um i think coronary calcium scores and so on were were not something that i had a lot to do with and they they were i think in australia in their infancy um and i've learned much more since and of course i've because of 56 years of diabetes i've i've had scans done uh and very surprisingly i've got virtually no calcium deposits at all uh amazing for a diabetic yeah yeah yeah congratulations on good luck and good management tony the question i would have your blood pressure was probably very well controlled your diabetes was excellently controlled and your ldl probably was never very high is that correct Yes, that's correct. And my triglycerides tend to be low, even when I wasn't on a low-carb diet. Wonderful. Actually, I wouldn't mind speaking to that momentarily. And then we might wrap it up because this is a fantastic conversation about LDL cholesterol, but we are getting close to time. The fact that you kept your triglycerides down, Tony, I think is critical in that wonderful description you gave around particle size. We know that as triglycerides creep up, then within the bloodstream, there are more and more. If you like the more atherogenic, the more likely to be problematic, small, dense LDL particles, the nastier type. So we can simply measure people's triglycerides or generate a ratio between triglycerides and HDL and know that if people are less than about 1.5, then they predominantly have the more favorable, large, fluffy, if you like, particles. And if they're above... And if their triglicide levels are elevated, they're in the other camp where their small, dense particles are elevated. But to come back to one of Karam's points, which is even if you've got the good LDL, it can still be a problem. One of the analogies I've sort of generated around that is if we think of where these particles are problematic, we're thinking about the pores or the fenestra within the endothelium. And we're thinking about particle size. Now, if you take each of those and enlarge them to something we can relate to, the finaster could be considered as a basketball ring in size. And if you take that as the basis, then the large fluffy particles are the size of a basketball. The small dense particles are the size of a volleyball. So not an enormous amount of difference. And that difference. is not a lot because density is related to radius cubed. The thing, though, is if you stand at the free throw line, you can toss a volleyball into that basketball ring. You can equally toss a basketball in. So too many, even if you've got the better LDL cholesterol particles, as Karam said, you can still end up with plaque falling through the hoop or... those particles falling through the hoop or those particles falling into the vessel wall. Warrick, I perfectly agree with what you and Tony said. The only other thing I would like to mention is because we are talking about it, that residual hypertriglyceridemia in diabetics can lead to microvascular complications. And I wanted to ask Tony if he agrees with that and whether he uses fibrates to reduce microvascular complications, retinopathy, but also obviously other microvascular complications. in his diabetic patients with high triglycerides. Sorry, before you answer that, just to explain that for the people listening, Karim's talking about those triglycerides, those so-called ugly fats in the bloodstream. If they're too high, they're literally... potentially problematic or toxic to the small blood vessels within major organs like the eyes, within the skin, even the feet and so forth. So, Tony, please feel free to answer Karim as he put the question to you. Yes. Well, I must admit that usually these people were under the auspices of cardiologists. So they were the ones that were more. I'd like to recommend that or the ophthalmologists were. I've never, to be honest, taken fibrates because my triglyceride was never high enough. But perhaps in a future session, they talk about what effect low-carb diets have as opposed to, say, the fibrates. Yes, there are people that did have very high cholesterol, sorry, very high triglyceride levels. used to prescribe fibrate for back then before i knew about low carb uh and you know whilst like as being retired now i i um i'm not prescribing anymore um i would be in you know if i was back then now knowing what i know i would be saying low carb first um and then see what happens actually i tend to agree with that tanya i would normally have the conversation about reduction of carbohydrate If that didn't work, then I think the fibrates are really indicated. There really is some good data behind them, as Karim alluded to. While we talk about that reduction of carbohydrate, we can swing back to those particle sizes again. I think it's also worth realising that when we see potentially a worse outcome in people with small particles. it's often beyond just the particle being the problem because they're an association with other metabolic issues like insulin resistance or raised insulin levels, which probably drives things like inflammation. Is that something that you would support there, Karim? Would you repeat that? I was just absent for one second. So when we think about... the small particles, LDL particles potentially being more problematic, it may not be the whole story that they're the problem of their own. It may be that they're also markers of other metabolic processes such as insulin resistance or diabetes or inflammation that are also contributory to that potential worse outcome for those individuals. Look, I think that's all correct. But, you know, in the trials, we've seen that almost any LDL is bad in these given circumstances where your cardiovascular risk is elevated. So if you take type 1 diabetics, type 2 diabetics, non-diabetics, and you look at people who have coronary disease and you lower the LDL cholesterol with statins, statins and esotrol, now PCSK9 inhibitors, you will see a reduction not only in plaque on imaging modalities that you're very familiar with, but also you will see reduced cardiovascular events. You know, while this is all correct, how applicable it really is in reality is a different question and how important it is for your average patient in front of you is a different question as well. Yeah, super important. Tony, would you like to make any final comments before we wrap up LDL and coronary artery disease? Certainly, my reading has led me to believe that the small LDL particles also have a damaged receptor, so they're not easily... retaken up by the liver and therefore that the particle size the number of them can increase uh and so that that can be another factor uh involved not just their size per se um so you know and and you know particle number is one of the things that is measured along with these these sub the sub fractions of of ldl uh there's also i guess some question about the actual way that cholesterol gets into the blood vessel lining and that that may be relevant. In other words, there's an alternative hypothesis to the one, I suppose, the diet heart hypothesis. And finally, with statins, there are pleomorphic effects, as I understand, in terms of they have an effect on the blood vessel lining to do with the chemicals involved in protecting that lining. and they also have some anticoagulant effect uh and so so you know is it the stats the cholesterol lowering that's actually causing the benefit, or is it the one or two of these other effects, which by pleomorphic, I mean that they're there along for the ride, if you like. They just happen to cause other good effects, but they're not the reason that the medication was prescribed in the first place. The only thing I would say, Tony, is that everything that lowers LDL, whether you do it with diet, which is difficult, as you know, or you do it with statins or esotrol, Well, even apheresis, you know, if you take a dialysis type approach and lower LDL, it all seems to have a similar effect. But you're right, there is additional effects of statins, the pleiotrophic effects that have been implicated in preventing certain cancers, that have been implicated in preventing inflammation. So I think it's probably a combination of these two things. Okay. This has been a fantastic journey through LDL cholesterol. I get the sense that LDL cholesterol overall is bad and runs the risk of ending up in people's arteries, that there are different types and some therefore run a greater risk that we know that... For people who have demonstrated problems within their arteries, lowering their cholesterol is valuable. For people who haven't got to that stage yet, it is understandable that it's harder to figure out what to do with those people and just treating the cholesterol probably doesn't make as much sense as perhaps imaging them. And quite interestingly, a passing comment at the end about the potential other effects that... statins may have over and above LDL cholesterol lowering. Tony, thank you so much for joining us. Karim, thank you as well. I think we should find some time for a couple of other topics because there's plenty more to talk about. Thank you. Thank you. Okay. Join the Healthy Heart Network and become part of our growing community. If you're interested in your heart health and risk of heart attack, then join the Healthy Heart Network for only $5 as a lifetime member. This represents $55 worth of value. We offer and help people understand their present state of heart health, what their current level of risk is, and the positive steps they can take to improve their risk of heart attack in the future. Go to www.healthyheartnetwork.com.au and click the join the family button.
