**EP416: Highlights of WCCL June 2025**
**Dr Warrick Bishop:** Welcome, my name's Dr Warrick Bishop. I'm a cardiologist, an author, and a keynote speaker. I'm the 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, and 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.
Hello and welcome. It's Dr. Warwick here, and thank you for joining me on my podcast and videocast station. Well, fairly recently in June of 2025, I had the chance to attend the Fourth World Congress of Clinical Lipidology, which was run in Vienna. I thought I might share with you some of the highlights and some of the bits and pieces that I thought were just a bit interesting. So here we go.
The conference went over a Friday night, Saturday, and Sunday. Some of the world leaders in clinical lipidology were available to share. I won't necessarily go through people's names, but I'll hit some of the points that I think were pretty interesting. One of the things that I didn't realize was that LDL cholesterol, the so-called bad cholesterol, can only be utilized by the liver. So it's not used by the rest of the body. It's not used for making sex hormones, for example. It's not used for vitamin D production, for example. It's not used for energy within the body. That's pretty important because one of the things we worry about is how low can we get LDL cholesterol. Well, because only the liver can use it, and because the liver can use other sources, it really doesn't matter.
We know that's probably the case because we've also had really nice data on hunter-gatherer tribes with very low cholesterol. We know our ancestral primates also run extremely low LDL cholesterol, much lower than current Western civilizations. Really importantly, and still on that same topic of lowering LDL cholesterol, there have been concerns that by lowering it, we may increase the risk of other problems, in particular, hemorrhagic stroke. Hemorrhagic stroke is the sort of stroke you have when a blood vessel gives way and bleeds into the brain. The other sort of stroke that we have is called an ischemic stroke. Ischemic means lack of blood flow. This is where a blockage occurs in the artery to a part of the brain and stops blood flowing there.
Well, it would turn out that the research we have at the moment all points towards no increase in hemorrhagic stroke by lowering the so-called bad cholesterol. That's really, really important to know because in the back of our minds, we don't want to be giving somebody a medication to reduce their risk of heart attack only to increase their risk of stroke. Interestingly, and over and above that combined data looking at the IMPROVE-IT study and other studies that have lowered LDL cholesterol to significant levels, such as the PCSK9 studies like the FOURIER and the ODYSSEY trials, all suggest reduced all-cause mortality. This is really, really important because also combining that with some fairly recent research that came out of Korea, we know that lowering LDL cholesterol also reduces all-cause dementia.
Well, why is all that important? Basically, if only the liver can use it, if our ancestral primate ancestors and hunter-gatherers have low levels of LDL cholesterol, if we're not increasing the risk of ischemic stroke, if we appear to be reducing all-cause mortality, and we appear to be reducing the risk of all-cause dementia, then that concern around lowering LDL cholesterol too much just doesn't seem to be a valid concern.
Next topic. We've got some important information around risk and how we deal with risk and how we calculate risk. Some nice points were made around how we seem to look at short-term risk, and this can be misrepresentative for an individual. So imagine we've got a 45-year-old male with a bad family history. Let's say he's a tradie. One doesn't want to generalize, but let's imagine because of his work, he doesn't have access to good diet choices because of the sites he works on. Let's say his five-year risk is considered low. This might be seen as false reassurance if we were then to compare that with a lifetime risk, and his lifetime risk might be 30 or 40 percent of a heart attack.
What we know is that the sooner we can get treatment in place, the sooner we can start modifying risk, then the greater the dividend in the long term. This is really, really important. It sort of means that this 45-year-old male probably shouldn't be reassured at 45 to 50 years of age, but should probably be having a really sensible conversation about how to reduce that risk into your 60s, 70s, 80s, and potentially even beyond. So what's the call-out here? Think about coronary artery disease as a lifetime condition. It builds from our young years and catches up with us in our older years. Having a low five-year risk in your 40s or 50s can be quite misrepresentative of your total lifetime risk. So start to think about it a bit differently for yourself, but I think this is also really important for doctors to be thinking about. I'm moving more and more towards trying to understand people's lifetime risk.
I'm going to mention a new agent called Obisetrapid, a cholesterol-lowering agent that works through the CETP pathway, cholesterol transfer pathway. It's interesting because other agents in this space have collectively been an absolute disaster in therapy. They've led to worse outcomes, liver impairment, and so forth. This group of agents raises HDL cholesterol. Obisetrapid, in particular, not only raises HDL cholesterol, but it also lowers LDL cholesterol. There's lots of feeling in the lipid community that this may well be beneficial. So watch this space for Obisetrapid. It'll be a couple of years away, and it certainly won't be called that on the box.
Here's an interesting one, and I thought this was fascinating because there's lots of talk about blue zones and visiting blue zones. Places like Japan, where in certain areas people appear to live longer. Certain blue zones around the Mediterranean, again, where people tend to live. I think certainly we've historically thought of this as being related to the region, to good food, to being outside, to walking around after dinner, to maybe not eating too much, to having an active lifestyle, maybe, I don't know, going out and doing your own fishing—all those sorts of things. We've called these places blue zones.
Well, a couple of places in particular in Italy were discussed in exactly this context. One was Campo di Melli, and the other was Le Bon Sul Garda. Both these regions are linked with longevity, with people living into their 80s, 90s, and even 100 without too much problem. I think to a large degree they've been labeled as blue zone regions, and to a large degree they may well be. However, there's more to it than that. In the Campodomale group, they've found that the population there have an interesting mutation of a particular gene called ANGPTL3. ANGPTL3 is central to cholesterol metabolism.
What's the upshot? Well, these individuals have lower levels of LDL cholesterol and triglycerides, offering atherosclerotic protection over their lifetime. Blue zone or just lucky genes? You decide. What about the lemon silgato? A group of people—well, interestingly, some scientists actually in the 70s identified a genetic variant in these individuals called APO A1 Milano. In these residents, they actually had lower HDL cholesterol levels, the so-called good cholesterol, but for some reason, these people with lower HDL levels seemed, with their APO A1 Milano mutation, to exhibit a significant reduction in the risk of heart attack and therefore longevity.
So you can change where you live. You can go to a blue zone. But remember, at the end of the day, you're going to be defined genetically by what your parents have given you.
I'm going to finish on one last concept, and that's a concept called CRISPR therapy. You may have heard of CRISPR. It's a way to modify DNA. It's not here yet, but it almost is. What does CRISPR stand for? Well, it stands for Clustered Regularly Interspaced Short Palindromic Repeats. Clustered C, R regularly, I interspaced, short S, palindromic, P repeats—CRISPR spelled C-R-I-S-P-R. This is a fascinating technology and one that will allow us to specifically target a genetic blueprint in an individual and then potentially alter the protein production that that person will be able to take advantage of for the rest of their lives.
Already, they're looking at trials in sickle cell anemia, but there's every chance that because a number of cholesterol-related disorders can be single-gene mutations, CRISPR therapy may be an ideal solution. So there's lots of work being done there, and it may well be that lipidology and cardiology lead the world in some of these new therapies and their implementation to broad communities.
Well, we touched on a heap of other stuff at this fantastic conference and Congress. It was just an absolute delight to catch up with some of the world leaders and be involved. We are talking about another Congress in two years' time, but this one was an outstanding success. Lots of good information. I hope what I've shared with you has been of interest to you. If you have any queries or questions, drop me a note at info@drwarwickbishop.online. If you've got any suggestions for future podcasts, let me know. I'd be happy to try and help.
If you enjoy these, I would be so grateful if you shared and liked. It is unfortunately the world we live in. I hate asking people to share and like, but if I don't, then it doesn't happen. As you're probably aware, we do really live in an age where social media shares and likes and all those sorts of things really do count. Not that I think that that's a good thing or a bad thing. It just is.
So till next time, I'd love you to share me, like me. And what I'd really like you to do is be as well as possible for as long as possible. Take care and bye for now.
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.
