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. And I'm absolutely delighted to say that today I have with me Dr. Karam Kostner, a lipidologist, a cardiologist, and an expert at looking after familial hypercholesterolemia. Hi, Karam, how are you? Very well. Thank you, Warrick, and thank you for the kind introduction. So today I'm very keen to talk about a condition called familial hypercholesterolemia. Well, what a mouthful is that? So I'm going to break it down. Familial means in families. Hyper means increased. Cholesterol is the sticky stuff we're talking about. Andemia means blood. So this is a condition within families of high cholesterol in the bloodstream. What do you reckon, Karim? There's a bit of it around how common is this condition? Yes, look, it's a very common condition. It's a condition where cholesterol is very high virtually from birth. It's inherited in an autosominal dominant matter. What that means is that 50% chance of the offspring, 50% of the offspring will get it. And it's like the toss of a coin. Since we get one gene for any condition from our mom and one from our dad. If one of the parents has it, you have a 50% chance of getting it. If both parents have it, as we see in some families, then there is a almost 100% chance of getting it. And there's also the chance of getting the much more severe form. But how common is it? It's about one in 200 to one in 300 in Australia. It's more common in certain populations, such as the Lebanese population, some middle European countries like where I come from. I'm from Austria. The Mormons are much more common. It's much more common in Askenazi Jews. And it's much more common in consendrinous families where cousins marry each other, for example. And even South Africans, as far as I'm aware, particularly. You're absolutely right. I mean, that's also one population where it's more common. And it's usually due to a founder effect who passes it then on to family members. So why is it such a big deal? Why do we have an interest in FH? Because I've got an interest in it as well. Yeah, tell me why you're interested first and then I'll answer your question. Well, a number of years ago in my early private practice, and I am a general cardiologist, I look after all comers. And in Hobart, we don't have any specific subspecialties or certainly didn't back 15 to 20 odd years ago. I had a patient who was from South Africa of Dutch extraction. And this particular patient had both parents with familial hypercholesterolemia. So she got a dodgy gene from one patient and a parent and a dodgy gene from the other parent. And she had essentially no functioning receptors for LDL cholesterol on the liver. It looks like a... if you like, a homozygous, but she was a compound heterozygous, which is a bit of a mouthful. Don't expect anyone to follow that. But she had cholesterol levels that were bouncing off the ceiling. And really my journey with FH commenced with starting to try and look after this lady as well as I possibly could. I might say that right at the moment she is just fantastically well. And it's been a fantastic journey for me to learn. and make sure that I've kept abreast of everything important to make sure this woman got the best care possible. That's a very good example. And it's a very severe case that many of us will never see because it's extremely rare in this form. But as you indicate, the problem with FH is that people with this condition will develop coronary disease. It is not a matter of if, but just when. And in some families where the family history is early, obviously earlier. But more importantly, in patients who have familial hypercholesterolemia and other risk factors such as smoking, high blood pressure, diabetes, obesity, they will develop coronary disease much earlier than others. But the reason why we're talking about it today and why you're interested in it and I'm interested in it is that it's entirely treatable. If we treat cholesterol from an early age in these patients and we start at child's age, You can prevent coronary disease. You can delay the disease progression and many patients will never have a heart attack in their life. So it's clearly a really important condition with these families with really high cholesterol levels. They run an unacceptable risk of heart attack prematurely. And I think that's the bit that's most troubling. These people die prematurely. Men in their 30s. and into their 40s women even in their 40s and 50s so at a very young age but I have lots of patients come along and say oh doc my cholesterol's up and my dad died of a heart attack at 65 and mum died at 75 with a heart attack and and so this so how do we separate the familial hypercholesterolemic patients how do we make that diagnosis from run-of-the-mill elevated cholesterol and run-of-the-mill people running into strife with heart attack at a relatively young age? Very important question, Warrick. And, you know, basically we use calculators that tell us what the likelihood of having FH is. And there's various of these calculators and apps available that GPs and specialists have access to. And they are all based on LDL cholesterol levels, non-history of cardiovascular disease, family history of cardiovascular disease, and clinical science. And some of these calculators, like the MedPET calculator, the Dutch lipid score, which is probably the most common one, or the Simon-Broom criteria, they simply give points for LDL cholesterol levels, clinical signs of FH, which is a thickening of the Achilles tendons or a white ring in the cornea. And history of early cardiovascular disease of the patient, but also their parents, obviously, and their siblings. And then we come up with a probability of having FH. That is from definite to likely or unlikely. The other thing, obviously, that can be done that both you and I have done is genetic testing. So you can look at genetic tests that tell you whether the patient has a defect in the LDL receptor, which is the receptor for cholesterol at the liver. the carrier protein of LDL, which is Apple B, or PCSK9 and other enzymes. But the problem with genetic testing is that in 20 to 30%, we don't find the genetic defect simply because it hasn't been described yet or it's difficult to find. Well, I think while we're mentioning genetic testing, it's incredibly topical at the moment because I understand that the medical benefits schedule is soon to release an item number to allow specialists in the area like you and I to actually run these genetic tests with Medicare support. So a very topical issue right at the moment. Very good point. And that's absolutely correct. Look, the issue about making this diagnosis, obviously, pulling together a number of criteria, which, if you like, tip the scales and push someone into the likelihood of having this condition. with high cholesterol, bad family history. They may have some sort of evidence of a heart attack or buildup of cholesterol in their arteries, some other clinical features. So all those things are really important. If we have found someone who we believe has familial hypercholesterolemia, what next? What do you do? It's a good question. In most people that have familial hypercholesterolemia, we start lipid lowering therapy very early. So once we've made the diagnosis, We start treating patients with familial hypercholesterolemia from the age of 10, initially with a small dose of a statin, when they are in their young adult years with a combination of statins and esetrol. And then once they have coronary disease, so if they don't respond enough to statins and esetrol, we basically also give them PCSK9 inhibitors, these new injectable therapies for cholesterol. But in addition to that, we also treat their other risk factors aggressively. If they are smokers, we try to get them off the cigarettes. If their blood pressure is high, we try to treat their blood pressure, diabetes, et cetera. And in some very severe cases, we even consider a liver transplant. If you have the homozygote form where you get the gene from both parents, like you indicated. Or we recommend something called aphoresis, which is almost like a dialysis procedure for cholesterol, where people are hooked onto a machine once a week, their blood is washed from, the cholesterol is washed out of their blood, and then they go home, basically. Well, I can just let you know that this woman who I spoke of earlier, she is on maximal dose statins. She's on ezetimibe. in combination. She has apheresis so she literally hooks up to a machine and currently that's once every couple of months to have cholesterol sucked out of her body and she's on the PCSK9 inhibitors, these new injectables and she's got the full hand but she's doing fantastically well. That's excellent. I think the significance of all this is that we're wanting to prevent wear and tear on the arteries, the buildup of plaque in the arteries, which can increase risk of heart attack in the future. So when you're seeing someone who's not had a problem with their arteries previously, do you try and evaluate what's going on in their coronary arteries or the arteries in their neck? Absolutely. And you're one of the eminent specialists in imaging, cardiovascular imaging in Australia. So I'll let you talk about cardiac CT, especially in a second. But I use all these technologies as well. We use carotid ultrasound in young people, looking at the intima media thickness and plaque in carotid arteries. You will tell us about CT and coronary calcium in a second. And we also use other tests, for example, imaging of Achilles tendons to look at the thickness. You know, we clinically evaluated, but we also use x-ray and ultrasound to look at Achilles tendons where cholesterol accumulates. But tell us a bit about cardiac CT and the role that cardiac CT plays in your opinion. So I think it's very important for us to match up. what we see biochemically with what we see in the individual. And although in these families with familial hypercholesterolemia, there's no question they carry an increased risk. I think it's really useful for the clinician and useful for the patient to have that risk matched up with something that's physically going on in the patient. So I think patient engagement is much improved by knowing what's going on in their arteries. In terms of taking imaging and pictures of the arteries, I think it can also help us with intensity of therapy and the sort of leeway we would accept or not accept when it came to possible side effects for an individual so that we have a better idea of matching up exactly what we're doing. Now, I'm the first to admit that if... we do see someone with familial hypercholesterolemia, then I see that raised cholesterol level as almost an environment for plaque or buildup of cholesterol in the arteries. So I generally want to try and modify it. But occasionally there are people who are particularly young or undertake particular dietary and physical lifestyle changes or have a philosophical... position which prevents them from wanting to simply take a drug unless they have a good reason so imaging can really give us information around that space and the number of times I've had patients have said look I don't take a tablet unless I really had to I scan their heart show them what's going on and they take the tablet without any troubles at all I think it's a I think it's invaluable technology for us and for the patient Is it very safe overall? I mean, that's a question that I often get from patients, especially cardiac CT with regards to radiation, et cetera. So look, 10 or 15 years ago, if you read the literature, you would believe that cardiac CT imaging delivered a moderate dose of radiation. These days, the current iteration of scans. is really much improved and we're able to take a picture of the heart with a high degree of accuracy with about the same radiation dose that you might expect from a mammogram which is well within the realm of what we see as an acceptable radiation dose for a preventative strategy so right it's doable you wouldn't do it all the time but it's not No, thank you. That clears that up very nicely. The only other thing I wanted to mention about FH is family screening is very important because for every FH patient that we detect, we can detect other family members. And that's one of the weaknesses in any healthcare system that we're often too focused just thinking and treating the patient in front of us. But with familial hypercholesterolemia, because there's such a clear genetic link, we can easily pick up brothers, sisters, and children of the patients that we treat. I think that's hugely important. And in fact, you and I both know that in Australia, we have a registry which has been set up for Australia and New Zealand so we can enter the details of individual patients and use that as a trigger to follow up on their family members. I think this is incredibly important and again reflects back to this new rebate for genetic testing to help us with some of that family screening. Look, we're just about at time, Karim. It's been... This is an incredibly important topic. And, you know, it is one that both you and I are very passionate about. For someone who's listening who has got raised cholesterol and there is a history or not of family problems with hearts, what would you recommend that these people do? I would recommend that they, first of all, see their GP, that they get an accurate lipid profile and a clinical examination and get on to therapy if they've got FH, obviously. And if the GP cannot sort it out, specialists like you and myself are very happy to help. And they should really be seen by a specialist who has an interest and the knowledge to treat familial hypercholesterolemia in those cases. So I'm going to wrap it up there. It's a very important subject. And it's one that you touched on. The absolute primary reason why this is so important is Familial hypercholesterolemia can prematurely end lives. And with the right therapy, we can give people full life expectancy back. And that is an incredibly powerful opportunity. I'm going to wrap it up there. I really thank you, Karim, for sharing today. For anyone who's listening, if you've got any queries or questions, drop us a line at members at drWarrickbishop.com, sorry, dot online. If you've got any suggestions for future podcasts, please let us know. As always, I thank you for your time. I wish you the very best. Until next time, 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.
