**EP333: Two Case Studies For Your Interest** **Dr. Auric Bishop:** Welcome, my name's Dr. Auric 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, cholesterol, for better health. If you enjoy this podcast, I would be honoured for a five-star review. You can share it with your family and friends. It may well save someone you love. **Dr. Rick Bishop:** Hi, my name is Dr. Rick Bishop, and welcome to my podcast and videocast station. Thank you so much for tuning in. I really do appreciate it, and I really hope I give you something that is interesting, informative, and most importantly, helps you on your best health journey. Well, today I'd like to share with you a couple of stories around managing cholesterol, and these stories underline how we are all different. We can't necessarily just buy a suit off the rack for all our patients because it may not fit. We sometimes need to be bespoke. The first case I'd like to talk about is Sue. I met Sue back around 2018. She was a 60-year-old woman who was really focused on looking after her own health. I really did appreciate that she was doing what she could. She was exercising regularly, going to the gym, doing weights, cycling, and walking. So, no question, she was making those investments for her future health. And a quick segue while we've got the chance: Remember, whatever you do today, it's not for your health today. It's an investment for your health in the future. Please don't forget that because it's what you do today that will count down the line in five years or ten years. And here's the scary bit: In five or ten years, if your health unravels, you can't wrap it back up; you can't wind time back. Please don't ever say, "I wish I'd done..." because when it comes to your health, there's nothing more important. All the money in the world won't give it back to you. So, back to Sue. She was looking after her health; she was being proactive. Her husband had come through and seen me in my rooms and had a scan on his heart, and she quite appropriately wanted to do the same thing. There was a family history of heart problems. Her cholesterol was up a bit. Her total cholesterol was 6.8, and her bad cholesterol, the LDL cholesterol, was 3.9. I took the opportunity to undertake, if you like, a 60,000-kilometre check. So, we did an ultrasound on her heart. It turns out the chambers were pretty well of normal structure and function, which is great. There was no valve problem. Maybe the heart was a little bit stiff, possibly in keeping with age, but we also checked blood pressure, and this was elevated. Now, super important because from that point, we were able to get Sue on appropriate blood pressure therapy. She's actually been on dual blood pressure therapy ever since, with beautiful control of her blood pressure. Now, that's super duper important. If you are interested in blood pressure and why I jump on it, please check out some of my other podcasts. Blood pressure is all about heart attack risk, stroke risk, renal failure risk, atrial fibrillation risk, cardiac failure risk, and dementia risk. So, it's a super important component of our management for long-term health, and it's super easy to treat. We've got really good medications, so never underestimate the importance of blood pressure. When it came to evaluating Sue's 60,000-kilometre heart check, structurally, her heart looked normal. Her blood pressure was up, and we pulled that down with dual therapy. A quick aside: dual therapy allows us to use lowish or intermediate doses of two agents in a synergistic way to try and pull that pressure down rather than taking a single agent and driving it really hard, which runs the risk of increased side effects. As we push one agent really high, that single agent may not give us the same return in terms of blood pressure lowering, but because it's a much higher concentration in the bloodstream, it will give us a greater risk of side effects. So, combining drugs makes plenty of sense for maximizing response or efficacy and trying to minimize our risk of side effects. So, you were waiting for it, of course. I went on and undertook cardiac CT imaging. This is the way I advocate for so many people to know what's going on with their heart. At 60 years of age, with a bit of a family history, elevated cholesterol, and elevated blood pressure, Sue was a perfect candidate to have this done. Now, her score was in the order of 30-something, not particularly high. However, when we looked at that score compared to other women her age, she sat somewhere between the 75th and 80th centile. Now, when we talk about centiles, we're really talking about if we took 100 women off the street at the same age as Sue and arranged those women from position one being the lowest score to position 100 being the highest score, where would Sue fit in that range? Now, obviously, the lower, the better if you can. She was sitting between 75 and 80. This tells us that she has a significantly greater propensity to put plaque in her arteries than other women her age. In fact, she was in the highest quartile. This really represents a three, four, or even five times lifetime risk increase of a cardiovascular event. This ties in with her cholesterol level and family history and is not made any better by that blood pressure having been high. So, what did we do? Well, of course, we looked to try and modify those risks. Sue was a fantastic patient to work with, and it is my blessing that so many of my patients, like Sue, are motivated, engaged, and really want to find the best solution for their journey going forward. I said to her, "Look, that cholesterol level's high. We probably want to pull that so-called bad cholesterol from 3.9 down to about two or even a little bit lower if we possibly can." So, we set off using a statin, absolutely standard first-line therapy in this situation. I prescribed her about 20-odd milligrams of atorvastatin and sent her on her merry way, thinking that we'd probably see a 40 to 50% reduction in the LDL cholesterol, which would bring us very close to what we were aiming for, that 2 millimoles per liter, which is in keeping with current Australian primary prevention recommendations. Well, it turns out Sue had a bit of trouble with the statin, and it was causing her some pains, and one thing led to another. Because she felt so fit and well, she just dropped off it. I saw her a year or so later. Lo and behold, she was off the statin. The cholesterol was high where we'd measured it before, and this was not ideal. We'd reign in the blood pressure; she'd continued with her exercise, which was great. But that cholesterol level was still too high. We know she had a greater propensity than the average lady of her age to put plaque in her arteries. So, we revisited that cholesterol-lowering regime. Instead of reintroducing atorvastatin, which really is probably the most commonly used statin in the community, I recommended we try rosuvastatin, probably the newest statin on the market, used extensively, very safe, but it has a slightly different chemical structure to atorvastatin. Rosuvastatin tends to be water-soluble, and we call that lipophobic, so scared of fatty tissue. Atorvastatin tends not to be water-soluble; it tends to be lipid-soluble. We call that lipophilic, or loving fat. So, they've got slightly different chemical properties. We commenced Sue on rosuvastatin. The long and the short of it was she came back reporting symptoms. This time I was only using a small dose, about 5 milligrams, and our top range doses are around 40 milligrams. So, really using about one-eighth of what we do for a very high-risk person if we're really trying to drive that cholesterol level down aggressively. Speaking with Sue, it became apparent that it took several days at least for the medication, if you like, to build up in her bloodstream and cause side effects, or at least this is how she reported it. It turned out when we talked about the atorvastatin trial previously that perhaps that was similar, that it took several days for her to run into problems. So, what we did was we retried the atorvastatin. Lo and behold, it literally took several days, about three or four days, before she felt that the drug had built up in her body and caused problems. Well, if you're paying attention, you're probably thinking, what would the next step be? And what am I thinking of? Well, if you're thinking, could you use those tablets on alternate days to avoid the buildup? Then you're right. That's exactly what I put to her. So, I said to Sue, "Look, it takes several days on either of these medications for them to build up and cause you problems. They are different chemicals and they have different chemical characteristics. So, there's every chance that we could use one and not have exactly the same problems if we continued with the second one because they're slightly different." So, we agreed on trialing pretty low doses of atorvastatin. We went for 10 milligrams, which is one-eighth of the maximal dose we tend to use, which is 80 milligrams. And we used 5 milligrams of rosuvastatin, which is one-eighth of that 40-milligram maximum dose that we used. And we used those on alternate days, one day on, one day off. Well, wonderfully, this did the job. She didn't report the buildup of this sort of aches and pains in the body, and these two drugs in an alternating regime did the job perfectly for her. She's tolerated them without problems. Indeed, I saw her only the other day. I noticed that that LDL cholesterol had crept up a tiny bit; it was a little bit over two millimoles per liter. I said to her, "Look, let's add in some ezetimibe, 10 milligrams a day. Do it every day because ezetimibe is a different agent altogether, but it'll have a potentiation or a synergistic effect with both atorvastatin and rosuvastatin, and there's no question we will easily, without side effects, pull that LDL cholesterol down under two millimoles per liter." And why do we want to do that? Well, at under two millimoles per liter, there's a very good chance we will start to completely slow down and possibly even arrest further plaque formation. Well, for a woman in her 60s with a bad family history, raised cholesterol, and high blood pressure, now treated, there's every chance, all going well, that we've mitigated future risk of heart attack. And remember, this is important. We often forget that women are affected by heart attack as much as men. We tend to forget because we often think about men having heart attacks, mainly because they have them sooner. Around about 50 years of age, men hit that intermediate to high-risk category; women often follow a decade later. But do not forget, as people are living longer, women still die from heart attack as the leading cause of death within the female population in the Western world. Cancer together accounts for about as many, but no single disease accounts for as many women being impacted as coronary artery disease. This is super important as well because we often focus on things like breast cancer awareness or even skin cancer awareness or pap smears or other female issues in particular that may not be as prolific or prevalent as coronary artery disease but often get more attention. Well, that's Sue. We had a great outcome for Sue. What I'd like to do now is tell you about Phil, who I met only just the other day, in actual fact. This was at a situation where I was presenting, and I was talking about cholesterol, diets, LDL cholesterol, and heart disease. Phil came up; he's between 35 and 40 years of age, he's a nurse, and he introduced himself to speak with me after the presentation, and it was my pleasure to share with him. It turned out that Phil had a terrible family history of heart issues. He had raised cholesterol and about five years earlier was way overweight. And we're not talking 5, 10, or 15 kilos overweight; we're talking 40, 50, or 60 kilos overweight. He was pre-diabetic at that stage, and he did some of his own sort of research and came to the conclusion he had to drop that weight, no question. The thing that he tried was a ketogenic diet. What's the upshot of a ketogenic diet? Well, it cuts your carbohydrates altogether. If you're burning ketones, then ketones are the energy fuel for burning fat. So, if you eat carbohydrate, your body preferentially burns sugar and you won't burn fat. But if you don't eat carbohydrate, then your body has to burn ketones because there's no sugar available, and to burn ketones, you release that from fat stores. So, being in a ketogenic state means that your body has to be burning the fat reserves you've got. Well, Phil was able to drop his 50-odd kilos and really had returned to a very healthy weight. The consequence of this was twofold, though. One was that he really became attached to the ketogenic diet because he felt so well on it. He didn't have fluctuating sugars, and he wanted to maintain this ketogenic diet going forward. He told me he eats a rump steak pretty well every night or a bowl of mince with an egg on top or some such thing. The problem, of course, is that a ketogenic diet, by virtue of the sort of foods he was eating, is enriched with saturated fatty acids. Saturated fatty acids are basically a fat you find in animal fats, as I just discussed, meats, but also cheese, butter, and cream. These saturated fats alter the body's own production of cholesterol. And so, by consuming an increased amount of saturated fat, you can drive up your cholesterol levels. Now, Phil's cholesterol levels were already pretty high. Now he's driven them up higher with his ketogenic diet, which he wants to adhere to. Now, here's the kicker. In amongst that time, as he was looking to look after his health, aware of his family history and aware of his cholesterol levels going up, he went to see his local doctor and organized a calcium score. Now, his calcium score was not dissimilar to Sue's, who I was just talking about. His calcium score was around 30. But for a bloke at 35-odd years of age, that calcium score percentile was over the 90th centile. So, this is a lot of plaque in the arteries for a young age. Now, to put absolute plaque numbers into context: Remember, zero is a low-risk feature; 100 is an intermediate risk feature; 400 is a high-risk feature; and 1,000 is a very high-risk feature. But that means that a score of 30-odd shouldn't raise immediate alarm bells except when we put it through the filter of comparing it to other men his age, and he's over the 90th centile. This is a real flag and for me would be something that really drove me to engage with this man and talk about his long-term or lifetime risk, not just this somewhat failed concept of just the next few years. As you can imagine, the GP sent this gentleman off to a cardiologist who immediately wanted to stop him eating his keto diet and wanted him to get onto statins. You can imagine that there was a little bit of a rub there because Phil wanted to remain on his diet, and the cardiologist wanted to lower that LDL cholesterol, and they were poles apart. Phil had seen six other cardiologists and was waiting to see one more at the time that he and I spoke. His story is important about trying to find the solution that best works for him. Phil was particularly attached to remaining on his ketogenic diet. So, how could we possibly do that in a way or at least open the possibility of that occurring? Well, I put to him that we could potentially consider doing a CT coronary angiogram of his arteries, which would allow us extra information. That CT coronary angiogram would inform us as to the quality of plaque that's in his arteries because it's possible that if we imaged his arteries, he could well have had only calcific plaque within his arteries. Now, that's a different story to if he has calcific plaque and significant non-calcific or cholesterol-dominant plaque. The latter, that cholesterol-dominant plaque, being far greater risk because that's where the inflammation sits and where plaque rupture can occur. Part of the reason, by the way, that Phil didn't really want to engage with these other cardiologists is that he'd had multiple trials on statin therapy at different doses and it had side effects. So, this really created a bit of a jam. I don't think that he'd been tried on ezetimibe, and I'm not sure that he'd tried intermittent dosing of his statin, but nonetheless, his cholesterol levels were going to be way high. So, I put to him, and we had this conversation that when we look at cholesterol and elevated cholesterol in people's arteries, there are often two situations. There's a situation where we find people with high cholesterol and bad arteries. These are often the people with the bad family histories, and that was his situation. In that situation, we really should be trying to get that LDL cholesterol down. The other situation where we see high cholesterol is where we see high cholesterol and, amazingly, we find clear arteries. Now, these people we can possibly look at either minimizing our doses of cholesterol-lowering therapy or agree to a very close surveillance strategy so that we don't lose control of what's going on in the coronary arteries. This was not Phil's situation. Phil had defined himself as someone who had the genetic predisposition that led to his LDL particles, for whatever reason, whether that's an amino acid variance, a change in the charge of those particles being caught in the collagen of the tissue that makes up the artery wall. For Phil, my suggestion was to look at CT coronary angiography to see what the plaque was like there. If it was high-risk plaque, then he probably would have to review his concepts around the ketogenic diet. He'd have to perhaps revisit LDL lowering, but the nice thing is he has potential options with ezetimibe, intermittent dosing, and possibly even the PCSK9 inhibitors depending on how high that cholesterol is and whether he actually fulfilled a diagnosis of familial hypercholesterolemia. The flip side is if he did have a CT coronary angiogram and nothing showed in terms of high-risk plaque, he only had calcific plaque, and this is a situation that we sometimes see in long-distance athletes. If he only had calcific plaque in his arteries, one could almost make an agreement or a pact with that patient to monitor him very closely, ensure the triglycerides remained down, ensure the HDL was maximized, which often happens with ketogenic diets, and agree to a repeat surveillance CT to ensure that that change in the landscape of the arteries wasn't changing. Now, I did say to Phil this is the sort of thing that I sometimes would engage a patient with, particularly someone in his situation, but before putting LDL lowering aside, I'd always also check the carotid arteries and make sure we're not missing an unbeknownst plaque that's developing there. Really, really important because there's no point avoiding a heart attack but having a stroke. Having said all that, what I really want you to get is that these situations can be complicated. The ketogenic diet is fantastic for helping people lower weight, avert diabetes, and many people feel really well on it, just like Phil. The ketogenic diet, though, because of the saturated fats, will tend to push up the LDL cholesterol. And this is exactly what's happened in Phil's case. A really good thing in this story is that Phil did get his arteries checked. And that gives us some insight into how we should be thinking about risk management. As I've alluded to, not all high cholesterol ends up in the arteries, but for Phil, it did. In Phil's situation, getting more information would certainly be valuable to tease out the difference between calcific plaque and non-calcific plaque. And in these situations of raised cholesterol, if there is ever a discussion about holding off on lipid-lowering therapy before committing to that decision, my practice is to look at the carotid arteries and make sure we're not missing plaque that may be forming there because that's critical. Well, there you go. I hope that's made a bit of sense. It is a complicated world when it comes to dealing with cholesterol, statins, coronary artery disease, and different individuals who have different responses to therapies and different objectives and goals. I really do hope you found that informative. If you have any queries or questions, as always, drop us a note at info@drwarwickbishop.online. As always, I really do appreciate you taking the time to listen this long. This is quite a long one. And as always, again, I hope you live as well as possible for as long as possible. Take care and bye for now. Did you know that coronary artery disease kills one in four people? So, most of us are likely to carry some risk or know someone who does. If you're interested in finding out more about how to evaluate that risk, check out www.virtualheartcheck.com.au. It'll give you information about risk and what else can be done to be even more precise.