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 welcome to my podcast and videocast station. Today, I would like to talk about is plaque that can either rupture or plaque that can erode. And that might sound like a weird distinction. Importantly, both types of plaque can give rise to Heart attack. And what I'd like to do is go through that in a bit of detail. Because when we think about plaque and formation of plaque, we generally consider that plaque forms at some point of stress within the artery, some point of wear and tear. There's generally some cholesterol associated because that's what builds up and cholesterol is a repair mechanism. And generally, there's a component of inflammation. So when we think about a normal artery, there's a nice, clear, open lumen. There's a fine, thin internal layer. There's the middle part of the artery, the medial adventitia. And then there's the outside of the artery, a bit like three coats of clothing on a... cold days so you might have your thermals on the inside you might have a thick woolly jumper uh on top of that and then you might have a waterproof shield over the top and the coronary arteries are a little bit like that what happens as plaque progresses is that the uh if you like the thick woolen jacket is the bit oh sorry the thick woolen jumper is the bit that accumulates extra particles extra lipids if you like extra And that, it's in that middle layer where plaque starts to form. When we look at plaque and we look at people who have had heart attacks, and obviously this is post-mortem because you can't section people who are still alive, but when we look through the arteries of people who have had heart attacks, then there are two ways the arteries can come to being blocked. One is when the contents of the plaque, i.e. the cholesterol and inflammation, come into contact with the contents of the blood. And when that occurs, a clot forms. And that really is the interaction of fatty cholesterol-inflamed plaque with the contents of the blood within the artery. And that is able to occur because the thin fibrous cap that separates the plaque from the contents of the blood vessel ruptures and breaks. Now about 60% of all heart attacks are associated with a ruptured plaque. If 60% are associated with a ruptured plaque, then that means 40% of... Heart attacks must be associated with something else, and in fact that is the case. And what 40% of heart attacks are associated with is what is called plaque erosion. In the setting of plaque erosion, the contents of the blood do not breach the cap that keeps the cholesterol within the artery. What occurs is that there seems to be a denudation. or a removal of the lining of the cells of the cap, which is often thick, separating the cholesterol from the blood. And it's simply that denudation or removal of those cells which allows a clot to form. In general terms, a plaque erosion is more likely to be... An unstable anginal type of syndrome where someone gets niggly pain at rest and it generally progresses often for a number of hours. Whereas a ruptured plaque is very sudden. It is almost instantaneous. So plaque rupture and plaque erosion, two different processes, both defined. By their fibrous caps. In plaque rupture. A thin fibrous cap. Breaking down. And allowing the contents of the blood. To mix with the contents of the lipid plaque. In plaque erosion. The fibrous cap. Remains intact. And for some reason. There is interaction of the blood. With the surface of that. Fibrous cap. which for some reason is demuted, and a clock forms there. So if we think about it, there's generally a progression over a period of time, there's information within some plaque, and there's lack of information within others. When they look at ruptured plaque and cross-section, very apparent that there are a number of features which really define the process that occurs, and that is obviously a rich cholesterol-based core, a thin cap holding it in place, that thin cap which is able to be ruptured. There's often calcium crystals floating around the place in different locations, and there are inflammatory cells as well. telling us it's a heady brew of unstable processes, unstable components. So when we look at that unstable ruptured plaque, the large fatty bit in the middle, that necrotic core, often is greater than 30% of the total plaque. The fibrous cap is thin and... Thin in pathological terms means less than 65 micrometers, so it's tiny. There are lots of inflammatory cells and there's some smooth muscle cells which are really falling apart. There is expansive remodeling of the lumen, so that changes shape to accommodate that plaque in the early stages. There is plaque hemorrhage, there is inflammation, and calcium is seen. In contrast, plaque erosion, really the fibrous cap is intact, but the lining, the endothelium that should be lining all the inside of the blood vessel, if you like, the Teflon within the blood vessel is missing above the thick fibrous cap of an eroded plaque. And that eroded plaque is a more stable phenomena in terms of what's going on within the medial or the woolly jumper layer of the blood vessel. What's going on there is far more stable plaque, less calcification, less inflammation, yet there is still loss of endothelium above the thick fibrous cap, and it's the loss of that endothelium that allows the contents of the blood to respond by forming a clot because it detects what it thinks is a breach in the circulation. If you get a breach in the circulation, a cut, then of course you have to form a clot. Otherwise, you would bleed to death. So eroded plaque, the endothelium is missing. There's no clear-cut morphology. It's a different beast to a ruptured, unstable plaque. It's scarcely calcified. There's rarely this expansive remodelling, and it's only sparsely inflamed. It really dictates that there must be local factors driving the process, and it really makes it quite hard to identify these plaque, which fortunately cause less than half of a heart attack. It's hard to identify these plaque as likely to be problematic in the future, because they can look relatively benign. So how do we assess plaque? Well, obviously we can do it histologically, so under a microscope, and we've just talked about that. There are the characteristics that I just referred to. We can talk about plaque in an inferred way, so someone who presents with symptoms, someone with catastrophic onset of chest pain, quite likely a ruptured plaque, somebody with staggering pain in an unstable way. More likely an eroded plaque. We can look at the ECG because changes on the ECG will indicate the blood's not reaching the heart muscle and that heart muscle demonstrates that by changing the way the electrical pumps work and therefore the ECG. We can use blood tests. A test called troponin allows us to get a feel for whether there's been any stress on the heart. It's a very sensitive test for telling us if someone has had a problem. or strain with the heart muscle. And we can do what's called functional testing, looking for evidence of lack of blood flow to the muscle, often by reproducing the symptoms or showing ECG changes as someone exercises. We can do that in combination with an ultrasound as well to look at the contraction of the heart at the same time. We can also use nuclear medicine isotopes to look for where blood flows around the heart. So functional testing gives us a good idea as to whether there really is a narrowing causing a hemodynamic significance. We can also image the plaque. We can do that non-invasively. And that's things like cardiac CT imaging if we want to look at the heart. But we can also, of course, look at arteries in the neck, for example, just using ultrasound. We can also look at the plaque invasively, and that means we can inject contrast down the arteries to show us an angiogram, and an angiogram gives us a silhouette, if you like, of the flow down an artery, and therefore we can see if there's a narrowing or a blockage. We can use this amazing... tool that we can thread literally down the coronary artery called an intravascular ultrasound and this is an incredibly precise way of looking at what sort of plaque might be in the wall of the artery and lastly we can use a tool called optical coherence tomography you don't need to remember that but that's even cooler than intravascular ultrasound it's a fine light or laser that's guided down the artery and we use laser beams or the equivalent that's near infrared to give us a feedback like a an image of what's going on within the plaque quite an astounding bit of kit so when we think about cardiac CT the resolution obviously is a issue but we can see fatty plaque, and we can see calcific plaque. It gives us really good insight into plaque burden, which is able to be measured. When we think about invasive angiography, of course we get that idea of what's flowing down the lumen. I mentioned intravascular ultrasound is an ultrasound probe down the artery, and it uses 20 to 40 megahertz to image the artery. This is in contrast to the probe that we put on the outside of the chest, which has to penetrate at least 10cm, sometimes 15cm to get a good view. We use 3-5MHz for that. So the higher the MHz, the less the penetration, but the better the resolution. So 20-40MHz is pretty impressive. Our optical coherence tomography uses near-infrared light, and that's wavelength is even shorter. It's directed at the vessel wall and gives incredible images. The advantage of OCT is that it can actually look through calcium, which is something that Ivers just can't do, but both modalities are fantastic for picking up the plaque angry necrotic lipid core, or a more stable core, and OCT, optical coherence tomography, is even detailed enough to allow us to measure how thick the fibrous cap is, so we can get a sense as to whether this is a plaque that might rupture or erode. Well, is all this important? Well, I guess the overarching question is, Can plaque regress? And if plaque can regress, then this information could be important. And in fact, if we're going to try and evaluate if plaque can regress, how do we do that? Well, one way is using intravenous ultrasound on some subjects before and after intervention. Now, there have been a couple of studies looking at this using high-dose statin and using PCSK9 inhibitor. And interestingly, both these studies run over either a year to 18 months. have shown that if you look to lower cholesterol enough, in a good percentage of patients, greater than 50%, you can modify plaque composition and get regression of plaque. We've also had a study that has shown us using OCT that not only can we get regression of plaque, fibrous cap thickness which borders between the lumen or the inside of the blood vessel and the cholesterol plaque and you can imagine if we're able to see increases or changes in size of the fibrous cap thickness then that would tell us that that particular plaque is heading towards plaque stability and there have even been studies using OCT To measure the thickness of this fibrous cap over a 50-odd week period, a clear demonstration that we can modify this particular risk. Well, the significance of all that is that it supports our premise of lowering LDL cholesterol to bring stability. to coronary arteries supports the LDL hypothesis. It really gives us a sense that we can bring stabilisation to arteries. It really tells us that with the best therapy, we can reduce ruptured plaques, or at least infer that that's possible. We don't have good information on whether we can reduce plaque erosion. That's a slightly different story that we don't yet understand, but an absolutely fascinating space, and one that we're going to hear and see. more and more about. So, I'm going to wrap up there. I hope you've found the concepts around plaque rupture and plaque erosion interesting. It's important to understand that that concept of plaque rupture and erosion explain why people can feel perfectly well up until the moment that something bad happens. Because, really, until the thrombus or the clot forms within the blood vessel, the flow is normal. Well, as I said, I hope you've enjoyed this very interesting area of cardiology. If you have any queries or questions, drop us a note. Any suggestions for future podcasts, of course, let us know as well. Until next time, I wish you lived as well as possible for as long as possible. Take care. And bye for now.
