Chapters Transcript Modern Approaches to Lipid Management in the Highest Risk PAD Patient Back to Symposium thank you and thank you for this opportunity. It's my pleasure to talk about my favorite topic which is cholesterol. So I'm a general cardiologist and I specialize in cholesterol management and lipid ology. So these are the factors that contribute to cardio metabolic risk. There's so many on this this chart. Uh There are some that are modifiable, some that are non modifiable. And we'll talk today about the modifiable risk factors. But just for completeness everything from insulin resistance to genetics, to age, race as we've heard obesity and then on the right the abnormal lipid metabolism. So LDL, which we're almost four more familiar with is the one we tend to think of. But there are so many other risk factors. High triglycerides, low HDL elevated lipoprotein A and all of those contribute to inherent risk for cardiovascular disease and in particular for peripheral arterial disease. Don't go to sleep When you look at this slide. Uh It is a very important slide. So I won't go into all the very specific, very elegant enzymatic processes. But the lunch that we just ate is going to be broken down in your intestines and then goes through a lot of very different enzymatic reactions through the liver where it becomes less triglyceride heavy and more cholesterol ester is heavy and then it becomes more dense so low density uh intermediate density that's what the V. L. D. L. Ideal mean. And the low density lipoprotein or LDL. So in the United States are our guidelines the A. C. C. H. A. Guidelines focused primarily on LDL. But outside of the United States and europe and in the rest of the world. The focus is really on what's called non HDL cholesterol. So let me explain to you exactly what that means. So essentially it's everything that is not HDL cholesterol. So you take your total cholesterol uh subtract your HDL and that is the only type of cholesterol morality that is actually anti estrogenic. Everything else in that process whether it's I DLV LDL lipoprotein A. LDL all of those are considered pro anthropogenic and thus increase the risk of coronary disease and peripheral arterial disease. So ideally if you take your total cholesterol subtract your HDL cholesterol You should be within 30 points of what the LDL cholesterol is Depending on labs. But most of the time it's it's about 30 points. If you're noticing that it's very off very different. Then that tells you that it's the story is really not just LDL for that patient. So that's when I start looking for things like lipoprotein. A triglycerides being very high or some of these other um kind of particle nuclear studies you can send looking at cholesterol synthesis. So triglycerides and HDL both contribute to cardiovascular risk. So high triglycerides low HDL independently actually increased the risk for cardiovascular disease and peripheral arterial disease. And this is a question I get quite a bit. So a lot of patients are very savvy and have read about. Should I get my my different cholesterol testing check. Should I be worried about my small dense LDL. And so this is a nice slide to show you the difference between LDL, even though the number is the same. So on the left you have an LDL of 130, same as on the right. But on the left you see that these are larger pilot particles. So the IPO B, which is that blue triangle is actually what is pro anthropogenic. So if you have larger particles there is less Appleby compared to on the right where there's LDL is the same but you have more a probie particles. And so the patient with the characteristic profile on the right has a higher risk of development of cardiovascular disease, peripheral arterial disease. Even though on paper this LDL looks the exact same and why is this important? It's it's so important because small dense LDL is very dangerous. It can go through the vascular epithelium. It is really disrupts the vascular epithelium causes macrophage aggregation, platelet activation, vascular epithelial disruption and so small dense LDL is what you want to avoid. And who has small dense LDL patients with diabetes. So patients who are diabetic patients who have high triglycerides that is the name of the game. That's how you get small dense LDL. So what can we do about it now that we know that cholesterol is very important. How can we decrease your cholesterol so many ways first and foremost is what we're all used to. So statins are the first and most important way because of all the play a trophic effects of statins. So the anti inflammatory effect, the vast grand epithelial kind of lining stabilization effect. So statins work on this in this process here by H M. G co A reductase. We have new medications however, that work further along in the process on the LDL receptors, for example, those are called PCSK nine inhibitors. We have medications like Zeta my bars area which work on intestinal absorption of cholesterol. Uh and then some of the older medications like bile acid resins don't use to commonly um fish oil for high triglycerides. Uh and some of the even newest medications like empathetic acid. So, this is a very important slide. I think if you can remember these four groups talking about what Kenny was mentioning, how undertreated patients are, If you just look at who should be on a statin and who actually is, it's probably at least in the uhh cohort that we've looked at, it's less than 35 to 40% of who should be on a statin and who is, so if somebody has a clinical indication for secondary prevention, that's an indication to be on a statin And LDL greater than 190, which is considered familial high cholesterol, another indication for staten The 3rd is if you have an ASCVD risk score. Um and and I'm sure you guys have calculated that before And then diabetes as well as the other one. This is a slide to show us the The different doses of statins and what is considered high and modern intensity. So you can look here that the two high intensity doses of atorvastatin are 40 and above or receive a statin 20 and above. And you can expect an LDL reduction by about 50%. When you put somebody on those medications, modern intensity statins are listed here. Different doses keep in mind we don't do simba et anymore. It just has more side effects In modern intensity statins you can anticipate usually about 30-40% drop in your l deal. So going through some of the data now for our newest medications called PCSK nine inhibitors there to there on the market right now, one is called evolution mob or hypothesis that the brand name and the trial that looked at that was called the fourier Trial. The other medications called alla Rakha mob or problem once. And that was what was looked at the odyssey trial. Both have very similar numbers as far as LDL reduction. And so I only go through one of the two trials but you can see here how the pcs canine actually works, how the medication works. So if you look at the LDL receptor on the surface of the liver, there's an enzyme or a marker called PCS canine. And that marker actually attaches to the LDL receptor and marks it for apoptosis. So that tells the liver take take in this LDL receptor. Break it down and then recycle the LDL receptor back to the surface of the liver. Um so if you're blocking that enzyme then you're going to prevent the degradation of the LDL receptor and this LDL receptor can then continually go back up to the surface of the liver and keep getting LDL out of your system. So I won't go through the very specifics of this trial is a large trial Shown here are 28,000 patients um they are injections so they're done every two weeks. Usually sometimes you can do it as a monthly formulation but usually every two weeks. Ah and you can see the primary efficacy endpoints here. But I think this slide speaks for itself. So on the top is the placebo. So, LDL reduction just with taking placebo versus the bottom, your LDL reduction with taking the path of a local mob. So not a subtle curve here. Finally, one of the newest medications to come out is is bamboo dock acid and there's two formulations. The brand name is called Next Little. When you combine it with the vibe, the brand name is next Lizette, it works upstream to wear PCSK nine inhibitors work so blocks an enzyme called a TPC trace. It was first approved last year. It is a pill. So it's not an injection and side effects are listed here most commonly you want to make sure patients don't have uncontrolled gout have higher gas and levels. And it can cause a little bit of tendon empathy. So patients who've had issues with achilles rupture, probably not the medication for them Two clinical trials uh and these are ongoing. So you can see here that it's effective. It lowered LDL by about 23% compared to 2% in placebo and where I use this medication, it's a very kind of niche medic mutual medication. But um for somebody who maybe isn't yet to the point of wanting to do an injection but needs a little bit further LDL reduction. That's where I might use this medication. Somebody who's statin intolerant who I don't want to jump straight to and um to an injection. Try this medication And it can lower your LDL. You can probably assume about 20 and last but not least. This is new data as far as the reducer trial. Looking at this IPO, which is prescription strength fish oil. This is the first trial that we have that actually showed benefit a 25% relative risk reduction with the SPAa. And this came out of two or three years ago. But exciting news about using triglyceride lowering medications is another way to overall reduce risk. Uh And finally, just a word on labor protein a because it's so important and it is definitely under checked undertreated uh and for many reasons. So I look at as another biomarker to assess cardiovascular risk and it's actually elevated in a good amount of the population. About 20% of the population. Why it's so dangerous is it's actually similar looking to plasma engine so it can cause vascular disruption. Um, it's it's pro anthropogenic Normal is less than 75. It's a binary test meaning it's either elevated or not. So, if someone has this checked, their LP is less than 75, you never have to check that again. They will never have that problem in their lifetime. No data yet supporting lowering LP A specifically that will improve cardiovascular outcomes. But again, just like with PCSK nine inhibitors, this is it's just too early to be able to say that we don't have decades of data yet to say that this is going to improve cardiovascular outcomes yet. And there's not a specific lipoprotein a medication as of yet, hopefully in the next 2-3 years. But we can use other medications to indirectly kind of lower labor protein a whether that's, um, PCSK nine inhibitors, niacin, potentially. Uh, and until we have some of the newer medications, that's what I work with patients on. And that's it. Thank you very much Created by Related Presenters Claire Sullivan, MD Cardiovascular Medicine, UH Harrington Heart & Vascular Institute Assistant Professor, Case Western Reserve University School of Medicine View full profile
