Cracking the Lipid Code

Narrator: 0:01

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased evidence, proven facts powered by ENCORE Research Group and hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren: 0:17

So our goal today is to crack the code and explain to the audience what all these numbers mean and have a better understanding of what we're talking about when we talk about lipid issues. All right, so we like to do a lot of audience participation here, so let's do a show of hands about knowing your numbers, which is very important when we talk about cholesterol, lipid issues. So show of hands. Number one here. Who here can say, yes, I know my cholesterol numbers and I know what they mean? Show of hands, that's pretty good, we have a very educated audience. Number two yes, I know my cholesterol numbers, but I don't know what they mean. Okay, there's a few. Those are probably the honest people. Not all doctors know what they mean. Three no, I don't know my cholesterol numbers and we have a couple of hands there. Okay, okay, well, we can help with that. We can actually help you know what your cholesterol numbers are during this process of education and ultimately having those numbers checked by us free of charge. And then, finally, four, who's going to say what's cholesterol? Okay, no, I don't see any hands. So that means we don't have to have a remedial session in the parking lot. So that's good news, all right. So moving on let's. Why don't you start us off and tell everybody what is cholesterol?

Dr. Victoria Helow: 1:45

Even though they said they didn't know, we'll go through it anyway and basically it's a fat that is absolutely essential for life. Every cell membrane has a piece of fat in it and cholesterol is the fat. All animals have it, not in plants and it's so important that every single cell makes their own cholesterol, except our eyelashes.

Dr. Michael Koren: 2:07

So that's a trivia question, if you ever get asked that on trivia at a bar.

Dr. Victoria Helow: 2:12

But the important thing is, not only do we have to have it and the cells are making it, but it's a fat. In fact doesn't like to hang around in the bloodstream, because the bloodstream is mostly water and you know fat and water don't like to go together and therefore we need the lipoproteins, and the lipoproteins are actually what we'll talk about when we talk about your cholesterol levels. And again, our body makes all the cholesterol that we need. In fact, it makes too much sometimes, and that's why we need to get it out of the system, put it in the bloodstream, away from the cell that made it in excess, and get rid of it.

Dr. Michael Koren: 2:47

Yeah, and this is really a very important point, this last bullet point. Our body makes all the cholesterol we need, so excess cholesterol needs to be cleared from the body. A lot of physicians don't understand that, and the easiest way to understand that is who here is a vegetarian? Okay, not too many of them. I don't see anybody. But when you take a vegetarian and you check their cholesterol, do you find anything? You do. So where does that come from? It comes from their bodies. Remember vegetables don't have cholesterol. Cholesterol is from animal products. One of the things we like to remind people when they ask us is is there cholesterol in something? If something that you're eating has a mother, it has cholesterol in it. That's the easiest way to understand it. Animals have cholesterol. They make cholesterol. Plants do not. So if you're a vegetarian, you're not eating any cholesterol, but your body still has a lot in it. So the stuff in your bloodstream is what your body is trying to get rid of. Okay, audience question. So where do we get? This is really to see if you're paying attention. Where do we get most of our cholesterol? One, from food from animals, food from animals. Two, our parents. Three, the government, or Four, our body makes it Okay. Anybody say one, a couple, our parents, a couple the government, okay, and our body makes it. All right. That's the number one source where we get it. A very, very important point. Okay, so what is the lipoprotein? Go ahead.

Dr. Victoria Helow: 4:31

So remember I was saying that the fats need to go into the bloodstream, to go to the liver, etc. To get rid of it, to clear it out of our system, and the blood is made up of primarily water and cholesterol is a fat, and so it has to have a little truck to carry it around, and that's what these lipoproteins do. They're a combination of some proteins that our body makes for the exclusive purpose, or one of the purposes, of getting rid of these fat molecules. They are also involved with, like it says here, hormone production, telling other cells what it is they need to be doing. So they're very important particles and they contain the cholesterol triglycerides and this protein component, as well as this phospholipid that helps it attract these fat molecules so they can carry them around. And then when we talk about them, we use the names of LDL, which is our bad cholesterol, HDL, which is our good cholesterol, and then the really, really, really, really bad cholesterol is lipoprotein-a, which they mentioned earlier, that I have a family history of cholesterol issues, with early heart attacks, early, young, young death, and it turns out because of this really, really, really bad cholesterol, and so when you're talking about your levels, do you know your levels? One of the first questions. These are the things that you would have levels of.

Dr. Michael Koren: 5:52

So a couple of things. One you're very passionate about lipoprotein-a, yes, I know. If you want to share some of the reasons for that, Sure.

Dr. Victoria Helow: 5:59

So I lost my sister unexpectedly at 53 years old and went and saw a cardiologist and he said well, you know, let's test this lipoprotein-a on you because you have a family history. My father had his first heart attack at 29, had three bypass open heart surgeries and then died at age 55. My grandfather had died at 42, and then my sister died at 53. And, lo and behold, I had an extremely high lipoprotein value and because of that, really, really, really, really bad cholesterol. I have to watch the other cholesterol as well.

Dr. Michael Koren: 6:34

So this is a very important point, this last sentence. So when people talk about their cholesterol or their blood cholesterol, they're really talking about lipoproteins, and lipoproteins are these complex molecules that you can see up here that contain different fats and they also contain protein, and that combination of fat and protein allows them to circulate in our bloodstream and ultimately to deliver lipid molecules and cholesterol particles to our liver so our body can get rid of it. Is that clear? Okay, very important. So lipoproteins are the key thing.

Dr. Victoria Helow: 7:16

They are our trucks for taking our cholesterol out of the system, so it's not in the bloodstream causing issues.

Dr. Michael Koren: 7:22

And this is a picture of the different types of lipoproteins. So the chylomicron, which is on this side of the slide, is a really big particle that comes out of the gut and that is a dietary fat that gets into our systems that has to be processed into these other forms of lipoproteins. So chylomicrons can turn into VLDL and then ultimately all the way on this side of the picture you'll see HDL, which is the smallest, densest molecule and that's the one that's the most favorable package. And both LDL and HDL can bring their lipid particles to the liver and ultimately work with the liver to get rid of that cholesterol and fat. But HDL is particularly efficient at doing it and that's why people who have higher HDL levels tend to do better. But our body can also get out cholesterol through LDL, through something called the LDL receptor, and a lot of the medications that we use to treat people with high cholesterol work by making that LDL receptor work better. Any comments about that?

Dr. Victoria Helow: 8:34

No, okay.

Dr. Michael Koren: 8:35

All right. So why don't you tell everybody about each of the individual molecules a little bit more?

Dr. Victoria Helow: 8:40

So again we were talking about it's the trucks that carry things away and the HDL. Even though it looks little there, it stands for high density because it's heavier, doesn't have as much fat on it, but it's very efficient at getting these trucks full of cholesterol to the liver and to the body, to get rid of them and loading back up again over and over, versus the LDL, which has tons of this excess fats on them that can also be damaging to the vasculature. So this one is actually protective because it helps with the vessel walls and reducing inflammation. It's not a rusty truck, an ugly truck. It's a nice, healthy truck taking the things back and forth. And this is the one that you can affect by having a healthy diet and a moderate amount of alcohol consumption. And although we've tried to come up with medications that could help you increase your HDL level, they don't seem to be particularly helpful. That is something you have to work with your diet and exercise, as well as a little bit of alcohol to increase.

Dr. Michael Koren: 9:50

And the LDL.

Dr. Victoria Helow: 9:52

And this one, like we said, it's the most common one and it can take a lot of the fat molecules, but as it's drudging along, it's also damaging to the blood vessels, causing swelling and inflammation, kind of like ruining the roads because they're so big and yucky, but lack of a better way to talk about it and that can lead to heart attacks and strokes because you're damaging these roads. They also drop their stuff off and create plaques and make the blood vessels narrower so you don't get as much blood flow coming from them, and so the big key is to lower your LDL cholesterol, and is now recognized as, without a doubt, the most important preventative treatment for heart disease.

Dr. Michael Koren: 10:37

A little bit about VLDL and triglycerides.

Dr. Victoria Helow: 10:39

We'll let you talk about those.

Dr. Michael Koren: 10:42

So triglycerides are another type of blood fat. They're typically associated with alcohol and carbohydrates, and it's a particular problem in patients who have diabetes. And the lipoprotein that holds a lot of the triglycerides is called VLDL, or very low density lipoprotein, and this is what we call an independent biomarker of metabolic health. So if you don't exercise, you maybe have a little bit of obesity in the abdominal area. You're probably eating a little bit too much sugars and starches. What happens is you develop a syndrome of lower levels of HDL and higher levels of triglycerides, often carried in VLDL. So triglycerides are actually important in terms of energy for your body. But again, too much of a good thing ain't good, and we see that for people that have what we call the metabolic syndrome, and one of the tools that we use to assess risk is looking at the ratio of triglycerides versus HDL. So in a perfect world, your triglycerides should be 100 or less and your HDL should be 50 or more, so that ratio should be two or less if it was perfect. But unfortunately, most of our patients don't fall into that category and we may see this ratio of even over 10, which means that your risk of having complications of metabolic syndrome or cardiac complications of having a high cholesterol or fat content are higher than most people. The other thing that you might hear and I'll just go through this quickly is something called APOLypoprotein B, and I know how well you can see it on the picture here. But with all these different lipoproteins there is a protein component that is usually one or two of these proteins that are attached to each of the lipoprotein molecules. So what that allows us to do is to count the number of particles, and because the size of the particles can vary, some doctors like to actually count the number of particles, and they can do this indirectly through APOLypoprotein B. So if you have something called an advanced lipid profile, who here has gotten an advanced lipid profile in their life?

Dr. Victoria Helow: 13:09

And had one of these levels given to them.

Dr. Michael Koren: 13:12

So if you had an advanced lipid profile, chances are you had this measured, but it's not part of routine practice and we don't always do it. For some people it's useful, but we just want to educate everybody that this APOLypoprotein B is the protein component of the bad lipoproteins, and that includes LDL, VLDL and lipoprotein- a. All right, so let's go back to audience participation. Know your numbers. Which of the below represents a favorable level of LDL? And these are the choices Less than 100 milligrams per deciliter, less than 2.5 millimoles per liter, less than 70 milligrams per deciliter, less than 50 milligrams per deciliter or as low as possible, especially if you've had a history of a heart disease and stroke. So who says one Couple, who says two? Who says three? Who says four Few and who says five? All right, we have a very smart audience, and that's the answer. And the reason that's the answer is that the number is a reflection of what's happening in your body in terms of its ability to remove cholesterol, but the way we treat the number is a reflection of your risk. So if you're a very low risk person, you can tolerate higher levels of LDL cholesterol and that might not be the worst thing in the world. So, for example, a pregnant woman who is in a very rapid metabolic state and is providing nutrients for a fetus needs to perhaps have more of these nutrients circulating. But say another person who is older and has had a heart attack or a stroke. We want that LDL to be as low as possible Because, again, we view it only as a molecule that can cause collateral damage. We don't actually need it because all the cholesterol we need is made by the cells. And then to jump in the numbers themselves, the general recommendation for the population, for all of us, is to have an LDL below 100 milligrams per deciliter, even if you're a healthy person without heart disease. Answer number two is a little bit of a trick question, because 2.5 millimolar is about the same as 100 milligrams per deciliter, but that's the way it's reported in Canada and in Europe. So a lot of other places in the world we use nanomoles or millimoles rather than milligrams, and I don't want to get into the chemistry of this, but they're essentially the same number 1 and 2. Number three is less than 70 milligrams per deciliter, which is what we recommend for anybody who has had a history of heart disease, and less than 50 is the recommendation for some folks who are at really really high risk. So if you've had a heart attack or a stroke and you have diabetes, you really should be below 50. But answer five really covers it for everybody is that you should be as low as we can get you, as long as that's one comfortable for you, and two, that it's appropriate to your degree of risk. And this gets into some of the numbers. So when you get a number back, there is a detail that's really important and that's how they got the number. Again, we don't expect the average person to understand this and, as Vicky and I have mentioned, not all physicians completely understand this. But the most common way to report out a LDL cholesterol number is something called the Frida-Wall equation and you're not actually measuring LDL directly. You're coming up with that number based on an equation that you can see on this slide, which is TC, total cholesterol minus the HDL, which is more easily measurable, minus the triglycerides divided by the number five, and that's an approximation for what the LDL is. But nowadays more and more labs can directly measure LDL so you get a more exact number for the LDL. Now there are certain circumstances where the direct measurement is really important. So, for example, if your triglycerides are high, then the equation that I'm showing you becomes far less accurate and in that situation you probably should get a direct measurement. In fact, some labs won't even do the indirect measurement if the triglycerides are above 400 or 350. The other place where this gets as important is when you're being treated. So when your LDL is getting to the lower levels, the Frida-Wald formula does not work as well. And for those people, for example, let's say you have a very serious situation where you've had bypass surgery on your diabetic, but we want you to get your LDL down to 30 or 40. And we're gonna use some advanced drugs to do that. And if we really wanna know where you are, then you should do a direct measurement rather than an indirect measurement to make sure that you're in a safe range for your LDL cholesterol. Whew, all right, all right. Go ahead and talk about some of the good news and bad news about the cardiovascular disease statistics.

Dr. Victoria Helow: 18:25

So over the past 30 years, we've had lots of better treatments and diet and awareness, and cardiovascular deaths did increase decreased over that period of time by 50%. We had ICU's developed, we've had just more awareness of this, including the LDL issues and statins, but we've been pretty stagnant since then and that's the bad news, if you can click. We've had no progress in the past five to eight years because there's not been any more drugs on the horizon and in fact, things got a little bit worse for a little while, probably possibly related to COVID, but just overall and these are some of the bad news statistics and the important one is it's gonna rise even in the next six years, by 2030. And that's where he was talking about we're beginning to understand other methods to help with your LDL issues, whether it's LPA issues or helping you get rid of it. Rather than statins, which help you not make as much of it, we can help you dump much more of it, and so the other obviously key thing to take away, especially this being February, heart Health Month is that one in five heart attacks are actually silent, including in my own family, and so here is again the big difference, and you see that it went up and it went up and then all of a sudden kind of went down and that was an issue with figuring out some of the issues with the medications that could help, as well as ICU's, et cetera. And now you see that there's this last thing of 2015, where it's talking about a thing called a PCSK9, that's the thing that he was talking about. That's on the liver. That's called a receptor because the LDL comes to the liver and the liver takes it in and gets rid of it, and we now know that you can have defects of that little grabber, if you will, of taking in the LDL, and that's a PCSK9. And we do a lot of research. Dr. Koren has been instrumental in some of the leading studies in the world for this and has it published. We can show you some of the things he's published on this.

Dr. Michael Koren: 20:35

Yeah, so the key elements of this slide again. This is looking at all cardiovascular deaths in the United States since 1900, and they increased rapidly and peaked actually around 1980. And then some of the innovations that Vicki mentioned started to kick in, including statins, and we actually saw that the number of cardiovascular deaths went down, despite the fact that the population was going up, but unfortunately, that trend changed in around 2015. So we now have to redouble our efforts to tell people about the problems with cholesterol and also get treatment for people, and one of the realities is that it's sometimes very difficult to get advanced treatments because they're so expensive, and one of the nice things about research is that we can help people with that. So there's a lot of reasons why we're not necessarily getting to where we want to be in terms of getting that trend to go back down, but we're here to try to educate and help people, and this is what you were referring to in terms of the impact of COVID versus other elements of cardiovascular death.

Dr. Victoria Helow: 21:42

So we have circled here the heart disease and the stroke, which are the obvious heart consequences, but we did have a huge contributor of nearly 350,000 people as of 2020, and again, it was only around for three quarters of 2020. And many of those people died because they had underlying heart disease, but it was a COVID death and many of those weren't having autopsies. We didn't go near some of those patients not understanding the disease, so that number could even be larger. And it's just so interesting to look at and how much awareness and activity we have around all of the cancers, which, again, is a horrible disease but pales in comparison to the number of deaths that we have.

Dr. Michael Koren: 22:24

Yeah, and again I find this very sobering is, even during 2020, when we saw the worst of COVID deaths, remember that that was the most virulent form of COVID that we're dealing with in the beginning that the number of cardiovascular deaths in the United States was more than twice as much. So this is still the number one killer of Americans and people in many other places around the world. All right fighting heart disease. Which of these interventional measures has had the biggest medically proven impact on heart disease? Exercise, mediterranean diet, statins, multivitamins. Do you wanna answer that one, vicki, or do you wanna give it to the audience?

Dr. Victoria Helow: 23:07

Show of hands who picks one?

Dr. Michael Koren: 23:09

Who says one?

Dr. Victoria Helow: 23:10

Who picks two, three and then four. Nobody picked four. So you're right. Three statins has been the biggest contributor to medically proven impact on heart disease. It's nice when you add that to a Mediterranean diet and exercise, but in and of itself you could still eat poorly and not exercise and if you take your statin your risk is gonna be less. It's not gonna be great, but it's still gonna be less.

Dr. Michael Koren: 23:37

Yeah, and this is not to say that exercise and good diet isn't important. They're very important and exercise does a lot of very important things, not only from the standpoint of living longer, but living better and feeling better. But when you actually look at the statistics, what makes the biggest difference in terms of reducing heart attacks and strokes and death related to cardiovascular disease? None of them come close to statins. So we wanna make sure that everybody understands that they're important parts of the way we treat patients, and this is a little bit wonky, but this just shows you. When people say, well, what's the proof for statins? The proof is summarized in this slide right here. These are all the different studies that were done blinded, highly scientific studies from around the world, and every study that shows that statins work has a point on this side of the graph, and any study that shows that statins don't work would have a point on that side of the graph. And you can see there are no points on this side of the graph and all the points are on that side of the graph. And now this is looking at now over a dozen studies here and this slide is a little bit old, so there are over 20 different scientific studies and they all show the same absolute results that statins save lives, reduce heart attacks and strokes, so that's important. In fact, if you look at these data, for every millimolar per liter reduction in LDL cholesterol, you reduce heart attacks and strokes by 21%, and that's equal to about 38.5 milligrams per deciliter, so roughly 40. If you lower your LDL by 40, you're gonna improve your risk quite a bit 21% in fact. Okay. But even though statins are important, there's some limitations.

Dr. Victoria Helow: 25:30

And you know we just showed you that it was extremely important and it does help there. People cannot take it sometimes because that might not be the only thing that's going to be useful. So to say that it doesn't work because it didn't help one particular you know, or one category of individuals, is important. And again comes back to that LP(a). You can take statins all day long and it may only help the LDL a little bit because, as we'll talk about LP(a) a little in a moment, you may need a second cholesterol medication. Some people just do not tolerate statins, although many studies have been done that show that some of the intolerances are the same whether you take a placebo or the statin, and there are situations where you can't use it. For example, we talked about a pregnant woman and there are very few, but they do exist medications that interact adversely with statins, so you wouldn't want to use them and, like we said, some lipoproteins just simply do not respond, such as lipoprotein-a. One of the bigger reasons that I've been hearing about lately is just a conspiracy theory about, in a variety of ways about statins, including recently.

Dr. Michael Koren: 26:43

Yeah, I've seen newspapers that have said things about statins. Well, they're not all that they're cracked up to be and they don't actually negate the data showing that they saved lives. But they'll talk about somebody, one person that had muscle aches related to statins which is true, it can happen but then they'll go on and on and on about that one person and not talk about the hundred people who didn't have a heart attack or a stroke because they took them.

Dr. Victoria Helow: 27:08

Or thousands.

Dr. Michael Koren: 27:09

So you have to be very careful about sensationalism in the media. All right, well, this is your baby. The really, really, really bad cholesterol.

Dr. Victoria Helow: 27:20

And so I mentioned earlier that my family has a history of this lipoprotein-a, which is something that we've known about for a long time. We only routinely not even routinely, I wish routinely check for it, and it is something that is significant if there is a family history of early cardiac death, and in and of itself, even without necessarily having bad LDL, normally it is also atherogenic, which means it causes those plaques and it also causes clots. Those can lead to not only heart attacks but strokes, and it causes inflammation and it actually helps those things occur at a faster rate in and of itself, and so those are the very things that cause us to have heart attacks and strokes the things that we know of due to our blood vessels being affected. And if you have it, it's what's called an autosomal dominant trait, and so you have a 50% chance of giving it to your child. All of my children, unfortunately, have it, and so it's a matter of now watching what's going to develop with time. And, in fact, 20% of people have elevated levels of LP(a). More the reason to be aggressive with getting our LDLs down. And just a little plug for those who are on statins and they're not responding like they thought that they should, or they don't have risk factors that should leave their LDL up. Make sure that you reach out. Come to us We'll do free LP(a) levels on you, or talk to your physician about getting that the recommendation actually from the American Heart Association and as a cardiologist, he can attest to this. The official recommendation is everybody should have it done, ideally the first time they ever get their lipids done, because you either have a problem or you don't. It's a genetic issue, and so here's some of the little quickies.

Dr. Michael Koren: 29:09

Yeah, I'm going to ask Dr. Helow about very specific scenarios. So what we like to do in these sessions is to hopefully reach out to as many people as possible in terms of their individual circumstances. So let's go through a series of individual circumstances and Dr. Helow is going to tell us would you screen for LP(a), meaning check that level? Okay, first one would you check an LP(a) in a healthy 18-year-old male whose father had his first heart attack at age 52?

Dr. Victoria Helow: 29:39

Absolutely. That's an abnormal age to have a first heart attack.

Dr. Michael Koren: 29:42

Right, and so, even though we don't expect the 18-year-old to have the heart attack anytime soon, that person should know their risk, right, okay, next, would you check an LP(a) in a healthy 56-year-old single female whose brother had an ischemic stroke with an unknown cause? Absolutely Okay. Does the single female matter? Does it matter if she's married?

Dr. Victoria Helow: 30:06

or not.

Dr. Michael Koren: 30:07

No, no, so that if she was a married female or any other status, she should have it, because her brother is somebody that got the gene, we think, and she has a 50-50 chance of having it.

Dr. Victoria Helow: 30:22

And it's just so easy to do, and no.

Dr. Michael Koren: 30:24

Okay. Would you check an LP9a) in a 45-year-old plumber named Mr. Wrenchworth whose LDL remains over 150 mg per deciliter despite being on high-intensity statin therapy?

Dr. Victoria Helow: 30:37

Exactly that's what I was referring to before. You have that LDL that just doesn't seem to respond, or is not responding as nicely to even high-intensity statin. You've got to look further.

Dr. Michael Koren: 30:48

Yeah, and that's a really important point, again, a point that not all physicians are even aware of, which is that statins do not lower LP(a), but in an indirect measurement the LP(a) will show up as LDL. Because you're not measuring it directly, you're measuring it indirectly, so the LP(a) will be one of the things that's left over and that will show up as LDL. So a very, very important point and we can help Mr. Wrenchworth clean out his pipes. Yep, sorry for the dad joke. Okay, would you check an LP(a) in a healthy 20-year-old volleyball player who has a mother diagnosed with aortic valve stenosis in her late 40s?

Dr. Victoria Helow: 31:33

So again, we've talked about heart attack, we've talked about stroke, but one of the other things we were talking about is how these things can be arthrogenic, making things thickened and damage that are part of the vascular system, and that includes the aortic valve. She's 40 years old and has this stenosis, so, whether we know the cause or not, it's worthwhile to check her and him for LP(a) little a as the reason to have this diseased state.

Dr. Michael Koren: 31:57

If she played pickleball instead of volleyball, would that make a difference? No, if she played field hockey, no, no, it would make a difference. Basketball. No, I don't care if she was a Okay, so make sure I got that right.

Dr. Victoria Helow: 32:09

Iron man, you would still test it.

Dr. Michael Koren: 32:12

Okay, and again there is an association between high levels of lipoprotein lillet and aortic stenosis, which is hardening of the aortic valve. Would you check an LP(a) in a healthy 50-year-old cyclist who had a coronary artery calcium score of 530?

Dr. Victoria Helow: 32:29

So let's first just say what is a coronary artery calcium score? Well, I keep falling back on that arthrogenic, and that's when the blood vessels become stiffened and there's excess calcium in them. So you can get this score very easily. It's a little CAT scan, it takes about 90 seconds and you can have a score of how much calcium is in your blood vessels and people who are having some chest pains or various things. It's a nice thing to have checked out 50-year-old cyclist. She shouldn't be having any symptoms and she shouldn't have any calcium in there. And well and behold, 530 is a very high number. Zero would be nice. And so, yes, we got to know why she had this excess stuff in her arteries and, independent of whatever her LDL is, we also want to know because there's, like we said, in and of itself is pro-arthrogenic, is pro-calcium-deposite, destruction to things in the blood system, in the vascular system.

Dr. Michael Koren: 33:25

Yes. So in this particular scenario the 50 number is important, but the cyclist is not. So as you get older you're going to have some degree of calcification of your coronary arteries. So if an 80-year-old had a calcium score of 530, we'd be far less worried, right? If a 20-year-old had a calcium score of 530, we would be rushing that person to the heart cath lab At a 50-year-old. We just need to understand what's going on and see if we can intervene and help that person through lowering their lipoproteins. Would you check an LP(a) in a healthy 20-year-old pregnant woman whose mother has atrial fibrillation?

Dr. Victoria Helow: 34:01

So she's pregnant, we know that her levels are going to be potentially you know elevated for LDL. She may or may not have a risk of having LP(a), but, more importantly, there's no association with cholesterol issues and having atrial fibrillation. And so, especially in a pregnant woman, when those values would not be entirely reliable, I would not do it.

Dr. Michael Koren: 34:21

Yeah, so that's the level where you might want to wait until sometime down the road. Would you treat an adolescent with an LP(a) level of 400 animals per liter?

Dr. Victoria Helow: 34:36

Again, 400 animals is a lot of LP(a) and we know that there's a risk of there being an issue. But they're an adolescent and it's a funny thing to test adolescents for things. Never mind treat them, because values can vary considerably. But I certainly would look a little further into maybe doing a calcium score on him. It would be rare that there would be an issue going on there, but I would look a little further before I would consider treating him.

Dr. Michael Koren: 35:07

Alright, so we're going to finish up our comments and then we'll open this for audience questions. But another really interesting area right now is the connection between cholesterol issues, lipoproteins and Alzheimer's disease.

Dr. Victoria Helow: 35:21

And longevity in general, absolutely.

Dr. Michael Koren: 35:24

And we're doing a study right now that's looking at a molecule to lower LDL, raising HDL and maybe also having positive effects on Alzheimer's. So I don't know if you want to comment on that about the lipid invasion model.

Dr. Victoria Helow: 35:39

briefly, no, I'll let you do that one.

Dr. Michael Koren: 35:41

Okay, well, I'll handle that. So, anyhow, as I mentioned, every tissue can create its own cholesterol and the brain makes its own cholesterol, and the brain is the organ in the body which has the most cholesterol per unit weight. So your brain needs a lot, a lot of cholesterol to function normally and it makes it itself, so it doesn't need dietary cholesterol to get cholesterol to the brain. But, interestingly, there's a barrier between the brain circulation and the rest of your body that's called the blood-brain barrier, and if that breaks down, there's a certain apolipoprotein again that's the protein in these particles that gets into the brain and seems to create havoc. It seems to cause amyloid plaques and tau protein tangles, which is what we believe causes Alzheimer's dementia. So one of the theories is that if we can get LDL in the circulation down and reduce this apoE, we may also be benefiting what happens up in the brain. So really, really fascinating research and we're proud to be part of it in here in Northeast Florida. As I mentioned, the one drug that we're using to look at this is a drug that's called the CETP inhibitor, and if you're interested in learning more about this, we have folks around and we can tell you whether or not you would be eligible for this type of study. And again, we think that this product can have effects both in the brain and to reduce heart attacks and strokes, so maybe one of those things that has multiple applications, once we understand it a little bit better.

Dr. Victoria Helow: 37:22

And I think even in medical school didn't we learn that many times? You know things all come to one issue. You know diabetes causes lots of other issues, but the problem is the same Too much sugar in the bloodstream causes destruction to the liver and kidneys and destruction to not getting blood flow to various areas, including the brain. And so you know it's very possible that all of these cholesterol issues and rise in heart disease that we saw numbers of people increasing with heart disease back on that slide. We weren't looking at percentages, we were looking at absolute numbers of people that were having issues even when the population wasn't growing at that rate, and so it's very probable that they're related. So old folks with high cholesterol live longer. Are you hiding this information from us, right?

Dr. Michael Koren: 38:14

So just to frame this a little bit, so we hear from audience members not you guys per se, but from people in the community yeah, it's all medical conspiracy. We're just trying to sell you drugs and make a bunch of money off of you by scaring people. You know, we hear this sort of thing and one of the little bits of evidence that people will present to us is well, I read that old folks with high cholesterol live longer. So what are you hiding? So you know, these are our, this is our response. The first one is hum-a-da, hum-a-da, hum-a-da. Like I don't know if you're. Does anybody remember where that comes from? It comes from the old Mooner series. Jackie Gleason used to say that when Alice caught him in a lie, he would say hum-a-da, hum-a-da, hum-a-da. So we just threw that in. Number two the government must be hiding something. Well, everybody likes to blame things in the government. In this case, I think they're probably free and clear. Don't believe what you read on Facebook. There's going to be a lot of conspiracy theory information out there. Or because our bodies make cholesterol, as we talked about, healthier older people make more cholesterol than sickly elderly people and live longer. So which of these things makes sense? Number four, of course. So the reason older people with high cholesterol live longer is because their bodies are working better, and we already discussed the fact that the cholesterol in your blood is the extra stuff that your body's trying to get rid of. Does that all make sense?

Dr. Victoria Helow: 39:42

It clears bud.

Dr. Michael Koren: 39:45

And these are some studies that show that. So, again, this is the difference between lowering cholesterol to treat people, when really we're just trying to help the body get rid of it, and understanding that people who don't have heart disease, who are in their 80s or 90s, don't need it to be treated, because it's a reflection, a reflection of the fact that their bodies are working appropriately.

Dr. Victoria Helow: 40:06

And again, it's higher levels of cholesterol than we talked about, the HDL versus the LDL, and these people tended to have a healthier ratio that we showed you earlier than those that don't. But again, their cells are the ones that are making it and we're getting rid of cholesterol we are making that is in excess.

Dr. Michael Koren: 40:27

And these are some of the studies that we're currently enrolling patients into. We talked about the PCS-K9 inhibitors that help the liver get rid of LDL cholesterol. We're doing phase three clinical trials now with Merck on a pill that can do the same thing as an injection. So right now there are two injections on the market for blocking PCS-K9. One is called Repatha, the other one is called Proliwent, and then there's something called Lekvia, which is quote, a cholesterol vaccine and we'll talk about that in a second which actually blocks the body's ability to make PCS-K9. So we're doing work in all those areas. We talked about the drug that may be good for both cholesterol and Alzheimer's. That's called ObacetraBib, you can see here. So we're working with that and we're also working with things to reduce LP(a), which are specific for that molecule, which is different, as we pointed out, than LDL cholesterol. And getting to the quote vaccine, I call it a vaccine in quotes because it's not a vaccine like a COVID vaccine or a flu vaccine, but it's a vaccine in that it's an injectable drug that you just give twice a year and it prevents your body's ability to make this bad protein called PCS-K9. And other studies are looking at other injectable agents that will have even a longer life after you inject to people. That will prevent your body from making PCS-K9. So this has the concept of a vaccine, which is that you get it infrequently, maybe every six months or once a year, and it protects you against that bad actor for an extended period of time.

Dr. Victoria Helow: 42:08

But not everybody has elevated PCS-K9. And so it may not be something that will work and you'll know that pretty much after the first vaccine it's either going to kind of work and help you get rid of that LDL or not. For the most part. Everybody makes some PCS-K9. Some make more than others.

Dr. Michael Koren: 42:27

It's uniformly pretty successful. So this is actually a study that I'll be presenting at the American College of Cardiology meeting, an international meeting in Atlanta on April 6th. If you're in Atlanta, come by and take a listen, we're more than happy to have you. But this is a major international conference with literally cardiologists coming from all around the world and I'll be giving a talk about this particular product and actually the data from this particular study show that everybody that was treated had at least a 30% reduction in the LDL cholesterol, so these drugs are actually pretty consistently effective.