The Hidden Killer: Lp(a)

In this MedEvidence rebroadcast, Dr. Albert Lopez explains lipoprotein(a), a genetically determined heart disease risk factor which still strikes people with “good” cholesterol. He also explains that plaque behaves like an inflammatory volcano that can rupture without warning. Dr. Lopez goes into how lipoprotein(a) increases the risk of heart attack, stroke, and aortic valve disease. Dr. Lopez then hammers home how important testing for Lp(a) is, especially for those at an increased risk.

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Music: Storyblocks - Corporate Inspired

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Transcript

Welcome And Live Rebroadcast

Announcer 0:00

Welcome to the MedEvidence Podcast. This episode is a rebroadcast from a live MedEvidence presentation.

Dr. Albert Lopez 0:10

Thank you everybody for showing up today. I want to thank Encore Research for the opportunity and you all for your time and coming here and WJCT for providing the space. I've had a passion for prevention for a long time. Can we drop that a little bit? For a long time. I got very frustrated about 20 years ago when I found I did all the data points to make everybody theoretically healthy, and they still presented with disease. And I started looking at new modalities, and I was called by several of my mentors an early adapter of new technology. And that brought me to looking at Lp(a) about 15 years ago, wondering what is this thing and what does it cause, what does it do, and what can we do about it. So, no further ado, I'd like to give you the presentation.

The Cardiac Risk Puzzle

Dr. Albert Lopez 1:02

The cardiac risk puzzle is that despite doing all the things we know we can do, still there's a number of people that present with cardiovascular disease, and we're doing a great job of preventing people from having death or side effects from having severe heart disease, but yet we still have a large number of people that still have heart disease, and that's a conundrum. Why is that happening? No talk is any good without kind of the baseline foundation of why is it your passion? And the big thing is that about 83 million people in the United States have one or more type of cardiovascular disease. That's over one in three people. That's about every 25 seconds, someone will have some kind of a coronary or vascular event, and about every minute somebody will die from some cardiovascular event. And many times the first symptom is death. It's those guys you see that go out in tennis court and they come home and they fall down and then you can't take care of them. Very often that's the one vessel we call the widowmaker. Almost a million people in the United States have died from either heart attack or stroke or some other cardiovascular disease in 2011. Again, that's one in three. And it's the number one killer in the United States. It's ten times more prevalent than breast cancer. It's actually actually even more prevalent than all the cancers put together. And that's become my passion. Why? And I had a friend ask me, you know, do you have family history with heart disease? I said, no, but it's one of the few things I can actually prevent and fix. Well, at least I think I can prevent and fix, and I think we've done a pretty good job at doing it in our clinic. And again, about 85, last time was 83. The newer data is about 86 million patients in the United States have some kind of cardiovascular disease. The costs are an astronomical, and the president has stroked his pen, kind of opening up, you know, clarity on health care and the cost of health care. But I think you can try to fix all you can, but the better process is how do you prevent it? Because then we can avert this $320 billion of healthcare cost in cardiovascular disease. Again, it'll claim more lives than all the cancers put together. And the visual works much better. You can see that in heart disease is much more prevalent than cancer. Stroke is the third leading killer in the United States, but the number one disabler in the United States. And the problem, it doesn't just affect that patient that has a stroke, it affects the whole family that has to take care of that stroke patient. You look at heart disease compared to stroke, it's by far a leading cause of death and cardiovascular disease. Women, don't be surprised. You wanted to catch up to it to us men, and you have. And I'm glad that gender disparity is changing in the forefront, and so is my daughter who judges me all the time. Women, unfortunately, you're catching up to men in heart disease. And part of it is that we've realized that we present with exactly the same symptoms as men do, and part of it is unfortunately you're catching up to what we do. And about 46% of women, their initial

How Plaque Really Forms

Dr. Albert Lopez 4:18

presentation for heart disease is a heart attack, and men it's about 62%. The standard of care. So most doctors out there are just looking at your cholesterol profile, looking at LDL. And they think, well, if we get LDL low, low, low, low, we can prevent it. And that's true, but that's not true in every single case. We're looking at plaque accumulation because they felt for a long time that that was just an accumulation of bad cholesterol. And when I was taught in med school 25 years ago, is that you had the vessel and you slowly laid sediment into it and then it closed off. We've come to a realization it doesn't work like that. It's more like a molehill, and it kind of rises up as you get more inflammation and there's a whole inflammatory response happening in there. But we know that even with lifestyle changes and prescription medication and reducing LDL cholesterol, and even though we've gotten much better at it, it's still the number one killer in the United States, but also worldwide. I put the slide up, and I actually, when I put this in front of physicians and nurse practitioners and PAs, they shudder. You know, we've been pushed that it's only an LDL disease, and this is the complexity of lipidology or lipids. It's not that simple. It's a very complex, beautiful cascade. When God created this whole modality, it wasn't so simple. Nothing He's created was very simple. And yet it's very simple, right? We're looking at cardiovascular diseases. I mentioned the healthy artery looks like this one in your top right. It has a very thin lining, that middle lining called the entom, which is a little yellow ring, looks beautiful. And then that outside of the vessel usually has beautiful stability and looks great. It's like a beautiful garden hose. It has pliability, it moves, it it works beautifully. It's an organ in of itself. But as we do certain things and uncontrol certain modifiable risk factors like blood pressure, lipids, no exercise, highly processed foods, you start getting damage on that little ring that's now black. And you see that yellow area starts thickening up. And then as that allows it to be more quote unquote porous, and then the cholesterol kind of deposits in there and it gets thicker and thicker and more inflamed. And then you have enough accumulation that you have presence of disease. You notice you're short of breath, you have a little pressure in your chest when you exert yourself. You may not be able to walk as far because your legs hurt. And then when there's enough disease presence, the inflammation gets more rampant, and then you have a vulnerable plaque or an area that's going to rupture much more easily. Almost like a volcano. That volcano has to have that lava presenting itself in inflammation. The crust has to get thinner, that little lining, and then it all of a sudden ruptures and you present a plaque rupture and a heart attack or stroke. What we're trying to do here is how do we never get there? So I love this slide because you know, classically we thought it was purely as of a lipid disorder, and we found that it really isn't that. And as they it says, I have some bad news. While your cholesterol is remain the same, the research findings have changed. Note that 50% of the people who have heart attacks have normal lipid levels with or without drug and still have a heart attack. So that's disconcerting, and that's what brought me to look at Lp(a) for almost 20 years, 15 years now. And that's why Dr. Carr and I said, you know, this was a great when this Lp(a) study, I just about got on my knees and begged him to let me work on this study with him. This is just another way to look at the circle that I had of multiple vessels. All the way on the left is a beautiful normal vessel. It looks nice and solid. As you start getting some inflammation and oxidation, you start thickening it out, and eventually you develop this volcano that ruptures. I love that volcano analogy because that's exactly what it looks like to me. You can have normal land, it's not hardcore, but once you start setting up an inflammation, that lava starts presenting itself, the core weakens. You have to have that perfect milieu of weakened core, that middle center getting inflamed and hot and goopy, and then unfortunately have that rupture and the heart attack. And the last 15, 20 years in our office, we've tried to make sure that we never let that end stage happen if we can prevent it. Or can we catch it early enough in the middle where we can send them to somebody like Dr. Koren and get the proper modalities or procedures done that that event never does happen. But we still missed a number of patients. So, you know, classically we'll tell patients look, you have modifiable and non-modifiable

Modifiable Risks And What’s Missing

Dr. Albert Lopez 8:55

risk factors for cardiovascular disease. Non-modifiable is your gender, you're born as a man or woman, your age. I can't reverse age. I am Lopez, not Ponce de Leon. And your family history, you can't change your genetics, you can't change who your parents are or what's there. But you can change your cholesterol profile and you can change your blood pressure, you can change your eating lifestyle by reducing the number of fatty foods or more so even highly processed foods, the number of carbohydrates, exercise and activity, movement therapy. I don't even use the word exercise much anymore because people are allergic to it. So I use the term movement therapy. You know, movement therapy. Smoking. Smoking is a hugely pro-inflammatory. Stopping smoking really reduces the events markedly. Controlling sugar, never mind diabetes, but even an elevated blood sugar above 95 doubles your risk of cardiovascular events. So controlling blood sugars, stress. New article in JAMA says in the Journal of the American Medical Association, go to vacation. It may reduce your event of heart attack rate. So de-stress, you know, chill out. There's actually a great study on 15 minutes a day of meditation or prayer reduces cardiovascular events markedly. Sleep. Sleep is very important. Seven, eight hours of good, good quality sleep. Important. Vitamin D deficiency, severe vitamin D deficiency is a risk factor. Oral health is a new emerging thought process and talk, controlling inflammation. And the question is, what next? Because this was a much smaller list ten years ago. The missing piece is probably now Lp(a). You know, cholesterol is really not evil, it's not bad. You need cholesterol to make things like sex hormone, normal skin, tone in your hair, and softness of your hair. You need a certain amount of cholesterol to live. But high Lp(a) is a killer, period. There's no discussion about that. This is a con this is a really kind of heavy slide, but if you look Sharon, what's the website that this is related to? The Preventative Nurses Association?

Audience 11:07

Cardiovascular Nurses.

Dr. Albert Lopez 11:08

Cardiovascular Nurse Association. This is it's actually a good website to look at, and it's a busy slide, but what is it? It's called LP parentheses little a, it's been called LP little a, it's been called lipoprotein little a, it's been called liproprotein L A, excuse me, and it's been called LP little A. So it has many names, and maybe that's why we haven't really caught it before. It's a sneaky little bugger. But unfortunately,

What Lipoprotein(a) Is

Dr. Albert Lopez 11:35

we think that 20-30% of the population has this little LPa gene. It's a gene. And that that unfortunately presents certain problems. It increases risk of heart attack at a younger age, it increases risk of heart attack with normal cholesterol, it increases vascular or excuse me, aortic valvular disease, the valve called the aortic valve tends to tighten up very early in life. If you have a it's genetically predisposed, so if your mom and dad had it, you have a chance of having it. And people with familiar hyperlipidemia have that have very high cholesterol should also be checked for Lp(a) much more aggressively than the average population. How common is it? We think we think it's 20 to 30 percent of the population, which would shorten up the gap of that question of why do people with normal cholesterol still develop heart disease. And that's part of what we're trying to do with this registry, this initial study we're doing is just a registry. How many people have heart disease, carotid disease, arterial disease of their legs, peripherovascular disease, or peripheral arterial disease, and have an elevated Lp(a). We don't know, and we're trying to just figure out how many of people that have cardiovascular disease have Lp(a) . And that's the first phase of this program we're trying to do. That's about two to three per hundred people. That means two to three of you in this room probably have an Lp(a) , maybe more. That's about 1.4 billion people worldwide, and about six and a half million people in the United States. That's a big chunk of people. Does it hit only certain people? Is it only Latinos? Is it only Anglos? Is it only what? But we look at it does happen across the board. You can see it happens in almost every ethnicity across the world, but there's a higher prevalence. In Africa, in Eurasia, India, Pakistan, very high prevalence of LPp(a). We also see it very high in North America, more native North Americans. We also see it very high in certain Eastern Europeans, we think. And then in Oceania, which is is mainly New Zealand and Australia. So there's a higher prevalence in those areas, and we also see it in Southeast Asians. We see this in Filipinos and Thai descent, etc. And so those areas have a higher rate, we think, but we know it's prevalent across the whole world. Another way to look at it, it's much more simpler than the map, is Asian Indians, again, Pakistani Indians, etc., Indian Americans, so American Indians, Hispanics a little bit, but African Americans are blacks. Very high prevalence. It's in the genes. So you can't decide you have it, you it's really hard to change it. You have a genetic predisposition for this. So if your mom and dad had it, or if you have it, you have a 50% chance of giving it to a child. And that's what makes it very frightening because it's genetically mediated. And then the question is, how do you change your genes? You just told me, doc, that you can't change your genes.

How Lp(a) Triggers Clots And Inflammation

Dr. Albert Lopez 14:45

It's genetic, right? Well, maybe. How does it fit in the puzzle? And this was this is what I find as a clinician, as a scientist, most interesting. It makes it proathrogenic, which means it gives you a higher rate of cardiovascular events. That's two to three times higher risk of heart attack and stroke. Much higher rate of aortic valvular disease. It's pro-thrombotic. It makes you clot easier. And the problem is once you clot, you don't get any blood flow past where the clot is. No blood flow, no oxygen, no oxygen, you get a charlie horse. And in our terms, that's called angina or chest pain. And then you have damage because there's no oxygen. And it's pleuroinflammatory. So we at Real Life Health in Lima, Lowell Pes Internal Medicine Associates, adapted the concept of pro-inflammatory issue in cardiovascular disease about 20 years ago, about 17 years ago. But it's become in the forefront in the last year and a half, two years. Everybody's not talking about inflammation and heart disease. But this marker, this genetic piece, this little kringle, actually increases the risk of inflammation, which means it allows that endothelial lining to thicken up, allows the quote unquote pores, so to speak, open up, and allows bad cholesterol, oxidized cholesterol to get in much more easily and make plaque and cause that event. At least that's how we think it works. And I put this not for you to understand, but there's two big things in here. And one is you see on the left, it's very pro-thrombotic, it means it's proathrogenic, it means it makes plaque more easily, it makes the presence of disease more easy. And in the right, you see it clots easier. In the center, all that KIVs, those are called Kringles. And so where'd they get the name Kringle from? That's a little Danish pastry that's wrapped in a circle, right? And that's how we got these Kringles. You know, we're all foodies in medicine too, you know. So you have this little Kringle that attaches the outside as Apo B or Apo A compound, which is part of a cholesterol profile, but it also increases oxidized phospholipids or bad cholesterol and oxidize. It's like taking metal and rusting it. It's the rusting of LDL that makes it much more prone to atherosclerosis or cardiovascular disease. But it's this little protein that sits on the outside, this Kringle, that really causes all the problem. It's a very dangerous player. It's genetically determined. I've said that several times. And the longer it sits in your system, in other words, the longer you age, the more it's going to oxidize it. And it's linearly related. The longer you live, the more chance you have of having cardiovascular event if you have Lp(a). And unfortunately, it's despite modifiable risk factors. So all the things I had in that one slide are modifiable risk factors, controlling blood pressure, watching how you eat, walking, controlling your blood pressure, your blood sugar, not smoking, it still is a risk factor. Despite that. And that's what makes it even more frightening. And it's especially a marker for premature vascular disease. So classically, we think 50, 55 for men, 60 for women. These are people who usually have events at a younger age. We think maybe more predisposed to having Lp(a). Now you know that I'm not just blowing smoke up your kilt. It's in the research. I mean, this is the journal that showed it hit several layers. It showed the Kringle, it showed the valve in the bottom, how it closes it down and stenoses it, it closes it down and makes it very hard to open up, and that it actually closes the vessels down. So I'm not just making it up. I didn't pull that out of my hat like you know, a magician. It's truly in the research, and this research has been out for a while. We think that one in 14 people with heart attacks, and it it increases the chance of having heart attacks to one in fourteen people and one in seven people having valvular disease. So it really augments the risk of these two parts of cardiovascular disease. So how prevalent is aortic valve disease? It's about three-quarters of a million people in the United States. And that's what we've diagnosed. We think about 15,000 patients die from aortic valvular disease a year in this country. And we think about five million people have uh aortic valvular disease. And then one in seven we think might be due to the LPa gene.

Who Should Get Tested

Dr. Albert Lopez 19:25

Screening? Screening is so important. You know, finding out what allows us to kind of figure out what we can do to avert the event. And we might be able to prevent one in three people having a heart attack if we can mediate or stop this Lp(a) from acting and misbehaving. We actually think maybe one in two cases of valvular disease may be able to be changed if we control Lp(a) . And you know, part a lot of you thinking, like, well, I don't know anybody that has it. Well, Bob Harper was in the world's greatest loser, right? The weight loss program. He's a 52-year-old man, top shape, high fitness, totally normal cholesterol, blood pressure, sugar, doesn't smoke, doesn't eat garbage, exercises like a fiend, and he had a massive heart attack. And they pegged it on as he had a very high Lp(a), genetically mediated. So why I'm here is it's time to face the challenge. What is Lp(a)? Who has it? And what do we do about it? The devil's in the details, and if we know the details, then we can try to fix and figure out what's new and try to mediate that issue. So if we do lower it, we can avert that heart attack and stroke, we can avert the valvular disease, and we can avert peripheral vascular disease or vest, you know, disease in your legs. This is another good website, and this is the Lp(a) foundation, and it it shows that in that tree is your whole genetics. And you'll see if you actually people that have elevate Lp(a), when you start filling this chart out, you'll realize that, Jiminy, there's a lot of people in my family that had this heart disease very early. And maybe I should really get tested and checked on it. So who should get tested? People with early history of heart attacks, pre-55 in men, 50 in men, pre-60 in women, or had strokes early, or had vascular disease, leg disease early, people with early aortic valvular disease or any aortic valvular disease, statin-resistant patients, you're on the statin it seems not to lower it. We think maybe that Lp(a) is not helping you lower it really well. People with strong history of family of heart disease or stroke, and people with normal cholesterols with vascular disease and no other risk factors, like Bob Harper. Again, a family member. Diabetics. There's ongoing research that diabetics probably have a higher risk of cardiovascular disease, four to six times higher rate of cardiovascular disease with diabetics, and we think maybe they have an Lp(a) gene that's mediated through diabetes. And people with familial hyperlipidemia, these are people with LDL cholesterols above 160, 170. Total cholesterols are usually well over 300. Am I at risk? The only way to know is to get tested. It's a really simple test. And if your doc's not willing to do it, we have this clinical trial that we're willing to help you identify that risk. It's done in several labs. I use several of these, and there are several labs, the bottom two or more specialty labs, but Cleveland Heart Lab is part of Quest Now, and it's easily seen. They're the 1200-pound gorilla, and they're everywhere. But it can be done, and it's an easy test to do. It's just a blood draw. Values may differ on Lp(a), and it's measured two different ways. And that's one of our problems as clinicians and scientists. We've got to get on the same page on how we kind of figure out this number. Are we centimeters or are we inches, right? Are we nanomoles or are we milligrams per deciliter? And we've got to get on the same page

Treatments Now And What’s Coming

Dr. Albert Lopez 23:18

with that and make it one way to kind of identify this. So what can we do about it? The big thing is awareness. Do you have it or don't you have it? So it's to get tested. And there are things that can change it. Niacin, which has fallen out of favor because it makes people with light hair and light eyes horribly flush. Niacin can drop it down, not a whole lot. PCSK9 is an incredible drug which Dr. Koren has been a huge investigator nationally on. We'll drop it by about 20 to 30 percent, or high 20s to 30 percent, but it's not indicated for lowering Lp(a), unfortunately. You have to have an event to get on a PCSK9, unfortunately. Aphoresis, which you get set up to a machine that cleans out your blood and takes out Lp(a). Well, that's a ball and chain. CTAP or cholesterol ester transfer protein inhibitors can do it, but we don't have any good drugs in that. We had one trial several years ago that didn't work out very well. There was a high death rate, not a good drug to be on. And then there's mipomersen, which is works on a different mediated pathway. It's hard to get, but it can be gotten. Again, but not indicated for Lp(a). But now we have two or three medications coming down the pipeline. We may be able to really change this. I'm gonna take out a little piece of paper because I want to quote another mentor besides Dr. Koren, Dr. Sam Semeikis out of U California, who said, quote, Lp(a) is a genetic risk factor, kind of like cystic fibrosis or breast cancer. The only way you can overcome the genetics that elevated Lp(a) is to shut down the gene that makes the protein, which is what antisense molecules do. And that's what we're researching is these anti-sense molecules. And it's specifically targets. This is not a broad blow-up of a large area, it's a very targeted shutting down of one little piece of protein in a gene. So it doesn't manufacture it anymore, and we stop making Lp(a), which is fascinating. So why test? If you look, if you did Lp(a) assessment, where we think there's 120 people that may never have it, actually 40 people may not truly have it, 67 maybe have intermediate risk for it, another 13 of those actually have high risk. So maybe we're not looking at it right, right? And then those with cardiovascular disease, where we say 41 definitively have Lp(a), maybe only 11 really have it. And about 26 have intermediate risk for it. So it kind of realigns how I look and physicians look at it and say, where's your risk? If you do have a high Lp(a), then we really got to work on this. How many people have been tested for Lp(a) in the room? I did it because I'm curious, not that I have heart disease or genetics for it, but just because I'm crazy. Great. It's really not a hard test to do. This one was measured in nanomoles. It can be measured, as I mentioned, as milligrams per deciliter. But when you get your if you do get tested and you look at your number, don't freak out, right? Don't let your hair get up, you know, because is it 100 nanomoles or to 50 milligrams per deciliter? You can see the difference in how you can freak out if you see it wrong. And and when you get above, you know, if you have a very high Lp(a), then really, then when you're really kind of at high risk. And men and women have about an equal parity of developing Lp(a). We don't think it's it's gender-based at all. So keep in mind, so you know, everybody says, well, what can I do about it? It's genetics, I can't change genetics. There's

Practical Takeaways And Closing

Dr. Albert Lopez 27:05

a whole kind of concept of proteogenomics now where what you eat may turn on and off certain genes in your body. Exercise may turn on and off genes in your body. So even though you may have a high predilection for it, if you're kind of doing movement therapy and staying away from highly processed foods, highly fatty foods, things with high nitrates, that maybe we can churn off certain parts of these genes and it won't express as well. So even though diet and exercise doesn't really lower Lp(a), you should still exercise and eat well. And it doesn't mean when you eat well, you don't eat, you don't eat deliciously. I'm a big foodie. We have a wood-burning oven in our backyard, we have a huge stove, and nothing's more pleasurable for me than cook a big meal and serve it to friends and family and watch them enjoy it, and comes a realization that there's very little fat in this, and there's a lot of good foods in here, and things that they would have never eaten, they've eaten, they've said, wow, that really tastes good. I never ate this before. So we think that maybe highly processed foods and even a non-plant-based diet, and I'm not saying everybody needs to go necessarily vegetarian, even though there's data that supports that may help, even two non-meat-based meals like meatless Mondays, may work very well to help. Statins may increase Lp(a), and you may not receive the full benefit of it, but statins are an incredible drug that have really changed the landscape of cardiovascular disease and reduced death markedly. Know if your LDL is oxidized or not, and I talked about those oxidized phospholipids. Is that LDL activated and going to cause rust in your arteries or not? And you can tell that by oxidized phospholipids. And then know if you have arterial inflammation. The most common one we've talked about, it's about almost 20 years old, is HSCRP, but there's several other arterial inflammatory markers like NPO, LPPLAT or plaque, adama. An easy test that we use for diabetics called microbiome will actually look at risk for cardiovascular disease as well. So, because of clinical research, we do have new treatments in the horizon, and we may be able to mitigate and change this risk and make a big difference. So, my end takeaway points is beware of your personal risks. Get tested. Know what your risk is personally, treat your risks and be strict and be strict to your goals. Stay healthy, stay active, exercise or move. Have fun and laugh. Thank you very much.

Announcer 29:40

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