Transcription
If you're watching this, you're probably like a lot of folks I see every week. You've already taken real steps to avoid a heart attack. You've dropped your LDL. Maybe you're tracking your APOB or your calcium score. You've cleaned up your diet. Maybe even started fasting. You're reading studies, watching videos, doing your homework.
But here's the problem. You're doing everything right. At least that's what they told you. And that plaque still seems to be growing. So, you start wondering, "What am I missing?" Well, you're not alone. There's a reason plaque keeps building even when the cholesterol numbers look perfect.
So, today I want to share a conversation with two good friends of mine, doctors Brad Bale and Amy Donine. I met Brad and Amy a few years back. They were among the first to say out loud what many of us were starting to see: that it's not just cholesterol driving heart disease. It's inflammation and metabolic dysfunction. They've spent years digging into the science connecting the dots between oxidation, insulin resistance, and plaque activity. And now they've released a new research project, an article that takes that idea even further.
In this interview, we'll talk about what that means in real life. How inflammation silently drives arterial damage, vascular damage, why simply lowering cholesterol usually is not enough, and what we've learned about reversing the process, not just slowing it down. You'll hear how their clinical work and data line up with what we see at Prevmed every day and how focusing on inflammation, metabolism, and lifestyle can change the story for your arteries and for your future.
So, settle in. This is a conversation you do not want to miss because when it comes to heart disease and prevention, Brad Bale and Amy Donine have been doing the Lord's work out there for decades, for a long time. And what they found might just change how you think about your own risk.
I'm excited to have my friends, uh, Brad Bale and Amy Donine, uh, from several years ago, uh, on the channel today. We've covered their content and their program many times on the channel. I think it was my third uh retirement. A friend of mine said, "Hey, you you're a prevention guy. You used to teach it at Hopkins. I've got some people that are very deep into cardiovascular or vascular disease prevention. I'd love for you to come see them." And it and I did and it turned out to be Brad and Amy. And we ended up working together for a few years. I learned a lot from B Brad and Amy. And uh, I'm excited to have you guys on board. Why don't you guys uh join me?
>> Yeah. Well, thanks for pleasure to be back with you and see you again. You're looking good. Looks like you're following the advice that we give to keep people healthy. That's great. But thanks for having us on your show.
>> Uh, yep. As I think both of you know, growing old's not for sissies. We talk about that all the time. And if you're going to age properly, you got to you got to do the work.
>> You got to m manage your diet. You got to manage your uh exercise, your sleep, and um, again, it's not easy like like Amy. Um, welcome Amy. And I know you're missing your morning run to be with us.
>> Yeah. Well, it's a good reason to miss it and be here with you and and um Ford, I really appreciate all the work that you're doing in the public education sector and it's a real thrill for both Brad and I to be on the show with you and it's been a while since we have seen each other in person, but um I appreciate your work very much. So, thank you for having us on.
>> I appreciate that. And I'll do a quick editorial comment if uh people heard that that uh notification that's on Amy's machine. We thought that we had gotten it fixed. I was doing her IT for her, but uh maybe not. We'll see. Maybe it helped a little bit. So, [clears throat] anyhow, what we're going to talk about today is an article that Brad Amy wrote with a friend. They've written a couple of articles with a friend of mine, David Vigorist. He's a world-class geneticist and lab uh technologist uh faculty at Vanderbilt. Well, he used to be at Vanderbilt. I think he's moved since then. But um regarding articles, you guys did one of the first articles that showed that tooth and gum disease actually ends up being the cause of some vascular disease. Most um metabolic disease guys like myself would say the vast majority of vascular disease ends up coming originally from um from undiagnosed usually undiagnosed uh metabolic disease and um I know you guys are deep into that as well but uh a lot of us have noticed that that uh correlation and you guys wrote a good article with Dave showing that you've also written And another article that I think is very very interesting and it has to do with inflammation. You know, it's a topic that that the two of you have been talking about for what 30 years now.
>> Yeah.
>> Why else?
>> You know, I remember I think I think you really got um got the notice of the public. I think you you had your um your moment of fame when you uh or or got introduced uh to the world when you were on um who was it was the Larry King show, wasn't it, Brad?
>> Yes. Yeah, the Larry King show. Yeah.
>> Was it after It was after the death the heart attack of somebody. It wasn't Tim Rustard, was it?
>> It was Tim Russard. It was on sudden cardiac death. Yes, that's correct.
>> And uh and your point as it has always been is you know what folks, it might not be LDL that bad cholesterol. It might be something a little bit more like inflammation. And uh we covered this article actually about a year ago. It was very uh popular with our geeky side of the audience. And as we discussed before the the our meeting this morning, we're going to try to uh provide some practical application for the rest of the audience. That other 80 to 90% that yeah, they have some interest in for sure they want to avoid vascular disease, heart attack, stroke, um blindness, kidney disease, and erectile dysfunction, but they're not quite as deep into it uh in terms of the science. But before we get to the practical part, let's hear a little bit more about the science and just what you said in your article.
>> Yeah, sure. I I'll do a quick caveat to kind of make it absorbable to everybody and then um I'll Brad will chime in and then I'll I'll follow up. But basically this article, you know, we use the word inflammation a lot in in everything in everyday life. I have a sliver. I've got inflammation. I hurt my ankle. My ankle's inflamed. We use that word so often and it's very appropriate, right? But what we wanted to do is give really a scientific understanding of what the inflammation is in the wall of the artery and and a a more proper uh definition of inflammation for arterial disease is oxidative stress which our bodies do all the time. We break down, we rebuild, we break down and rebuild. But when there's a misbalance of that um that's when we wind up into problems. So this article used the lens of oxidative stress um to provide meaning to what and how vascular disease even manifests itself. How does it start in the artery? And then as we use that lens of oxidative stress, we can appreciate how different treatments affect arterial health and also um reduce cancer risk, reduce dementia risk and even affect our our longevity, you know, affect our our longevity. So our ultimate goal is that our health span matches our lifespan. So that was kind of the premise from a very generalized standpoint of the importance of this article. And Brad, I'll let you chime in and then I'll I'll pick up the pieces also.
>> Yeah. Well, I like what Ford said earlier and actually I use a slide in our course that actually shows a rusty car and the rust is the spark the most common spark to initiate the disease process for arterial disease. And rust which is is oxidative stress shortens lifespan increases the risk of cancer increases the risk of central nervous system diseases. So it's not just the arterial disease. When you get rusty you're going to have problems throughout the body and you're not going to live as long. So, I love your analogy of rust and I actually have a slide where we use that when we're teaching.
>> Thanks, Brad. Amy, before you start, I think I'll go a little bit deeper on this whole thing about rust for uh again for the folks that aren't haven't heard it so much before. If you're in high school chemistry, they call it oxidation. It's combining with an oxygen molecule. If you're a boy scout, uh it's called fire. It, you're combining the wood, the carbon in the wood with oxygen and it's forming CO2. Um, if you're in your local mechanics office, it's called oxidation. And if you're in a a presentation with Brad Namy, it's called oxidation. You know, at the end of the day, this is combining with oxygen. It's burning. It's the human body and how it burns fuel. And um the vast majority of oxidation is caused by what we call metabolic disease or how we burn fuel. It starts out with a problem burning carbs, glucose. Uh usually uh resist insulin resistance, resistance of the insulin receptors in the cells. But very quickly as um our brain notices that our our glucose is going too high, it's telling us to put out more insulin. So what starts off as a as a problem with burning one of our major fuels, carbs, very quickly turns into a problem burning both of our major fuels, because having high insulin causes problems with burning the other fuel, fat. So Amy, why don't you go ahead and get us started on inflammation because th this article points out something that's very interesting to a lot of us geeks that go into this space and that is okay. So having too high of glucose or having too high of insulin or as you guys have pointed out so many times there's a bunch of other things that can do it too. Smoking, rheumatoid arthritis, other inflammatory diseases. But these things cause inflammation in the artery wall. Once you get that inflammation, what happens?
>> Yeah. Yeah. Let me um I'm going to back up just a minute and and highlight what you just said, which is so wonderful. And that is when we think about all the causes that drive inflammation. And I'm talking about, you know, if you think about a garden hose, I'm talking about the hose wall itself, right? We want to know the health of the hose, the the wall of the artery. We call it arteriology. We've got 30,000 miles of these arteries. Some are so tiny, they're no bigger than a human hair, and they feed nutrients to the brain and the eyes and all the way down to the toes. Some are larger like the ones around the heart, the aorta, etc. But 30,000 miles of these quote unquote highways that we are responsible to take care of if we want to prevent the chronic diseases of aging, um, and obviously the big things like heart attack, stroke, dementia, etc. So, what are those root causes that drive this inflammation? And we're going to use the verbiage of oxidative stress to define that inflammation. So there's a lot of lifestyle factors which Ford you've talked about on your podcast in such a wonderful way as well, but we have things like gut dysbiosis, we have an unhealthy diet, obesity is definitely an issue, we have periodontal health, um endodontic disease, of course lipids, but more so free fatty acids. So really when we're looking at uh free fatty acids uh and remnant cholesterol is an issue of course nicotine and a big one which you just touched on for is insulin resistance which is one of the most powerful drivers of oxidative stress and insanely common in people that have um the the artery compromise that have plaque in their arteries or inflammation. And then we get to other issues like traditional high blood pressure or you mentioned autoimmune diseases whether it be rheumatoid arthritis, systemic lupus, atherosclerosis, all of this sort of autoimmune sort of world. Um, and then chronic infections can be a problem, low vitamin D or nutrient deficiencies, even things as air pollution. So when you think about the globality of uh what drives oxidative stress, you can really appreciate that the idea of just saying okay it's nicotine, it's cholesterol and it's blood pressure. We realize how many of these root causes are left out including I didn't mention sleep um disorder, sleep challenges, sleep apnea, etc. airway factors as well but all of those have equal play. And as you'll notice in this diagram that we put together, there's a there's a bidirectional relationship. So for example, if someone is insulin resistant or pre-diabetic, they're going to struggle with high blood pressure issues as well. And they're all sort of combined. But when's the stimulus of oxidative stress? So Brad, I'm going to I'm going to go to the oxidative stress and then I'm going to hand it I'm going to hand it off to you to kind of describe how we get cholesterol that can trap in there. But let's be facetious just for fun. And let's say you are the luckiest human on the planet. Your lifestyle is perfect. You don't have remnant cholesterol. You don't have insulin. You have none of this except you live in a a highly air polluted area and environment. How would that cause plaque in the arteries? So using that idea that any of these have equal play to drive oxidative stress, then we start to get change in the wall of the artery. Um, and all arteries are built the same. We've got, you know, a lumen that's open like in a garden hose. That's where the water flows. And we've got an inside lining called the endothelium. We've got an intima. We've got smooth muscles media. And we're out of there. So what happens in oxidative stress is the artery wall itself gets transformed to become an sort of an um inflammatory environment where the healthy smooth muscle cells get transformed to smooth muscle cells that are maladaptive. And I'm going to leave it at that and let Brad kind of talk about the trickle down effect of that and how something like air pollution could cause plaque development in the arteries.
>> Yeah, that's excellent. You did a good job covering the numerous things that can cause a rusty situation, including, like you said, low vitamin D, which can be an easy fix if it's measured in somebody and you see it's low. So, some of these issues can be fairly easily solved. Others can be a little tricky. Like if you live in a high area of air pollution, what are you going to do? You can do some common sense things and if somebody's really bad, maybe they have to move to a better location with less air pollution. But that oxidative stress, that rust causes the contractile smooth muscle cells in the wall of the artery to get genetically transformed and to migratory secretory smooth muscle cells which move out of that medial layer into the intimal layer which is that first layer after you start going through the wall of the artery and it causes a substance to form that will electrostatically trap cholesterol as it's normally flowing through the wall of the artery. All the bad cholesterol contains a protein called apo which carries a positive charge. The substance that the smooth muscle cells create carries a negative charge. So it gets stuck in there. Once that cholesterol gets stuck in the wall of the artery, the immune system of the body turns on because you want to try and clean that up and then that starts the fire in the wall of the artery. And if you continue to trap the cholesterol, the fire is just going to get bigger and bigger until you form disease and until the disease misbehaves and causes a heart attack or stroke. So, does that make sense Ford?
>> Yes. So, before we go on, Brad and Amy, uh, Brad, you just mentioned a term that's very popular these days, APOB.
>> Yeah.
>> You know, there's a ton of people that that used to be in the LDL camp. They're now in the APO camp.
>> Yeah.
>> Uh and I've I've read a bunch of uh those uh articles and you know, one of the the things that they say in those articles is well uh the other apo particles are like uh IDL, VLDL, remnant cholesterol, and therefore they're very much associated with metabolic disease. So that's why APOB is the issue. If you read your article and you don't have a a deep background in this, your article seems to say there's a lot of stuff about APOB, which you just me.
>> Yeah.
>> I think there's a major distinction between what you're saying about APOB and what you might hear Peter Ailla, Tom uh Schneiderman, and some of the other folks saying about Apo. Do you want to clarify that?
>> Yeah. So, first of all, we've got over 40 years of evidence that clearly has told us apo is much more predictive than LDL cholesterol. And now knowing how the disease actually starts in the wall of the artery and that's a trapping of APOB, it absolutely makes total sense that APOB is the most predictive measurement much more so than LDL cholesterol. Apo B is a protein that's woven through all the lipoproteins that carry the bad cholesterol. And apo carries a positive charge [clears throat] or negative charge, I'm sorry. And the the substance that's created in the intima carries a negative charge. So it gets stuck
>> because APO B all the bad cholesterol other than the huge particles like chylomicrons that are present really only right after you eat they're all and they're all so small they flow right through the wall of the artery all the time. That's happening in all our bodies now. Most of the particles are so small they go right through the healthy arterial wall. But if you start getting that change in the smooth muscle cells that create the substance that traps the APOB, that's when you form start forming arterial disease and that's what turns on the immune system. It's the body's normal response to try and clean it up. But APOB because it carries that charge that's what makes it much more predictive than LDL cholesterol. LDL cholesterol has APOB wrapped in it. So it's the electrostatic trapping of the cholesterol in the wall of the artery and that happens because of apo. So,
>> so as I listen to you, I'm reminded of that whole um saying storm in a teacup. Um I I think there's still a significant difference between what you're saying and what the APOB crowd is saying. I think the APOB crowd is saying that APOB is causing the problem. I don't think you're saying that. No, oxidative stress is causing most of the problem because it causes those contractile smooth muscle cells to create the substance in the intima that will electrostatically trap apo and apo contains all the bad cholesterol. So
>> So for the folks that have gotten totally bewildered, let let's go back and just and say something. So, uh, whether the the APOB crowd is right or whether the inflammation crowd is right, I think there's a whole lot. Part of the reason I say storm in a teacup is there is a whole lot of overlap between what both groups would say to clean this up. So, Amy, you want to tell us a little bit more about what what I mean by that?
>> Sure. Um, I mean, I don't think we're we're disabled with with the with the understanding that APOB is a problematic factor. So, and much more predictive and appropriate um than LDL measurement alone. But if we use that lens of oxidative stress and we appreciate all the causes of oxidative stress um that can lead to the trapping of the apo within the wall of the artery. It also answers the question, and you've mentioned this on your podcast before for it, and that is some people with high cholesterol, we'll call it LDL or what have you, high cholesterol don't have heart attacks, and some people with low cholesterol do have heart attacks. And it's kind of a head scratcher. People don't quite understand that. But if you have a causal factor of oxidative stress like I mentioned before, gut dysbiosis, lifestyle, insulin resistance, nutrient deficiencies, um sleep apnea, periodontal disease, any of these root causes of oxidative stress, they are going to change the environment of the artery that makes it um as Brad said, these smooth muscle cells get genetically transformed because of that oxidative stress. dress and they release these proteoglycans that have an opposite charge of apo. So as the cholesterol is innocently flowing through in a situation of oxidative stress it literally gets trapped in there and then our body really tries to help. That's what we do. So on an autoimmune response to that we try to fix it and in a process to fix it we end up with um at the end of the day plaque in the wall of the artery. So if someone presents to us forward, they've already had a heart attack. We already know they have heart disease, they have a positive calcium score, they have a positive IMT, they have plaque in the arteries. Our job is to step back and say, why is it there? And it's pretty advanced but yet simplistic a um approach. So why do you have plaque? Treat the why. See the inflammation go down and see that plaque stabilize. I mean, that's ultimately the goal so that people can live a life free of vascular consequences. Um, so, you know, there's a published pie at the end of our life. It's like a 13-year pie um that affects our the lack of ability for our health span to match our lifespan. So if you think about what's in that pie, it's it's all of the things that this approach by keeping the arteries healthy can prevent. That pie is filled with diabetes, heart disease, heart failure, stroke, memory loss, dementia, peripheral vascular disease, chronic kidney disease, etc. And that's when we spend the most on healthcare and have the poorest quality of life. So using this lens of oxidative stress for all the reasons why we might have plaque or or inflammation in the arteries allows us to stop that high in a sense and allow our health span to match our lifespan. I mean that because that's ultimately the goal.
>> Yeah. Let me just add that's excellent that if you want to prevent a problem, you have to stop the first step that causes the problem. The first step for arterial disease that causes the problem is the oxidative stress kinetic transformation of smooth muscle cells. If you stop that, you're not going to get that substance in the intima to trap the apo the disease will shut down and the body can heal it. So the way to stop arterial disease is to stop the first step involved in forming arterial disease. It's really pretty simple. I just have to laugh. I mean it's not that complicated really. And it's it's magnetic factor that causes arterial disease.
>> So how do you stop that oxidation brand? You have to have a comprehensive management of everything from sleep to vitamin D. You do have to look at obvious things like hypertension, nicotine, insulin resistance, diet, physical activity. One of the best things to prevent oxidative stress is exercise. And another great thing, of course, is an antioxidant diet. You know the foods that you eat can cause oxidative stress or they can prevent oxidative stress. So there are numerous things that can can cause the oxidative stress but they can all be managed. And when you manage them all optimally you shut down the oxidative stress. You quit trapping cholesterol the apo in the wall of the artery. The disease stops and then our bodies can clean it up. That's how we regress disease. It really is not that complicated.
>> So you're referring to go back to the root cause oxidative stress and it's lifestyle components for the most part that drive that. So like diet, diet is king. How does diet impact oxidative stress in the artery wall?
>> Yeah, the healthy foods are antioxidant. [clears throat] So when you start, we all have oxy create reactive oxygen species all day long. If we didn't, we'd be dead. You do that when you create energy. But you want to
>> combining So you're combining with oxygen.
>> Yeah. And most of it comes from the mitochondria. But what you want to do is balance out those reactive oxygen species with antioxidants. And healthy food is one of the most powerful antioxidants that you can get your hands on. So that's why diet helps shut down arterial disease or prevent it if you don't have it in the first place. It helps create a a balance between reactive oxygen species and antioxidants. And that the other big spin-off, which is wonderful, of course, you're going to live longer when you shut down oxidative stress. You're not going to have as high a risk for cancer, you know, so your dementia risk goes down. The payoff is huge. And as a Brad, which foods are antioxidant? All your vegetables basically and your fruits and the degree that they can be good antioxidants of course will depend on how they're grown uh to some degree whether they're organic or not how many chemicals may be used on them. So the degree that they can be antioxidants can vary, but basically all your fruits and vegetables are antioxidants.
>> Very good. So how does exercise improve oxygenation?
>> Yeah, exercise has been shown in numerous studies to boost up antioxidants in your body. So the studies actually show exercise is probably as powerful as diet in terms of causing a good balance between reactive oxygen species and antioxidants. It's a monster. And obviously you can overdo anything just like you can overdo foods, right? You can eat too many healthy foods and get into problem too. So you have to have a balance with the physical activity and with diet even if they're healthy foods. You know it's like a uh Dr. Pierre Lamberer has a quote from a a professor in Switzerland. It's the dose that makes the poison. There's a lot of truth to that
>> for sure. No question. Or the the other thing just to to piggyback on that when we think about lifestyle, I always want to be thoughtful to not ignore um psychosocial health because when we look at drivers of oxidative stress, we also have um numerous years really of data associated with um depression, anxiety, post-traumatic stress disorder as far as drivers of oxidative stress. So the complexity of driving heart disease is is psychosocial. If we're thinking about a lifestyle standpoint, psychosocial health, um sleep is is so critical. A balanced diet, um movement or exercise. And then the sheer simplicity of finding joy um is also really important as far as decreasing the oxidative stress that our body's dealing with. So the idea that it's just cholesterol um really if you appreciate the role of oxidative stress and how many things that we live in every day um how we can avoid that oxidative stress and mitigate it is just so critical. Um the brain's the most powerful pharmacy we have. Right? So the idea of keeping our emotional health intact is also very clear. And if someone's coping mechanisms happen to be healthy like running or walking or dancing or something that's physical, then that's going to be a really good thing, mindfulness, etc. So I just want to put a plug in there that often is missed and that is the importance of emotional health and protection. And the best definition of stress is really to be in an environment for which you perceive a lack of control. Um and there's these little you know all in shaped centers in the base base of our brain that are called amygdala. And when we're in an environment for which we perceive a lack of control, those amygdala fire and say, "Get out, you know, get out of there. This is danger." Because we're made to run from tigers and lions and bears, obviously. But if we're in an environment where we can't get away and our perception is that we are not in control, that's when we start to see the same principle of oxidative stress where we get those smooth muscle cells to genetically transform to the secretory migratory smooth muscle cells which release the proteoglycan that trap that apo cholesterol. So the best thing we can do is through counseling and um good techniques to manage stress is to change our perception of control um and those amygdala cool off and stop firing and our arteries become healthier because of it.
>> You know, I'm so glad Amy you brought up a couple of things. The the lean mass hyperresponder group, which I'd like to mention in in a few minutes because I've got tons of those folks in our patient group. But before I do, I want to respond to what you just talked about. My favorite topic out of all of this is having a purpose in your life and a purpose that's bigger than your immediate needs. And I'm going to uh that's not very popular on the channel, by the way. Every time we do a video on it, it's uh we we get crickets. But let's step back in the mental health uh world and look at a group that's just you can't get more conservative and old school than that and that's the public health folks. Ask any public health person that knows anything about what's going on and they will tell you one of the biggest comorbidities or disease pairings that we see is diabetes and depression. And uh it's no surprise to me that um something like exercise, I know you guys know the these studies that have compared uh exercise to the most popular uh antidepressants,
>> right?
>> And guess what? The exercise does just as well as medications and in some ways better than medications in terms of quote curing depression. It gets back to some of the core chemistry that I think you're talking about. It gets back to uh the fact that dep uh diabetes is a is a problem with the way we burn our fuels. Exercise is a solution to the way we burn to that problem. And um your brain is just as susceptible as the rest of your body in terms of struggling with burning fuels correctly.
>> Absolutely correct. Yeah. And again, if you look at the diagram in that paper, you'll see the arrows go both ways with lots of these conditions. So insulin resistance or pre-diabetes oxidative stress stimulates that causes that. So depression causes oxidative stress. So guess what? It's going to be associated with diabetes. A sleep issue causes oxidative stress. Guess what? It's associated with diabetes. If you use nicotine, it causes oxidative stress. Guess what? It's related to the uh diabetes. If you have poor dental condition, periodontal disease, it causes oxidative stress, it's associated with increased risk of diabetes, etc., etc., etc. It's really pretty simple. As one of our providers stated when we published that paper, it's like the Rosetta Stone. It really answers anything. And so like the cold immersion, polar plunge, I was doing a podcast and the interviewer asked me about that and I said, "Well, there is evidence that it can reduce cardiovascular risk." Said, "I'll look into it after the podcast, but my guess is they've got studies showing a polar plunge reduces oxidative stress. It helps you not be as rusty." And I'll be darned. That will that's it. So you filter anything through the oxidative stress filter. Stopping oxidative stress SOS. There's a new meaning for that old Morse code. If you want to live long, you don't want to get cancer. If you want to keep your mind healthy, avoid arterial disease, SOS, stop rust. Well, it's really pretty simple. It's so simple. You have to laugh about difficult.
>> So Amy, you mentioned these folks a few minutes ago. Let's go back to that that debate that everybody wants to have. What was the root cause that Brad had mentioned a few minutes ago? Was it uh rust, oxidative stress, inflammation, or was it LDL or was it APOB? And you mentioned there's a group of people that have really high LDL values. Um, and yet they don't seem to be forming plaque. They don't seem to be forming uh having a problem. I don't know if you guys are seeing many of those in your practice, but I've got tons and tons of, you know, it's um Dave Feldman who coined the term lean mass hyperresponder is a friend and associate of mine. So, he's been on the channel a few times as well as Nick and Adrian Sodto who work with him in that project, but um I don't know if you guys are getting a lot of those or not. Are you?
>> Well, yeah. I mean, we get we get a lot of we have a shingle on our door that says come see us, you know, if you want to prevent heart attacks and stroke. So, um, the I'm going to answer your question, but in a little bit of a different way. And and we know that 50% of people who have a heart attack have normal cholesterol. Um, and there are some people with high quote unquote cholesterol who don't have a heart attack. And going back to the basics of what causes a heart attack, right? You have to have plaque in the wall of that artery. So, what causes plaque? Plaque is caused by all the root causes that drive rust or oxidative stress that cause cholesterol which innocently passes through the artery all day long from the time we're born. It it hits the endothelium, it hits the intima, goes through the smooth muscle cells, hits the media adventitia, it's out of there and it's recirculated. But in the presence of oxidative stress from like we said psychosocial health, periodontal health, insulin resistance, etc., etc., those conditions cause this wall of the artery to become maladaptive. And it doesn't matter if you have quote normal cholesterol, it can get trapped in there. And when it gets trapped, it starts to oxidize or break down. And then we're off to the races as far as plaque development. So, it goes both ways like like cholesterol has been such a I don't even know what to say like a flagship of the cause of heart attacks when really it's the least of our problems to be honest. It's it's everything else that's more global in its ability to cause the oxidative stress that leads to the trapping of cholesterol that ultimately causes fatty streaks and plaque development. So it if I do a longitudinal view of an artery and you've got plaque underneath here, what causes a blockage of that artery? It's when we get a secondary sort of inflammatory event and sometimes it's totally unpredictable. It could be an abscessed tooth. um that comes on when we're on vacation or what have you. And if someone isn't protected, that plaque can rupture through and the body's natural response to an injury, no different than if I cut my hand. A natural response to that injury is to send in clotting cascades, uh red blood cells, white blood cells, fibrin, all the stuff that causes a clot to fix it. No different than if I cut my hand. Well, if that clot lands in the arteries around the heart, the heart muscle isn't going to get oxygen, and that's called a heart attack. If the clot happens in the brain, we're going to call it a stroke. The more common manifestation of plaque rupture thrombus are little little tiny vessels, little tiny guys that you don't think, oo, I just think I had a small, you know, little capillary that got blocked. No, it happens chronically and and men are picked up earlier with this condition because they have an organ in their body that stops working. So we call it erectile dysfunction, right? That is microvascular disease. Women our first symptom of microvascular disease is chronic kidney failure or dementia. So the idea of of systemically treating arterial disease means we can avoid those chronic diseases of aging that are also associated with plaque development and problems down the line. And and so it's just it really if you use the lens of oxidative stress, you can even appreciate how certain medications um with their ability to reduce oxidative stress like aspirin and with thromboxane A2 and its ability to reduce oxidative stress also reduces colorectal cancer. Statins through the lens of reducing oxidative stress, preventing the conversion no matter what the root cause is of those smooth muscle cells to become the maladaptive smooth muscle cells that trap the apo cholesterol. Statins also through the lens of autophagy um help rid the brain of amyloid beta plaque and tau protein. So yes, they reduce dementia and Alzheimer's disease. So when you start to think about the treatments and the crossover, it makes sense if we use the lens boxate stress.
>> Yeah, that's excellent. Let me just add one thing for to your LDL question. We have the science. It's well known that LDL cholesterol in its native form is not inflammatory. It has to be trapped in the wall of the artery and there it gets oxidized and then it can create inflammation. But LDL cholesterol in its native form flowing around through the bloodstream is not inflammatory at all. In our paper, we point out the only cholesterol particles that are inflammatory out of the chute are the huge chylomicrons, VLDL, and IDL particles because they have the free fatty acids that can actually cause rust before they're trapped in the wall of the artery. So, it's no mystery at all that people can have very high LDL cholesterol levels and not have disease. It's not inflammatory. It has to get trapped before it causes inflammation.
>> And my prediction is that we will see that. We're already starting to see that in a lot of the lean mass hyperresponder studies. Obviously the the other side of that debate is fighting those as hard as they can but you know uh progress marches on and I think that that battle is effectively already lost for that side
>> on the for your side for the inflammation side. I need to wrap us up but as I do I'm reminded of the old uh saying about seeing the forest for the trees. You guys are way way deep in terms of looking at trees right now. Let me take us back out to look at the forest. You two have been doing the Lord's work for decades in terms of helping people understand how to prevent vascular disease. You know, a lot of people start off thinking this, and I know you run into this just like I do. You'll have people come to see you saying, "Oh, I I started to see you because of fear of heart attack. Now I realize that it's so so much more. It's uh it's stroke, the number one cause of permanent disability, um rapidly being taken over by uh cognitive decline or Alzheimer's, uh blindness, kidney disease, and as Amy mentioned, it's, you know, some men would think it's unfortunate, but in other ways, it's fortunate that we have the problem of erectile dysfunction to give us a canary in the coal mine to understand that we have a problem with our arteries and we need to get focused and fix it. So, uh, as you guys have gotten deeper and deeper in your what 30 years or more of doing this work, you've seen some things that are very, very deep in terms of how this happens. And your perspective is no, you know, your typical doctor says it's just your LDL. So, therefore, it's really simple. You take a a blood test, you look at LDL, if it's high, you give a statin, and you move on. And the two of you have been very strong ever since I've known you about saying, "No, it's a little bit more complicated than that." It actually starts with a thing called inflammation. And I can tell you, uh, again, I have u have every respect for you and the work that you're doing. Any uh comments to finish us out before we go?
>> No, I appreciate you having us on. Again, I think the simple concept SOS, the Morse code, if people live by that, think stop oxidative stress, move, eat correctly, don't smoke, get adequate sleep, make sure your vitamin D is adequate, make sure your mouth is healthy. All that stops oxidative stress. SOS. Just remember, if you want to live long, live by SOS.
>> That's great.
>> Amy.
>> That That's great. Um, just to piggyback on that a little bit and what you said earlier, Ford, when we think about the value of lifestyle, that's really such a global thing that we need to meet people where they are because if we say go out and exercise, it's good for you. It helps with insulin resistance. It helps with aging. Sometimes that means stand up during the commercials. You know, it's different for everybody. And so, the idea that movement, however much we can get and and meet people where they are, is just critically important. And the idea of medicine as being the the golden ticket to treat um risk or oxidative stress, a lot of it is lifestyle driven. We use meds, of course. We do if someone has plaque. Um, because the meds, it's not about just making cholesterol pretty. It's about preventing those smooth muscle cells from trapping the apoB cholesterol. So medications are used for disease management and on top of that the umbrella of lifestyle and an antioxidative sort of approach to that um including mental health etc. is just so critically important. So, um, I sure appreciate you having us on and and all the work that you've been doing over the years for it. It's it's a thrill to be here.
>> Thank you. I I'll make one other detailed comment uh on the way out and it'll have to be something that maybe we cover later. I remember when I first met you guys and I had obviously I knew prevention. I'd been there. I taught it at Hopkins decades before except I never really spent a lot of time uh on labs. Uh there was a a head of uh internal medicine at Hopkins long ago and I'm blanking on his name um but he was the one that said he was in that Oakland panel the the amphitheater at Hopkins and a junior doctor was stumbling around working with a patient trying to figure it out and he jumped up slammed his hand on the on the table and he said doctor if you just ask the patient, he's trying to tell you his disease.
>> And um again, maybe if we record an intro later on, I can remember the name of that doc. Uh but Oller, William Oller,
>> there you go.
>> And so I always felt like, you know, it's all in the history. Well, maybe it is in terms of knowing what's going on with the patient, but you guys were way deep into labs. And I learned that from you because what I learned next was the patients often don't listen to doctors, but they really listen to their labs.
>> I love that. And and the idea for that we're trying to treat something we hope they never feel, right? If you feel a plaque rupture thrombus, we didn't do our job well. So things like imaging of arterial health, whether it be, you know, carotid IMT or CTA with clearly overlay to say this is what your plaque looks like. It's vulnerable or it's stable. And coupling that with the labs with really the most frequent labs we draw are the inflammatory labs. And if they do go up or they're not managed appropriately, we pause and ask, "What are we missing? What root cause are we missing that is causing a residual inflammatory cascade in your arteries?" So, those are the most common labs that we look at every three to four months with patients to know that they're safe. And then couple that with imaging so patients can understand and and you talk about compliance. Um, it's all about understanding what's going on in our body and giving people the opportunity to make those healthier choices because they understand what's going on. And prevention takes time. Um, because we're really, like I said, treating something I hope my patient never feels. They do. I didn't do a good job.
>> Thank you guys again.
>> Thank you.
>> Thank you.