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welcome back to another episode of the regenerative health podcast now. I am very, very excited to be bringing you this episode. It is with dr michael wyman, who I believe is one of the world's leading decentralized cardiologists. So, michael, thanks for coming on.
Dr Michael Twyman:Thank you for the opportunity. It's going to be a fun one.
Dr Max Gulhane:Great. Maybe we start with your credentials and how you arrived at this part of medicine.
Dr Michael Twyman:So I'm a board-certified cardiologist. I did all my invasive cardiology training at St Louis University School of Medicine and ended up staying in the area. So I launched my own practice here about five years ago, where now I just focus on the prevention of heart attacks and strokes. I took all my invasive skills and didn't care really sick people in ICU and use those to kind of reverse engineer what you need to do so you don't end up in those situations.
Dr Max Gulhane:Yeah, reverse engineering. I love it and that is what I try and do when I'm thinking about optimizing people's health and trying to understand what is going wrong so we can understand how to prevent it from happening. So maybe let's start with some definitions, because ischemic heart disease and heart disease is one of the biggest, it is the biggest killer in society. So let me, or can you please, define for our listeners what are the exact meaning of atherosclerosis, coronary artery disease, atherosclerotic cardiovascular disease, ischemic heart disease all these key, very important definitions.
Dr Michael Twyman:So for the majority of those that you just listed, they're basically synonyms. Finishes so for the majority of those that you just listed, they're basically synonyms. But you have nearly 60,000 miles of blood vessels. 99% of your blood vessels are significantly smaller than the human hair. It's the microvascular system and as cardiologists, we're mostly focusing on the large blood vessels that you can see when you're doing procedures. But it's really looking at what is damaging the arteries and causing it to get inflamed and then plaque to build up. And when that plaque starts to develop and calcify, that's when it first usually starts getting picked up on some of these screening tests and your now diagnosis having atherosclerosis or coronary artery disease.
Dr Max Gulhane:Yeah, and the question that I kind of get a lot and I think a concern that people have is one what caused my plaque or what caused the deposition of calcium in the blood vessels and maybe that's been picked up on something like a coronary artery calcium score or maybe it's been seen more directly in something like an angiogram. So can you talk through the listener about how you think about coronary artery plaque and why it's developing and how it's developing?
Dr Michael Twyman:So it takes a few explanations. But it's mostly about the lining of the arteries. There's a layer called the endothelium and it's one cell thick. If you took out all your endothelium it'd be the surface area of six tennis courts. So it's one of your largest organs and one of its main jobs is to release nitric oxide, which is a very short-lived gas. That gas causes the artery walls to relax, so that keeps your blood pressure normal. But that nitric oxide also keeps the blood flowing well, so things don't stick to the artery lining.
Dr Michael Twyman:But only in past few years it was a little bit more recognized that there's something that actually protects the endothelium. That's known as the endothelial glycocalyx. It's a protective gel coat for the endothelium. So if you think of taking a fish out of water and it's slimy, that's essentially what the glycocalyx is, and I know your audience is pretty well-versed in the quantum world.
Dr Michael Twyman:Well, that glycocalyx is heavily structured in water and so that's kind of like the beginning part is that if that structured water collapses, then the lipoproteins, the white blood cells, they start aggregating or sticking to the artery lining and then that may kick off that cascade of where, if you don't stop it, plaque will build up. But there's infinite insults for that glycocalyx. But the body can only respond with three responses and this I learned from one of my mentors, dr Mark Kusin, many years ago. Those three finite responses are oxidative stress, inflammation and autoimmune dysregulation. So those are normal responses, but they get dysregulated the longer they go on and it's like a fire. If you don't shut the fire off, then the plaques start really forming in the arteries pretty significantly.
Dr Max Gulhane:Yeah, that's a great explanation.
Dr Max Gulhane:And let's really be clear about the physiology of the blood vessel and the lining of this blood vessel. Because, say, we're taking a cross-section of an artery and we've got the lumen or the inside of the vessel where the blood is flowing, and then if we progressively go down the layers, then, as you mentioned, the first thing that we'll get to is a layer of structured water or exclusion zone water, and we've got this, uh, glycocalyx, which is can be thought of, as you mentioned, is a slippery, slippery, like almost fish like substance, and I did some, I did research in in mucins and as they relate to the gastrointestinal tract and they, these glyco, the glycocalyx, can be thought as just a bunch of mucus-like stalks that are sticking out of the endothelium and providing a very slippery surface, and below that we've got the endothelial layer which, as you mentioned, is only one cell thick. So the question is and maybe again define this for everyone what is the difference between these larger blood vessels in the artery and the venous system compared to the smaller as we go down in size?
Dr Michael Twyman:So arteries are pretty much similar, even getting down into the capillary side, but on the venous side there's no smooth muscle in it and so they're much thinner, less rigid vessels. So the real key is that, like you know, atherosclerosis is, you know, it's mostly an artery-facing disorder. Now there is a possibility to develop plaque in the veins, just not nearly as common, probably due to, like, there's lower shear stress going across the glycocalyx and the venous side. But, as you had already mentioned, there's a layer of the glycocalyx, there's endothelium underneath, that's the intima, then the media, then adventitia. So if you think of an artery as, like in cross-section, you're slicing a garden hose in half, you're mostly looking at what's going on in the wall of the artery. Too often in conventional cardiology they're just focusing on what's in the lumen, either by looking at your blood or doing an angiogram and saying like you don't got a lot of blockages, so you don't get a stent, or you get a lot of blockages, here's your stent.
Dr Max Gulhane:Well, the stent relieves the obstruction, but it doesn't fix why you developed those plaques in the first place and fix why he developed those plaques in the first place and then you're just playing a game of whack-a-mole, you're putting in short stints and you haven't really treated the 60,000 miles. Yeah, yeah, exactly. And the question, therefore, that would seem logical step to me is that, before we can even get to damaging the lining of the blood vessels and, like you mentioned, damage to that endothelial lining and the glycocalyx seems to be the prerequisite for forming plaque, requisite for any blood contents, whether they're red blood cells or lipoproteins, to actually enter the subintimal space and actually form plaque.
Dr Michael Twyman:So I think it's not you know a either, or I think it's just more of a case where the more lipoproteins you have, the more glycocalyx disruption and nithelial dysfunction you have. The conditions are more likely you will develop plaque. It's kind of the quantum world. It's not a guarantee, it's just probability. But there are cases where lipoproteins can get into the entomal space and you still have a fully intact glycocalyx and nithelium.
Dr Michael Twyman:There are different receptors in the glycocalyx but it just tends to be more when intact glycocalyx and endothelium and there are different receptors in the glycocalyx but it just tends to be more when the glycocalyx has been shed. And again, it's kind of like thinking about seagrass at the bottom of a water source. Is that if that seagrass gets shed then there's different receptors that are kind of sticking out and then you know more of these lipoproteins and white blood cells and platelets start aggregating and sticking to that endothelial surface and then are more likely to kind of get in. I really don't like the term and you may not either, but like leaky gut it's essentially like leaky arteries. There's more gaps, more places for the lipoproteins to get through.
Dr Max Gulhane:Yeah, and I think the point that you made is particularly relevant. Maybe we're going to get to the difference between people with an actual pathological lipid physiology, which is people with mutations in various genes, with related things like familial hypercholesterolemia, compared to people with intact lipid physiology, and I guess the angle of the question was that to me it seems like if we have an intact structured water layer above our glycocalyx in someone with a normal lipid physiology, then it seems to me very difficult for any type of glycocalyx damage or clot or plaque formation to be initiated and therefore continue yes, I mean the glycocalyx is, you know, continually being shed and continually being rebuilt, and it's one of the things where it's like glycocalyx is heavily negatively charged because of all the sulfur units in it and the lipoproteins, the red blood cells, they're all negatively charged as well, and negative repels negative.
Dr Michael Twyman:and so with my patient I talk about like kind of being like a, and the lipoproteins, the red blood cells, they're all negatively charged as well, and negative repels negative. And so with my patients I talk about like kind of being like a maglev train. If your arteries have a very healthy layer of the glycocalyx, those lipoproteins should be repelled from it and slide on by. But there's something that's going to damage the glycocalyx. And then it's a positive and a negative. Things will attract, and then it's a positive and a negative.
Dr Max Gulhane:Things will attract. Yeah, that's a fantastic analogy. I really like that. So say there is damage to this glycocalyx, maybe explain what happens next? Because clotting, I believe, is underlying this whole process of both acute plaque rupture but also the chronic process of plaque formation.
Dr Michael Twyman:So inside the glycocalyx it's kind of like another way to think about. It is like think about a marsh. There's different creatures that live inside this marsh and then some of these things are helpful at knocking down oxy of stress. So there's superoxide dismutase You're continuously breathing oxygen to make energy in your cells. That oxygen can be toxic to the arteries. So the superoxide dismutase knocks down some of the reactive oxygen species and there's different clotting factors inside the glycocalyx. And so think of it as kind of like something where, like if it gets scratched, you want to be able to clot as needed. But there are certain things that will tend to really kind of denude the glycocalyx, and then that sets it up where you're more likely to clot than you are to bleed, and so it's going from a normal physiologic process to a pathologic process when the glycocalyx is severely shed and you start becoming more hypercoagulable.
Dr Max Gulhane:And what are some of the factors that are going to be contributing to this? Again, to disturb this structured water and then start shearing or damaging this protective seagrass layer.
Dr Michael Twyman:Yeah, the biophysical is, you know, pressure. So hypertension. You know, I often tell people it's not necessarily a disease, but it's a marker that you're not really having a healthy lining of your artery. Your arteries probably have very low levels of nitric oxide availability and the arteries are very stiff. But the higher the shear stress, the more that's going to damage that glycocalyx layer. And then there's a whole host of biochemical things, but dysregulated insulin and glucose are high on the list. More likely the oxidized lipids are going to damage it. Infections, microplastics, heavy metals, toxins like air pollution there's numerous things that can damage the glycocalyx and the body's always trying to repair. But it's when you kind of overwhelm that repair system that you tend to go into points where the person starts developing endothelial dysfunction, vascular inflammation, soft plaque, hard plaque and events. But you have many years to intervene before they have those events.
Dr Max Gulhane:Yeah, and explain to us what the difference is between the soft plaque and the hard plaque. And, as you said, this is an exercise in prevention and just like there's steps along the way of detecting insulin resistance before someone becomes fully blown type 2 diabetic, there's steps along the way that we can identify the progression of atherosclerotic cardiovascular disease before someone ends up in the emergency department with acute chest pain.
Dr Michael Twyman:No, and that's a great kind of segue into it is that in the United States, every 40 seconds somebody has a myocardial infarction and often the first time that they have a symptom is having the heart attack. They had no warning sign. This was going to happen, but it's been building up in them for many years. Most likely it sometimes starts in your teens and twenties, where you first develop glycocalyx disruption, endothelial dysfunction. Then you start developing vascular inflammation where the intima starts to swell. So as more and more lipoproteins get retained in the intima it starts to swell, much like if you sprain your ankle it's going to swell, or if you get a splinter it's going to swell. The territory as the white blood cells come and investigate why are these lipoproteins getting retained in the entomoma? And then, like a game of Pac-Man, the monocytes start gobbling it up. They became foam cells and then this is the nidus to start developing these quote soft plaques. The soft plaques, the body's going to keep trying to take care of it. It's going to put smooth muscle down over it to kind of scar it over, and eventually it will ossify it or calcify it. So the body, if it calcifies it, that's probably going to be a stable scar and it's probably not going to cause you any symptoms, unless that scar builds up to a state where you have now a 70% or 80% blockage or stenosis in your artery and the lumen is not flowing very well.
Dr Michael Twyman:So that is one of the cases where that's really late to the game and sometimes that's the first time that people end up seeing a cardiologist is that they start having chest pain with exercise or shortness of breath or exercise intolerance, and then they go get a stress test and it's abnormal and they're like oh, you have severe coronary disease.
Dr Michael Twyman:You know we're going to do an angiogram and they get a stent and they think they're all fixed. But that's just their introduction. You know you haven't fixed their endothelial dysfunction, their vascular inflammation or really talked about why their lipoproteins might be damaging their arteries. So that's kind of conventional. But there are a whole host of testing you can do that looks at the health of the lining of the arteries and then you can look for the degree of soft plaque with carotid scans using ultrasound. You can use different CT scans to look at the softer, hard plaque in the corneal arteries and you can really tell people hey, you have advanced disease, even though you've not had any symptoms. And then those are the people that want to be more aggressive with pharmaceutical agents, supplements and lifestyle interventions.
Dr Max Gulhane:Yeah, and I want to be really clear about the exact pathophysiology of what's happening when someone is having, maybe chronic vessel damage that's leading to plaque formation, versus that acute event that leads to occlusion or obstruction of an artery that leads again to symptoms. So explain the difference to us.
Dr Michael Twyman:So in the first case that's going to be more stable angina, where this plaque has been building up over time. The body is forming smooth muscle over this plaque and then it calcifies it. The lumen is where the blood is flowing. So again, if you think about a garden hose and you slice it in half until the lumen is occluded 70%, most people are not going to have any symptoms. You're getting enough oxygen nutrients downstream, where the tissues can continue to make energy from the blood. But once you start going above 70%, most of the time when it's under physiological stress, either from mental stress or exercise, the person starts having symptoms. They may feel a pressure, tightness, squeezing in their chest. They're short of breath or the exercise that they used to be able to do, they just can't do it. They stop the activity, the heart rate slows down, the cardiac output goes down and then the symptoms improve. But every time they do that type of activity or get their heart rate back up, they typically keep having those symptoms.
Dr Michael Twyman:Now where it's more concerning is when the person has no symptoms. They may have only a 30% plaque or blockage in one of their arteries. They cannot feel that plaque and these plaques can become unstable. Often in this situation where there's a lot of inflammation and oxidative stress, think of these plaques as like pimples on the wall of the artery. If it's a really thin pimple and it's inflamed, then that pimple could pop and then all the oxidized, damaged cholesterol, white blood cells and other cellular debris that's in this plaque, which is kind of like an abscess in the artery wall, it spills out into the bloodstream and now the body basically thinks it's bleeding and then all these coagulation cascades kick in and form a clot.
Dr Michael Twyman:It's a big platelet plug and it seals that plaque rupture but it acts as a dam to all the tissues downstream so no oxygen nutrients go downstream. So when these plaques rupture in your heart, that's what we would call a heart attack. If it's in your brain, it's a stroke. Now there are other heart attacks where there's aortic you know dissections tearing down into arteries, or the spontaneous coronary you know dissections. You know there are some ulcerated plaques that occasionally rupture, but the majority of plaques it's a. You're going along fine and then when these plaques ruptures, the blood clots, you start having your event.
Dr Max Gulhane:Yeah, and that's a really important point to make, because the degree of disease or maybe occlusion that we might have detected on something like a CT coronary angiogram doesn't necessarily correlate to the probability of having an acute myocardial infarction. And that is what I'm presuming is because the occlusive event is a massive thrombus or blockage of the artery from red blood cell accumulation. And whether you have 30% stenosis or 70% stenosis, it is an individual process. But equally, depending on the underlying vascular inflammation, could those two situations lead to an AMI and an emergency presentation?
Dr Michael Twyman:Correct. Yeah, and that was always kind of. The scary thing is that there's people who come in and they had no symptoms and often they had quote normal cholesterol and people are like, well, they just had bad luck. It's probably genes and, yes, there's probably some genetic role for some of these people, but you know, it's really something in their life disrupted their glycocalyx and their telium for a long period of time and this cascade happened. It does not generally happen overnight, and so that's why it's most cases where it's like if you start looking earlier, you start finding those people that, hey, they really low nitric oxide, their arteries are stiff, they're starting to have higher blood pressure. Check some biomarkers and they got high sensitivity to your PLV. Okay, what's going on with this person? And start trying to find out, well, before they ever have their first symptom.
Dr Max Gulhane:Yeah, and I think one case that really illustrates this well is Stephen Hussey, who I've interviewed and I'm sure you're aware of. He's talking about the quantum and circadian implications of heart disease and he had an acute myocardial infarction and basically occlusion of his left anterior descending artery artery. But when they looked at his, when they did the angiogram, he had no disease, he had no hard clot. So that is indicating that the process of his heart attack was a spontaneous clot and in the setting of those inflammatory factors that we talked about really briefly earlier.
Dr Michael Twyman:Greg, yes, and it's one of the cases where you know you don't always have, you know, a severe stenosis when these people have heart attacks so the goal needs to be keeping that endothelium as stable and as least inflamed as possible in in my mind.
Dr Max Gulhane:Would you agree with that?
Dr Michael Twyman:absolutely. Again, it's you know, it's the three finite responses, it's the oxidation, the inflammation and autoimmune dysregulation. If you can keep at bay, you don't tend to keep going down those pathways where these plaques build.
Dr Max Gulhane:And maybe one more concept to delineate before we go further is this idea of Virchow's triad and as it relates to blood clotting and coronary artery disease and AMIs.
Dr Michael Twyman:Sure, and actually it had been a while since actually I thought about the actual triad. But it's, you know, you know, it's uh, you know, injury, there's stasis, and then there's this hypercoagulable response. Um, and it fits in the. The story of the glycocalyx is that, you know, something damages the glycocalyx, that sets off the case where these hyperpochromic factors get released and the blood's more likely to clot. But what we call stasis, well, I mean that would be, you know, in the kind of quantum world, you know it's low redox potential. You don't have enough net negative charge to have the blood flow, you know, on its own, essentially over the negatively charged glycocalyx, you know. So that's where I would try to think about it. Stasis is a lack of electrons.
Dr Max Gulhane:Yeah, and you can imagine that a lack of electrons, from a lack of grounding and a lack of negative charge, that is, repelling those red blood cells away from each other and away from the lipoproteins and away from the glycocalyx, could potentially cause stasis and the other two I mean hypercoagulability in a state of insulin resistance and, yeah, I mean vessel injury from whether that's you know, just a decade of smoking and those particulates are cleaving and shaving off your glycocalyx, cleaving and shaving off your your glycocalyx. Maybe it's actually a good opportunity to talk about briefly the perspective of cardiac physiology that relates to the, the microcirculation and the fact that maybe the heart is having not was not the only source of propulsion on flow in in blood vessels. What's your perspective on this idea is the heart is not a pump.
Dr Michael Twyman:So I have read Dr Cohen's book and I know some of Dr Hussey's postings are talking about this. It's an interesting theory. I think it's plausible, it makes sense to me, but is it something that I give a lot of credence to? No, I don't really think too much about it because either it is or it isn't, but it's the same things I'm going to teach people. It's like I want them outside grounding, I want them getting full spectrum sun on their body, I want them to avoid fluoride in their water.
Dr Michael Twyman:So all the things that are going to improve their net negative charge is going to improve the flow through this 60,000 miles of blood vessels that you have. But it is interesting that the heart is one of the most energy-dense organs but, even that being true, it may not have enough force to be able to truly pump blood through that kind of a distance. And I know that there's been some studies where they've just shined infrared light on blood vessels and the flow continues to go. So that's an interesting experiment and, yeah, I think it's plausible, but I don't spend too much time worrying about it.
Dr Max Gulhane:Yeah, and you're right. If the implications of it are the same, then, yeah, the practicalities is what matters, and I think you're referring to Dr Gerald Pollack's recent paper on the driving of blood beyond the heart, I think, and he showed in a chick embryo the shining of infrared light was able to potentiate blood flow. So, yeah, it's a very interesting area of development. So talk to us now, michael, about what are some of these indicators that we might look into for gauging our endothelial health, if we've accepted what you and I have said for the first 20 minutes of this interview that inflammation in our blood vessels is important, endothelial dysfunction is important and the health of those blood vessels are important so how can we get an insight into their health?
Dr Michael Twyman:So with my patients I always talk about that. There's two things we need to look at. We need to look at the biophysical and we need to look at the biochemical, because if you just look at one or the other you don't really have the full picture. So I always just start with you know what is actually going on with the arteries, because that is really going to tell you how aggressive to be with the things that you see floating through your blood. So the endothelium there's a few things you can use to test it. You know, at home it can just be as simple as is your blood pressure less than 120 over 80? Good, that's a good start. You know, if you're a man, do you have erectile dysfunction? If you do, you're probably going to have some microvascular disease. Now you got to figure out, okay, why do you have microvascular disease? You know, in the office. You know there are tests you can do where you can test your salivary nitric oxide levels. It's like a little salivary sample on this. You know, litmus paper type, and the brighter red it is, the more you can make nitric oxide through that salivary pathway. There's devices that look at pulse wave velocity. So essentially, how elastic are your arteries. If your arteries are really elastic like an accordion, they're probably making good nitric oxide. If your arteries are like a lead pipe, they're probably pretty sick.
Dr Michael Twyman:There are tests that look at your ability to release nitric oxide when a vascular stressor has been applied, and this would be called the endopat test. It's a 15-minute non-invasive test where you have a blood pressure cuff pumped up on your arm, higher than your systolic blood pressure, and you have probes on each of your fingers measuring the flow. And then, after a five-minute occlusive period, you open up the blood pressure cuff, the blood rushes back down into your hand and that blood's going to flow over the glycocalyx that is transduced to the underlying endothelium like hey, here comes a big slug of blood and the nitric oxide gets released. The smooth muscle in the artery relaxes and the flow rushes back down to your hand and your hand wakes up. And then with this system we can calculate well, how much do arteries dilate when there's this vascular stressor? And optimal your arteries should triple or quadruple in size.
Dr Michael Twyman:But if your arteries, you know the cutoff is 1.68. So if your arteries don't dilate more than 168%, then you have endothelial dysfunction and you got to go looking in through the biomarkers or their lifestyle. Okay, what's driving that? So that's how you kind of test the endothelium, and then on the biochemistry part of it, you would look at labs such as homocysteine uric acid, adma, which stands for asymmetric dimethyl arginine. And then there's just that old school urine microalbumin creatinine ratio. So if you're leaking protein into your urine, that means you've damaged the glycocalyx to the arteries in your kidney and you're leaking protein. So those are kind of the starting points to tell a person how healthy their arteries are. And then we can get into talking about, like, okay, once that has been broken down, what can you expect with soft plaque, hard plaque and what tests you should look for that?
Dr Max Gulhane:then Thanks for that, michael. Yeah, and it's a good place to mention that. Nitric oxide, this highly labile gas that you mentioned, has an incredibly important role in vasodilation, or opening up those blood vessels, and it is essentially stimulated or released, liberated when we get ultraviolet light on our skin. I think that's the key distinction. Previous listeners of my podcast would have heard the episode with Professor Richard Weller, who was instrumental in discovering that pathway and therefore joining dots to show that people with higher UV light exposure have less cardiovascular death, less cardiovascular mortality and less cardiovascular disease. With regard to those assessments of endothelial dysfunction or health, do you typically see, I'm guessing you see people with type 2 diabetes who smoke regularly? I'm guessing you see people with type 2 diabetes who smoke regularly who have never grounded before?
Dr Michael Twyman:They have poorer endothelial health. On those metrics they would, but I would say I probably have a more health-conscious-minded practice at this point. So I think I'm kind of on the hand of my. I have nearly 900 patients. I think less than five of them still actively smoke. How many are actually truly type two diabetics? Probably less than five. As well, there's a lot of pre-diabetics and people with early signs of resistance. But people who are frank diabetic with A1Cs near 10, like I used to see all the time very, very few. But those are the people that, yes, you're basically probably going to be more secondary prevention for those people.
Dr Michael Twyman:This isn't their first rodeo. If you're smoking, that is like the number one thing that's going to damage the glycocalyx. It's not the nicotine, it's all the heavy metals and other toxins and then combustible cigarette. It's the delivery form. That's the problem. That then shears off your glycocalyx and now everything else is going to be starting to stick there. Oh, and you got an A1CF10? Okay, well, great, You're never going to regrow that glycocalyx and you're just going to have all this microvascular disease. And that's what you see. These patients go blind, they lose their extremities, they have kidney failure. Yes, they also tend to develop some macrovascular disease where they're getting stents. But it's the microvascular system and those people that you really see kind of go downhill quickly.
Dr Max Gulhane:Well, it sounds like you've selected for a very health-conscious patient population. But I love the analogy of the seagrass and the grass because it actually reminds me of regenerative farming, which is one part of the optimal health puzzle that I like to talk about with regard to food sourcing. But I'm just imagining grass and if you're constantly mowing it or you're constantly whippersnapping it with a brush cutter and then you're not letting it grow back, then maybe you're spraying herbicides on it. That's maybe an analogy for what's happening to the endothelial glycocalyx when we're inhaling the diesel particulate fumes and eating drinking Mountain Dew every day and that glycocalyx is just getting hammered by the fluctuating blood glucose and all those micro particulate particles.
Dr Michael Twyman:I think that's a perfect analogy. I often use that one about seagrass. Is that? Yeah, because the glycogalix has these like little strands out there and it's sensing the flowing blood and it's sending information to the underlying endothelium and there are certain things that will damage one patient's glycogalix. That won't necessarily damage others, but it's sometimes. Thousands of micro cuts is what's doing it and you have to go figure out like hey, what are the major drivers for this person?
Dr Michael Twyman:Unfortunately, there's a lot of things you can do, even if you don't get to the absolute root cause. You know we've talked about some of them. It's just like you know proper sun exposure, grounding, you know proper hydration that doesn't have fluoride in it, like you're just trying to allow the body to have as many kind of building blocks as it needs to start regenerating the glycolysis, because the body is pretty resilient if you get out of its way. But you know, I was recently on a podcast and they were asking about the microplastic situation. You know there's a recent study that was talking about that about half the patients that were getting carotid endodirectomy surgeries. They were finding these microplastics inside the plaque and it's presumed that they're probably ingesting them. But they could also be inhaling them.
Dr Michael Twyman:But the more interesting thing wasn't that, like, there was these microplastics in the plaque? In my mind it's why didn't all of them have it in their plaque? What was reducing the risk of some of those people not getting it? My suspicion is that those people had bad glycocalyxes, briefly, but they were doing some more things that prevented the microplastics from getting retained in there. So, you know, that's how I kind of think about it. It's like you know, what can you do to improve the lining of the glycocalyx? Well, you know, there are some, you know, patented nutraceuticals that kind of give the building blocks to the glycocalyx. But a lot of it is just trying to remove the insults because we're all going to be exposed to things. It's just, you know, everybody has a different threshold for when those insults are going to really lead to the diseases.
Dr Max Gulhane:Yeah, great point. And that specific trial or study was very interesting and I'll just reiterate that it showed when they took, essentially reamed out the inside of these carotid arteries in people and they analyzed the plaque that they removed and found microplastics. And yeah, you're right, that is the right question, which is why did some people have this and others didn't? And Dr Jack Cruz made the point that I mean melanin. If we've cultivated our melanin and our quantum point of view, our melanin is acting like it's a heavy metal complex or another form of antioxidant, then that's one particular reason why we could help to detoxify or remove those types of substances. And the question I wanted to ask you was specifically about homocysteine, so you mentioned it. What degree is a raised homocysteine a risk factor in the context of perhaps no other deranged blood markers, and how is it having its effect on raising the risk of atherosclerotic cardiovascular disease?
Dr Michael Twyman:having its effect on raising the risk of atherosclerotic cardiovascular disease. So homocysteine is an amino acid that's supposed to get converted to methionine. I usually like to see a level of homocysteine less than eight and often if it's elevated the person may have chronic kidney disease. That might be driving it. It's just the detoxification pathways don't work well in the people with renal failure, but often it's a person who has an MTHFR mutation, either homozygous or heterozygous, 677 or 1298 mutation and you need to be able to methylate the homocysteine to methionine. If you build up high levels of homocysteine it will often drive up the asymmetric dimetharginine and asymmetric dimetharginine competes with endothelial nitric oxide synthase to produce nitric oxide. So the higher ADMA levels, the lower your nitric oxide. So in patients who have high homocysteine and then you discover that they have a methylation issue, then often you will support them with different methylated products. Drive the homocysteine back down. You see the AD omega down. Often they start making more nitric oxide and it's all about keeping nitric oxide high and available.
Dr Max Gulhane:Interesting because the other things that can drive up homocysteine are like a B12, obviously a vitamin B12 deficiency, riboflavin and a folate deficiency as well, so it's tied into cardiovascular risk via nitric oxide.
Dr Michael Twyman:Correct. And yes, that's usually when I say people have a methylation issue. They're often going to have either low B12 or folate, or likely both in some instances, and then you give them a combination replacement to get their levels of B12 and folate back to optimal. Those are cofactors. There's a few other things like biopterin that then help this methyl tetrahydrofolate reductase enzyme convert the homocysteine back into methionine.
Dr Max Gulhane:Okay, yeah, that's a little bit of a technical but interesting point, thank you, so say we've done these, and maybe one more that you could describe for us is the high-sensitivity CRP, and C-reactive protein is obviously cleaved, produced by the liver and is an indicator of inflammation, but how do you look at high-sensitivity CRP as a cardiovascular risk indicator?
Dr Michael Twyman:It's included in my panel that I check for all new and established patients. It is a quick check on the inflammation system. I tell patients it depends on if you're coming in and this is pure on screening. Your HSCRP should be normal, but if you recently had an infection, surgery, musculoskeletal injury, you should expect it to be slightly high. It's not a problem if it's high and you have a ready explanation.
Dr Michael Twyman:The problem is when it's you know two, three, four for years and you don't know why they have this high sensitivity to CRP elevated. So then you got to start doing the detective work. Now, often it's untreated sleep apnea, it's insulin resistance, it's some type of you know, sensitivity to gluten. Possibly you know there's something that's going to be driving it and then you try to withdraw that and the CRP goes down. But it's not the be-all, end-all test. But it's one of those cases where, like if you have high sensitivity, crp high and lipoproteins, you're much more worried about that person. And then this is the kind of idea of why you know stans have this potential pleiotropic effect at lowering inflammation. That may be one of the reasons why they actually work, not just lowering the lipoproteins.
Dr Max Gulhane:Yeah, okay. So we've looked at these specific biomarkers and then we really get to the lipid panel and there is so much controversy over and, I think, a lot of ambiguity as to what people are talking about when they're referring to cholesterol and these other blood lipids. So maybe give us a quick overview of what are the main lipid components in a lipid panel. What do you look at and to what degree are they helping us predict this disease?
Dr Michael Twyman:So in a traditional lipid panel there's four things that you know mostly get reported. You know there's total cholesterol, hdl cholesterol, triglycerides and LDL cholesterol, which sometimes is just calculated. You really want to have at least a direct LDL-C, but I'll get to that in a moment like that's probably still not enough. So in a traditional panel if the total cholesterol is over 300 milligrams per deciliter and the LDL cholesterol is over 190 milligrams per deciliter, then the person may have familial hyperlipidemia, which is a genetic abnormality, often with the LDL receptors, where the person just doesn't clear lipoproteins very effectively from the bloodstream, and then they have these higher levels of total cholesterol and LDL cholesterol. So I will always look at that in every patient. But there are some patients who had quote normal panels. They do one of these kind of more restrictive diets where they're full keto or carnivore with high saturated fat and they may see this panel happen even though that they don't have FH. But I don't put a lot of stock in the traditional panel to predict risk because again, half the people coming into the hospital who have heart attacks have quote normal cholesterol In the traditional panel. Yeah, I will look at the triglycerides because it's often a sign. Is the person insulin resistant or not. I generally like to see the triglycerides less than 80, but you'll see, some people are very fit no evidence of insulin resistance and they have high triglycerides. Now there's certain genes that affect lipoprotein lipase at times that raise the triglycerides. So it's not a perfect metric but in many people it's a marker of insulin resistance if it's high.
Dr Michael Twyman:And then the HDL cholesterol. It's anybody's guess at this time. Now there's just actually a recent trial that came out where they were infusing HDL in patients having STL elevation MIs and it showed no benefit for these patients. So the HDL side of the equation is still very, very murky. I really dislike the term good cholesterol. You should almost basically not look at your HDL cholesterol. Focus more on the LDL side of the equation first, especially if you have plaque in your arteries. So that's what I do when I look at the traditional panel. But if anything, patients are going to see me, for they're going to be doing some of the advanced lipoprotein analysis. So we're doing themr analysis and then checking an apob and then that's really where you can get into, like you know, helping people understand, like what the risk is yeah, and maybe we won't specifically go into the, the nuances of lipidology.
Dr Max Gulhane:Uh, this, this conversation, because I really do want to get the rest of your thoughts on a range of other topics and maybe we can come back to it but say you've assessed someone's risk based on some blood work. Maybe now explain to us what you're going to do next and I think, before we even go there, you can explain those three concepts of primordial prevention, primary prevention and secondary prevention.
Dr Michael Twyman:So yeah, so start there. So, secondary prevention you've already had a heart attack, you've already had a stroke, you have stents in your arteries, you've had bypass surgery. We're trying to prevent you from having it again. And yes, I do have some patients I've had prior events. Often they're not under my care. They've had them out in the real world and they come to see me to try to not have it again. Little in-depth duty at that point. You know that's honestly where most cardiologists play. You know they're only treating people who've had events, and so that's why they're not going to talk about a lot of things that I'm talking about, because, one, they've never learned about it and two, these aren't the patients that they're seeing. They're seeing the sick as the sick, and so they're throwing the kitchen sink at these people. But primary prevention in the classic world is that you've not prior had an event. But if you're only using conventional tools, you're going to miss things. And so if you use a lot of these advanced testing, they're probably not necessarily primary prevention, they're probably like 1.5. They're not one, they're not two, but primordial means.
Dr Michael Twyman:Like you're born, you have perfectly healthy arteries. How do you stay that way? That is really really challenging. There are certain tests that I do a CT angiogram test which uses AI to look at the arteries. It looks for plaque.
Dr Michael Twyman:I've screened a couple hundred patients over the past three years. I've only seen two women with perfect scores. I've never seen a man not have some degree of salt plaque in their arteries. Now I'm starting to start screening people less than 40. That is a caveat is that most I'm screening patients over 40, but last year I saw a 36-year-old gentleman who had a calcium score nearly 1400.
Dr Michael Twyman:Ct angio had severe right coronary stenosis and he got stented before he came to see me and then we were doing deep dive. Okay, how did you end up with such serious disease at 36 years old? So I think primordial prevention is the goal and we really need to kind of keep teaching the primary care doctors and even the pediatricians what to be looking for, because this is a disease that starts in your teens, twenties, and a lot of your habits they're set and not stone, but like a lot of your nutritional habits are set when you're a teenager and your exercise patterns are set as a teenager. Those are two big levers that people need to kind of optimize as they move forward.
Dr Max Gulhane:Great and I want to make the point of how relevant this is in terms of lifestyle and how our lifestyle in this modern age right now, I believe, is increasingly responsible for the development of atherosclerotic disease at younger and younger ages. And I believe there was an observational study done of a Catarvan population who are living a traditional lifestyle in their island location. They're eating mainly coconut oil as a kind of a fat source, they're eating fresh fish, they're obviously grounded, they're getting a heap of sun and I think they even smoke. They have a high rate of smoking and the amount of coronary disease that they have is is very, very little. And whereas you're you're talking about now the fact that if everyone is doing everything wrong with regard to these risk factors that we've briefly talked about, then you're gonna, we're gonna see a deposit of deposition of plaque um earlier and earlier, and younger and younger.
Dr Michael Twyman:I definitely agree with that. I mean, you know 80, 90% of this really could be prevented with. You know the things that you know you and your audience frequently would talk about. You know it's setting your circadian rhythms, it's grounding, it's, you know, avoiding. You know toxins when you can. You know it's improving your net negative charge. Those things make you more resilient for the infinite insults you're going to see as you go forward. But I think it's the story of that. Our technology is great to be able to talk across the world with each other, but too many people get drawn inside in front of these things all day long and they never touch the ground outside. They never see a sunrise, they never spend more than three minutes outside in any one day.
Dr Michael Twyman:They highly ultra processed food and you know it's. You know I sometimes get pigeonholed and think that you know. People ask me like well, you don't have, you know a diet to recommend every cardiac patient? Like it's individualized. You know. Like you know I didn't know, like your maternal haplotype. Where do you live in the world? What are your goals? Like are you trying to lose weight? Add weight, you know, add muscle. Like there's going to be some nuance to it. But food is important. But you know, as Dr Cruz talks about, you know, it's maybe five, six, seven down on the list me. They haven't even started to even think about that as the big thing that they had been missing in their life. Why are they showing up sicker than they should be? Nope, they have not really slept well and the circadian rhythms are way off.
Dr Max Gulhane:How do you think about the sunlight and the circadian rhythm as it particularly pertains to the development of atherosclerosis?
Dr Michael Twyman:I mean the body has different circadian timings in the heart. At nighttime your blood pressure is dropping it should drop by at least 15% while you sleep and it starts to increase in the morning as cortisol starts to rise. This is why a lot of times heart attacks happen between 3 am and 6 am, as cortisol is rising, your blood's getting stickier, your blood pressure's going up and then there are reasons why that if you don't have your circadian rhythms dialed in, you're going to be more insulin resistant. So it is all connected. But I think you had said it earlier. It's like teaching the person how to use the sun appropriately.
Dr Michael Twyman:I'm not telling people to go outside 24-7 and bake. It's getting morning light in your eyes. Set your circadian rhythms Ideally expose more skin so that your skin is preconditioned for when UVA and UVB come out later in the day. But the more infrared A you can soak up, the more nitric oxide is going to get liberated from your skin and keep your blood pressure normal, keep your blood flowing like red wine, not so much like ketchup. So it's just teaching people the simple ways to kind of rewild themselves, just get back into nature.
Dr Max Gulhane:Yeah, yeah, I love that. So let's talk about screening and maybe risk stratification, because what type of imaging would you suggest for people at different stages of this heart disease prevention journey?
Dr Michael Twyman:And that's a good point is that I do recommend imaging. I mean, there's a lot of different risk calculators people can use and they're good at a population level, but you really want to know do you have plaque? What do you need to do? So you need to go look at the arteries. So, head to toe, there's different scans you can do. If you've had other scans for other reasons, you can always look at the results and see if they ever mentioned that you have any calcified plaques in the brain or your abdomen. I've seen some ones where people get panorexes of their teeth and they see some plaque in their carotid artery that's calcified. So look at your old imaging if you have access to it. But if you don't have those often, I will start with patients getting a carotid intramedial thickness ultrasound no radiation, takes about five minutes. The scan of the arteries on the side of the neck. It's something that you can repeat generally yearly.
Dr Michael Twyman:You have a baseline and see what has changed. If you're doing things right, things shouldn't change year over year. Ideally you see things getting better. If they already had intimal thickening and you've got it improving. It was Dr Thomas Sunderham in the 1600s. The famous saying a man is as old as his arteries. So if your vascular age is higher than your biologic age, you got a problem. That being said, you know there are other tests. You know you really want to look at your coronary arteries noninvasively.
Dr Michael Twyman:You know, for somebody who's you know, probably around the age of 40, and this is kind of in the primordial, primary prevention a CT-coordinated calcium scan is a good starting point. Often joke it's kind of like a mammogram for the heart it's going to put you in buckets. Are you truly low risk and you have a calcium score of zero? Or do you have a calcium score over 400 and you're high risk? Now it's common people will develop a positive calcium score sometime in their life. But I've seen people in their 80s and the scores have still been zero. But I've seen a 36-year-old with the score nearly 1400.
Dr Michael Twyman:So just looking at somebody from the outside, you have no idea what the coronary arteries are going to look like unless you do one of these tests. But the downside of the calcium score test is that it will not see any of the soft plaque. So if the person has a strong family history of early cardiovascular disease or they have quote scary blood work, then maybe you would add on a CT-coordinated angiogram. It's a little bit more radiation, there's a contrast risk, so you have to have an IV, have normal kidney function and there's a cost risk. It's probably a factor of 10 to 15 times more expensive to do a CT angiogram than it is a calcium score test, but it's a more sensitive test and will tell you with a high degree of certainty how much stenosis you have in your arteries. But it's more going to tell you about the soft versus hard black in your arteries, and so that's a good starting point for most people.
Dr Max Gulhane:It's like do something that looks at your carotid arteries, do something that looks at your coronary arteries. Yeah, and I've talked to radiologists about this problem and in the emerging field, which is something that I'm trying to cultivate, of decentralized radiology, there's a lamentation that all this imaging is being done for CT chests, for abdominal MRI, abdominal CT, and the biggest findings that are relevant to the patient's long-term cardiovascular metabolic health aren't even being reported on, and that is the presence of calcified hard plaque in these arteries. There's an incidental finding that the radiologist might have made a note of it in their head but they don't put it on the report. And if they don't put it on the report, then no one does anything about it and people can go for 10 years, 15 years, and then they wind up in the emergency department and I see them in the emergency room with chest pain and maybe this could have been prevented if the radiologist had made a comment on it 15 years ago.
Dr Michael Twyman:No, that's a very good point and that's something I've been doing for many years is just looking at any old imaging and finding stuff. I'm like did you know that they reported your coronary artery was calcified 10 years ago? I'm like nobody ever told me that. I'm like well, that's not surprising, it's unfortunate, but I was recently at a conference where they were talking about how they're using AI to basically tackle this. One problem is that they're going to take old images and they're going to feed it through the machine and look for these cardiac calcifications and images that weren't designed to look for it. So they're not going to be as precise because they're not gated images, but it's better than nothing and it's already basically free data. It's already been done. So if you can give some information to the patient that, as something that they did five years ago, you might kind of be able to help intervene well before they're having symptoms still.
Dr Max Gulhane:Yeah, exactly, and that's something I've been in discussion with a cardiac radiologist about. So if any radiologists are listening and want to actually start reporting the important metabolic findings, then get in touch with me. But the next question that I have for you, michael, is when? So you mentioned that the calcium score is a great start and it's cheap. In Australia, I believe, it costs about it's about $150 from any kind of radiology practice. You just get a request from your GP and if you want to do a CT coronary angio, that's a bit more involved and what would be the indications for you to step beyond those tests? But even what are the implications of some of the findings of the calcium and the CT coronary angio?
Dr Michael Twyman:So, starting with, what would you normally see is that most general cardiologists are not going to do this type of testing. They're only going to do this testing once you have symptoms and they're going to recommend some type of stress test and stress tests are useful if you're having symptoms. They're going to try to recreate your symptoms in this environment where they're exercising you and see, like, oh, when you have chest pain, it happens when you get to this heart rate and then you have a wall motion abnormality on echo or fusion defect on nuclear imaging. But again, it's kind of a late to the game type of finding so often you know the images that you find on a calcium score, ct angio, you know you're just helping risk stratify that person into buckets.
Dr Michael Twyman:You know, like on the CT angiogram, you know there's a company in the States called Clearly that uses AI and machine learning to quantify the quality of the plaque. That uses AI and machine learning to quantify the quality of the plaque. They have a scoring algorithm that's zero, one, two or three and it's kind of like cancer screening. You know, are you kind of like a local cancer or is it metastatic? So the more plaque you have, the higher cardiovascular events occur, and so those are the people that need much more intensive occur, and so those are the people that need much more intensive pharmaceutical supplement and lifestyle interventions. And so you're often using these tests mainly to risk stratify people like how aggressively am I actually going to treat this person?
Dr Max Gulhane:Because that's such an important point? Because I've seen calcium scores done and patients get referred to a cardiologist and that is a indication, or, dare I say the word, excuse for invasive angiography, stenting and bipolar surgery, maybe in someone that doesn't even have any symptoms. So the question that I want to know, and what you think about, is to what degree is collateral flow, a collateral blood flow formation, play a role and to what degree are we potentially opening people up to over-servicing if we're doing these images?
Dr Michael Twyman:No, and I've definitely seen it both ways, where the calcium score test is kind of an opening to doing more stress testing and invasive testing. But you're wanting to literally just risk stratify the person. Now, on the calcium score test a normal score is zero but approximately 8% of those people with a calcium score of zero they can still have significant plaque in their arteries. It's mostly soft plaque that hasn't yet calcified. So symptoms will always trump what you find on this imaging. So, that being said, on a calcium score test if your score is over 400, that's considered high risk. Over 1,000 is very high risk, high probability one of your three corneal arteries is going to have a moderate to severe amount of stenosis. But highest scores I've ever seen seen one that was over 7,000. The other year Person reported to be asymptomatic and we did a stress test. They had a kind of indeterminate stress test so we ended up sending him for an invasive cath and he had some moderate to severe disease and he ended up getting a coronary intervention and he does report his exercise tolerance is a little bit better with it. So maybe he was a little bit minimizing some of the symptoms and so exercise tolerance improved. Okay, maybe that's a win for that gentleman. But using the calcium score test in people who have no symptoms and it's high, that is somewhat of a gray zone In my practice when I was still doing invasive testing.
Dr Michael Twyman:If the calcium score is over 400, it's reasonable to do a stress test to see can you provoke ischemia at peak activity. But I didn't automatically recommend cath unless people had symptoms. Now if their score is over 1,000, there was kind of a push to kind of like automatically cath people if it's over 1,000. But you can't make somebody who feels normal better by doing something to them. And it was in my experience. Half the time I'd get in there they had no appreciable luminal stenosis. Their arteries look like concrete pipes. They had big fat arteries and the lumen's wide open and people are like how's that possible? Like well, it's Glasgow's principle. Their artery got bigger and the plaque is like an iceberg. Most of the plaque is still on the wall of the artery. They're still very high risk of having cardiovascular events but they're not needing a stent today. They don't need to go off to bypass surgery.
Dr Max Gulhane:I think I want to really impress that point on the listener and really reemphasize it again which is just because someone has had a high calcium score doesn't necessarily mean that the lumen of their coronary arteries is stenosed and therefore the blood flow in those coronary arteries is impaired.
Dr Max Gulhane:And what you've just described and I've heard the same thing which is a patient goes for an invasive angiography which, again for the listeners, is the passage of a wire through the radial artery and then the injection of dye to visualize directly using dye and the openness or the flow in those vessels. So what she found in this particular patient was that there was a massively high calcium store, but exactly the same as what you've mentioned, Michael, which is in pristine flow. So it just shows that the process of plaque deposition was a a what the body's response or a healing process to deal with the, the endothelial damage and the endothelial inflammation dysfunction that had been happened because they'd been again breathing in diesel smoke or having high uh fluctuating blood glucose or running a marathon Maybe they ran 300 miles in a row, but it was the body's response. So I think that point that you made is so important and critical.
Dr Michael Twyman:Yeah, and I was actually just recently at a cardiology conference and there was a debate, you know, between the interventionalists and the kind of more you know, non-invasive guys, and it was really come down to where, like you know, the imaging is important because you know, irrespective of the symptoms, that person's at higher risk of having events. So treat that person more aggressively with lipid lowering therapies, blood pressure medications, if lifestyle alone doesn't get them down. Those are the people you're worried about, the people who are symptomatic. Those are people pretty easy to treat. There's various antigenals you can use and then if the medications don't get them to be controlled, then it's not unreasonable to offer that person a coronary intervention to help them feel better.
Dr Michael Twyman:But I always tell patients like stents are tools. They'll make you feel better sooner than waiting for the medications. But unless you're having a heart attack and the stent is used to stop the heart attack, the stent is not reducing risk of having a heart attack. The stent isn't extending your lifespan. It's spot welding a small area of stenosis in your artery and you still have 60,000 other miles you have to treat hall area of stenosis in your artery and you still have 60,000 other miles you have to treat.
Dr Max Gulhane:Yeah, and the reason is because I think so often when in conventional cardiology, to the man with the hammer, everything looks like a nail and if your job is an interventional cardiologist and you deploy stents into people's arteries all day, I mean you're going to find reasons to do that and there's data that shows that that isn't a benefit in people that don't have symptoms. And yes, if you're having an ST elevation, a myocardial infarction, we rush you to the cath lab and there's a benefit, but not in a patient that you've just described. So talk to this idea of collateral flow. Why are they able to idea of collateral flow? Why are they able to deal with this depositional plaque and maybe even stenosis of their arteries without developing symptoms, and why are others simply not able to cope with that?
Dr Michael Twyman:No, it's a great question and it's. You know, something that even in reverse, you sometimes see, is that you know you do an invasive angiogram in somebody, their three corneal arteries are quote wide open. You're like you're good to go, you don't need a stent, but they're having classic angina. Well, that microvascular disease you know, and so that's something that's been recognized for many years, at least in my practice. And at this big conference they're starting to more and more talk about this microcirculation.
Dr Michael Twyman:But for those patients, if you're developing plaque over time, the body has an amazing ability to make new blood vessels. You make your own bypasses so that hypoxic kind of myelo causes the stem cells to get activated. Hypoxic kind of myelo causes the stem cells to get activated. You start making these bypasses and so oftentimes you can get in there, find that the person has a chronic total occlusion, their artery is 100% blocked and they've had no symptoms and you see bypasses, the arteries kind of help each other out. But the people who do worst are the people who have no collateral flow. It's they had this 30% blockage and then boom, it clots. Now you have 100% blockage. The other artists haven't had the time to build collateral flow or build these natural bypasses and those people tend to do worse at times.
Dr Max Gulhane:Yeah, and that's exactly what, circling back to the beginning of the conversation, which is if there's some certain factors that are causing an acute damage to that endothelium and acute disabling of your endothelial healing process and you get a massive denudation of your glycocalyx and you form a big thrombus and you just clot off, then there's obviously no time to develop collateral flow in that acute setting. The other point that seems reasonable to me is that if you're getting things like regular sunlight, and you're getting especially sunlight on the chest, and you're building nitric oxide directly in those vessels repeatedly, that seems to be like a good strategy for helping encourage angiogenesis or the development of collateral blood flow.
Dr Michael Twyman:No, definitely, and there was a very fascinating trial done a few years ago. It was in Israel. The patients were having ST elevation of MIS. I believe there was only 12 patients in the trial, so a very small kind of like proof of concept trial. But all the patients got standard of care. They got rushed to the cath lab, they all got stented, all the usual medications, but half the group got photomodulation during the cath a day later and three days later, and they didn't directly treat the heart, they treated the patient's tibia. So they were activating mesenchymal stem cells with the light therapy. And so there are protocols where you can either use your shin or you can use your manubrium, your sternum, and activate the stem cells there, and then the stem cells can help activate some of the angiogenesis.
Dr Max Gulhane:Yeah, that's absolutely incredible. I talked to Andrew Latour of Gemba Red, who's a photobiomodulation company, and he's described the same thing, which is this so-called absorble effect, where you can treat one part of your body and have a benefit in a completely different organ. But to me it makes so much sense to use infrared light for acute cardiovascular care, whether that's an AMI or acute pulmonary edema or decompensated heart failure Because if we assume that there is infrared flow potentiating the blood through the cardiovascular system at the microcirculation level, then any bonus to aid in in in um cardiovascular flow is going to be helpful. And whether, yeah, so things like photobiomodulation device, I mean you get zero infrared light in in in the cubicle of the er room correct and yeah, this is probably the whole reason why you know sauna therapy actually has such, you know, compelling data in it.
Dr Michael Twyman:You know, and you know it's a lot of it's been done in japan and like heart failure patients and they're doing, you know, at least four sessions a week. You know, you know in the quantum world that's obviously helping structure the water and so you know you get that, you know going, you get the flow going improving. You know you get all that benefit of, you know, detoxing from heavy metals, sure, but it's probably more. That structuring of the water is probably the main benefit you're getting yeah, that makes sense to me.
Dr Max Gulhane:so say we've got all these people and say we're classifying people at different cardiovascular risk all along the spectrum, and that is from the person with absolutely no disease young guy wants to just optimize his heart health and endothelial health all the way to the gentleman who's had coronary artery bypass grafting and is now getting stable angina. So there's a massive spectrum of patients and people, from the most diseased to the healthiest. But I think the key point is that the behaviors and the lifestyle that we're going to recommend to everyone is actually going to be the same.
Dr Michael Twyman:It's going to be very, very similar. I mean, I often talk about being four lovers. You know, there's nutrition, there's exercise yes, they're important. But the other two that people sometimes don't always dial in is, you know, the stress that people are going to be exposed to. You know, I tell people, you're always going to be exposed to stress, but how do you manage or mitigate the stress, how do you recover?
Dr Michael Twyman:And then the fourth pillar, which is actually probably the base of it, is sleep. I know that I did not sleep well during my medical training, Every third night sleeping in the hospital, working under artificial lights, not knowing any of this stuff that I know now abusing yourself like crazy in your 20s. But once I figured out this stuff, I stepped out of the hospital, stopped doing the damage and didn't take any major hits by doing that. But it's telling people that you have to figure out how to sleep as best as you can, because if you don't sleep well, you will not age well, and it starts with your light environments and the timing that your food comes in.
Dr Max Gulhane:Yeah, and that's something that I've talked about at length, and everyone who's followed the podcast is really going to be kind of up to speed with those type of interventions. Maybe we can start now by contrasting this decentralized, holistic approach that you and I are advocates of, compared to this conventional approach, because to me there's radically different strategies for this primordial primary and secondary prevention of heart disease if you're a mainstream trained cardiologist or family medicine doctor, compared to someone like you or I.
Dr Michael Twyman:Yeah, and this is where I sometimes give a lot of props to my conventional colleagues. It's a hard road to get to where they're at. It's 10 years of training to be a cardiologist. You know it's really hard to take all that knowledge and run out to practice and then say like I'm going to abandon all this and I'm going to try to do it a different way. That's it's going to be a kind of a gradual process. You know I often joke that it's like the matrix. You know you eventually step out of the matrix and you don't necessarily want to go back in, but you know that how you would need to if you went back in. So there's always going to be a place for conventional cardiologists Until the world wakes up and does all these lifestyle things that we're talking about.
Dr Michael Twyman:People can keep having cardiac events that need hospitals. Hopefully it decreases in our lifespan, but I'm not holding my breath for that just yet. But the way to think about it is that, like you know, you just want somebody who is curious. You know, because if they're not curious they're not going to progress in their learning. You know a lot of stuff I've learned in my training. I no longer recommend or do, or I've heavily modified it. I don't abandon it all.
Dr Michael Twyman:Use the tool that works. You know wise healer uses the most effective tool with the least amount of side effects. Sometimes that is conventional medications, and I talked about the pre-op. I guess you know sometimes you need to be able to reverse engineer. If you don't do these things, you're going to end up in cardiogenic shock in the ICU. These are the things that can mitigate that risk. But the quantum world? It's fascinating. But one beef I have with the quantum world is that sunlight and grounding is not going to fix everything. It's a good start for many, many things, but sometimes you have to use more aggressive therapies.
Dr Max Gulhane:Yeah, and people on various degrees of bought in to lifestyle. And I like to say and a mentor of mine you know he taught me he said it only works if the patient does it and it only works if you do it. So, and you can recommend these gold standard lifestyle interventions to people, but if they don't do it, then they're going to be at high risk and you need to bring other options onto the table. So I mean, I'm completely on board with what you said, michael, and I agree completely and I see myself as same as you, I'm guessing is that I'm just here to provide options for my patients and it's up to everyone what they want to take and as long as they have informed, explained, consent about the risks and benefits of every option, whether that's medication or lifestyle, then that that's my job done oh, very much.
Dr Michael Twyman:So I mean my whole job now is just as an educator. You know patients come in, you know I basically you know, interpret any of their prior testing from through a different lens, talk about you know what their arteries are doing right now and do the advanced blood work and then have a conversation. Okay, like this is your risk right now. These are your options.
Dr Max Gulhane:What risk do you feel comfortable taking at this point? Yeah, and it's such a holistic process that we have to go through and, as we mentioned, it starts when we're very young and there's all these insults in our environment that are contributing to potentially building our plaque and damaging our blood vessels. So it's an ongoing battle for everyone and it's understandable that some people go through a rougher time where they can't prioritize their health or they have a stressful period and we didn't mention the mechanism, but Dr Malcolm Kendrick talks about it a lot in his book the Clot Thickens, which is high level, is actually going to impair the function of the vascular endothelial progenitor cells. So your ability to repair glycocalyx damage or endothelial damage is stopped or slowed or delayed or retarded when you're acutely stressed, whether that's someone dying, a family member passes away, or you're about to get fired for your job, or someone breaks up with you, et cetera, et cetera. So yeah, it's a process.
Dr Michael Twyman:No, and that's just a quick side note, that's stress-induced cardiomyopathy, that's Takotsubo syndrome. I definitely saw many cases of that in my career. A patient shows up after a stressful event. The EKG looks like a heart attack. They're having all the same symptoms of the heart attack chest pain radiating up to the neck or back, rushing to the cath lab. Their coronary arteries are wide open. You do a left ventricular gram. The base of the heart barely moves. The apex is pounding away. It's a stress-induced cardiomyopathy because that extremely high cortisol and adrenaline vasoconstricts all the microcirculation and then once the acute stressor is kind of mitigated, often use some beta blockers to kind of knock down some of the adrenaline. That left ventricular function improves back to normal. So if it can happen acutely, it definitely happens chronically for patients as well.
Dr Max Gulhane:Yeah, and what is going to drive up this cortisol level? Maybe subclinically over a long period of time? And that is blue light and being exposed to artificial light at night and dysregulating your cortisol melatonin curve. That is inherent or is critical in your circadian rhythm. So that's another mechanism that the light stress could contribute to the development of heart disease. But let's talk about. Because we're on the topic of conventional treatments, let's talk about a conventional doctor wants to reduce someone's risk of heart disease and look, let's say that they've addressed these common traditional risk factors. Addressed these common traditional risk factors, and by that I mean blood pressure, diabetes or insulin resistance. Obviously we can't do too much about family history. You know smoking. They've all addressed those. So we got to this last one, which is lipid level and cholesterol level. So what is their approach and how do you agree or disagree with them?
Dr Michael Twyman:So let's say, in the conventional world you know they're going to be thinking about anti-pliotherapy, so aspirin, 81 milligrams for the majority blood pressure control, you know, ideally less than 120 over 80. And they will often use, you know, combination of diuretics, beta blockers, calcium channel blockers, ACE inhibitors or anti-intensive receptor blockers. Of those I honestly prefer that they would use the ACE ARBs or the calcium channel blockers because those actually lower central aortic blood pressure. The diuretics and the beta blockers make your blood pressure look pretty when they check your arm but if you actually put a catheter back up in their heart their pressures are not necessarily controlled with those medicines. So I try to limit those medicines to like third or fourth line.
Dr Michael Twyman:And then they're going to use generally a high dose statin, like it's going to be Lipitor 40, 80. It's going to be Crestor 20 or 40. And those are the options. You know I tend to use a lot more low-dose statin therapy if I'm going to use it and we use the advanced testing to kind of you know, kind of guide to say like, okay, well, is this person likely a hyperproducer of sterols? Or if they're a hyperabsorber of sterols, well, maybe a zetamide is a better option for this person. So it's mostly, you know, statin, aspirin and some type of blood pressure agent is kind of the standard to care. But those are good starting points but they don't really improve nitric oxide availability in the majority.
Dr Max Gulhane:Yeah, and a quick mention about those blood pressure lowering medications. I've just released a course called the Solar Calus course and I'm talking about medications that can increase our photosensitivity or likelihood of sunburning. And this is important because if we're getting out into full spectrum sunlight that includes ultraviolet light then we don't want to be taking anything that's going to make us sunburn. And it happens that hydrochlorothiazide, thiazide diuretics, fruzomide, as well as medications like statins and atorvastatin and amiodarone are all responsible for increasing our photosensitivity. So it's a little bit of a catch-22 when we've got a situation where we're trying to lower someone's blood pressure by giving them a thiazide diuretic that's perhaps precluding them from getting full spectrum sunlight, when the actual solution to their problem is UVA light to promote the nitric oxide, to essentially do it in nature's way to reduce their blood pressure in Mother Nature's way.
Dr Michael Twyman:Right, yeah, the pharmaceutical ways of doing things. They work, but do you have to pull them out all the time? No, I mean, somebody runs into your office and their blood pressure is 200 over 110. Well, you got to throw the kitchen sink at them while you're trying to figure out. Why are they so dysregulated. But one of my favorite things to do is deprescribe medications. Patients come in with a whole host of meds. You start working on these lifestyle things. You just start trying to peel all these medications back whenever you can.
Dr Max Gulhane:So I agree with that. That's very satisfying, but let's talk about this primary prevention in someone who hasn't had a heart attack and all they've got essentially wrong is a high APOB or LDL cholesterol, and they don't have atherogenic dyslipidemia, which is a medical speak for the high risk panel, which also includes a low HDL and a high triglyceride. So let's just say that they have a high LDL-ApoB, which is typical or possible on a low-carb or carnivore diet not in everyone, but in some and their conventional doctor prescribes them a torvastatin. What's your opinion on that?
Dr Michael Twyman:I mean I've seen a lot of those cases where patients have had relatively normal lipid panels. They go carnivore, keto and they have these severe dysregulated lipid panels. And, yes, generally it is that they do not have high triglycerides or low HDL in the panel. But that doesn't mean that those particles are not necessarily atherogenic. I've had some patients like you got to show me that you have healthy nitric oxide levels, you don't have vascular inflammation, and a calcium score test is a good point. But if you want a bonus, do a CT angio and show me that you don't have a lot of salt plaque building up.
Dr Michael Twyman:But not everybody who eats those diets has that type of lipid response. You know it's really maybe about 20% of the population has a pretty significant response to higher saturated fat in their diet. Sometimes in these patients if they cut their saturated fat to less than 8% of their total calories, eat more fish, more olive oil, they may not have significant bumps in their ApoB particles. But in my practice I typically will use the Boston Heart Lab panel to look at not only their ApoE status, because it's the ApoE4s that tend to have this happen more often, but the people who are hyperabsorbers of sterols, especially the beta-cidesterol. They tend to have this pattern more often and the stans might work. But if the person is not willing to change their diet, then azadamide would work better, prevent the sterols from being ripped away from the gut and you generally get a significant reduction in their lipoprotein burden then.
Dr Max Gulhane:Yeah, that's an interesting point that you made and I think it's relevant because people sometimes go on a carnivore type diet and they have this high ApoB or LDL and they're almost, you know, kind of say, okay, I'm at low risk because I'm eating carnivore, and my, my perspective is that you're addressing perhaps one of the contributors to endothelial damage and and poor vascular health, and that is insulin resistance and perhaps fluctuating blood glucose. But if you're getting blue light, if you're blue light toxic, if you're not grounding, um, if you're getting blue light, if you're blue light toxic, if you're not grounding, if you're doing other things that are disrupting your structured water and you have endothelial dysfunction, which is what we've just talked about, then there's no protection against that sudden clotting event that can occur and therefore your risk of AMI is not zero.
Dr Michael Twyman:Right and I think that's a nuanced approach to every patient. It's that you know, can carnivore make people's gut health better and their joints feel better? Of course it is. But you know you still have to look at like, what are the arteries doing with this lipoprotein burden? You know you're mimicking familial hyperlipidemia. Now there are people with FH who don't go on to have severe disease and if you have a calcium square of zero and you've had FH, good for you. That means whatever you're doing means you have a healthy glycocalyx. But not everybody who's carnivore is necessarily going to be that same pattern.
Dr Max Gulhane:Yeah, so it really seems like we have to focus on. Yeah, so it really seems like we have to focus on the endothelial health first and, as you said I really like your framing is that you have to the patient has to prove to you that their blood vessels are healthy in order to be able to tolerate or be able to deal with that perhaps higher lipoprotein burden and that not necessarily contribute to the deposition of plaque. I'm really thinking about a lot lately, because there's almost two armed camps that are polarizingly assembling with weapons raised on either side. On one side is the strict carnivore. Any type of raised ApoB isn't an issue at all.
Dr Max Gulhane:Obviously, the troglodytes rides are low and the HDL is reasonable, reasonable. But then the opposite side of the picture is guys like dr muhammad alo, who has made I mean, some of his calls have been a little bit, have been well, they've been outlandish and just patently false, but he's really advocating for statin therapy for basically anyone who has an apo b above this arbitrary threshold, which is, um, you know. So I'm just wondering yeah, do you have any more thoughts on those two kind of polarizing opinions and how to split the middle the most effectively?
Dr Michael Twyman:You know you're very much right. You know it is polarizing. It's that you know the patient is just trying to find out, like, what do they need to do for themselves? And you know, like Stans, you know they're tools, they should not be in the water where we're all taking them and they're not horrible for everybody. You know I often get the concerns, you know, like, oh, it's a mitochondrial toxin, it's going to give me diabetes, like it doesn't take somebody who's not insulin resistant and make them frank, diabetic. You know, is it mitochondrial toxin? A little bit, but it's probably taking out the weak mitochondria so that you replace them with better.
Dr Michael Twyman:And it's the. You know it's risk versus reward. You know, nothing is risk-free for the most part, you know, but in the right selective population. You know statins can be the right tool for that person. But the other side of the equation, you know, having an AOB of 20, that is not evolutionarily feasible for everybody. Are there people that have low APOBs? Yeah, my own father has an APOB of 43 with no meds, but he has a loss of function PCSK9 gene. His grandmother had that. She lived to 106. So okay, but not everybody has that pattern.
Dr Michael Twyman:Do we need to use three pharmaceutical agents to drive everybody down there? I don't think so. It's never been studied or shown that that's really where we need to be targeting people for. So I just really think that we've had a great conversation. I was like what is the glycocalyx doing? How much can you support the structured water in the body? I often talk about being like it's a force field. If your force field's up, it's less likely that these lipoproteins are kind of crashing the gates and getting through. It's possible, but just not as likely.
Dr Max Gulhane:Yeah, no, that's great advice. I mean, I've delved into the statin as mitochondrial toxin issue as well, and there's a particular paper that I have in mind I think it was published in 2017. And it details there's a number of mechanisms biochemically, and obviously what is happening at the bench level or what we find in the lab is not always translatable in vivo, but there was mechanisms involving reduction of mitochondrial membrane potential, there was acceleration of apoptosis, there's a range of mechanisms. So to me, uh, it doesn't seem like a drug that we need to be. We should be throwing around willy-nilly, and the rhetoric that you hear out of so many conventional, mainstream, uh, centralized cardiologists is that this is a drug without side effects, and that is the impression that you get when you hear some of their rhetoric.
Dr Michael Twyman:Yeah, I mean they definitely have side effects and you know we talked about some of them earlier. I mean the musculoskeletal ones are real and the trials, you know it's a few percentage points but in the real world, you know a quarter of the patients might have some symptoms who really queered them hard enough. But I do a pretty comprehensive screening in some way before I'm going to recommend these things. I want to know what their ApoE genotype is. If they're an ApoE4, I'm probably not going to push it very hard on them. What is their vitamin D status?
Dr Michael Twyman:If you're vitamin D deficient, you pretty much always get myelosis on statins. If your CoQ10 is low at baseline, well, you're just going to make it worse adding the statin on board. If you're hypothyroid, much more likely to have muscle symptoms, and then in some instances that people have already tried them and had a lot of issues, you know. Then I'll do some genetics and there's a gene called SLCL1B1. If you have an abnormal copy of that, you know you're two, three, four times more likely to have muscle symptoms with statin. So no, they're not risk-free. But there's patients that you can select that generally are going to tolerate them. Well, and if they can't tolerate them, or they just only say like hey, doc, I just don't want to take this.
Dr Max Gulhane:Okay, there's bimedoc acid, there's red yeast rice, there's bergamot, there's berberine there's PCS9 inhibitors, zetamide, there's a whole host of other options if you're really going to go down the route of trying to help somebody lower their lipoproteins. Yeah, and I think the one mechanism we haven't mentioned in terms of lipid lowering is the sun, and there are multiple randomized control trials showing that sunlight, uv light, lowers lipid profiles, lowers, ldl lowers, apob lowers, I believe triglycerides too. You might ask okay, well, what is the effect size? And maybe the effect size isn't as dramatic as rapidly changing the diet to a low-carb or rapidly doing those, but there is observational and interventional evidence that sunlight reduces ApoB. Can you talk to this precaution of these E4 carriers and why you might not prescribe them as statin?
Dr Michael Twyman:So when you have an ApoE4 allele, it's going to affect your LDL receptors. Your LDL receptors are going to be not as plentiful and they're probably not going to be as functioning. So your LDL receptors stand on the outside of the liver and they grab these APB particles as they go by and pull them into the liver. But the APB4 carriers they're at increased risk of diabetes. They're at increased risk of Alzheimer's, which is likely a form of insulin resistance in the brain coupled with subclinical or I should say more microvascular disease. So the same things that are causing plaque in the coronary arteries are the same thing that do it in the brain and then when you hit enough neurons, then they're going to call you Alzheimer's. But the APU4 carriers they just tend to have more side effects with the high-dose statin. So often I'll just use low-dose or sometimes even intermittent-dosed resuvastatin in those people.
Dr Max Gulhane:Yeah, and look, there's so many other areas. I believe Dr Malcolm Kendrick wrote a really good article in 2018 that's worth reading. That was looking at the odds ratio of the development of Lou Gehrig's disease, which is essentially, you lose your motor neurons basically voluntary muscle contractions and the odds ratio for statin use is enormous and, again, it's a rare disease. But if you go on from eight cases per 100,000 to 40 cases per 100,000, that's a significant relative increase and those are pretty compellingly linked to to statin usage.
Dr Michael Twyman:So I don't know if you've encountered that or come or have an opinion on that I haven't seen that uh, particular study, but you know again, it's, you know nothing's risk-free and so it's like you know if you've had you know your grandmother die at you know 59 and you're 40 and you know stan's been recommended, maybe the you know 59 and you're 40 and you know Stan's been recommended, maybe then you know your risk of atherosclerosis taking you out is higher than a neurological. But if you're, you know a 25-year-old woman with, quote, high cholesterol, yeah, stan's probably not the right tool for that person.
Dr Max Gulhane:Yeah, look, it's such a good advice and it's really hammering home the point that this needs to be an individual decision and so many, unfortunately, the way that there's not a lot of access to for people to get a nuanced opinion like by a practitioner like yourself, michael, so that people seem to be doing a lot of self-decision, self-diagnosing and self-treating based on what they listen on the internet and really they need someone to take into account all their risk factors, their endothelial health and everything that we've talked about to make an individualized opinion. It's hard, when this decentralized movement is growing and there's so much contrasting and conflicting information, for people to make the right decision.
Dr Michael Twyman:No, and I appreciate the opportunity to come here and chat with you and your audience. I mean, I think people probably should go back and listen to this one. You know once or twice and you know they'll hear a lot of the same themes. You know we're talking about nitric oxide, endothelial function, the glycocalyx, vascular inflammation. You know it's all you know connected. You know I tell patients, you know sometimes these words are complicated, but when you actually sit down and think about what you need to do on a day-to-day basis to have healthy arteries, it's really not that hard. It's really just. Can you keep nitric oxide levels high? Can you keep inflammation low? And if you need to modulate lipoproteins, figure out which best lifestyle supplement medication you're going to be able to use to modulate the lipoproteins in.
Dr Max Gulhane:Yeah, great advice. Well, thank you so much, michael, for coming on. Do you have any parting thoughts that you want to share with the listeners, or any topics or questions? I didn't ask you.
Dr Michael Twyman:No, I just often tell patients that you do have to be your own doctor, and your doctor is supposed to be your guide. Be your own doctor and your doctor, you know is supposed to be your guide. You know your health is in your own hands and you know your lifestyle determines about 80 to 90% of what's going to happen with you. So in your mind, just try to set up. You know what an optimal day is for you and try to win that day every day.
Dr Michael Twyman:You know, it should start with seeing morning light. It should be including some amount of grounding outside. Ideally, do some stress management and then highly prioritize your sleep. You should be sleeping seven and a half eight hours every night and feeling very well rested. If you're not sleeping well, start there.
Dr Max Gulhane:Yeah, fantastic advice, michael Twyman, thank you so much for coming on the Regenerative Health Podcast.
Dr Michael Twyman:You're very welcome, thank you.
Dr Max Gulhane:And where can people find you, follow you, even employ your services if they're interested?
Dr Michael Twyman:So my practice at Polycardiology is in St Louis, missouri. We are still accepting patients. Our patients always come to us initially for their first visit. We do a comprehensive head-to-toe cardiovascular assessment. I call them toys. We have all the toys in the office to test your endothelial function, your vascular health, and then all follow visits can be done remotely. I'm relatively active on social media on Instagram.
Dr Michael Twyman:I have an IG Live every Monday night 6 pm Central Time. Right now I'm kind of doing more just an Ask Me Anything type of format. So potential patients or just people who are interested in following me. They submit questions ahead of time and some of the questions are similar to tonight about lipoproteins or grounding or sauna or something along those lines that benefit other people. And then my website lines that benefit other people. And then my website, drdwimancom. You have some links to my other podcast and people are interested in following out where else I'm online. It'll be on drdwimancom.
Dr Max Gulhane:Great, fantastic. I'll include all that information so the listeners can have ready Sure, thank you you.