How to Prevent Heart Disease with Mitochondria, Muscle, and the Endothelial Glycocalyx | Dr. Michael Twyman

Dr. Gabrielle Lyon: 00:00

Most people think heart disease starts with a bad cholesterol number, but the truth the damage often starts decades earlier, before you feel it, before you see it, and before your doctor catches it. And once that early damage begins, it's silent, but it's not inevitable. You just need to know where to look and what to do next. Most cardiologists don't talk about nitric oxide. They don't measure VO2Max. They don't ask about grip strength or muscle mass, but they should, because muscle is one of the most powerful protectors of your heart and mitochondrial health that might be the key to your entire cardiovascular future. In today's episode, you'll learn why standard cholesterol labs are incomplete, how the loss of skeletal muscle speeds up heart disease, what biomarkers matter more than LDL, and why diagnostics not guesswork, are the future of prevention. This is the medicine of what's possible, and my guest today is one of the few cardiologists practicing it. Dr. Michael Twyman, expert in mitochondrial optimization, arterial imaging and a bio individual muscle centric prevention approach. So if you could prevent a heart attack before it starts, wouldn't you want to know how? Let's talk about what it really takes to become heart attack proof with Dr. Michael Twyman.

Dr. Gabrielle Lyon: 01:43

Dr. Mike Twyman, welcome to the show. Thank you for having me back. Has it been 40 seconds yet?

Dr. Michael Twyman: 01:54

Not yet.

Dr. Gabrielle Lyon: 01:54

Okay? Well, as soon as it reaches 40 seconds, someone in the US had a heart attack, and every 33 seconds, someone dies of cardiovascular disease.

Dr. Michael Twyman: 02:05

It's a horrible stat.

Dr. Gabrielle Lyon: 02:07

You know? It makes me think, how have we not gotten better at treating that?

Dr. Michael Twyman: 02:15

I think we're getting there, but it's still the number one killer. You know, we did this episode three years ago. Stats haven't changed that much since then, and I think we're gonna dive into a lot of the topics today that I think might be beneficial to really help people become more heart attack proof.

Dr. Gabrielle Lyon: 02:30

Can someone actually die of a broken heart?

Dr. Michael Twyman: 02:33

Absolutely, that's known as Takasubo Syndrome, or Broken Heart Syndrome. Takotsubo is a Japanese kind of fishing vessel, fishing pot that they catch octopus in, and that's what the left ventricle looks like when people have this broken heart syndrome. So they present after an emotional event, you know, somebody in the family dies, they're in a car accident. They smoke cocaine. Something happens where their sympathetic drive is very high, and they present to the hospital, like if they're having a heart attack, and we would rush them off to the cath lab find out that they didn't have any significant blockages in the arteries. And then when we did the left ventricular gram, the heart wasn't pumping very well, and so kind of supportive care after a couple days, usually the heart function returns to normal, but it's a high risk of sudden cardiac death.

Dr. Gabrielle Lyon: 03:15

When you have that is it mostly women or men?

Dr. Michael Twyman: 03:19

Generally women, older women, particularly.

Dr. Gabrielle Lyon: 03:21

We hear the term heart disease all the time. But what is heart disease?

Dr. Michael Twyman: 03:28

That's the umbrella term. I mean, there's coronary heart disease, there's heart failure, there's valvular heart disease. So you really have to do defined terms. But vascular disease, 60,000 miles of blood vessels, you got to go looking where the disease is at.

Dr. Gabrielle Lyon: 03:46

You know, as I was preparing for this episode, cardiovascular disease, as you had mentioned, is still so prevalent and it's not getting better, which is surprising, and it makes me think, Okay, what do we know that drives heart disease? And again, it is an umbrella term, so perhaps we start with, I don't know, take your pick, stroke.

Dr. Michael Twyman: 04:13

So stroke can be either ischemic or thromboembolic. So ischemic means there's not blood flow coming to the tissue, and without oxygen nutrients coming to the tissue, starts to die. An thrombolic event is where more of a blood clot forms. Many times in heart patients, it's due to atrial fibrillation, a clot forms in their left atria. That clot breaks free, gets lodged in the brain and steals blood flow from the territory downstream, and that tissue will die unless it's revascularized. So stroke, obviously, is probably more scary to many people because heart attacks, if you survive to get to the cath lab, you usually do pretty well, but a stroke can be debilitating for the rest of your life. But the same risk factors for heart disease are the same things that contribute to stroke in most people. And what are those things? I mean, it's the common ones. It's smoking, it's high blood pressure, it's diabetes, high lipids. If. Physical inactivity. Those are probably the top five, but there may be 395, other things that can really damage your arteries.

Dr. Gabrielle Lyon: 05:07

Do we know, if we take smoking out of it, do we know what would be the biggest contributor of heart disease?

Dr. Michael Twyman: 05:14

It's probably pretty close between dyslipidemia and high blood pressure. You know, lipids gets a lot of the headlines, you know, because there's a lot of dietary intervention. Some people can do that make their lipids change. But blood pressure is really that silent killer. You don't feel it often. You know, if you're starting to feel your blood pressure, it's pretty bad now, usually pretty close to having a stroke or going blind. So it's really called the silent killer for a reason. Your organs are getting pounded with this high pressure for years and just started to age faster than they should.

Dr. Gabrielle Lyon: 05:43

How would someone know that? Do you feel heart disease?

Dr. Michael Twyman: 05:48

Generally? No. I mean, the unfortunate fact is that when people have heart attacks, that's often the first symptom that they had heart disease. If you're having chest pain, tightness in your chest with exercise severe, shortness of breath or exercise intolerance, those are often signs that you're developing severe atherosclerosis in your coronary arteries, the arteries that provide the nutrients to the heart, but typically you're not going to have that sensation until your arteries are blocked 70 to 80% with plaque. So most people have no symptoms until they're pretty late to the game.

Dr. Gabrielle Lyon: 06:19

You know, Matt, my producer and wing man over there, we were talking about exercise, and then we were talking about obesity and heart disease. And Matt was saying, you know, if someone is struggling with obesity, they have a much bigger body mass and the heart has to work so much harder.When you add in exercise. Is that safe? How do we begin to think about introducing exercise without overloading the heart?

Dr. Gabrielle Lyon: 06:52

What would be a safe way to incorporate exercise? Someone is listening to this. Maybe they have seen a cardiologist. Maybe they haven't. Is it safe to start with cardiovascular activity? Is it really based on the pace or the heart rate, or would it be better to lift weights? Is there some kind of standard?

Dr. Michael Twyman: 06:52

I would say it's probably a combination of kind of perceived exertion. You know, there's the Borg exertion scale, you know, 1010, like you're only able to do this for a few more seconds, you know, the Tiger's chasing you. Or is this a pace you could do it all day long if you had to. But when you start kind of losing your breath, that's when you start getting start getting into probably 70% or so of your maximal heart rate when you really can't, you know, maintain it much longer if you kept going higher and higher than that. So if you get to the point where you have a little bit mild breathlessness, probably okay, but if it's severe, or you're getting tight in the chest, you got to really back it off and get that worked up first.

Dr. Michael Twyman: 06:52

I mean, used to be about 50% of people had heart attacks. You know, that was their first sign, and they didn't make it to the cath lab. So, yeah, higher percentage than should be.

Dr. Michael Twyman: 06:52

It's a great question, and if somebody has truly been sedentary for many years, oftentimes, they probably should consider a cardiac evaluation to make sure that they're gonna be safe enough to really push it hard with exercise. You know, if they're doing body weight exercises or walking, I'm not really concerned for those people. But if they're saying, hey, I really want to get into HIIT training, I really want to get into heavy lifting. Okay, show me that your heart, cardiovascular system can tolerate that, and then maybe as simple as just, you know, getting an evaluation. Okay, what is this person's blood pressure? Maybe they do a, you know, CD, coronary calcium score, like, do they have heart plaque in their heart? Block in their arteries already? And then for some people, you would actually consider doing a stress test, and stress tests are good tests if people are having symptoms, as said before, somebody has a 70% blockage in the arteries, you're usually able to pick that up with a stress test. But stress tests are no guarantee that you're at risk for a heart attack. If you pass the stress test, you can still have a heart attack later that day, but they can give somebody an idea of their exercise capacity. So put them on a treadmill. It's often it's gonna be the Bruce Protocol, or every three minutes, treadmill goes a little bit higher and a little bit faster, and you push them until they say, I can't do this anymore, or you see some EKG change say, Hey, stop. But if they can't go seven minutes on that stress test machine, they have pretty low functional capacity, and they're gonna have to work out from there. But you're just making sure you're not you're just making sure you're not seeing some high risk findings while they exercise.

Dr. Michael Twyman: 06:53

Your question about the ER, I mean, there's like, over 8 million presentations in the ER a year for chest pain, and you got to rule out the bad actors. Is it a heart attack? Is that a blood clot in your lungs? A pulmonary embolism is an aortic aneurysm where your arteries are tearing. Isa pneumothorax, but three times out of four, it's not a heart attack. When people have chest pain coming to the arm, and there's a lot of dollars spent working these people up. But if you're having severe symptoms where. Know, you feel like you have impinging doom. You feelthat there's an elephant on your chest. You absolutely can't breathe. You know, if that doesn't go away, in here a few seconds, you got to go in and get it checked out, make sure it's not you know, ST elevation, MI, where you've ruptured a plaque in your coronary artery. And those can often be fatal unless you're revascularized, but if you've not having symptoms, that's probably the better questions. Who needs to be screened?

Dr. Gabrielle Lyon: 07:20

When should someone go see a doctor?

Dr. Michael Twyman: 07:26

And when would someone think to go to the emergency room? Right? Because, if heart disease and heart attacks are really as robust and prevalent as we believe that they are, it seems as if they can be fatal. How many heart attacks are fatal?

Dr. Gabrielle Lyon: 10:22

And who would you say? Who needs to be screened?

Dr. Michael Twyman: 10:25

Essentially, everybody, everybody has a heart. It just, just what age and what test should you be really considering for those people, you know, people have very strong family histories. My family included, you know, my grandmother on my mom's side, started having cardiac events in her 40s, had ultimately bypass surgery, strokes. Had peripheral arterial disease revascularization. She died at 63 from a stroke, way too young. My mom, she has a very high risk calcium score, but no symptoms, well managed at this point. So people have strong family histories. Really should get checked out earlier, probably under 40. I used to think 40 is kind of the starting point for many people, but I've seen more and more people in their 30s have very high risk calcium scores the past few years.

Dr. Gabrielle Lyon: 11:05

And can you explain what a calcium score is, and what does that mean to be high risk?

Dr. Michael Twyman: 11:10

So you have 60,000 miles of arteries. The coronary arteries provide the nutrients to the heart tissue themselves. There's a test called a CT coronary calcium score. It's a low dose radiation scan that looks at the coronary arteries, and if there's calcium in the walls of the arteries, calcium is supposed to be in your bones and teeth. If you have calcium in your artery walls, then that indicates that there's hard plaque in your arteries. The higher the calcium score, the higher the risk. So as you live your life, you know you can have a calcium score of zero. And I've seen people in their 80s with scores of zero. I've seen a gentleman who's 36 years old who had a score of over 1400 that's extremely high for somebody at any age. But the general cutoffs are, you know, over 400 on a calcium score is high risk. Over 1000 is very high risk. And I always ask, what's the highest score I've ever seen? 7770 was highest score I've ever seen.

Dr. Gabrielle Lyon: 11:58

You don't say, yeah, that is really, really high the calcium. Where does the calcium come from? Is it dietary calcium that then gets deposited, or is it damage that then creates a cascade where calcium is then deposited in these arteries?

Dr. Michael Twyman: 12:18

It's kind of a in game where the body's trying to repair the damage to the artery. So on the top layer of the artery, there's something called the glycocalyx. It's a protective gel coating. Think of a fish coming out of water that's slimy. That's kind of what your arteries are covered in. It's a carbohydrate gel coat. Underneath that's the endothelium, one cell thick. If you took out all your endothelium, which would be very hard to do, be about the surface area of six tennis courts, and those are kind of like the protective barriers to the lining underneath, called the intima. Once things start getting to deposit in the intima, then you're off to the races. Developing plaque in the arteries, and the body's repair mechanisms will include depositing smooth muscle into the arteries and eventually calcium. Think of it as like just forming a bone to kind of solidify that plaque to prevent it from rupturing.

Dr. Gabrielle Lyon: 13:03

Hmm, you know, it makes me think the vasculature of the heart has a mechanism if there's damage and that's calcification, I don't know what that mechanism would look like in skeletalmuscle. You know, I mean, because it seems like the body has these very interesting processesto protect itself. And the calcium deposit isn't. It's not the cause. It's, it's the response to whatever's happening, right? It's the scar, essentially, yeah, you know, and in the brain there's tau proteins. I it just makes me think, what is that like in, skeletal muscle? I again, I don't know, but it's, it's just, it's something to think about. How long have you been practicing cardiologist?

Dr. Michael Twyman: 13:56

I finished my fellowship in 2012.

Dr. Gabrielle Lyon: 13:58

Okay, so that's a while. And you did your fellowship in preventive cardiology.

Dr. Michael Twyman: 14:03

The fellowship was in general cardiology. I graduated and was an invasive cardiologist for many years. So I was doing heart procedures in the cath lab, you know, doing angiograms to determine how much blockage people had in their arteries. But eventually got more interested in the preventative side of things.

Dr. Gabrielle Lyon: 14:19

Now, by the way, you are wearing blue. Would those be blue, light black and glasses?

Dr. Michael Twyman: 14:26

They are.

Dr. Gabrielle Lyon: 14:26

Now, this is a very different version, if you guys do not know Dr Michael Twyman, who, again, is my cardiologist, and it is, is the guy that we send everybody to since I've known you, which How long have I known you?

Dr. Michael Twyman: 14:37

Now, think it was around 2019.

Dr. Gabrielle Lyon: 14:40

Okay, I have never seen you without those orange lens glasses

Dr. Michael Twyman: 14:46

Unless I'm outside, I usually have them on. Why? Helps with my circadian rhythms. Helps with my sleep. So sleeps very important.

Dr. Gabrielle Lyon: 14:53

No, don't know about that. Hard pass on that one. But do you wear it for? Circadian biology, or does it affect Do you think it affects cardiovascular disease?

Dr. Michael Twyman: 15:06

I think it does. I think it helps, mainly by optimizing your circadian rhythm so that you're able to sleep better. And when you sleep is when you repair your mitochondria. And I've had a, you know, sleep tracker for at least nine years, and I've just noticed my data would always be better when I would do this. And the main thing is, you know, you're evolved to be under full spectrum light. So we evolved to be outside and sunlight. We were never evolved to be in front of artificial light that tells our body it's different times a day than it is. So I'm always just trying to let my body know, okay, it's daytime versus it's about to be evening. It's evening time. And these daylight glasses just help my body stay in that kind of rhythm.

Dr. Gabrielle Lyon: 15:45

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Dr. Gabrielle Lyon: 17:12

Talk to me about red light therapy and photo biomodulation.

Dr. Michael Twyman: 17:17

So photo biomodulation is using light therapy to change your biology. The target of red light therapy is the mitochondria, and there's various devices, but skin contact is better, because the major issue with light therapy is the acronym R-A-T-S. Light Reflects bounces off the skin, so red light, 60% of it just bounces off the lights Absorbed, the lights Transmitted, which with red light therapy, it's not going all the way through. It's not an x ray. Or the light Scattered, the light comes in, bounces around and maybe gets in the mitochondria, or maybe it bounces and goes back out. So you want to try to maximize how much lights coming in. So ideally, the device is on the skin or as close as possible, is recommended by the manufacturer. But once the light comes into the tissues, the main location where it's working is the mitochondria. The mitochondria absorb the red infrared light cytochrome c oxidase, for the geeks out there, and that does a couple of things. It releases nitric oxide from the mitochondria. It increases ATP, which is an energy currency in the mitochondria, and it decreases reactive oxygen species, and has, you know, multiple 1000s of studies. Most of it's going to be based off of, you know, musculoskeletal injuries and repair, but it helps lower pain, inflammation, decrease the swelling, helps tissue regrow.

Dr. Gabrielle Lyon: 18:33

Wait, it helps tissue so hold on. We gotta, we gotta, we gotta rewind on this photo, biomodulation, red light therapy, but it has to be on the skin, like those masks, because I sit in front of panels all the time.

Dr. Michael Twyman: 18:47

So most the trials are using laser technology and then later led but that's the challenge is. How do you know what dose you're actually delivering? And that's what's challenging with I call it the wild west the red light companies right now is because there's a lot of claims out there what their devices can do, but you need to know a few things. You need to know the wavelengths, what color of light is coming off of the device. That should probably be some form of red and infrared.

Dr. Gabrielle Lyon: 19:12

What are the wavelengths that you look for?

Dr. Michael Twyman: 19:15

There's many, but like 660, generally in the red, 810, 850, in the infrared spectrum, then you got to look at what's known as the power density, or the irradiance. That's how many photons of light are coming out of the device divided by the beam area. So are using, like, a pinpoint type of thing on the skin, or using a big panel?

Dr. Gabrielle Lyon: 19:34

I've been to your office, yes, you have the world's largest panel. How big is that panel?

Dr. Michael Twyman: 19:41

Eight feet tall by four feet wide.

Dr. Gabrielle Lyon: 19:43

Okay. Number one, that looked very expensive. And number two, did you test the radiance?

Dr. Michael Twyman: 19:48

I don't have a laser power meter, and that's what you would have to have to actually, accurately, accurately measure it. But when they say that, everything has to be at least 100 milli per centimeter square to get. Benefit. That's not true. You know, most of the trials, least in the cardiovascular world, you know they're using like, 10 milliwatts per centimeter squared. So you don't need these high irradiances to get the benefit. So you have to know the power density, so like, how many photons of light are coming out, and then the time, how long are you using that device for? And then that equals, basically the dose, and the dose is different for the tissue types. So there was a cardiac trial, more kind of limited in scope. But very interesting was it was a Israeli trial where they took patients who were having ST elevation and miser having the worst kind of heart attack they got, rushed off to the cath lab. I believe there's 12 people in each group. Each group got standard of care. They all got stents, but half the group got photobiomodulation during the procedure, a day later and three days later. It was a device that was utilizing 10 milliwatts per centimeter squared. They used it for 100 seconds, one joule. This is what's interesting. It was not over the heart, it was over the tibia, so their leg bones. Why would you do that? There are stem cells in those tissues. What they had studied is that they gave the dose during the case, day later, three days later, the people who got treated had troponin levels that were approximately half those that weren't treated. So troponin is a protein inside of the heart that gets released when the heart cells die. So when the heart cells die, it's like popping a like popping a balloon. All the contents spill out. If you measure to front in the blood, heart tissue is getting damaged, and high enough levels can indicate a heart attack. So the people had half the size of heart attacks when they got treated. Everybody got the same treatment. Otherwise. How would that work? Well, when stem cells are activated, potentially, that's helping lower inflammation in the heart. You're also putting energy into the system while the heart is starving of energy because there's no blood flow going downstream. Proof of concept study only at this point, safe to use it, but very interesting to think about that they weren't even treating the heart. These people had, quote, smaller heart attacks. So this is why photobombulation was really fascinating for me. It's like, you know, I'm a cardiologist, but where can most people use it? It's musculoskeletal injuries. That's where most of the data is at. So if you get injured and you can't train one, that sucks, but two, then you're not going to be able to get the cardiovascular benefits long term if you keep getting hurt. So this potentially helps you recover faster and get back into the game.

Dr. Gabrielle Lyon: 22:18

You mentioned that it has to be on the skin. Can the red light penetrate through the skin?

Dr. Michael Twyman: 22:26

It's preferable to be on the skin, if possible.

Dr. Gabrielle Lyon: 22:29

But, can it penetrate to muscle?

Dr. Michael Twyman: 22:32

So infrared light at best, probably penetrates three centimeters. Most data shows that like maybe five millimeters is kind of a red and then infrared start to hit, but maybe up to three. But think of it like a lot of photons at the top of the skin and then only a few getting down deep. So that's why it's kind of the recipe. So again, the time is important, because you could use a higher radiance for one minute, you could lose a lower irradiance for a longer period of time and get the same dose. So it's kind of analogy of like cooking a turkey. Do you go low and slow, or do you drop the thing in a boiling pot of water and fry the thing?

Dr. Gabrielle Lyon: 23:09

But is it the effect on the skeletal muscle, or is it the effect on other areas that then generate the help of the tissue?

Dr. Michael Twyman: 23:17

It's decreasing pain receptors, it's decreasing inflammation. It's decreasing swelling in the tissue. And it's potentially that swelling in the tissue, particularly around the nerves, that causes some of that delayed onset muscle soreness. And so this is why you potentially want to use it, you know, after training. Now there's some debate on like, what is the perfect time after training? Because if you immediately run to the red light panel after you do, you know strength training exercise, you know you might blunt that inflammatory adaptation. You might not be a sore but you might not get as much hypertrophy if you use it immediately afterwards, same story like why you wouldn't do a cold plunge immediately after doing a strength training episode.

Dr. Gabrielle Lyon: 23:56

You know, I've thought a lot about that, and I would say, to be fair, the influence might be really small, you know, like, I don't know if, if someone, if you're going to use red light, I would, from my perspective, go ahead and do it. I don't think it's going to affect their

Dr. Michael Twyman: 23:57

I don't think for most people to make a big deal. Like, you know, if you're an Olympic athlete, maybe you need to time it down to the minute. But also get asked, like, what time of day? Think of these devices, almost as a joke, as a sun plement like sun up to sun up to sundown is when you ideally would like to use the thing. Yeah, if you use an evening time, just gonna be mindful that in some people, it's not the wavelengths of light, it's the intensity, the lux, that affects their sleep. So if you blast yourself, particularly in the face, with these panels, 20 minutes, we want to go to bed, and might effect your sleep in some individuals, other people, has no effect. Some people, they sleep better with it. You just have to be kind of a biohacker and see what time of day works best for you.

Dr. Gabrielle Lyon: 24:43

You know, I was looking at some data. It seems that there's a potential for certain red light to improve eyesight. Is that true?

Dr. Michael Twyman: 24:55

It is true. I don't know which irradiances they were using. Using those trials, but it's a very short period. I believe the treatment session is only, like three minutes long.

Dr. Gabrielle Lyon: 25:06

Where else would you use various lights when we were upstairs, all of us, and you pulled out this device again, I feel like it's Christmas when you come over, because there's all kinds of gadgets, although you should leave some here. Yes, I did. And you said, Oh, this is cool. You put it on because it's blue light.

Dr. Michael Twyman: 25:25

So blue light doesn't penetrate the skin very deep, so it's for topical use only, so the dermatologist will know about its benefits. So can help treat acne, but on skin contact, it may help liberate nitric oxide. And that's obviously one of my areas of expertise and interest, is that anything that can prove nitric oxide maybe helps arterial elasticity or blood pressure? So, I bought these wearable patches a couple years ago and played around with them. I haven't done enough data with them to say that they absolutely release nitric oxide yet, but theoretically, but I thought was pretty interesting when I was reading up on them. Is how they kind of showed that they did work? Is that they got some recruits, probably some college students, paid them 20 bucks, and they made him stand in front of the tennis serving machine, and they blast him 80 miles an hour in their quads. And I was like, I don't know if I'd do that for 20 bucks or whatever they paid him. But half the kids got the light patch. The other kids didn't. They got, you know, here's some Motrin and some cold packs. But the people got light therapy. They had like, 40% smaller bruises the next day, because it helps break up the hemosiderin, so it just helps speed up that wound recovery.

Dr. Gabrielle Lyon: 26:28

People talk about red light for wrinkles, all those red light masks, which, by the way, I think I have three or four. Does blue light help with wrinkles or skin integrity?

Dr. Michael Twyman: 26:40

It would actually probably make it worse. Yeah, blue light is oxidizing to the skin. This is probably why people who have, okay, so don't put that patch on your face. Yeah, do not put that patch on your face. And this is probably the reason why when people have a lot of screen time, they tend to get a lot of fine wrinkles, is that blue light is dehydrating their skin. It's oxidizing.

Dr. Gabrielle Lyon: 26:56

Did you know that? Absolutely not. So do you put a flux on your screen?

Dr. Michael Twyman: 27:03

I usually have different software on my computers that pull it out, and then, if you've been to my office, I always, always have, in the corner, I have a red light panel that's on at that distance. It's not really for photobomb modulation, but it's trying to balance out the spectrum of light that's in my office so that red and different lights kind of bouncing off my computer monitor back into my eyes.

Dr. Gabrielle Lyon: 27:22

Could you protect your skin and eyes with some kind of panel over your screen? It's hard, because it penetrates the screen. But if, if someone were to come to you and say, hey, I want to protect my eyesight, I want to protect my skin, what do we do?

Dr. Michael Twyman: 27:37

So I don't know, the companies that make it anymore, the one I used, I think, went out of business, but they're used to make these, like, orange acrylic plates, and then you would just physically put them in front of your monitor for the people who don't want to wear the glasses for any reason or control over here, yeah, like, it's like the marine recruits of the birth control glasses. No, it was no the case where, you know, I got some of them because, you know, I have nieces and nephews, and they're not wearing these glasses. So I was like, would they put these in front of their, you know, like an old school screen protector? Some would, some wouldn't. But no, there's always options. But the physical blockers, they work well. And then, you know, it just being mindful that try to use some red light therapy when you're using a lot of blue lit devices.

Dr. Gabrielle Lyon: 28:22

Does it have to be red light therapy? Or could it just it just be a red light lamp?

Dr. Michael Twyman: 28:23

The lamp is just helping more kind of balance out the spectrum of light in the room. But if you have the red light mask, or you have a panel, it doesn't have to be skin contact for the face mask, but that helps stimulate collagen production, which is decreasing the wrinkles. That's why it works.

Dr. Gabrielle Lyon: 28:37

But I mean, so for example, like last night I'm working on this book. I have to turn in my edits, and I put the nighttime screen situation on, you know, you can, you can switch it on your Mac. But I also use a little lamp. It's not red light, per se, with the infrared and and, you know, all of that massive, intense red light, it's just a little lamp. Is that helping to balance out the blue light? Or is it just something? Yeah, how does that work?

Dr. Michael Twyman: 29:17

I would say that it's helping balance out the blue light and it's just helping maintain your circadian rhythms. You want to bow down the intensity sunset. So, yes,

Dr. Gabrielle Lyon: 29:28

Are there things that you've now introduced into your practice? Say, over the last two years, I know that you're talking a lot more about nitric oxide. You're talking a lot more about this endothelial glycocalyx, which nobody can spell. What is new on the horizon that you've really landed on.

Dr. Michael Twyman: 29:48

I think the endothelial glycocalyx is the biggest thing over the past couple years. Is that when I kind of transitioned out of traditional cardiovascular care, where you're more reactive and not. I'm a little bit more proactive, is you kind of go down that pathway where you find functional medicine, and you realize that, like nutrition and exercise are extremely important, and there may be some supplements and instances that are helpful, but eventually realize that that's not the whole story. And so then you find maybe the biohackers and the circadian biologists, and you start doing some of those things. But once I was found that pathway, I came upon Dr. Mark Houston and Dr. Nathan Bryan, and they really taught me a lot about how nitric oxide was important to the vascular system that is released mainly from the endothelial lining. But in the past few years, has been noted that there's another layer called endothelial glycocalyx. It was first visualized in the 1960s but only the past few years is getting a lot more attention as people have potentially treatment options for it, and some of the diagnostic testing that I offer in my office, or potentially you can do at home that can tell you the health of that glycocalyx and underlying endothelial layer. I think that's where really it starts, is that if you have a healthy layer of glycocalyx endothelium, it's not that your arteries are completely bulletproof, but it's much less likely you're gonna develop severe atherosclerosis. And I think Cardiology is doing a great job treating people when they have the end stage disease, but sometimes it gets a little bit too lipid focused, then lipids are important. I'm sure we're gonna talk about today. But if you keep the glycocalyx endothelial healthy, you don't have to worry so much about the downstream effects.

Dr. Gabrielle Lyon: 31:17

Does what I'm hearing you say is that this endothelial glycocalyx is really at the root. For example, I believe muscle is the root, and the health of skeletal muscle is the root. You believe and correct me where I'm wrong, that the endothelial glycocalyx is, in part, really the root. And if you can address the health of that, then things like lipids, LDL, cholesterol, apo-B are important, but not necessarily at the root of heart disease. Is that, is that what you're saying correct?

Dr. Michael Twyman: 31:51

I think it's too myopic to focus on one risk factor. You know, focus on the layer that is the first line of defense. You know, it's your force field. If your force field is healthy, you're not likely to develop plaque in the first place. Or if you've already developed plaque, and you've picked that up on a calcium score or a CT angiogram, if you repair the glycocalyx and underlying endothelium, you stop laying down plaque, and then you have the potential for plaque regression, which I know that's going to be a question. You know, can plaque be shrunk or regress? The answer is yes, but you have to stop doing the damage first. And in part, that's improving the nitric oxide pathways that help support that endothelial glycocalyx.

Dr. Gabrielle Lyon: 32:30

How can someone who is at home listening going, Gosh, my mom had a heart attack, and she had a heart attack really early. I am just entering menopause, and menopause seems, there seems to be major changes in LDL, cholesterol, apo-B, all kinds of things. And they're thinking, well, how can I measure if my endothelial glycocalyx, not that I can spell it, but how can I measure it?

Dr. Michael Twyman: 32:57

Sure we just got the EGX going forward, if you'd like.

Dr. Gabrielle Lyon: 33:00

E-G-X.

Dr. Michael Twyman: 33:02

Yes, so there's not a direct way you can actually measure the EGX at this point, there are some more research options where they're using certain type of intravital microscopes, typically in the sublingual space, where they're looking at the how well the red blood cells are basically repelled from the glycocalyx in the blood vessels under your tongue, and that correlates with what's potentially going on in the rest of your 60,000 miles of blood vessels. So, they have done that for sepsis. And there are some tests that are still researched where they look at the glycosaminoglycans, (athe gags) that come off of the glycocalyx when it's damaged. So you can pick that up in blood and urine, but at this time, there's not a commercial lab that does those tests.

Dr. Gabrielle Lyon: 33:46

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Dr. Michael Twyman: 35:19

So you have to kind of look down to where the endothelium is. And again, that's one cell thick layer that lines your entire artery. Layer. It's kind of like the air traffic controller, which determines what stays in your blood and what gets into the walls of the arteries. And testing that can look at that is one you could do blood pressure. If your blood pressure is normal, what would you define normal? Normal is under 115 over 75.

Dr. Gabrielle Lyon: 35:41

115 over 75?

Dr. Michael Twyman: 35:42

That should be optimal. 120 radius. Quote, normal.

Dr. Gabrielle Lyon: 35:45

Oh my gosh. So I've got Julia here. She's on my team. Julia, what's your blood pressure? I think it's 112 over like 68 112 over 68. That's awesome. Well, one so what is it?

Dr. Michael Twyman: 36:06

115 75 is where...when it starts getting about that the risk of atherosclerosis increases.

Dr. Gabrielle Lyon: 36:06

But do some people have a higher vascular tone? Because I'm going to measure my blood pressure. You're going to measure it actually, with your very fancy machine that you've you always come, I love it when you come to visit, because you have about 15 obscure items that could probably save my life on a plane. That's the plan. Yeah, that number this 115, over 75 so if someone is at home and they're thinking, Well, how do I measure their How do I measure my own blood pressure, they need to sit down for 15 minutes, five minutes, five minutes. No caffeine, right?

Dr. Michael Twyman: 36:42

No caffeine, no nicotine, yeah. Feet on the ground, back supported arm at heart level, and on the bicep, thick, away from the ones that are on the wrist, because they're generally highly inaccurate. So on the bicep, take a measurement, record the number, and look at trends. One number is not the problem. Is the blood pressure load, and so if you're consistently you know over 140 over 90, you need to talk to your doctor, potentially gonna need to be on pharmaceuticals while you're working up. The root cause why your blood pressure so high? But that is just one sign that potentially have low nitric oxide availability. As your blood pressure starts to rise, there's test strips the salivary nitrate test strips. They look like litmus paper. You put them in your saliva, the brighter red they are, the more nitrates you're potentially getting in your diet. So think beets, green leafy vegetables. Those compounds conventionally become nitric oxide in your stomach. And then there's pulse wave velocity, which is essentially a marker of how stiff the arteries are. So the aura ring can measure it. I have a device over here called the I heart that can measure it. So the arteries, when the blood comes into them, it's kind of like an accordion. The blood expands them, and then they snap back. And these tests can measure their arteries really elastic, or are they really stiff? Are they like a lead pipe? If your arteries are getting stiff, your arteries are aging faster than you are on the outside.

Dr. Gabrielle Lyon: 38:00

115, over 75 and is that across all age groups?

Dr. Michael Twyman: 38:04

That's the cutoff. When we start going above that the risk of acidity starts to increase.

Dr. Gabrielle Lyon: 38:09

But what about so I did my fellow you know you're from St Louis. I did my fellowship in geriatrics, and we kept the geriatric population closer to 130 over 90, maybe even higher, for cerebral perfusion, for someone listening or watching, that's blood flow to the brain.

Dr. Michael Twyman: 38:29

Correct. And those trials, like the SHEP trials in the past, that was what was thought is that, you know, let the older population run a little bit higher. But more recent studies, the SPRINT trial, had shown that irrespective of age 120 Radia is really the goal for treatment. Dang.

Dr. Gabrielle Lyon: 38:47

Speaking of treatment, what is nitric oxide?

Dr. Michael Twyman: 38:51

Nitric oxide is a gas. It has a very short life. You know, it's around for about a second, but it's a signaling molecule and a hormone. From a vascular standpoint, it was so important for its discovery in the vascular system that it won the Nobel Prize for Medicine in 1998 for the three researchers who discovered that, from a heart standpoint, nitric oxide helps with arterial dilation. So it helps keep blood pressure normal. It acts somewhat like Teflon, preventing the cholesterol particles, the white blood cells, from sticking to the artery in the first place. And I'm sure the question is going to be, how do you improve nitric oxide? Well, in part, it's exercise as blood flowing across you, that artery, lining that glycocalyx, it stimulates underlying, the feeling to release nitric oxide. The arteries dilate. You know sunlight, particularly the wavelength of UVA that hits your skin, the nitrates are liberated from the surface of the skin, releasing nitric oxide. And then, dietary wise, it's mostly the green leafy vegetables, so spinach, kale, arugula and beets, as those nitrates come into your oral pathways. You know you chew them if you have the oral. Oral microbiome. That oral microbiome, the nitrate reducing bacteria, break down the nitrates eventually becomes nitrites, and if you have stomach acid, becomes nitric oxide. So those are the three big lifestyle things that can boost nitric oxide. And then there's various nutraceuticals and pharmaceuticals that can also help.

Dr. Michael Twyman: 40:17

And the way that someone would be able to tell if their nitric oxide is where it should be is test strips.

Dr. Michael Twyman: 40:24

Test strips are a starting point, but there is a caveat. Is that if you have an oral infection, they'll be falsely positively high, so you can't rely on just one data point. But if your test strips are low in white, sometimes it's the person. Maybe they're carnivore. They don't eat any vegetables, so they're not putting any nitrates in. Maybe they're a vampire and they never go out in the sun. Maybe they don't exercise. Okay, you have all these redundant pathways, but if they all start breaking, you're probably gonna start developing vascular disease, and that gets picked up by your arteries get stiffer on these pulse wave velocity testing. Or you can start seeing people's blood pressure start to rise, and it can start rising, you know, just very mildly at the beginning. But you know, if they go get tested, yeah, they may have low nitric oxide support them. Those things can be reversed. What

Dr. Gabrielle Lyon: 41:06

is the most effective way? So if someone is coming in and their blood pressure is over, let's say it's 125, over 85 or something. So it's not grossly high, it's not emergent, and you give them a nitric oxide precursor. What kind of dose are we looking at? Because what I'm hearing you say is that one reason blood pressure, potentially one reason that blood pressure gets high is that people are nitric oxide deficient. Is that a right, a correct word? How would we dose in behavior? Again, I understand that that's probably a very specific question, and some people you know are more sensitive to the diet and they might produce more. How do we go about dosing and course correcting blood pressure using nitric oxide?

Dr. Michael Twyman: 41:58

So I would start first with, a good lifestyle history, like, are they exercising? Are they eating the green leafy vegetables? What is their stress load? Double stress isn't bad. That's how we are resilient. But are you chronically stressed and not recovering from that stress? Do you sleep poorly? Do you not allow your body to repair at night? So figure out, Okay, is there some obvious lifestyle intervention you can utilize if you've done all those things and don't see it, then that's where blood work can come in. You know, some people have high homocysteine. You know, it's an amino acid that, when it's high, it affects some of these nitric oxide pathways. If you have high uric acid for numerous reasons, you know, you know, you drink too much alcohol, or you ingest too much fruit dose and have high uric acid, that uric acid can damage the glycocalyx, affecting the nitric oxide pathway. So sometimes it's getting to the root cause of what's causing the nitric oxide. During removing that and the nitric oxide gets back into homeostasis.

Dr. Gabrielle Lyon: 42:50

That is very helpful. I suggest everyone get nitric oxide strips, just because it's fun. You'll be very disappointed at your nitric oxide levels. Most of us, I know that I was tell me about there's a lot of talk in the cardiology space about a few things. Number one, testosterone and cardiovascular disease, and also GLP ones and cardiovascular disease. You choose what you would like to talk about first. But again, this is very relevant. And then finally, there was that study that was the Keto CTA trial. So cardiologist choice.

Dr. Michael Twyman: 43:33

Let's go for the low T.

Dr. Gabrielle Lyon: 43:34

Okay. Oh, I love that. All right, talk to me about that.

Dr. Michael Twyman: 43:38

So something that when I was in training, wasn't much discussed. I trained at St Louis University for my internal medicine, and we did have a world famous geriatrician there, John Morley. He's the one that actually came up with the ADAM questionnaire, the androgen deficiency and aging male questionnaire, which is so often used for people to figure out, like, are the symptoms due to low testosterone or not? He was big proponent of it for people who were sarcopenic, which was a term that I only learned because I still had geriatrics at SLU, but that was something that, you know, I just put in the back burner for a while, did my cardiology training, and then started taking care of people who were more on the High Performance end, and they're, you know, kind of super physiologic testosterone, like, well, we know that that can be a problem. But what about people who are on the low side? Okay, what is the risk? Well, if you don't have a lot of muscle mass, you're probably going to be more insulin resistant, you may have more inflammation. So those are not good things, you know. So you know, always look at, you know, is low testosterone, you know, something that first has an easy, reversible cause, like the person sleeping four hours a night and abusing alcohol. Can you get them to stop those things? And testosterone is kind of a biomarker of like, are they doing their lifestyle things that could support a, quote, healthy testosterone level, but if they're doing all the right lifestyle things, and their testosterone is 250 on a couple occasions and they have horrible symptoms, then it's reasonable to replace those people. But in the past. It was thought that testosterone was going to be cardiotoxic, and actually the black box warning from the FDA for many years, until the recent traverse trial came out. The traverse trial was done in men who were hypogonadism, middle age and above, and they were using topical gel preparation, which still is used, but probably is not the most common way that most people replace testosterone, and it at least showed that people did not have more cardiac events when they were on testosterone. Didn't show benefit, but didn't show harm, which was a good thing, but some of the caveats for the traverse trial is that over 60% of the men who started testosterone stopped it before the trial was done, either because they felt better and they just want to come off and see what happened, or the gel wasn't working well enough for them, and maybe they went to something else, don't know. And the issue is that the doses that they put them on didn't really put them into really optimal levels. And there's might be a real range where people say it's optimal, but damn, 500 to 1000 is generally what I see kind of thrown around, is that most people best around that they barely got these people up to, like, 350, 400 on gel. So did they get, you know, benefit? No, but they didn't have harm at the doses that they replaced them to.

Dr. Gabrielle Lyon: 46:13

It's a really important point. And basically the traverse trial really addressed the risk benefit use of testosterone. And there has been this long standing belief, like you said, that, and especially cardiologists. They, at least before I met you, for the majority of the cardiologists that I have known, they were very anti-testosterone and anti-hormones. And that seems like that's a bit outdated, and always again, takes evidence to kind of change people's minds over time. But what they found at the traverse trial is that there was no increased risk of heart disease with the utilization of testosterone. And I think that there is evidence that low testosterone is a risk for heart disease.

Dr. Gabrielle Lyon: 47:02

Do you think? Do you happen to know why they thought that testosterone utilization was contributing to heart disease.

Dr. Michael Twyman: 47:02

Absolutely. And they have higher calcium scores. They have higher risk of diabetes, you know, all cause mortality. So it's one of those things, right? Is it a chicken egg? Is the low testosterone causing those things? There's just that the person has so many comorbidities that their testosterone so low. So one thing I sometimes explain to patients is that, think about your heart and brain being very energy dense. You know, they're gonna take the lion share of energy if the body is kind of starting to fail, it's gonna take away energy from the sex hormone cascade and say, like, we don't need to think about reproduction right now. We need to think about keeping your heart and brain alive so your testosterone level is gonna be low for now.

Dr. Michael Twyman: 47:06

My understanding is that it was some poorly designed trials that had shown some potential increased risk, but when they actually went back and looked at the data, it probably was neutral at best. But because of those trials, the testosterone got a black box warning. And many cardiologists, you know, they're busy, they're taking care of, you know, whatever. They're 40, 50, 60, patients a day. And if someone says it's a black box, they're like, don't use that stuff. And they move on. But the more interesting thing is, like, why is low testosterone a problem from a cardiovascular standpoint? Most likely it's because when you have low testosterone, you don't have the ability to aromatize it into estrogen. And it's the estrogen for men that's probably more cardio protective. When estrogen is in more optimal ranges, it helps support healthy nitric oxide levels. It helps support lipid lipoproteins. Being more optimal, you need the estrogen for brain function. You need it for libido and bone health. So it's the estrogen that's probably the benefit in many of these guys.

Dr. Gabrielle Lyon: 48:37

That's fascinating. And is there a range where you like to see estrogen, we have a range. I don't know. Is there a range that least 30? Yeah, so we like 30 to 70, or is it 70? It depends on the lab, but I would say at least 30. I think that that's a good range. You know, there was a period of time when everyone was on anastrozole, and so that is in a somewhat of an estrogen blocker decreases estrogen, and people really felt terrible. So things are changing. What about GLP-1s and heart health?

Dr. Michael Twyman: 49:15

It's very interesting. Yeah, when the drugs came out, they were first approved for diabetes, and at that point I was already a full-fledged cardiologist. And so I wasn't I had many patients who were diabetic, but they had endocrinologist or internist or family practice doctors who were managing it, and most times, the cardiologists were kind of hands off with their blood sugars at that point. And so I didn't really pay much attention when they first hit the market. You know, I had a very wise attending when I was at SLU who said, like, don't be the first doctor to use a drug, and don't be the last one. So let's see how this plays out. So great data on people who are diabetic, but yeah, I got my current practice launched up in 2019, busy taking care of people who are more proactive. And I honestly, probably, on one hand, can count how many diabetics have my practice. It's so few. Two. So I see a lot of patients with insulin resistant prediabetes, but those aren't necessarily the patients who are going to be on GLP ones. So I didn't think much about it for a while, but went to the American College of Cardiology conference back in 2024 and the Select trial had recently come out, and the Select trial was looking at GLP ones, particularly semaglutide in patients who were not diabetic, they were just overweight, and you know, be what it is, you know, BMI above 27 or 30. And these patients, you know, had known vascular disease, coronary disease, I had prior events, but not recent events. And that was like 17,000 plus patients were evaluated on the trial. And at the end of the, I believe it's 40 months, the people who were on treatment had about a 20% decrease in mace may reverse cardiovascular events. So it was the first trial in non diabetics that showed people had less cardiac events. And so that was really a game changer. And so the push is really to be more aggressive, potentially with these medications and the right population, I don't think it needs to be in the, you know, the water, you know, everybody being used and stuff, but it should be more liberally used in patients, particularly that known coronary disease.

Dr. Gabrielle Lyon: 51:11

Known coronary disease. Is there a range? And does someone not have coronary Is there a spectrum? I guess, is a better is it better question?

Dr. Michael Twyman: 51:21

That's a great question, and that's one of the challenges that trying to apply, you know, clinical trials to the person who's sitting in front of you. You know, the classic terms are, you know, primary prevention and secondary prevention. Most cardiologists are living in the secondary prevention world, so the person's already had a heart attack. You're just trying to help them not have another one and very clear evidence. You know, use your statins, your beta blockers, your GLP ones. There's a lot of new tools out there that can help those people not have another event. The real question really is the primary prevention people, the people who've never had a heart attack, stroke, stents or bypass. How aggressive should you be treating those people? And there's a window, is that, if you don't look and you just plug people's numbers into a risk calculator, which can give some idea of risk, but I'm more of the mindset like look at the arteries themselves. If you look at the arteries in this plaque, that person's high risk, irrespective of what some little calculator says, start treating the person more aggressively, particularly they have a strong family history. Your grandma started having heart attacks in her 40s. Maybe the family should be screened a little bit earlier and treated more aggressively for their blood pressure. Their blood pressure or their lipids. And so treat the person who's in front of you to the best of your ability, but base it off, you know, data. You know, if that person has placking their arteries, they're at higher risk of having events down the road. And maybe they're not necessarily primary prevention anymore, and they're not secondary, they're maybe like 1.5

Dr. Gabrielle Lyon: 52:39

You know, there's a lot of backlash against statins. Could someone reverse heart disease with diet and exercise alone? Let's say that they have plaque and they have a greater than 400 calcium score. Could they do it with diet and exercise alone?

Dr. Michael Twyman: 52:57

Depends on where their their lipoproteins are starting with, and that's why I say it's one risk factor. You know, if you have a 90th percentile APO-B, for example, you know your APO B is 150 is diet. And you know exercise is going to get you down to an April B of 70. There's no way. It's just not going to happen.

Dr. Gabrielle Lyon: 53:14

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Dr. Michael Twyman: 54:51

There's so much genetic control for you having those levels that high most the time. I know we're getting into keto CTA trial in a second, so those people, you can do whatever lifestyle intervention changes. But most people, unless they're on kind of, like extreme dietary kind of platforms, you know, they're keto or they're extremely, like, high carb, making dietary changes doesn't have the biggest driver to affecting their lipoproteins.

Dr. Gabrielle Lyon: 55:16

Yeah, I was reading some data, and it's really, it's interesting, because we make these dietary guideline recommendations, for example, cholesterol recommendations, which dietary cholesterol is taken out of the guidelines in 2015 but the saturated fat percentage, when you think about those dietary influences, it's really 20% of people that seem to be really affected by dietary fat and just nutrition. It seems as if there's a genetic predisposition. Remember Bob Harper? Yes, for those of you listening for my gen Zers, Bob Harper was the trainer in the Biggest Loser. He was super fit, very healthy, and he was running on a treadmill, and he had a heart attack, and he again, ate, quote, very healthy. And it was he had genetic hypercholesterolemia.

Dr. Michael Twyman: 56:15

He actually had lipoprotein little a.

Dr. Gabrielle Lyon: 56:16

Oh, how high do we know? Don't know. And lipoprotein. Little a, Mike, Dr Twyman, can talk about that. Those are it's a genetic marker. Again, there's a series of markers that we look for, LP, little a, apo, B, yes, LDL, cholesterol, which will then bring us into this keto trial, are there other markers? Are those? Would those be your top and what are they?

Dr. Michael Twyman: 56:46

So I usually kind of break it down into three big buckets. So I look at tests that affect your nitric oxide pathways, so uric acid, homocysteine, look at urine, microalbumin and creatinine, old school test to look to see if you have kidney disease. But if you have protein in your urine, you're damaging the glycocalyx to the kidneys. So, if we're damaging that potentially, you're damaging the heart artery ones. So, that's kind of one bucket. There's a few others, you know, like the salivary nitric oxide strips and blood pressure. Second big bucket is the oxidative stress and inflammatory markers. So HS-CRP, Lp-PLA2 activity, which is a marker of inflammation in the artery, Myeloperoxidase, which is a marker of white blood cell activation, which is potentially going to be damaging your HDL and the top layers of the arteries. Interleukin six (IL-6) is an inflammatory marker. And then there's a bunch of oxidative stress markers. So often start with GGT, gamma gluteal transferase. It's a test, simple. It's on a complete metabolic panel. But if the person has high GGT, they have low glutathione, they have low glutathione, they have a lot of oxidative stress, potentially. And they can look at the oxidized LDL, oxidized phospholipid, Apo-B, if you look at those things, those people are at higher risk. And then you get into the lipids. So I usually start like that is like, Okay, Okay, we saw the nitric oxide; now let’s look at what shows inflammation. Now we'll take a look at the lipids. So yes, I was always look at the traditional lipid panel. It's free. It's included. So if the person's total cholesterol is over 300 and their LDL cholesterol is over 190 they potentially have familial hyperlipidemia. But the Keto CTA trial, we'll talk about lean mass hyper responders in a second, but I will look at their HDL cholesterol, but it's not really that predictive for most people. You know, there's people with low HDL of heart attacks, or people with high HDL that have heart attacks, but sometimes it's an insight into the metabolic health and then their triglycerides, which turn I like to see less than 80. You know, if there's some genes less than 80, that's that's pretty low. That's pretty aggressive, yeah, but if it's not below 80, then you guys are looking like, is this person likely in some resistant or, you know, what is their kind of carbohydrate tolerance? And then looking at the lipoproteins themselves, it's the lipid proteins that actually predict risk, but our particles predict risk. Another way to say it, the cholesterol is just being transported in these lipoproteins. The lipoproteins can be measured directly. You can get an LDL particle number, but you can also look at APO B or APO lipoprotein B. So the example I use for patients is that the lipoprotein is a tennis ball. The cholesterol is going inside. Triglycerides go inside vitamins like A, D, E and K, and different phospholipids, which are building block for salt, all go inside these little tennis go inside these little tennis balls, but on the outside of the tennis ball, that white stripe that's essentially APO B as a structural protein holds that thing together in a sphere and then acts like a little key to bind into different LDL receptors. There's an April B on the outside of every LDL particle. There's an APO B on the outside of LP(a). V, LDL, I, LDL. So LPA is very similar to LDL. It has an Apo- B, but it has an extra protein, apo lipoprotein A on it, and it's like a little corkscrew protein. And that protein allows it to kind of dig into that glycocalyx, a little bit easier to damage it.

Dr. Gabrielle Lyon: 59:56

What number would. Would you want to see LP little a, and when would you get concerned?

Dr. Michael Twyman: 1:00:06

So it's generally better to measure this, and that this is the one challenge is that it's measured in animals, or it's measured in milligrams, and you want to go for the milligrams per deciliter variant, and generally want to see it less than 75 everybody has LP little a, but there's a genetic control with it, where up to about 20% population has higher levels than that, and it's almost linear. The higher LPL a the more vascular risk, and it can double your risk of having a heart attack or stroke compared to having normal levels.

Dr. Gabrielle Lyon: 1:00:34

Do you think there's any way to predict who's gonna have a heart attack?

Dr. Michael Twyman: 1:00:38

Yes, but it's mostly based off plaque and vascular inflammation and low nitric oxide. You can just almost see the people who are going to be the train wrecks.

Dr. Gabrielle Lyon: 1:00:47

Oh gosh, you know, we are going to talk about the Keto trial. I have a couple questions prior to that, alcohol and heart health? Can people drink alcohol and have healthy hearts?

Dr. Michael Twyman: 1:01:04

The short answer is yes, but the question is always going to be, what dose you know, alcohol is a poison. Yeah, I tell people I'm definitely not a teetotaler. I have a very nice teetotaler, person who doesn't drink alcohol. Okay, I'm not, yeah, I have a very nice bourbon collection. I have a very nice wine collection, but it's measured at this point. You know, I have to have a very good reason, good family, good friends. Gotta be a good celebration. I just had my 25th wedding anniversary. I enjoyed the wine pairings at dinner. It was great. But congratulations, well, thank you. But is it heart healthy? That's a little more debatable. You know, nobody who's not drinking should pick up drinking for some perceived benefit for their vascular resveratrol of wine, correct? They should not pick up drinking red wine just because I think it's gonna be good for their heart. That being said is, what is it doing to the person's sleep? That's probably the biggest concern, is that alcohol, for many people, once they get over like one glass, it's gonna start impacting their quality of sleep. And while you're unconscious with alcohol on board, you're not getting that reparative sleep. And that's the challenge. You know, you're in a very low HRV the next day, likely with alcohol on board the night before. Does it impair your decision to go train the next day like, you know, that's the thing that I'm concerned about. When people have a routine alcohol habit.

Dr. Gabrielle Lyon: 1:02:17

How come alcohol then? You know, really heavy alcohol use. This is what we are taught in training causes cardiomyopathy a bigger heart.

Dr. Michael Twyman: 1:02:29

It's basically, it's an alcohol cardiomyopathy. And I definitely saw a few cases of that in my career earlier. And I don't know what the exact dose is, but as you know, someone probably neighbor to like, you know, a 12 pack of alcohol every single day for weeks on end, makes your heart better. Well, the alcohol directly poisons the cardiomyocytes, and then the heart just becomes weak and doesn't pump.

Dr. Gabrielle Lyon: 1:02:45

Well, oh gosh. What about caffeine and heart I'm just asking for a friend that doesn't drink enough energy drinks to kill a draft horse. But yeah, asking for a friend?

Dr. Michael Twyman: 1:02:58

Yeah. I mean, everybody has a different tolerance to caffeine. Generally, if people stay under 400 milligrams a day, probably can be pretty neutral from a vascular standpoint. So a cup of coffee has about 100 milligrams for my coffee, yeah, the super strong coffees. But not everybody who drinks coffee or caffeine from any source necessarily has any heart issues. But those that have palpitations, they feel their heart fluttering, you know, they're measuring their blood pressure, and they assume their blood pressure going up, or they have some of these fancy toys that look at arterial stiffness at a certain threshold, everybody's already started to have some kind of impact. And then the other issue is sleep. You know, it blocks the dentist and receptor, so it affects how easily some people can fall asleep. So ballpark, six out of 10 people are slower metabolize their caffeine. So those people they need but more careful with that, particularly on their timing, they should keep caffeine to earlier in the day, so as a better chance to start washing out of their system before they're going to bed.

Dr. Gabrielle Lyon: 1:03:55

You know, I recognize that I didn't finish the question on statins, you know, because I was so excited about alcohol and caffeine. If an individual shows calcifications, and again, we share many patients together in our medical practices, if they are given a statin, can you reverse that hard and soft plaque?

Dr. Michael Twyman: 1:04:20

It generally will not reverse the hard plaque, though, I have seen some calcium scores go down on statins. Typically, you actually see the calcium score going up on statins, and the thought is that it's taking the soft plaque, which is more prone to rupturing, and causing it to become more firm. And so the calcium scores will go up. If you do a calcium score test and then don't make any changes, the calcium score test will generally go up about 20% a year. If it makes that's really high.

Dr. Gabrielle Lyon: 1:04:44

Yeah, it's 20% a year. So no wonder everyone's dying of a heart.

Dr. Michael Twyman: 1:04:50

So that's why you got to look for it as early as possible and start intervening. Yeah, like I said, I saw third six year old with a cousin scored nearly 1400 a six year old, 36 year old, 36 year old, and so that person. Sudden it didn't happen in from 35 to 36 had been happening since Brian has 20 so the sooner you can find it, the sooner you can start intervening. But if you do an intervention and you see a calcium score stay about, no more than 5% increasing, you probably got ahead of the game, and you've stalled that plaque buildup, and there's a chance that the saw plaque will shrink, but you're not going to see that on a calcium score does. You'd have to do the CT angiogram to see that part.

Dr. Gabrielle Lyon: 1:05:22

How do people then, you know, when we talk about regression, what are we talking about?

Dr. Michael Twyman: 1:05:28

Generally talking about the lipid rich cores of the plaque shrinking down. So you can think of the plaque as almost like a pimple, and it has a thick cap over it. Hopefully, the ones that have thinner caps over it, they're more prone to kind of opening up all that damaged cholesterol, white blood cells, the smooth muscles, all that stuff spills out into the blood, and now the blood clots, and you go from having a 50% blockage to immediate 100% blockages. The platelets are sticking in that area, and that's what essentially most heart attacks are. The statin is helping that lipid rich core shrink and also putting a thicker cap over that plaque so it seals it off.

Dr. Gabrielle Lyon: 1:06:04

Does heart disease cause erectile dysfunction?

Dr. Michael Twyman: 1:06:08

Absolutely can. So the analogy is, ED equals ED, so erectile dysfunction equals endothelial dysfunction and vice versa. So, if guys are starting to have issues with erections, oftentimes it's a vasculogenic cause. They're not getting enough blood flow into the sexual organs to allow an erection to happen, and it's due to low nitric oxide.

Dr. Gabrielle Lyon: 1:06:27

When you see patients, how early does this seem to start?

Dr. Michael Twyman: 1:06:30

ED can happen under 40, but it tends to happen more when people are over 56, years old.

Dr. Gabrielle Lyon: 1:06:37

And do you treat with vasodilators, or do you use agents like Cialis as a cardiologist?

Dr. Michael Twyman: 1:06:44

I do on occasion, it's kind of the canary in the coal mine. Question is that if guys are having Ed and they're asking for, you know, the low blue pill, or, you know, Sildenafil or Tadalafil, it's not that it's a problem that they need to use those things, but it's a marker that they don't have good nitric oxide to begin with. And that's somewhat of the myth, is that these are not nitric oxide promoting medications. They just keep nitric oxide around longer. You have to get the nitric oxide, I call like into the funnel. You have to be eating the greens. You gotta be exercising. Gotta be in the sun. You gotta be taking the nitric oxide promoters into the system. And then the tadalafils and the Viagras, they just keep the nitric oxide around longer, so that it has more effect on the vascular system.

Dr. Gabrielle Lyon: 1:07:22

That's fascinating. I didn't, I didn't actually know that. And in my mind, that seems like there could be a great combination of, you know, we use Cialis in our practice, and Tadalafil, if you use that in conjunction with a, I don't know, beetroot juice or something like that. Seems that seems like that would be very helpful. And just a real nerd note, arginine increases nitric oxide.

Dr. Gabrielle Lyon: 1:07:52

Thatis true, and I'll hit that one in a second. But that is a good point. Is that those medications, they work, but I'm sure you've seen some non responders, you know, you keep ramping it up, and they said this stuff doesn't work. Or by time you get to the highest doses, they're having headaches or back pain, like, I can't take this stuff. Well, maybe if you got the nitric oxide boosted up, you could use a lower dose, and they get the effect. But the question about Arginine is that the greatest majority of people are not deficient in arginine. So what happens with arginine, which is an amino acid, and the presence of oxygen? You need this enzyme called ENOS - endothelial nitric oxide synthase. The ENOS enzyme converts the arginine into citrulline and nitric oxide. So you can shove all the arginine you want into the system, but if the ENOS enzyme doesn't work, you're not getting nitric oxide on the backside, and a lot of supplements, that's all they are, is arginine. So if it doesn't work for the person, it's kind of a de facto that ENOS enzyme isn't working, and after age of 40, that enzyme is significantly reduced in its capacity to kind of crank arginine into citrulline. So that's why you have to kind of back up with the oral pathway or sunlight or doing something else to support people. Because why vascular disease gets more prevalence? People say, prevalent people's age, because that Enos enzyme becomes less and less functional.

Dr. Gabrielle Lyon: 1:09:06

How do you know that?

Dr. Michael Twyman: 1:09:07

Lots of training and learning, and Dr Nathan Bryan taught me that many years ago.

Dr. Gabrielle Lyon: 1:09:12

And would someone supplement with the enzyme?

Dr. Michael Twyman: 1:09:16

You don't not the enzyme directly, you would supplement with things that could support the ENOS enzyme, recoupling, turning back on, or some of the product technologies, when they are lozenges, they dissolve, they release nitric oxide gas. And that just gives it to you, nitric oxide directly, without having to have that hard gene pathway working.

Dr. Gabrielle Lyon: 1:09:33

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Dr. Gabrielle Lyon: 1:11:05

That's really fascinating. I - can you do me a favor? Sure, I hear a lot about niacin and HDL. Someone very close to me came home and I found a bottle of niacin ordered off of Amazon. I'm not going to say who ordered it, Shane, my husband. And I said, Honey, why are you taking that? And he said to me, well, the flushing and it improves my HDL.

Dr. Michael Twyman: 1:11:39

Both are correct. The flushing definitely is going to happen. That means it's actually working for those people. So for the people who are going to take niacin under the direction of their doctor, if you have the no flush niacin, it is not going to give you any type of cardiovascular benefit. You have to get the flushing because that means that the prostaglandins are being released. But the theory that using some type of supplement or medication to raise your HDL is going to have a positive cardiovascular benefit has not been proven. You know, all the old CTEP trials show that when they use drugs to raise HDL, the people who got those drugs, they died faster than the placebo group. How did you throw out that niacin? Not necessarily, it just that maybe it's neutral. But what dose are you going to use? Most people aren't going to tolerate going up to like, 2000 milligrams of niacin, where most people need to if they're gonna have that significant effect on their lipids. So I use it on occasion. It still does work for some people who are stand intolerant or just prefer not to be on a statin for any reason. But it's sometimes a harder drug or supplement to use, because to get to the doses that work, most people have significant enough flushing that they're like, I can't tolerate this stuff.

Dr. Gabrielle Lyon: 1:12:44

But to be clear, does niacin affect health outcomes with HDL? I mean, I, when I was looking at the data, I wasn't convinced. I felt like it might change HDL, but it's doesn't seem to affect any significant health outcomes.

Dr. Michael Twyman: 1:13:03

That's the best way to probably explain is that, like they show them, like date show, numbers will go up. But is that mean that the person has less heart attacks, stents, strokes, that things patients care about, probably not. And I don't think any of the trials today that actually shown that niacin does that.

Dr. Gabrielle Lyon: 1:13:13

Do you think that there's anything that people are really missing that seems to be really toxic for heart health?

Dr. Michael Twyman: 1:13:21

Poor sleep.

Dr. Gabrielle Lyon: 1:13:23

See that I have two little kids. I started two and a half hours last night. Season of Life, season well, yeah, except my daughter is going on six, and my husband's in residency.

Dr. Michael Twyman: 1:13:36

Right? Remember residency like the worst time of your life for sleep. I mean, you don't sleep in your own bed, you know, except for every, like, third night, and when you're working or working 36 hour shifts without sleep, you do because you have to do it. But in hindsight, you're like, that's like, the worst thing you possibly ever could do from, you know, a health standpoint, long term. And so you do it when you're young, but once you realize that, like, Hey, this is going to kill me. If I kept trying to do this, you have to do something different.

Dr. Gabrielle Lyon: 1:14:03

Okay, aside from sleep, yes, aside from sleep. Would it be, for example, people are really into CBD gummies or CBD. There's just a whole host of things that there's always these evolving or, you know, the biocharger that's up in our bedroom. Thanks, Kim. Are there any items, whether supplement, substance, drug and or activity, that someone would not necessarily think about being very damaging?

Dr. Michael Twyman: 1:14:38

I mean, the CBD one is interesting. I don't proclaim to be an expert. I have some patients that have utilized it, and I said that the biggest challenge is that, like, it's not regulated in a way where there's a standardized dose that, you know, okay, like, this dose from this dispensary is comparable to this dose from this dispensary. I'm least relatively neutral for CBD from an anti inflammatory standpoint, or if it can help the person sleep. Right, but where the challenge comes in, but more is when there's more THC in the product. Now, in certain instances, it's beneficial. You have epilepsy, I'm not talking about that, or if you have cancer, it's just like the general kind of use case for it. There's definitely some increased risk of increasing your triglycerides with it. There's increased risk of atrial fibrillation, which is a heart rhythm issue that potentially increases the risk of stroke. So something you probablydon't want to play around with unless you have a strong medical reason to be on it.

Dr. Gabrielle Lyon: 1:15:27

THC, I see, Let's talk about the epic lipid inflammation and controversy of the Keto CTA trial. So I am going to let you kick this off, because I am certain that you've gotten a ton of questions.

Dr. Michael Twyman: 1:15:45

Yes, and I've seen many of these lean mass hyper responders over the years. And what is that? It's a phenotype where the person is lean. I believe the BMI has to be less than 25 they have no evidence of insulin resistance or prediabetes. And then on their labs, they have this panel where, you know, before they went on to a low carbohydrate diet, the LDL cholesterol had to be less than 160 milligrams declared, and they didn't have to have any genetic abnormalities with their lipids. They start aketogenic diet, the LDL cholesterol goes north of, generally 190 I've seen them as high as 500 in my practice. LDL, I see a 500.

Dr. Gabrielle Lyon: 1:16:25

But were not before, just before. Just to understand this, for the listener or the viewer, a lean mass hyper responder is someone who changes their diet, goes to a lower carbohydrate diet. And is it a higher fat diet or just

Dr. Michael Twyman: 1:16:38

low carb? It's low carb, but generally it's higher

Dr. Gabrielle Lyon: 1:16:41

fat, high fat. And instead of improvements technically, they shoot their their cholesterol changes drastically.

Dr. Michael Twyman: 1:16:53

Correct. Their lipids look like they have familial hyperlipidemia, and now their other parts of their traditional lipid panel, their triglycerides are low, their HDL high. And, you know, they will often say, like, well, I'm, you know, metabolically healthy, so this other cholesterol doesn't matter, maybe, maybe not. And this is what they're trying to look at in this observational trial. I applaud them for at least looking at the arteries, because in the past, it used to be that like, well, I don't have diabetes resistance, so I'm pretty protected from vascular disease. It's like, I believe, yes, that. You know, there are other things that drive plaque and arteries, other than just LDL cholesterol, but that is one variable that is like, blinking red, like the check engine lights on. You got to go looking like, is it causing damage to the arteries? Because I used to get a lot of patients who would have this kind of phenotype, they go get justa calcium score, and might say, my calcium score is zero. So I don't have to worry about this. You don't have to worry about it right now, and maybe in a year. You looked your labs like this, for the next 10 years, unknown, you're likely to have more plaque neurons based off of Mendelian randomization trials in the past that say that if your LDL cholesterol is here, you're more likely to have plaque. Doesn't mean it that you're guaranteed, but you know, it's risk. So it's like, you drive your car. You don't expect to crash your car, but you wear a seatbelt. This is sort of like if you're LD, your LDL cholesterol is 500 if it's causing plaque in your arteries, maybe you want to do something about that LDL cholesterol. So at least in this keto CTA trial, they're actually looking at the arteries with more invasive, or say, non invasive, technology. They're using a CT angiogram, and then they're using the Cleerly, AI overlay on top of it. So Cleerly is a company that uses AI software to analyze the images and can quantify the type of plaque that's in the arteries. So I believe it's like 100 patients were in the trial. It's an observational trial. I think it was volunteers from kind of like a social media outreach so it's a highly selected population of people who are motivated to see what's going on with their vascular system. And interesting is that these people had been on this type of diet for a couple years, and they've had these high lipids for many years and were untreated. So either they've gone to a doctor and the doctor said, like, Hey, I recommend you stop this diet and start meds, or they just said, like, I'm not gonna go to a doctor because the doctors can yell at me because my numbers are so high. So they get a CT angiogram at baseline. They stay on the keto diet. They confirm it by using the Keto Mojo strips and such, and confirm that, you know, they stayed on that diet for the full year, and then they repeated CT angio at the end of the year. And the primary outcome in the initial study was supposed to be how much change in non calcified plaque was present. So non calcified plaque is soft plaque, plaque that's more potentially vulnerable to rupture and causing heart attacks. It's not the hard calcified plaque that's usually kind of a scar in the artery. So that was their initial primary outcome. But in the actual paper, they really kind of gloss over that, and they focus more on that, like, well, these people had high APO B, and they didn't seem to have more plaque because APO B. But when you actually look at the actual graphs, the non calcified plaque increased in almost every person in the study, and it increased like 18 millimeters cubed of plaque in that time frame. It would be more than what a kind of general healthy population would be. So it's still kind of early. Let's say it's observational. It's kind of, you know, hypothesis generating doesn't prove that this diet is healthy. Doesn't prove that this diet is going to cause you to have heart attack next year, but it does mean that you have to look a little bit deeper. So that's why I always kind of go back to what we talked about earlier. It's like, it's the root cause, like, what's going on with the glycocalyx and endothelium? If that layer is healthy, maybe you can get away with having these LDL cholesterol as a 500 for years. But the second you see that the glycocalyx is damaged and the feeling of dysfunction is happening and your arteries are stiff and your nitric oxide is low, that person's the time bomb ready to go off in a few years. And you don't want to reduce the risk of a heart attack in one year. You want to reduce the heart attack risk for the next 30, 40 years.

Dr. Gabrielle Lyon: 1:20:44

You know you had said something earlier that there's a 20% increase in plaque year over year the calcium score. The calcium score was that the same as those in this keto CTA trial.

Dr. Michael Twyman: 1:20:59

It's kind of apples and oranges, because mostly people did not have calcified plaque at the beginning, because they're too they're young, yeah, and relatively, quote, healthy.

Dr. Gabrielle Lyon: 1:21:06

You know, again, you and I have been friends for quite some time. I want to talk about muscle excellent. I want to talk muscle and heart health. I believe that skeletal muscle is the most important muscle, and you believe cardiac muscle is the most important muscle? We will probably have to come to some understanding, and I am very curious as to that muscle, heart connection, from your perspective.

Dr. Michael Twyman: 1:21:35

Let's just say that they're synergistic. I don't think one is better than the other. You need both, and that's something that you know I have say, other than my geriatric training, I didn't learn about a lot in my cardiovascular training, the only people that would talk about it would be the heart failure doctors, because those patients who were ending up on heart transplant list, they usually were sarcopenic. They're cachexic because their heart is failing. Their body's demanding all the energy resources being sent to this weakening heart, their skeletal muscles are getting eaten up by all the inflammatory compounds that are coming from a failing heart. So those are more guys that really, really worried about muscle health.

Dr. Gabrielle Lyon: 1:22:13

Do you think it's important to measure VO2Max and grip strength? Think

Dr. Michael Twyman: 1:22:15

Both are important. Grip strength is very easy. I check in almost every single patient that comes to my office.

Dr. Gabrielle Lyon: 1:22:21

Do you check your own I do. I'm pretty Shane's like, oh, so Shane's my husband, if you're a first time listener. And he is a third year urology resident, which is pretty funny. His I won't say the joke, but anyway, he's always checking his grip strength. Where is he at? Now, I don't know. Probably superhuman.

Dr. Michael Twyman: 1:22:41

Okay? I mean, he's way more muscular than me, but I'm pretty happy, like I'm 130 pounds on the right side, 120s in the left side, so I'm top 1% for my age.

Dr. Gabrielle Lyon: 1:22:50

Okay, looking great for 25 friend, looking great for 25. Do you routinely? You know, in our clinic, we don't, even though our clinic is largely remote, except for my private patients, we don't measure VO2Max. We just a lot of patients, they don't want to, they can, but you know, we, we have people that will measure it for us. I am curious, from a cardiovascular muscle connection standpoint, do you think it's necessary to measure VO2Max?

Dr. Michael Twyman: 1:23:23

Necessary? Probably not beneficial. Yes, if you're willing to do it, I've done at least two on myself. Yeah. And they're not fun. I mean, you know, you go to you absolutely feel like you're about to die, and then, like, okay, you can stop now and then, you know, at that point, yeah, when I did it, they're like, your average for age. I'm like, great. I'm not trying to be an Olympian. Like, I want to live well. I don't want to be at peak aerobic capacity all my life. I don't have that much time to train to be an Olympic athlete. I don't know. You could probably do it. I could probably do it if I wanted to. I'll tell you a funny story about when I did a stress test, I was in the fellowship in a minute, but the VO2Max, it's a good metric of your aerobic capacity. You know, how well can your mitochondria engines actually work for you? So, you know, it's very similar to, you know, doing a regular stress test on treadmill, but you have a mask on that's capturing your expired gasses, and they can figure out, like, well, where's your capacity to continually utilize that oxygen? And then where do you hit that threshold ballpark, you know, you know, 20 to 40 is kind of like where most people are going to fall. People are going to fall. If you're above 40, you're doing something right. If you're under 15 and the cutoff was 14 when I was still doing kind of like hospital work, if your VO2Max was under 14 and you had a bad heart, that was kind of a cut off saying, like, Yeah, we should list you to get you a heart transplant.

Dr. Gabrielle Lyon: 1:24:38

And you don't routinely, just to kind of close this out, you don't routinely measure VO2Max.

Dr. Gabrielle Lyon: 1:24:44

If patients are very interested, I will send it for it. I have the frontier x2 chest strap, which is probably the most sensitive heart strap you can use for exercising. It can measure a EKG while you're exercising. And they claim to be able to kind of relatively accurately measure. Your estimated VO2Max off of that. So I think it's good enough for most people. But if you're really hardcore, gotta go do the real thing.

Dr. Gabrielle Lyon: 1:25:07

Why don't you think more cardiologists focus on skeletal muscle health?

Dr. Michael Twyman: 1:25:14

Because they're focusing on cardiac muscle. Yeah, the analogy is, time is muscle in the cath lab. You know, when your arteries aren't, you know, open. They're rushing to open those arteries up because the muscle cells in the heart are dying until they get their restored blood flow. So at least they use analogy time is muscle, but they're thinking about cardiac muscle.

Dr. Gabrielle Lyon: 1:25:31

If you you know, you've covered a lot on how to protect your heart. And really, if we were to sum this up, it was lifestyle, be active, sleep well. I'm going to fight you on that one. Listen, a lot of parents don't have an option. Get outside, wear blue, blocking glasses. Maybe eat a diet that augments nitric oxide. Keep your blood pressure low, keep your stress under control. Don't drink alcohol, caffeine. Okay, drink alcohol moderation. Figure out if you are a high or low metabolizers of caffeine, and if you are high, 400 or more is just fine. Just kidding. Check with your doctor, did I miss anything?

Dr. Michael Twyman: 1:26:24

No, that's an excellent review, and it's the basis of, you know. Test don't guess like everybody's has their own individual, you know, story, their individual genetics, and then they go out in the world and do the things they need to do. But some people are at higher risk of vascular disease than others. If you do the right testing, you figure out who those people are and which libraries you can pull back on to reduce that risk.

Dr. Gabrielle Lyon: 1:26:43

If you could pick three tests, you covered the blood test, the blood tests that we talked about were LP, little, a, apo, B, LDL, cholesterol, hscrp, yes. And then also you talked about Myeloperoxidase, I will say that in our clinic, almost every woman seems to have higher levels of Myeloperoxidase. Is there a reason?

Dr. Michael Twyman: 1:27:06

It's associated with autoimmune conditions, and women are at higher risk for autoimmune conditions. Highly Myeloperoxidase can be a marker of HDL dysfunction. So just having high HDL doesn't mean that it's necessary to anything beneficial to your vascular system. You know one of the rules HDL is to go into the arteries, pull out the cholesterol and take it back to recycle it. But if you have high myeloprostase, it keeps damaging the HDL, and the liver has to keep replacing it. So your HDL numbers are going up in your blood, but they're not actually working. But if you have high Myeloperoxidase you gotta look and see, do they have some of an autoimmune condition or some other chronic infection that's driving that?

Dr. Gabrielle Lyon: 1:27:40

And if they don't, how do you fix that?

Dr. Michael Twyman: 1:27:41

Pomegranate potentially helps.

Dr. Gabrielle Lyon: 1:27:44

Okay, you know, I wonder if it's pomegranate or I wonder if it's your Urolithin A. So for those of you listening, we work a lot with Timeline and Mitopure is this clinically tested your Urolithin A, are you taking it?

Dr. Michael Twyman: 1:28:00

Not yet.

Dr. Gabrielle Lyon: 1:28:00

Okay, well, I have some, I'll give you some, but I think it's probably, maybe it's not the pomegranate, but it is the, I don't know. I mean, we should probably, yeah, look into that. The other tests. And, you know, I'm curious as to what home tests are accurate for looking at heart health.

Dr. Michael Twyman: 1:28:18

It's a great thing that kind of look into that, because the contents of your blood, it's easy to obtain for most people, but it doesn't tell the whole story. It doesn't tell you what's going on in the arteries. And so, you know, yes, I have a whole fancy, you know, lab of equipment in my office at Apollo Cardiology, which you've been to a few times, and we put you through the battery of testing.

Dr. Michael Twyman: 1:28:37

Whenever you want to come, I'm happy tohave you back, yeah. But in the office, you know, the biggest test we probably do, test, which we didn't talk about here today, and that's probably the gold standard way to really test what is your nitric oxide availability and ability for the arteries to dilate. So for those that haven't heard of the test, which most people haven't, the end of that test is a non invasive test. Takes about 15 minutes. You're laying down comfortably. Your fingers have probes on them, and they're measuring the flow in your fingers. They do a five minute warm up, and there's a five minute period where we have a blood pressure cuff on your arm, pump it up higher than your systolic blood pressure, and the flow cuts off. Your hand goes numb, generally, not dangerous. And after five minutes, you open up the stop cock, the blood rushes back down into the arm. This simulates exercise. As the blood rushes back down into the arm, it stimulates the glycocalyx. The glycocalyx says, oh, here comes a bunch of blood. The underlying endothelium releases nitric oxide. The smooth muscle artery opens up, and the blood rushes back down to your hand. Your hand wakes up, and then the test can measure, well, how much do the arteries dilate with that response? And your arteries should at least double in size, but optimally, triple or quadruple in size if it's less than 1.68 so your arteries are only dilating six to 68% you have what's known as endothelial dysfunction. The arteries can't release nitric oxide on demand. It's kind of like the force field is down. You're more prone that whatever's floating through your blood the cholesterol particles, the white blood cells, they're more likely to stick to the artery and. Going to develop plaquing arteries unless you do something about it. So it's the stress test for the arteries that we do in the office. Now you can't do that at home yet, but our tests that you can do that can give you an idea. Is this a problem? And so we talked about it, and we got some.

Dr. Gabrielle Lyon: 1:28:37

I'm due, by the way, aren't I, or in another year.

Dr. Gabrielle Lyon: 1:30:12

Oh, here comes the toy. The toys that All right, so for those of you who are listening, not watching, I'll describe them. So let me, let me try them. So I just drank stuff. You're not supposed to drink any.

Dr. Michael Twyman: 1:30:26

You're supposed to wait at least 15-20 minutes.

Dr. Gabrielle Lyon: 1:30:32

Ugh, the Center of the Earth, isn't it cool? All right, you talk about this. I'm gonna, she's gonna play around. I'm gonna play around with it. It's okay. This is not gonna be accurate, yeah, because I just have been drinking

Dr. Gabrielle Lyon: 1:30:36

And this is a pulse ox?

Dr. Michael Twyman: 1:30:36

This is basically a pulse ox. So this one's called the iHeart.

Dr. Gabrielle Lyon: 1:30:36

So this is a little black box that looks like a pulse ox that I have in my emergency travel kit, correct?

Dr. Michael Twyman: 1:30:36

So they look like a little litmus paper strips. There's a little pad on it that you put saliva you then bend the tab over. There's a little developer pad on the other side. And if you have nitrites in your salivary pathway, the thing will light up red. If it does, that means you're generally getting a lot of nitrates into your diet, and you potentially have good bacteria in your mouth. You have the nitrate reducing bacteria in your mouth to be able to break that stuff down to break that stuff down that ultimately becomes nitrites and nitric oxide. Not everybody has high nitrates in their diet because they're not eating green leafy vegetables, or they have dysbiosis of the oral microbiome because they're using mouthwash, they're using things with fluoride, and her numbers are really not red, so she's getting good nitric oxide through that pathway. So that's step one. I talked about pulse wave velocity. So I'm wearing an OURA Ring. The reason I got the Gen three was because they did add a feature last year the cardio age, which is measuring pulse wave velocity. So as the blood rushes past the ring sensors, it's looking at how fast the arteries expand and contract, and you can look at the wave forms and determine how stiff the arteries are. So you want your cardio age to be close to your biological age. Mine is aligned, which is normal.

Dr. Michael Twyman: 1:31:02

So it's going to give you your heart rate and oxygen SATs. But I'm not gonna pull out my phone right now, but if you had the app running, you do like, a two and a half minute run for it, and it will measure the arterial stiffness and will give you a vascular age reading, which can change throughout the day. But generally, when I do this, it's usually at my biological age. You're much younger. If it's higher than biological age, don't freak out. Like, look at your life.

Dr. Gabrielle Lyon: 1:32:22

Don't do anything. Yeah, figure

Dr. Michael Twyman: 1:32:26

Figure out why it might be high. Like, oh, I slept two hours last night. I, you know, just did a bunch of nicotine before I jumped on this podcast, or something, whatever. That's probably gonna

Dr. Gabrielle Lyon: 1:32:34

How bad is nicotine? We have a lot of people, people that let me, let me see wait. So we have a lot of friends and people that we know, Matt producer, who use a lot of nicotine. What does that do?

Dr. Michael Twyman: 1:32:46

It's a vasoconstrictor, and so similar to caffeine, you know, it can cause people to have higher blood pressure, can cause palpitations. And so it's one is, again, like test don't guess, like, certain amount nicotine, maybe it doesn't affect your blood pressure, cause you to have, you know, issues with palpitations. But you know, if you're going at a person level, a level where it is got to dial it back, you know. And I understand, you know, it's a nootropic for some people, you know, it has cognitive booster, but, you know, but can also be a vasoconstrictor. So, so for people have coronary disease, sometimes it may contribute to them having chest pain with activities.

Dr. Gabrielle Lyon: 1:33:21

So everyone is throwing their Zins out the window. Matt, he has six, six milligrams. I tried to just try it, I almost threw up, like, immediately, yeah.

Dr. Michael Twyman: 1:33:36

And if you're not, since, if you're not sensitive to it, or I should say, if you're sensitive, you're like, you know, less than a milligram most people pretty nauseous.

Dr. Gabrielle Lyon: 1:33:42

Was a terrible idea, and, of course, I tried it again. What else you have in there?

Dr. Michael Twyman: 1:33:47

Next toy. So this is a new one that I'm pretty interested in. This is the Connect QT Pulse. It's a little box that measures blood pressure. So it has a brachial blood pressure cuff, so you'll get your traditional number, you know, it's going to say whatever, you know, 120, over 80, which? 20, over 80, which is a good starting point, but that's the blood pressure just going down to your hand. The thing that this box does that no other one to the market yet does is it measures central blood pressure. So when I'm still an invasive cardiologist, we would feed a catheter into a radial artery or femoral artery, and put a pigtail catheter in your aorta, and we can measure blood pressure in your aorta and then measure the blood pressure in your left ventricle.

Dr. Gabrielle Lyon: 1:34:28

Why would someone want that?

Dr. Michael Twyman: 1:34:28

Well, when you're doing a procedure, it's kind of a good idea to know, kind of like, how well their heart's working. You know, how hard is the pressure coming out of their heart? Because the higher the pressure in the aorta, the higher the pressure in the coronary arteries, and the more likely that high shear stress could damage the coronary arteries. So nobody wants me putting catheters in them just to measure that pressure, but this device can assess what that pressure would be. So the cuff is on your arm, and after it takes the regular measurement, you'll feel it kind of pulsing a little bit. It's basically assessing how stiff the arteries are. Because, for example, if your heart's beating 60 beats a minute, the left ventricle pumps, the blood comes out of the heart, goes down to your legs, and. It's gonna hit those arteries in your legs, the iliac arteries, and it's gonna be a reflection wave. So it's kind of like splashing water at a wall. The water comes back. You can measure how fast that blood is coming back, and that estimates what is the blood pressure as it's coming out of your heart. Because that central blood pressure is what the blood pressure that your brain when you talk about the patients are geriatric, and you know, you don't want to infect their central perfusion. It's that central pressure that you want to focus on. That's the pressure that the coronary arteries, the heart arteries, and then also your kidney arteries. That's what they sense. So if your central blood pressure is normal, less than 120 rady, but the arm is 150 leave them alone. Their perfusion in the brain is perfect. Don't mess with them. So you want to treat their central blood pressure you don't want to treat just brachial

Dr. Gabrielle Lyon: 1:35:44

if we were to kind of pause and think about that, blood pressure medication, beta blockers. What else? What is first line that you're using?

Dr. Michael Twyman: 1:35:54

Generally ACE inhibitors, angiotensin receptor blockers or calcium channel blockers, or first line beta blockers? Interesting, particularly the older ones. They lower brachial blood pressure, but they have no effect on that central blood pressure, so you're not really getting the benefits. But the ACE inhibitors, the angiotensin receptor blockers, calcium trap blockers, they lower both brachial and Central

Dr. Gabrielle Lyon: 1:36:13

and what are the main side effects of those drugs?

Dr. Michael Twyman: 1:36:15

It depends which class, but ACE inhibitors, generally it's cough. Angiotensin receptor blockers, not a lot. Sometimes, you know, if you get your blood pressure too low, they just got back up in the dose calcium channel blockers, peripheral swelling in their feet sometimes cause some constipation at higher doses. And the beta blockers classically pretty hard to use, particularly in younger people. Particularly people are very active. You know, they're gonna block catecholamines, so they're blocking adrenaline being secreted. So it can be useful for people have a lot of palpitations or performance anxiety, but for blood pressure, they really weren't that potent. And then the person's probably gonna have exercise intolerance. Their extremities might be cold. They might have sexual dysfunction in guys, so hard to use. But the newer class of beta blockers like Nebivolol (Bystolic), it does have an effect on blood pressure because it affects the nitric oxide pathways. So, it's pretty much the only blood pressure medicine in the beta blocker class that I'll use if we're going to be using it, but it's going to be probably third or fourth line after they've exhausted the angiotensin blockers and calcium channel blockers.

Dr. Gabrielle Lyon: 1:37:18

The reason I asked you that question is, if someone is just getting a brachial artery blood pressure, which is what would be standard, and one an individual is treated off of that, is it true that they might not need it because it's not actually measuring the central blood pressure

Dr. Michael Twyman: 1:37:35

Correct. And that's sometimes the case is where the person says, like, I'm taking the medicines, I'm getting really lightheaded and dizzy at home. I don't feel good. And you check the blood pressure in their arm in the office, and they're like, 125 you're like, well, your pressure's a little bit high. Their center pressure is probably, like, 100 over 60. And their brain is like, hey, I need a little bit higher perfusion pressure. So maybe need to back off, let the breaker run a little bit higher. So that's why this device is going to probably, be a game changer for many people who are at high risk or just very interested in their vascular health, because this is kind of like the check engine light going on when your central pressures start to rise you have a problem. The device also can measure things that will look at the stiffness of the arteries as well. And this is a good kind of add on to somebody who has a calcium score of zero. Great. You have a calcium score of zero, but a calcium score of zero means that you haven't developed hard placing orders yet. But this is the can tell you, like, if your arteries are getting stiff and your central pressures are high, you're more at risk for that. So for those people in that keto CTA trial, this might be an interesting device for them to have if you're because I know that going into that trial, they had to have normal blood pressures, which, if you see a cardiologist in the real world, everybody has kind of the Triumph to it. You know, they got high blood pressure, they got diabetes or pre diabetes, and they got high lipid issues. Nobody just has just lipid issues in the real cardiology practice. But if you have stiff arteries with this type of device, maybe you want to start backing off on that kind of keto diet, because maybe you're making a ton of oxidized LDL that's affecting your arteries.

Dr. Gabrielle Lyon: 1:39:02

That's really fascinating, and that's called the connect, connect Qt, okay, well, we Hey guys, we're all trying that immediately. What? Okay, yeah, okay. Julia said we'll put links to all these devices, just to close out, are there a handful of supplements that are evidence based, not anecdotal, but that have randomized control trials and evidence in humans that you think are valuable for heart health?

Dr. Michael Twyman: 1:39:34

The short answer is yes, but it's not a blanket statement where, like everybody, should take all of these things. You know, you have to look for deficiencies, and you got to look for time. To look for tolerances of certain ones that start again with the glycocalyx and the endothelium. If you can make nitric oxide, there are products out there that can help with that. There's products that can support the glycocalyx. If the glycocalyx is getting damaged, there's supplements that can help regenerate the glycocalyx.

Dr. Gabrielle Lyon: 1:39:59

Yeah, there's that be like a beetroot juice and Neo you sent me, like a neo 40s, a little tab,

Dr. Michael Twyman: 1:40:05

Yeah, the little tabs, yeah, Neo 40. That was initially the product that Dr Nathan Bryan developed. He now has a competitor that is in his own company called M 101, which I often utilize. There's an opera called Vascanox from a company called Calroy. Full disclosure, I speak for them sometimes, but it doesn't affect your ability to like talk about because I often, I'm taking that product myself, because I've looked at their research and it works well for me. And I do this testing, my numbers are good. So I'm a pretty good biohacker. I try almost everything on myself first and make sure it works. And then I talk about with my patients. And then, you know, they're saying scale like CO Q 10. CO Q 10, you know, may help with people who have, like, muscle symptoms when they're on statins. You know, omega threes. Prefer people eat their seafood than supplement. But if they're gonna supplement, you know, generally two grams a day on fish oil.

Dr. Gabrielle Lyon: 1:40:53

It's also really hard to get enough omega threes. It's generally really hard the CO Q 10, is there a dose and is there a form?

Dr. Michael Twyman: 1:41:02

So generally, you want to just target blood levels over three, yeah, you can either do your biquanol or your biquanone, yeah, the nubiquinol should be absorbed a little bit better, but it's more expensive. So I just tell people like, okay, yeah, pick a good brand that your doctor works with, but check blood levels and then whatever dose it takes. So ballpark, you know, if you are deficient, you're gonna probably need between 100-300 milligrams a day. If you're on a statin or beta blocker, add 100 milligrams per drug that you're on that depletes co Q, 10. Magnesium, for the threehundred reactions the body. So anybody has blood pressure issues, palpitations, coronary disease, sleep issues, or

Dr. Gabrielle Lyon: 1:41:40

75% of Americans who are deficient consider magnesium Yeah.

Dr. Michael Twyman: 1:41:44

And you know what forms basically not oxide, because oxide isn't absorbed from the gut. You have your constipated take oxide, but if you're not,

Dr. Gabrielle Lyon: 1:41:52

but if you have a big event, do not take magnesium oxide. Or if you are going on a plane or any kind of long trip, correct? Not ideal.

Dr. Michael Twyman: 1:42:00

Yes. Those probably are the big ones that I would say.

Dr. Gabrielle Lyon: 1:42:04

Well, thank you so much, Dr. Michael Twyman, you are just a wonderful human, a wonderful doctor. I am so grateful that you are willing to take care of me and our patients and just you do such a fantastic job. Thank you so much for coming on.

Dr. Gabrielle Lyon: 1:42:24

By listening to this episode, you're already doing what most people never do, thinking about prevention before the problem starts. Most heart attacks are preventable, but only if we look deeper than LDL, only if we challenge outdated norms and only if we value data diagnostics. If this episode shifted your mindset, send it to someone you care about, because heart disease doesn't wait, and neither should we if you haven't already subscribed to the show. Thanks for being here. See you next time you.