Gladden longevity — Episode #68

Steve Reiter: Welcome to the Gladden Longevity Podcast with Dr. Jeffrey Gladden, MD, FACC, founder and CEO of Gladden Longevity. On this show, we want to answer three questions for you: How good can we be? How do we make 100 the new 30? And how do we live well beyond 120? We want to help you optimize your longevity, health, and human performance with impactful and actionable information. Now, here's today's episode of the Gladden Longevity Podcast.

I'm Steve Reiter and, Dr. Gladden, we just got done interviewing Rhonda Rhyne from Prevencio Med, and they provide these cardiovascular tests. We get into the specifics of it, but these tests that you have integrated into the Gladden Longevity practice and you've found very beneficial.

Dr. Jeffrey Gladden: Yeah, no, that's right. We've been using them for a number of years now. I think the audience is going to find this interesting because, with a simple blood test, you're starting to get information about answering the question: ‘What's my risk for a heart attack in the next year or the next three or four years, for that matter? Or what's my risk of actually having a significantly obstructive blockage in my arteries?’

Steve Reiter: Yeah.

Dr. Jeffrey Gladden: And what's cool about this is that this is not just somebody's idea of what might work. It's all been distilled through what you'll hear about this machine learning AI algorithm that's discovered things that you never would've thought actually played a role. So, I think you're going to enjoy hearing this podcast to figure this out a little bit.

Steve Reiter: As a guy who has heart disease on both sides of his family, I'm super interested in this, and I'm super interested in making sure that I just don't all of a sudden die of some kind of cardiac event. And so, a test like this is really intriguing to me. And a test that, if I have to pay out of pocket, my insurance isn't going to pay for it; it's not breaking my bank. 

Dr. Jeffrey Gladden: That's right. No, that's right. Well, you should come down to Dallas, Steve. We can scope you out, man. Got that going on. 

Welcome, everybody, to this edition of the Gladden Longevity Podcast, Age Hackers Podcast. I'm here with my co-host Steve Reiter. Steve, good to see you today. How are you?

Steve Reiter: Good to see you too, Dr. Gladden. It's a beautiful day here in Colorado.

Dr. Jeffrey Gladden: Oh yeah. Good. Yeah, you've had a lot of snow up there, I heard. So, glad to hear it. I'm here today with Rhonda Rhyne. I met Rhonda two or three years ago now, not face-to-face. We're actually meeting face-to-face for the first time. But I came across her technology a few years ago and was really fascinated by it, and I'd like to introduce it to you. It's an AI machine learning algorithm used to predict who's going to have a heart attack or who's likely to have heart disease. And it's quite fascinating. We've incorporated it into our global cardiovascular evaluations. But Rhonda, welcome to the Gladden Longevity Podcast. 

Rhonda Rhyne: Well, thank you so much. It's great to be here with you, Dr. Gladden, and Steve.

Dr. Jeffrey Gladden: Yeah. Great. Tell us a little bit about how you got into this high-tech approach to diagnosing cardiovascular disease. What's your background? How'd you come to this?

Rhonda Rhyne: Sure. I have a Bachelor of Pharmacy and an MBA, and I've spent most of my career in cardiovascular medicine in the industry, primarily medical devices. I was involved with General Electric medical systems and also CardioDynamics, where we were looking at non-invasive cardiac output. And was always fascinated by the biomarker world. When I was in San Diego with CardioDynamics, we had a biosite there that was introducing BNP and other single biomarkers. And when I moved up to Washington State, Prevencio was looking for a CEO to help lead the company toward developing multi-analyte or multi-protein tests. And we had seen a lot of the combinations of the-. 

Dr. Jeffrey Gladden: But tell us-

Rhonda Rhyne: ... gene.

Dr. Jeffrey Gladden: Let me interrupt you for a second. You're talking about multi-protein tests. Tell us what we're talking about there. Give the audience some sense of context for that.

Rhonda Rhyne: Sure. Well, if you look at multiple gene tests, they use a lot of those in oncology to diagnose, but they had never really done that in cardiology. We know that proteins are a closer reflection of the disease state than genes. Genes can be pretty static. Proteins are more dynamic. So, our theory- 

Dr. Jeffrey Gladden: This is the real... Yeah, sorry to interrupt again, but this is a really interesting point that you make because we've been doing genetics around cardiovascular disease for over a decade, I'm sure more. Well, probably. I got involved with it when it first became available, which is now probably almost 20 years ago when, I think it was, Berkeley HeartLabs came forward with a few genes that we could test. And I was impressed by that and started testing it on everyone just to see what we could learn. And we learned some really interesting things about who might have a proclivity for early heart attack, or more complications from high cholesterol, or less complications from high cholesterol, or who might respond to a statin well, and who might not respond to a statin, who would actually benefit and who wouldn't, things like that. And it moved into the pharmacogenomic space. 

And it's interesting that we learned a lot from genes, but to your point, it's not really about the genes; it's about how they're being expressed. And it's in the proteins that we actually see what genetic expression is at this point in time. So, you're now taking it from the genetic understanding, somebody's genetic predisposition for cardiovascular disease. Now you're saying, ‘Okay, but where are you in terms of how those genes are being expressed?’ Did I get that right?

Rhonda Rhyne: Absolutely.

Dr. Jeffrey Gladden: Okay. Take us through the next step. You're looking at these different proteins...

Rhonda Rhyne: We are, and we were fortunate to partner up with Massachusetts General Hospital and Dr. James Januzzi. And he had a very large cohort of patients that had all undergone a coronary heart catheterization. 

Dr. Jeffrey Gladden: Okay.

Rhonda Rhyne: And so, we assayed that blood for more than 110 proteins. We had follow-ups up to five years, about 2,500 different clinical parameters, and fed all of that data into a machine learning, which is a statistical program, and told the machine learning: "This group of patients has 70% or greater obstruction. This doesn't." And the machine learning goes about differentiating which proteins or clinical parameters are most accurate for any given endpoint. So, the first test that we developed is HART, H-A-R-T, CADhs for coronary artery disease. And we also have a second lead test HART CBE for cardiovascular events looking at a patient's one-year risk of heart attack, stroke, or cardiovascular death.

Dr. Jeffrey Gladden: Just so people get the gist of this, you're basically looking at protein files through this cohort of people, and you're correlating it with their cardiac catheterization results, which is looking to see to what degree is an artery obstructed angiographically. And then you're also correlating it with whether or not they ended up having a heart attack or they ended up having something else, unstable angina, something that was in that acute coronary spectrum we call it, to see if they became symptomatic, let's say, from their coronary disease. 

And so, in the past, when somebody would have a heart attack, we would measure something like a troponin to see if there were any signs of muscle damage, if there was a leak of troponin into the blood. And now there are troponins that are high sensitivity troponins that are, to my understanding, about 1,000 times more sensitive than the troponin that you might get measured if you went into the emergency room with chest pain. That can give you an idea of whether another microscopic amount of damage is being done to the heart. And I know that that was one of the proteins that shows up in your profile, but you identified some other proteins that, actually, we never even thought to think about. And maybe if you'd like to, you could tell us about what some of those proteins are for the CVD, and maybe start with that, and then the CVE, we can talk about that.

Rhonda Rhyne: Sure. So, for CAD, we have three proteins and three clinical parameters. In addition to that high sensitivity troponin, the machine learning also selected adiponectin, which deals with glucose and fatty acid metabolism. And that is used sometimes clinically alone. And then also there's a third protein: kidney injury molecule one, which is also referred to as KIM-1, and that's looking at the relationship between the kidneys and the heart, which, as you know, Dr. Gladden, they're highly interrelated and correlated. But it's not just individual proteins or looking at those three; it's the algorithm that the machine learning derives, or the weighting of each of those proteins and the three clinical parameters of sex, age, and "Have you had a history of a cardiac intervention?" So, it's the weighting of those six parameters that really give it the accuracy. 

If you look at the accuracy of troponin alone for diagnosing obstruction, it has an accuracy of about 61%. So it's not very good alone. It's good alone for diagnosing: "Are you having a heart attack?" But it's not good as a single protein to say: "Are you obstructed and at imminent risk of a heart attack?"

Dr. Jeffrey Gladden: Yeah, that's a great distinction. One of the things that we do for all of our patients is cardiopulmonary exercise tests. And we get a good look at arterial function, left ventricular function with exercise, and whether or not the left ventricle starts to decrease its function as the heart rate goes up, which is an indicator many times of some decrease in blood flow to the heart, many times not because of a 70% or greater obstruction, but just due to endothelial dysfunction, where the artery simply doesn't get the signals to dilate appropriately as it should, in response to the exercise stimulus.

One of the other things that we measure is high-sensitivity troponin. And it's interesting to us that people that don't exercise all come back in a normal range, and people that exercise all come back a little bit elevated. And my analogy here is that if you go to the gym and you're lifting weights, you're going to do a little bit of muscle damage, so a little bit of CPK from the muscle is going to be leaked into the blood, indicative of the fact that you just lifted weights. And it's part of the hormetic stress of lifting weights that your muscle then responds to and gets stronger.

And so, when we see a little bit of high-sensitivity troponin, again, this is 1,000 times more sensitive than what you'd be looking for if you were coming in with chest pain for a heart attack, so we were looking at microscopic amounts of this. We feel like somebody's probably not exercising adequately unless we're seeing a little bit of leak, almost like you'd have to see a little bit of CPK to know that somebody was actually lifting a weight. And I just wonder sometimes if that may confound the data for you, if you have people that are avid exercisers, whether or not the algorithm can take that into account, that just a little bump in the high sensitivity troponin maybe without the KIM-1 and maybe without the adiponectin. So, I'm just curious about that.

Rhonda Rhyne: Yeah, it's a very good point. And we have not seen a challenge with that. And it's, again, because of the algorithm and the weighting. It would have to be pretty elevated for one protein to throw the algorithm off. So again, it's the power of the machine learning and the weighting. 

Dr. Jeffrey Gladden: Right.

Rhonda Rhyne: It's a very interesting point, though.

Dr. Jeffrey Gladden: Yeah. And adiponectin is interesting also, because we look at adiponectin genetically and we see if people are prone to have more or less adiponectin, and we know that adiponectin protects the arteries from oxidative stress, and it is associated with glucose metabolism, getting glucose into the muscles to be able to work properly, things like that. And also, its counterpart for us is leptin, which has to do with fat mobilization, and actually satiety, sending the signal to the brain that you've had enough to eat. So, what we find in obese people is that their leptin levels go up because they have leptin resistance. They're not actually getting the signal to the brain to stop eating. It's one of the reasons that they tend to overeat. But it's interesting because when we see our people that are in the best shape, they'll have a little bit of elevation in their high sensitivity troponin, their adiponectin levels will go up close to 30 or so, and their leptin levels will go down maybe to two, or three, or four.

And that, for us, is a really healthy pattern when we see that, which is different than what you're looking at. But it's just interesting that these markers can be used in some cross-related kinds of activities. The thing that we don't measure is the kidney injury molecule, the KIM-1. We don't have any other way to measure that. And I love the fact that you're able to measure that because we do know that the kidneys and the heart are interrelated, and being able to have all three in this algorithm, which is a proprietary algorithm as I understand it, is another nice window for us to look at the heart through and see, ‘What do we think is going on, here?’ So, it's interesting how this plays out in different scenarios.

Rhonda Rhyne: It is really fascinating. And as you mentioned, usually a higher number is not good, and that's true for high-sensitivity troponin and kidney injury molecules, but high adiponectin is good. 

Dr. Jeffrey Gladden: That's right.

Rhonda Rhyne: Conversely, a low is not good. 

Dr. Jeffrey Gladden: That's exactly right.

Rhonda Rhyne: It was very fascinating to do the research with Mass General because we were fortunate enough to meet and work with Dr. James Januzzi, who's a world-renowned cardiac biomarker expert, and he really liked the, he calls it ‘an inductive approach of the machine learning’. 

Dr. Jeffrey Gladden: Yep.

Rhonda Rhyne: We didn't set out with a bias on which proteins the machine learning would select. We just right-fed it, everything. And it was interesting. Kidney injury molecules showed up in both HART CADhs for obstruction and also the one-year risk of heart attack, stroke, and cardiovascular death.

Dr. Jeffrey Gladden: Yeah, it is fascinating. I love that you went into it just asking the question, not with any preconceptions, because in the pharm industry, many times they come in with a preconception: "Is this molecule going to do the following?" That's the question they're asking. In this particular case, you were just a priori: "Just show us what's there." And I think that's part of the beauty of machine learning and AI is that you can learn things that you never even knew that you wanted to know, but all of a sudden, there they are. And that's a fun way to discover stuff.

Rhonda Rhyne: It really is. Have you had, in your practice, interesting cases of being able to take the heart results, intervene and see the numbers improve?

Dr. Jeffrey Gladden: Yeah, we test this on people about once a year because it takes about a year for us to have a big enough impact on some of the markers. But we have. We've seen people that have come in with higher-risk scenarios that have moved to lower-risk scenarios. Just so the audience understands, these are graded on a one to five scale. I think each of them is on a one to five scale, if I'm not mistaken, five being high risk, and then one being low risk, one or two being low risk, or maybe it's zero in one. I don't know. Correct me if I have that wrong, but is that right? Is it zero to one, or is it one to two?

Rhonda Rhyne: It's zero to two for CADhs. 

Dr. Jeffrey Gladden: Okay. 

Rhonda Rhyne: That's the low, moderate is three, and then four and five is high risk.

Dr. Jeffrey Gladden: Okay. Yeah. So, I was close. We have seen people that have gone from high down to moderate or moderate down to low with interventions. And a lot of times, that will come down to a constellation of things. It's not just about trying to lower cholesterol; it's really about trying to control blood sugar, and appetite, and exercise, and bumping adiponectin, and doing these things that actually are a lifestyle, but then actually putting in some supplements that we know are also very helpful for the heart, enough COQ10, and maybe using berberine, or things like this, or bergamot to help lower cholesterol, some things like this. So, what we see is that when we get it right and when the person is compliant, or follows through, or really takes ownership and implements what it is we're suggesting, we do see improvement, which is obviously very satisfying.

Rhonda Rhyne: And something that we like, and I'm wondering if you get this feedback, it seems not only physicians but patients understand our test report because it's very simple: green, yellow, red.

Dr. Jeffrey Gladden: That's right. No, it is simple to understand. And people do gravitate toward it. And when I talk to people about doing it, I tell them that: "We're doing this test. We're going to look at your heart through several different lenses, but we're doing this test because we want to understand what is your risk for a heart attack in the next year?" And virtually everybody is interested in that. You get some of that information, let's say, from a coronary calcium score, from a clear CTY, from a catheterization, from a cardiopulmonary exercise test. Many things can feed into that. But to have an algorithm like this, it's just a simple blood test, is appealing to people. So, that's pretty interesting.

Rhonda Rhyne: And I'll tell you a secret, Dr. Gladden. 

Dr. Jeffrey Gladden: Oh, good.

Rhonda Rhyne: The data-

Dr. Jeffrey Gladden: I'm listening.

Rhonda Rhyne: The data actually goes out to four and a half years for the risk.

Dr. Jeffrey Gladden: Okay.

Rhonda Rhyne: But we've marketed it as a one year, and the accuracy has been tested at one year because we feel that'll get the physician and the patient's mind-share versus if they think they've got four or five years, they're not as-

Dr. Jeffrey Gladden: Yeah, they're not as motivated- 

Rhonda Rhyne: ... attentive.

Dr. Jeffrey Gladden: ... to make the intervention. 

Rhonda Rhyne: Yeah.

Dr. Jeffrey Gladden: Okay. Well, that is interesting to know. And in your data sets, I'm clearly not the only person using your test, and we're kind of a low-volume clinic by design, if you will. But I'm curious if you're seeing that people are making lots of strides as they're using this as a metric, can they show that people go from high risk to low risk, or medium risk, or whatever?

Rhonda Rhyne: Yes, they certainly do. And we're in the process of collecting data and doing case studies, but one of them, it shows beautifully over a year and a half on a CBE score, which is one to 10, going from a nine to an eight to a seven.

Dr. Jeffrey Gladden: Nice.

Rhonda Rhyne: That's really reinforcing for the patient, also, and reassuring that, ‘Hey, I'm following what my physician's telling me to do, and I'm improving.’

Dr. Jeffrey Gladden: Yeah, absolutely. Talk to us, you've talked a little bit about the proteins that go into the CVD. What about the ones that go into the events? You said adiponectin, I think, shows up in, no, troponin shows up in both, I believe, But-

Rhonda Rhyne: Kidney injury molecule does. So, the four-

Dr. Jeffrey Gladden: KIM does, okay.

Rhonda Rhyne: Yep. The four proteins in heart CBE for the one-year risk of heart attack, stroke, and cardiovascular death are NT-proBNP, which is a commonly used single protein, and it looks at really the amount of stress on your heart. The second protein is osteopontin, which deals with calcification and plaque. And the third protein is TIMP1 or tissue inhibitor of metalloproteinase-1, and that looks at plaque rupture. And then the kidney injury molecule, again, is looking at the cardiac-kidney functions. 

Dr. Jeffrey Gladden: Nice. 

Rhonda Rhyne: But that's really interesting in that the machine learning did not retain any of the clinical parameters. Early on, it did, but sometimes with machine learning, more is not better. You can create noise. So, we've developed a proprietary process for building up a panel, which, you know, sometimes it can be 20 proteins, which is not-

Dr. Jeffrey Gladden: Right.

Rhonda Rhyne: ... commercially viable, but then reducing it down while maintaining the accuracy and reducing some of the noise.

Dr. Jeffrey Gladden: Yeah. Interestingly, it's that few proteins that you can get that much information from that few proteins. I think that's encouraging. We're doing some things right now in the aging process. We've started a new company in conjunction with another company looking at the transcriptomics and proteomics of aging. 

Rhonda Rhyne: Interesting.

Dr. Jeffrey Gladden: And so, we're starting by looking at a wide spectrum of things, and then we have ways that we can go in and actually impact how these genes are expressed, the ones that are at the center of this protein abnormalities, if you will. And so, I liken it to the fact that the body is really like a complex ecosystem, and it's really about: ‘How do you bring the ecosystem into a state of harmony?’ It's not really about: ‘Well, if this is high, if your adiponectin is low, we're going to raise it as high as we can.’ That's not the answer in an ecosystem. It's: ‘How do you modulate things into balance?’ And so, in what we're doing in the aging space, we're just now starting to launch into being able to modulate genetic expression using custom-built peptides that can go into action.

Rhonda Rhyne: Fascinating.

Dr. Jeffrey Gladden: Yeah. Modulate genetic expression. And it may be that as we go forward that we'll find a role for this in cardiovascular disease as well, and there may even be a chance, as I'm thinking out loud here, to overlap with some of what you're doing and go in and maybe even modulate some of these things to the benefit of people. So, that's interesting. 

Rhonda Rhyne: Science is fascinating. And we are so appreciative of you finding benefits in our test and using them for the benefit of your patients.

Dr. Jeffrey Gladden: Oh, yeah. No, we've really enjoyed it. Do you have other things that you're working on? Are you just pretty much into trying to implement the test and get it accepted, or is it covered by insurance these days? Or it's not covered? Or where do you stand with all that?

Rhonda Rhyne: Yeah, we are receiving Medicare reimbursement for two lead tests, HART CADhs and CVE, the tests that we've been talking about. And we have quite a few developments on the horizon. We have a test called HART PAD, which is looking at, ‘Do you have peripheral artery disease?’ Which, as you know, there's no real easy way besides a peripheral cath to accurately detect that. We also have tests for diagnosing whether you're going to have acute kidney injury due to a coronary catheterization or a- [inaudible 00:23:20]

Dr. Jeffrey Gladden: Oh, wow.

Rhonda Rhyne: ... cath.

Dr. Jeffrey Gladden: That's a massive one. I think I'll just interrupt you for a second. I've done, I don't know how many thousands of cardiac catheterizations, and stent procedures, and things. And when I was doing that work for 25 years in practice, one of the biggest issues is taking care of people's kidneys, particularly if they had some baseline kidney dysfunction. You're also very, very cautious about how much contrast you gave. And so the audience understands, the dye that you would inject down the coronary artery to give you a silhouette of the artery on the x-ray can be toxic to the kidneys. And so, there's always this trade-off of getting the picture that you need so you can see what you're doing with the heart and yet minimizing the contrast, so that you're not overstressing the kidneys. And we had lots of different strategies to protect the kidneys, and we actually developed some really innovative strategies to minimize contrast use, so we could actually do people with sick kidneys and do a whole stent procedure with only 20 ccs of contrast, which is-

Rhonda Rhyne: Wow.

Dr. Jeffrey Gladden: ... almost unheard of. Because almost everybody's using two or 300 ccs for something like that, maybe even more. I don't want to go into the details of how we did it, but we got amazingly good results by doing that. But we were also very, very sensitive to the kidneys. My kidneys were damaged when I was five when I had post-strep glomerulonephritis. So my kidney function's always been a little bit below where I want it to be. So, this is near and dear to my heart. So, I would probably never get a clearly CTA, for example, because I wouldn't want to expose myself to the contrast.

But if you have the ability to predict who's likely to have a complication from contrast, that's a holy grail kind of test. Because some of these people, they go on to acute kidney failure; they go on to dialysis, they go on to massive changes in their life. It can be a life-altering event for them. Many of them will recover over a few weeks, but it can be pretty touch-and-go. It can be a long hospitalization, all these kinds of things. So, being able to actually predict ahead of time whose kidneys might be damaged, I'm fascinated by that. Do you know the proteins that go into that, by any chance? Not to-

Rhonda Rhyne: I-

Dr. Jeffrey Gladden: ... put you on the spot, but I would be curious to know. It might be the KIM-1, who knows?

Rhonda Rhyne: I pride myself in knowing everything, but we've been so focused on these two tests... If you want me, I can go look it up, but let's go on.

Dr. Jeffrey Gladden: No, that's good. Well, maybe we'll put it in the show notes for people.

Rhonda Rhyne: Okay. Yeah. And the one test I really want to share with you is this. It’s the only test that we didn't develop in partnership with Mass General Hospital, and it is for Kawasaki disease. And it's a diagnostic for Kawasaki disease, which, as you know, is an acute vasculitis in children, typically under five; fever and rash are the presenting symptoms. And we know there are a lot of children with fever and rash. And time to diagnosis is critical because time to treatment's critical for Kawasaki disease. So, Seattle Children's Research Institute had samples. They had heard about our ability and expertise in developing machine learning-driven tests, and they came to us right about May of 2020 when MISC was in the news, and Kawasaki was in the news around COVID. And we were able to use our platform or process that we had developed with Mass General to very efficiently and accurately develop a diagnostic with about 92% accuracy for Kawasaki disease. 

Dr. Jeffrey Gladden: Wow.

Rhonda Rhyne: That test is not commercialized yet, but it's just in the process of being commercialized.

Dr. Jeffrey Gladden: Okay. Yeah. That's fascinating. Just for the audience to understand this, it does affect children. They have a fever and a rash, but what happens is that the arteries and it's the arteries that feed the heart muscle itself, that get inflamed, if you will. And when those arteries get inflamed, they can have thrombosis, they can have damage to the heart, almost like a heart attack. But one of the things it can do is it can actually weaken the wall of the artery to where they develop these aneurysmal outpouchings off the artery. And it's a very characteristic image if you do a coronary angiogram, or clearly CTA, or something like that. So, it can be a big deal.

Steve Reiter: How common is that? And what are the long-term problems that come out of that?

Dr. Jeffrey Gladden: Yeah, I don't have the exact incidents. It's not like it happens, you know-

Steve Reiter: Yeah.

Dr. Jeffrey Gladden: It's not like every other kid gets it, right? But when it happens, it can be a big deal. So, in my career of doing- We did not do pediatrics. I was not a pediatric cardiologist, but we would see it occasionally in adults, where we would do an angiogram, and we would see what had to have been Kawasaki's disease because they had the classic arteries of that. But it's more on the rare side, quite honestly, but I don't have the figures off the top of my head.

Rhonda Rhyne: In the United States, it's about 6,000 diagnosed cases a year.

Dr. Jeffrey Gladden: Okay.

Rhonda Rhyne: But so many more children are showing up with the fever and rash.

Dr. Jeffrey Gladden: Yeah. It's undiagnosed. 

Rhonda Rhyne: Yeah. Unless you're a specialist, it often goes undiagnosed. And as Dr. Gladden said, you might see it years later, but some of the children develop such bad aneurysms that they, one, live a long life of cardiac complications, and many of them have these aneurysms and have a premature death.

Dr. Jeffrey Gladden: Yeah. Well, that's interesting. So, you found a constellation of markers of proteins that will predict if somebody has Kawasaki's or not? Is that what it is?

Rhonda Rhyne: Yes, there are three proteins. Interesting because there's a lot of overlap in some of these tests. The proteins that were selected by the machine learning, again, was NT-proBNP, high sensitivity CRP, and also unusual, a thyroid type of marker.

Dr. Jeffrey Gladden: Interesting. Yeah. That's fascinating. I love the fact that the machine learning grabs something that you never would've thought of to add and finds that that actually is linked. Yeah. That's very, very cool. What about the PAD, the peripheral vascular disease? Is that available yet?

Rhonda Rhyne: It's soon to be available. It's probably a year, year and a half off. What we prided ourselves in, Dr. Gladden, is we just didn't develop the test at Mass General Hospital, but for our two lead tests, we went and externally validated at the University of Hamburg in Germany and also in Nova in Northern Virginia. 

Dr. Jeffrey Gladden: Okay.

Rhonda Rhyne: And that's what we like to do with all of our tests. So, right now, for Kawasaki disease, we're planning an international study at six different sites. And before we would release a peripheral artery disease for patient use, we would want to externally validate it. And that leads us right into this; we have 32 peer-reviewed presentations and publications. 

Dr. Jeffrey Gladden: Nice. 

Rhonda Rhyne: Our science is very well documented and accepted by the medical community, and we're using immunoassay platforms to measure the proteins. So, those have been around for decades and are very well accepted in clinical medicine.

Dr. Jeffrey Gladden: Nice. Yeah. That's very, very cool. And do you know off the top of your head how many proteins you're measuring in the kidney injury susceptibility test?

Rhonda Rhyne: I still haven't found that, but I will.

Dr. Jeffrey Gladden: Okay. I just keep coming back to that. It's personal interest. So, I would suspect-

Rhonda Rhyne: Well, it'd be-

Dr. Jeffrey Gladden: ... KIM-1 might be in there.

Rhonda Rhyne: Yes. If you do a good enough job on this podcast, we'll let you know.

Dr. Jeffrey Gladden: Yeah, okay. Good enough. Appreciate that. Cool. Well, that's great. So, you've been with the company for how long, then?

Rhonda Rhyne: In August, it'll be 10 years.

Dr. Jeffrey Gladden: Okay. So, you've got a long-term commitment here. I know you've got things in the pipeline to go forward; it sounds like over the next three, four years for sure, to bring these to market, if you will. Yeah.

Rhonda Rhyne: We do. And what we've also done, Dr. Gladden, is looked at patient cohorts that are really important, we feel, clinically, such as diabetics. We actually presented at the American College of Cardiology in 2022 data from HART CBE on diabetics showing that if you are a diabetic, a patient with diabetes, and you're high risk, you have 25 times the likelihood of having a one-year heart attack, stroke, or cardiovascular death compared to if you're a patient without diabetes and low risk. So-

Dr. Jeffrey Gladden: Wow.

Rhonda Rhyne: Some tests are not as accurate on diabetes, but we were very pleased to present this data and are hopeful to be helping this very important patient population. 

Dr. Jeffrey Gladden: Yeah, absolutely. Absolutely. Yeah. And that's part of what we do, quite honestly, at Gladden Longevity, is we end up doing a two-hour glucose tolerance test with an insulin curve for every single client because we've been stunned at how many people have insulin resistance even though they're thin, even though they're fit, and there are genetics that factor into that also. So, like in my own case, my genetics around the incretins in the stomach, which are released when sugar would hit the stomach to signal the pancreas to start releasing insulin in response to what's coming, those signals are loose and faulty. And so, if I drink 75 grams of glucose, my sugar can go as high as 160 or 180, where I'm actually diabetic for an hour. And then my insulin gets the message, and it comes in strong, but two hours later, my blood sugar will be 50, and I'll be shaky and sweaty.

So, it's a classic case of people that aren't diabetic. My hemoglobin A1C is like five, right? So, I'm not diabetic, but it just goes to show you there's a lot more to this than people realize. And when insulin levels are high like that, to control that perceived threat, and when sugar glucose levels are high like that also, people can be damaging their arteries and not know it. And they damage the glycocalyx; we've done a podcast on that, which is these proteoglycans that line the inside of the artery, so to speak, and are actually signaling molecules for when the artery should dilate, et cetera. But when that gets destroyed, then the artery becomes vulnerable to plaque formation and things like that. So, it's interesting that cardiovascular disease develops in real-time. So, while you're eating the ice cream, it's actually happening right now. It's not like, ‘Oh, it's going to happen.’ Yeah. No, it's actually happening this very minute. While I'm eating the ice cream, it's actually happening. So, that's fascinating, too.

Rhonda Rhyne: And the sad thing is pretty soon the ice cream's gone, but the damage remains.

Dr. Jeffrey Gladden: That's right. Yeah. The ice cream is gone, but the tattoo remains. That's right. It's like a bad decision with a tattoo. ‘How am I going to get rid of it?’ Well, cool. Well, it's been really, really nice chatting with you. Are there other things that you would like to bring to bear, or Steve, do you have any questions you'd like to ask?

Steve Reiter: Yeah. Rhonda, you mentioned that Medicare is doing reimbursements for or is covering your tests. For someone who may not be covered, their insurance may say no, how much are they? And can we order it ourselves? How do we find a doctor who is interested in using this as a test?

Rhonda Rhyne: If you visit our website, we can connect you with a doctor that is using the test. And also, there are 37 states in the United States that allow direct-to-consumer tests, and we can arrange the logistics for getting a kit and getting a blood draw. 

Dr. Jeffrey Gladden: Nice.

Steve Reiter: And how much are the two main tests?

Rhonda Rhyne: They range between $199 and $400.

Steve Reiter: Ah.

Rhonda Rhyne: So-

Steve Reiter: That's-

Rhonda Rhyne: Very, very-

Steve Reiter: That's affordable.

Rhonda Rhyne: ... affordable. 

Steve Reiter: Yeah.

Rhonda Rhyne: And as Dr. Gladden brought up, there are no side effects with getting a simple blood test. You are not exposed to radiation or dye. During COVID, many individuals deferred or delayed testing, and heart attacks went up, and adverse cardiovascular events went up. And it's just so easy to get a blood test versus, say, an imaging or a treadmill test. And if you compare, again, the accuracy of our data to the treadmill test or the coronary artery calcium scores, those latter two had accuracies of about 57 to 61% compared to our accuracy in the 85 to 90% range.

Dr. Jeffrey Gladden: Nice. Yeah, no, it's good. It's been a nice addition. We've been pleased to be able to utilize it for our people, so that's been helpful.