Dr. Tom's Keynote on Inflammation & Cardiovascular Disease for the 2023 A4M Spring Congress.

Very happy to be here. And I am going to be honest with you and tell you we may get a little bit conventional here, but I hope to keep half as inspirational as Dr. Jill and Dr. Vincent. Love the diaphragmatic breathing, big believer in mindset and I will start with a full admission here in light of humanity. That may make more sense as we go on here. I'm not going to be at all judgmental about food. Will present some perspectives, but will freely admit I have binge eating disorder. I almost lost my life to binge eating disorder. I did lose my youngest brother Basil, may he rest in peace, to binge eating disorder. And so my perspectives come from both tens of thousands of hours of professional clinical perspective, but also a very personal one. So I hope that that comes through in some way, shape or form as we move through inflammation as it relates to cardiovascular disease. You know, is it smoke, is it fire? I'll make the case. I think it reflects disease often and there are sources that we need to be very careful about. Some very conventional, but hopefully some insights you'll get regarding them, whether it's lipids or insulin sensitivity, blood pressure and so forth. Go into some select biomarkers and talk a bit about autoimmune disorders where I think there is a real risk of inflammation going the other direction and driving cardiovascular disease. And some lifestyle intervention examples from the real world, as well as a tale from the Amazon of the Bolivian Tsimane. Has anyone heard of the tribe in Bolivia from the Amazon, the Bolivian Tsimane? Cool. Well, we're going to talk a little bit about the interesting high levels of inflammation but very low rates of cardiovascular disease in this semi modern horticulturalist group. And I'll give you some summary of what I think are some biomarkers and labs that you might want to really consider. So we see here that inflammation is really at the scene of many crimes, not just cardiovascular disease, cancer, dementia. Many people would consider, I think rightfully so many cases cardiometabolic in nature, particularly vascular dementia. And then of course autoimmune disorders. As I mentioned earlier, this statement is we're focused on cardiovascular inflammation is really important and I think that the chicken or the egg scenario is critical because we want to chase the right source that's causing the fire. And in my opinion, and anyone's free to. Well actually you're not free to throw literal spears at me, but I'm happy to talk about afterwards that the inflammation is a sign of a source of a problem such as LDL particle deposition in the artery Wall, which we'll talk about, not so much the cause in and of itself. And this was the subject of the center for Science and the Public Interest article many years ago, actually. Really still good and I think solid piece on fighting inflammation by a PhD, Bonnie Liebman. Not as simple as some may claim. And the summary of that was that yes, inflammation is markedly associated with many disease states we'd like to avoid or mitigate at that time. And I'd say still, I think it's a bit simplistic to say losing excess weight. I mean, it's about body composition. We could talk about visceral fat and active muscle, but bottom line is a healthy, leaner body is going to often reduce total body inflammation, vascular or otherwise physical activity, short of the acute response of exercise if it is not extreme. Because if you're super sore for the next few days, you're going to be building muscles from micro trauma. But you might have temporary increase in inflammation, but can reduce it if you have high baseline levels and of course eating healthily. But there's a lot to be said there, even in terms of the pointer there in terms of margarines. At that time, of course, trans fats were saturated in margarines and we no longer have that issue. Basically. Trans fats, artificial trans fats, have been banned and out of the food supply for a few years now, thankfully. And so it came down to this question now of omega 6 fats and of inflammation. And we all probably read whether it's Barry Sears, the Zone, et cetera, et cetera, and the purported risk of high omega 6 or linoleic and arachidonic acids producing eicosanoids and prostaglandins that were more inflammatory than omega 3. And you'd want to have a ratio. And I really thought there was a lot of valid thought process to that and I think there was. But when it came down to really studying the data closely, at least from plant based sources, linoleic acid was not at the scene of the crime. And if anything, as you see there, the polyunsaturateds are on the left, Omega 3 and Omega 6, and then there's mono and then there's saturated and trans fats going to the right and Omega 6, as we'll see, and I'll show you some labels on oils, has not been associated with increased cardiovascular risk, as a matter of fact, maybe the opposite. And has a somewhat cholesterol lowering response, maybe even more than somewhat, depending on the person, and doesn't have the predilection for depositing in the viscera, as does saturated and trans fat with monounsaturated fat kind of being in the neutral. And you can see the depiction of the influence of fats on mortality over time. Obviously trans fat off the charts, saturated fat above the line. And you see we're mono, but then polyunsaturated fats, both omega 3 and omega 6, pointing towards improved mortality. But where do you find these? Because in fact I think we'll see a picture where a sunflower seed sunflower was associated with omega, but it depends on the source of the sunflower. So if you're looking at oils, for instance, and I don't believe in using a whole ton of oil in the sense of how calorie dense they are, but you can see that while the grapeseed oil has high polyunsaturated fat, the safflower oil being high in monounsaturated fat, you would think that sunflower seeds might be also high in poly. This particular type, depending on the breed, was high in mono unsaturated fat, which certainly if replaces saturated fat is going to be leaning towards benefit. But maybe the leaning towards a polyunsaturated fat in moderation, such as grapeseed oil might be the. Might be the better choice. Of course then there's always flavor because sorry, but you know, olive oil tastes great. So does chocolate chocolate Minhagen Dazs, which I will, by the way. I don't believe in any zero tolerance approaches. I am a flexitarian, I will admit. I talk about the 5% fun zone with my patients all the time. I don't talk about cheat days and guilty pleasures. But I will freely admit I have found a way to completely stop my absolute top non negotiable chocolate, chocolate mint Haagen Dazs, which I can swear to you I have not had a single bite since the day they stopped making it. That was quite a day. But in RCTs, as you can see here in the summary of this aha document that replacing saturated fat with polyunsaturated vegetable oils, which are largely omega 6, of course there's some linolenic omega 3 walnut oil, for instance, based vegetable oils per se. The cardiovascular risk though drops significantly. So it's a matter of calorie control. Yes, but as far as quality control, we have pretty good evidence that omega 6s polyunsaturated fats are not the inflammatory enemy. Something I can't emphasize enough when we're looking at vascular inflammation. Low is good. And this is in terms of Blood pressure, insulin resistance and LDL particle concentration, or LDL particle particle number, if you will. We'll talk about it. But the lower, the longer, the better. Just getting healthy three months prior to lab tests and then going off and doing what someone was doing prior is not. Is kind of sticking head in the sand. In fact, I remember going to a Blue Zone. How many familiar with. I think Dan Buettner is going to be the keynote speaker in December. So we know blue zones, right? The longevity hotspots from Sardinia, Italy, where I've been to and Loma Linda, California, Okinawa, Japan, Ikaria, Greece, and then in the Nicoyan Peninsula of Costa Rica, which I went to visit. But while I went there, I wasn't eating like Blue zone at all. And in fact I had my LDL particle number checked before, well under 1000 and just not even two weeks after. And it was almost 1400. So that's like a 500 point increase, basically 50% rise in my LDL particle concentration. Fortunately, it was just for a short 5% fun zone period. Now we go to where I think the real instigate, one of the main instigators is when it comes to vascular inflammation. And this depiction is really good as far as the explanation goes. The picture is kind of basic and I'm going to give you much better images in a moment. But as you can see, it says LDL creates and it's not just oxidized, it's any ldl actually. LDL particles create an injury by burrowing into the artery wall, almost like bacteria burrow into the skin and creates a boil or a pimple. I often call atherosclerosis acne of the arteries. That is what then triggers the immune system to send inflammatory cells in, try to clean up the area as it says they're gobbling up. We have a pointer here where the pointer is gobbling up the LDL cholesterol, right? And then these LDL stuffed macrophages form a fatty streak because if the LDL particles don't stop invading, that's what's going to happen. And then of course, over time, decades, in this case, cholesterol, connective tissue and calcium. And talk about this in a moment, when it comes to coronary calcium scores and how this is smoke, not fire, but it is there and is a marker of that there's been a significant amount of inflammation occurs. Of course, if that inflammation doesn't stop as it's trying to do its job, including capturing and sequestering cholesterol with a fibrous cap but that inflammation can, of course, then ironically burn away the fibrous cap, causing the cap to rupture. Or like the pimple popping. If a kid squeezes it and wants to pop their pimple, your blood pressure can squeeze your pimple, your atherosclerotic plaque, and then all of a sudden, you've got a clot forming. No problem if it's on the top of the stage, but if it's in the very narrow arena of the lumen of an artery, you've got a major problem for whatever's downstream from that, AKA heart attack or stroke. So let's take a little closer look. These LDL particles, as you can see, this should be a red background, right? There's blood in the lumen, but nevertheless, there's the endothelial cell layer. The LDL particles are burrowing into the artery wall. The signals for, oh, my gosh, we're getting invaded our scent. And we see immune cells, monocytes, in this case landing on receptors, T cells in this case landing on receptors, coming in, trying to clean it up. There's the pac man. Gobble, gobble, gobble, gobble, gobble. Of course, the LDL particle concentration, probably being pushed in by high blood pressure and welcomed in further by inflammation as time goes on in a vicious cycle, becomes a plaque. There's the pimple, right? But luckily, it's got a fibrous cap over it. We're trying to, like, stuff it under the rug. Let's see if we can just cap this off. Of course, over time, as I repeated here, over decades, the calcium builds up, the inflammation builds up, and that fibrous cap can be very weak at the shoulders, and you end up having a rupture. And then it takes 30 years for this 30, 40% plaque to develop. And in 30 seconds, it ruptures, and you have yourself a thrombus and a sad case like James Gandolfini or one of many hundreds of thousands that happen, largely preventive, with healthy lifestyle over each year. And this is just a depiction of how important it is to know that in one third of cases, the first sign of coronary artery disease is sudden death. Because the plaque size has to be basically 50% or more before you get symptomatic. Running up the stairs and getting chest pain to give you a warning. These 30 to 40% soft plaques, vulnerable like a soft pimple, you start going out. And if you're in Detroit and you're shoveling the snow the first season, first snow of the season, and you know you're thinking I'm just as in shape as whatever NFL football team was. I was just watching. But I've actually been sitting in the chair eating chips and drinking beer the whole time and taking 20, 30 pounds heaves. Your blood pressure goes sky high. You pop one of those plaques. And I'm sure many of you, if you've had an ER background, have seen the first snow of the season in Midwest, like in Detroit, where you get a lot of incoming patients with massive myocardial infarctions, lowering the inflammation, particularly via lifestyle changes, can really calm down the even if it doesn't shrink the plaque immediately, can calm down the inflammation and reduce the risk of a rupture. Rupture. And one of the signs you can see as you saw the calcium in one of the previous slides and a test to consider is a coronary artery calcium scan. I've had three. I'm not saying necessarily that would be right for you. I'm just saying that in a patient in which there's any suspicion that there could be asymptomatic cardiovascular disease, particularly if it's a man over 50 or a post menopausal, a woman, I suppose I would even say if you're 40s and you're chronically smoking. But coronary artery calcium scan can be very helpful to see who is at risk and who has some smoke that can be detected, that's calcium. And then hopefully you can intervene with some lifestyle changes, potentially. Medications. I can't say I have not written for lots of medications, but I always write for a lifestyle as an intervention first. And any score above zero is associated with increased mortality. Any score. In fact, there's been some recent evidence that very high coronary calcium scores may be associated with lower rupture risk because essentially the patient's gotten lucky and they've sealed off the plaque with hard enough roofs that they haven't ruptured. Anyone else has already passed away from cardiovascular disease before getting to that high coronary calcium score or gotten lucky, had a major event and then intervened and hopefully been able to adjust their inflammatory driving risk factors. Just a moment on ldl, because I want to be clear that I'm not talking about LDL cholesterol. LDL cholesterol, at least in individuals. Maybe not population health wise, but it can be very misleading, especially if there's high triglycerides. You can have low LDL cholesterol and have high LDL particle concentration, not just due to the difference in size in the LDL particle. And we're just measuring the content of the internals of LDL when we measure LDL cholesterol. But if you have there's the same amount of cholesterol here as here, but it's the particle number that is same amount of cholesterol here as here, but it's the particle number that drives or apob, if you will. There's two ways you can check by NMR for LDL particle concentration or an apob assay. It's the particle number that matters and what drives the risk. But it's not just the size of the particles, it's also triglyceride content. You can have the same size, but since LDL particles carry cholesterol and triglycerides, if you've got high triglycerides, you're going to displace the amount of cholesterol per particle that can be carried. And you can have a scenario there too where LDL particles are high despite LDL cholesterol being low and not as often. But the opposite is also the case. You can have higher LDL cholesterol but low LDL particle number if you have really big LDL particles and very low triglycerides. As someone who has genetically driven to have very high lipoprotein A, we've heard of this dastardly deed driver, lipoprotein little A. So this is a type and form of LDL cholesterol. It has a plasminogen kringle, a protein attached to it that basically is a decoy for clot breakers and attracts enzymes that would otherwise should be focusing on breaking down clots to it almost in a sense saying oops, just kidding, clots actually over there. And you end up having a higher risk for cardiovascular events. This is particularly in Caucasians. It's a complex issue. But elevated LP little A or lipoprotein little A, it's not seemed to be as much of an issue in African Americans, but nevertheless is worth checking I think at least once in a lifetime. I'll talk about levels in a moment. And especially if there's a family history of early cardiovascular disease and it's not quite clear what's going on. Estrogen is known to lower lipoprotein little A. And if you see a dramatic rise in cholesterol after menopause in a female, it is almost assuredly due to the lack of estrogen then driving up lipoprotein little A. And therefore you have one of the not only issues that cause the immediate the very quick equalization of cardiovascular risk in men. And then postmenopausal women. So I'll admit this is my lipid panel. I can violate my own hipaa, so it's okay. And as you can see here, I have concordant LDL particle numbers. They're below 1000. One might argue if someone had cardiovascular disease, maybe less than 800 or 700 here. But this is low, as is my LDL cholesterol. But my triglycerides, not by genetics, I can assure you of that. Genetics loads the gun, lifestyle pulls the trigger. But the triglycerides are very low. So this is normal and good for in a scenario where you have low triglycerides to have LDL cholesterol and LDL particle number be concordant. But if you had triglycerides here of 160 and of course something 260, 360, you could very well see an LDL cholesterol of 83 and an LDL particle number of 70, 1700 or more. So that's the main point I wanted to point out here, in addition to the emphasis that despite this genetic factor here, I've had zero calcium score, probably have another one five years from the last 55 this summer. So I will have one at 56, just to double check, make sure the pandemic didn't mess up my calcium too much, because I can't tell you that the strength stress didn't drive me towards lesser forms of Haagen Dazs a little bit for comfort. All right, so check once in a lifetime. It is genetic, so it's not going to be affected by lifestyle. Trans fats can increase lipoprotein A, but as we know, trans fats are pretty much out of the food supply. But at least you'll know that you can be more vigilant about and check other family members, including children or brothers, sisters, et cetera, so they can know that they have a risk factor. And if you have levels, depending on how they measure it, of greater than 30 milligram per deciliter or 75 nanomoles per liter, as it was measured, the previous test that you just saw, you know that you could really up your game in terms of blood pressure, LDL particle concentration, weight management, particularly, I should say insulin resistance management. And then of course, resulting reduced levels of inflammation. And there is evidence that LP Little A does drive inflammation as well as does blood pressure. So pressure, I'm going to try to keep it simple in the spirit of Einstein, pushes LDL particles into the artery wall as well as causing muscular stress and then stiffening of the artery wall, which can create a vicious cycle of hypertension as well. But as you can see here, blood pressure stimulating inflammation is a major issue. And how we check blood pressure is a topic I'm going to discuss in just a moment because I don't think we do it, and I'm guilty of it as anybody, but certainly improving substantially. Learning more and more about it. How we check blood pressure, how often we check it, is really important. And there's something about masked hypertension I'll discuss, I hope is a nugget for you to take away from this conference and probably the sodium that's driving a lot of blood pressure, which, I'm sorry, I come from the motor city. So the analogy is salt causing rust in a car. There's oxidative stress to the endothelial wall that occurs with excess sodium intake and sodium accumulation that can instigate inflammation as well. So when you're eating in a healthier, more natural, high potassium to sodium ratio manner of eating, although, although I can't say that it's not true. We don't have over 10 randomized controlled trials on replacing sodium salts with potassium salts for blood pressure as well. But I'd like to think mostly we'll get there through healthier, more minimally processed eating. We can lower blood pressure, lower vascular inflammation in the process, and cardiovascular events. And then what about the other trigger, of course, when it comes to visceral fat. And we could argue that you know, peripheral fat as well, but to some degree. But visceral fat, the kind that's located around the organs that you don't often and easily detect, we certainly know that in general, although every individual deserves to be considered in Asian populations, a mild amount of overweight can result in significant visceral fat accumulation. So significant insulin resistance, high triglycerides. So don't BMI and visceral fat correlate in a large population? But you cannot judge the book by its cover in Cookie Cut. We all know apple versus pear body shapes, just to give a basic depiction of that in our mind, but no question in terms of excess visceral fat driving inflammation as well in the liver, particularly, by the way, I mean, that's what fatty liver disease is. And what is the main treatment for Nash or non alcoholic steatohepatitis, which is some form of hopefully healthy and sustained weight reduction. It's basically, you know, foie gras, you know, instead of just stuffing the animal, overstuffing the animal, we overstuff ourselves and you end up getting fatty liver which is often detected by elevated altogether, which I won't talk a lot about in the, excuse me, comprehensive metabolic or liver panels that we do. And by the way, bummer, we used to think that fat cells couldn't actually multiply after you're fully grown, but it's not true, particularly peripheral fat cells. So that's another reason I don't necessarily recommend that we try to tell people to achieve a normal BMI if their BMI is, you know, for instance, 40, 45, it may never be realistically possible for most to do that. Nor necessary could actually have some untoward risk to pushing someone that hard. But on the. Including muscle loss and so forth, which is one of the reasons that a normal BM, someone who has type 2 diabetes or pre diabetes with normal BMI, that's a real risk. I mean, think about it. You can't really recommend that someone whose normal weight lose weight to deal with their type 2 diabetes. They probably have a scenario in which they have a lot of muscle loss, high fat to muscle ratio, particularly high visceral fat to active muscle ratio. And their goal wouldn't be weight loss so much as body composition change with resistance exercise and optimized nutrition, presuming they're ready and willing to do so. That's another topic of trying to push behavior modification onto people who are not ready and how we talk to people based on stages of readiness for change. You can lead a horse to water. I think you all know the rest. So insulin resistance is not just about body weight or even body fat, but actually active muscle and muscle loss over time. So hopefully we are all engaged in some form of muscle stimulation, whether it's weightlifting or some form of resistance training your own body weight, heck in any way, shape or form move at all. And we're finding more and more that every step counts, every bit of movement probably counts, especially if you're just talking. If you're talking to someone that isn't moving at all, just getting them to move a bit, not necessarily having to Turn into Jack LaLanne, by the way. Jack LaLanne. Anyone know Jack LaLanne? Remember? Right. What, what was his. Was it exercise as king, nutrition as queen, or vice versa? I can't remember which one is which. Together you, you make a kingdom. I think his father died of a heart attack in his 50s, right. And he pulled off till almost 97, working out till the day before he died. Not that I want to be in the San Francisco Bay pulling 70 boats on my 70th birthday in a of state straight jacket or Whatever he did that was a bit much. But so ldl. I hope I've made an impression here that LDL particle invasion into thumb endothelial space, which obviously would be highly increased risk for having happen if you have high LDL particle concentration. Looking at apob, for instance, or if you want to use a standard lipid panel, at least non hdl. Are we familiar with the the concept that we now know non hdl, that's total cholesterol minus the HDL is more aligned with cardiovascular risk and LDL cholesterol, not better than LDL particle number apob, but non hdl, okay, at least we know that. But LDL particle concentration with high blood pressure and then inflammation inducing visceral fat and you've got yourself a scenario where someone's LDL cholesterol might be low, but you're really in a high vascular inflammatory state. And what is driving a lot of this beyond just high saturated fat and so forth, is our calories, just excess calories. If you're trying to shove a lot of extra carbon through an electron transport chain, the final electron acceptor of which is oxygen, and you're going to get a lot of just like an overly rich fuel run car. Sorry, another Motor City analogy. You're going to get a lot of unburnt fuel, which in the case of a human body is going to be carbon buildup in the artery wall and free radicals as a part of the process. And we have a lot of crap. And please keep in mind this is not a pejorative. It is just an acronym for calorie rich, refined and highly processed. I know it sounded like crap food, but that's not the crap you were thinking about. Or maybe in half, tongue in cheek it is, but. And I enjoy a little crap. I think I've made it pretty clear, you know, it's the dose that makes the poison. But we have to be very careful. The side effect profile of excess crap is pretty high and drives up free radical production and of course vascular inflammation as well as its own contributor. And here's how we've done in terms of calorie intake. By the way, look at how our fruit and vegetables have done since 1970 all the way out to 2010. And it's pretty similar to now. I mean, fruits and vegetables have gone basically nowhere. While you know, you can argue carbs, fats, they both have been increasing. Particularly refined starches, the numbers of which you see going up because these are largely refined. 430 calories up to 610 and then refined, mostly refined fats. These are added fats and oils. These are not nuts and seeds. And omega 3 fish we're talking about from 340 to 562 is really amazing. Of course our fruits and vegetables have been stagnant. Now this is based on calories. Pie charts. Interesting analogy, right? Interesting term, right? Pie. Pie charts. Anyway, how about in terms of weight of food? You notice how small the area was for fruit and vegetables when you talked about the amount of calories. But when we talk about weight of food, and this is going to get to something called calorie density in just a moment, you, you see fruits and vegetables make up a larger part of the pie. Nowhere near the half the plate we're supposed to be at, but still a larger amount. And I want to discuss why that's the case because there is a, it's not a hack, it's a randomized controlled trial proven way to help patients feel full on fewer calories by helping them understand calories per bite of food, which is largely driven by water content, intrinsic water. We'll talk about that more in a bit. But what we're really intaking is a lot of calorie dense, a lot of calories very small, in a very small amount of food. So you're getting very little satiety or at least fullness per bite. And of course, when it comes to sugar water, you're getting almost no satiety per calorie. And therefore you can see why we are still stuck in a very precarious scenario. Just to make it really simple, the American Institute on Cancer Research would recommend that calorie density on average, remember foods range from 100 calories per pound to 4,000 calories per pound, or basically essentially from less than a calorie per gram to 9 calories per gram. I've just taken you from broccoli to butter and oils in one fell swoop. So it's the average to prevent cancer at less than 1.25 calories per gram. So that buys you room to do just about anything depending on how often, how much. But oop, we're going to go backwards here, but we are at about 1900 grams of food on average per day for close to 3,000 calories. So we're really pushing it. And it's not fruits and vegetables that's driving the calories per bite or calories per gram or pound, whatever weight unit you want to use. It is all of the very enticing tyranny of the moment driven crap that most of us, like at least a little bit of. And it's free for us to do and, and take risks. We take risks all the time. Take risks while driving. My brothers take risks skydiving. It's not the risk I choose to take, but I can't tell them they're wrong. Cigarette smoking. I don't think I have to convince anybody in here. I'm not going to spend a lot of time on how cigarette smoking can increase the risk of vascular inflammation. It is, it's, it's so well described. What's good to know is that how quickly vascular inflammation can improve when someone quits smoking. The trick is how do you judge somebody's readiness for change and how do you talk to them about it? I just don't personally believe in brow beating methods. How you present your case really is important. Remember, physician or otherwise, I hope we all get to the point that there's a difference between being a document and being God. We are navigators on the patient or client's journey. We are not the pilot. We can't take over the journey. And talking to someone who is in a pre contemplative state of readiness for change is a very different scenario. You are obligated to mention that you're concerned and that there is risk but you can't push it. You could say, look, when you're ready to discuss this, I want you to know I'm here for you. But if you start pushing and browbeating someone who's coming in for their high triglycerides about their smoking and they're not really interested in talking about lifestyle change at all, you know, you're going to have to save some of your energy for the patient in the next room who is actually ready and doesn't want to see the late burned out version of you as you try to swim upstream with someone who wasn't as ready for lifestyle change. So I think by now you know who I believe is on first, who knows these guys, Abbott and Costello. Who's on first, what's on second? I don't know. Thank you. Third base. I heard it. That's my man there. So to me, I really think, in my opinion the critical factors driving vascular inflammation number, not completely, our blood pressure, LDL particle concentration, visceral fat and smoking as the big ones. And at the very least, right, they cannot be missed. At the very least, don't ignore these, don't be distracted, make sure these are as well focused as you possibly can, preferably with lifestyle, but medications if necessary. And how we check blood pressure I mentioned earlier is really important in knowing that a resting blood pressure of less than 120 over 80 is what is considered optimal. In fact in the recent multi ethnic study of atherosclerosis assessment of blood pressure they had actually found that the risk of cardiovascular disease actually starts rising in asymptomatic. I'm not talking about people who are getting dizzy and falling down, but if somebody has a blood pressure of 90 systolic they feel fine. Please don't ask them to do things to raise their blood pressure that is there. It's not a dramatic rise in cardiovascular risk going from 90 to 115. It's small. But with a massive population like the multi ethnic study of atherosclerosis they pretty much determined that blood pressure not via drugs. We don't have evidence of driving systolic pressure below 130 with drugs due to the side effect and it not being entirely a band aid but you know, really not the same as controlling with lifestyle is is not unhealthy at all to have naturally low blood pressure and a lower resting heart rate is a great marker of longevity potential. In fact, someone who has a healthier lower blood pressure has less of a cholesterol problem than someone with equal level of LDL particles because as I said earlier, they have less pressure pushing over time LDL cholesterol into the artery wall. But how do we check a blood pressure? Ideally we should be both feet flat on the floor, back against backrest, resting, quiet environment, at least two minutes depending on the guidelines. You look at arm supported at heart level, supported preferably by a table or someone holding it. But when someone's holding an arm, it's hard for the patient to relax. They're typically going to be contracting their deltoid a little bit which is squeezing their axillary artery and and making the blood pressure downstream from that here, which is just a surrogate for what? Excuse me, what we're interested in, which is of course the aortic blood pressure and making that blood pressure look higher. So as relaxed as you can be and with back against backrest, both feet flat on the floor after a couple minutes resting, preferably no caffeine, alcohol or nicotine for over half hour, then you've got yourself a resting blood pressure still deserves to be repeated. In fact, checking it at home with a FDA approved blood pressure cuff is really even better. Just a one time check in the office is not going to be ideal. And the reason isn't just because of white coat hypertension as I promised earlier and admittedly learned through Luke Laffin, one of the directors of hypertension for the Cleveland Clinic, before finding out it existed in the literature, is that there's mass hypertension and there's a massive number of people who have hypertension that is not apparent in the office. It is the opposite reflection of white coat hypertension. So you have about 20% of patients who have elevated blood pressure that is high outside the office, but not in. Maybe it's because in the office, instead of being freaked out by the doctor, they feel calm, they're in a safe environment. I don't know exactly what the explanation is, but they have consistently high blood pressure outside the office, not in. And that's scary because then you're missing people. So whether, even if it's at a imperfect drugstore, blood pressure station, whatever it takes, because if they're like, I'm not going to get a blood pressure machine, you know, you're just trying to negotiate, get your foot in the door, check the blood pressure somewhere else just to make sure that it is as normal and wonderful as it seems here. Not that I don't trust you, but just trust, but verify. As far as lab tests, high sensitivity C reactive protein is probably the most studied inflammatory marker. It is very sensitive, though, to a number of other issues beyond cardiovascular inflammation, as you'll learn in the story of the Bolivian Tsimane, who have very high HSCRP but very low rates of cardiovascular disease. I won't give away why just yet. So if it's great, if it's low, fantastic, less than 1, excellent. But if it's higher, you don't know if it's necessarily bad. But you should certainly be looking for drivers that might be increasing the crp, including liver disease, which since it's produced in the liver, could be a reflection of some occult liver disease. And since it fluctuates a lot, we're kind of stuck with this should be measured twice over two week or more time, preferably without obviously any acute cold or viral infection or some other acute issue that might cause it to increase. So you can see the dramatic changes that can happen over short periods of time, not so much when it's low. If it's really low, that's probably good, but if it's higher, you might want to double check. So with all this variability, is there a different marker that could be more consistent, not have variation? I can check it one time. It's highly associated with mortality risk. Maybe Glyca, maybe been assessed in huge studies, including Jupiter composite inflammatory biomarker integrates multiple acute phase biological proteins in the serum and will give us something that we can again have without worry about widespread fluctuations. Right. Biological variability is very little definitely significant for mortality and in a sense isn't able to be just masked by statins, which we see. CRP drops as the effect in the liver of statins might decrease where the CRP is produced based on statins. But glycae is a maybe better detector, maybe. I think it's a worthy one to know about at least there's my glycae level there and essentially considered less than 400 here in a very low inflammatory risk zone as far as mortality is concerned. All right, now, insulin, we talked a bit about this by virtue of visceral fat, but we're going to talk about insulin resistance. C peptide is a marker as a test that many use. I prefer fasting insulin. We can talk about that afterwards if someone's interested. I believe that a combination of not only an optimal fasting glucose and A1C but add a fasting insulin is the wiser approach. And I may be a bit extreme on this, but I think that an optimal fasting insulin is not in the normal range of what a typical lab will tell you because that normative range is based on a United States sample population which we are swimming in 90 million people with prediabetes, 90% of which don't know they have it. So that's not the reference normal I want. I'm going to differentiate normal and optimal and tell you I believe that less than 5, using the units that all US labs use for fasting insulin with a fasting glucose of less than 100, maybe even less than 90, would be truly a marker of at least hepatic insulin sensitivity, liver sensitivity, which is a big deal. So I guess in the interest of time, what I'll state here is that beyond inflammation, the fasting insulin, or in this case C peptide level matters. It can independently help you predict cardiovascular events, as it says here, need to target hyperinsulinemia in type 2 diabetes and I would argue in insulin resistance in general for cardiovascular event prevention. And that is, that's particularly the topic here in terms of mortality. This is not good to have high inflammation in general, but I've been asked to speak about cardiovascular disease and inflammation. So hence the conclusion there. Right. Elevated, I would say fasting insulin, C peptide, if you choose to use it, fine, but a strong cardiovascular event biomarker. And don't forget about checking that because it's arguably Also major, I would say contributed to cancer, breast cancer, colon cancer, not friendly to a hyperinsulinemic environment, which isn't always correlated with bmi. I should say it's correlated, but that's not as strongly so as we might commonly think. I just wanted to mention briefly, although it's a very specific and not very sensitive test that this cheap test, the urine protein or urine albumin to creatinine ratio, really reflects vascular inflammation in the kidneys, which reflects vascular inflammation everywhere, not isolated to the kidneys and in hypertension and even insulin resistance at any level. Consider checking a urine albumin to creatinine ratio. If you get an elevated albumin to creatinine ratio. We're not going to detect this protein with a regular, excuse me, with a regular urinalysis that's not going to be sensitive enough to find these small, small amount of albumin that reflects vascular inflammation in the kidneys as a urine albumin to creatinine ratio will. It's a very cheap test. And just as an aside, I think we spend too little time and focus on explaining and telling patients about their gfr. Not really a glomerular filtration rate which gives. Gives you your level of kidney function. I explain to patients that this is basically how many milliliters per minute of blood your kidneys are cleaning. And although filtration and cleaning are, you know, maybe you say that's not specific or precise enough, it's precise enough to get the point across. For all intents and purposes, to a patient, how many milliliters of blood per minute are your kidneys cleaning? And I can tell you you can detect a lot of problems. And we're not going to be talking about expansive topics like multiple myeloma and other things you might oddly detect by, well, maybe not so oddly by understanding and paying attention to gfr. But you get somebody who's dropping their GFR over time. There's someone who's at super high mortality risk, don't forget it. But with all of that making the case that the instigators are blood pressure and insulin sensitivity, or insulin resistance and LDL particle concentration causing the inflammation and not the inflammation causing the cardiovascular disease, the cases where we're talking about systemic inflammation from autoimmune disease can be a different, can be a different story. Maybe not so much in the case of rheumatoid arthritis, but possibly, and they still should be vigilant about it, in my opinion, although they resolved of this analysis was that people with RA are more likely to develop heart disease as they have a number of issues like blood pressure and trouble with movement due to pain. And of course NSAIDs that treat pain, raise blood pressure, et cetera, et cetera. And maybe it's not the RA directly, but it's these other factors. But I can tell you when you have a patient that's ready and has the mindset right, these are what I consider the five keys to optimal health and well being. Our mind matters, or psychology, if you will, made up by mindfulness, mindset, mental health. I'm not here to discuss the five transcendent or what I believe the five transcendent and not related to ethnicity at all can apply to any ethnicity. Principles of nutrition physical activity beyond exercise, non exercise activity time. Our food environment. We are what we eat, but we eat what surrounds us, our social environment. Because if our partners in life are not with us, it's very hard to swim upstream against them. And even understanding our physical environment, heck, just even knowing that winter is coming. Oh, that's Game of Thrones, isn't it? But in Michigan, when winter is coming, a lot of people really lose their physical activity, even though they could have planned for and had a warning called the fall three months prior to. But when somebody's really ready and ready to be accountable and compassionate accountability here. I'm not talking about Jillian Michaels whipping people on a treadmill and making them vomit. I'm talking about engaging with a coach. And I imagine many of you are, and if not everyone in here, a coach. You're coaching people as a navigator on people's journeys. Like Lyn, who you can see has some severe rheumatoid arthritis that was debilitating, caused her to be on disability and was too embarrassed to show in this picture on the left. But and frankly, although it's not typically the case, it's more about mindset. And her case was she was absolutely ready. But her learning about calorie density and that there are foods you could eat to help you feel full on fewer calories because she tended to like to be like myself, be a higher volume eater. And it's, you know, much easier to get someone to eat less calories than less weight of food. Portion control is certainly part of it. And I've learned some skills as a binge eater and what I call the one minute halftime and stopping halfway in the middle of a meal, not restricting how fast I eat the first half at all, but how I will at least at halfway through the meal, stop, put down my fork, drink some water and say hold on a minute, am I eating just the rest just because it tastes good or because I'm actually hungry? But for her calorie density and feeling full on fewer calories was huge. And to this day, eight years later, she's maintaining not only her almost 100 pound weight loss. Not a bariatric surgery case. Not that I have anything against bariatric surgery. I've managed hundreds of patients with bariatric surgery as well. But her inflammatory markers are 50% less. They're not as low as maybe what you and I could achieve without the case of rheumatoid arthritis, but a huge amount of her inflammation and function. She went back to work as a, as a pharmacy assistant for some years after achieving what she did. But she was ready. She was ready. Other forms of autoimmune vascular potential relationship with vascular inflammation Psoriasis. How much of it is controlled? When you ultimately control the psoriasis, you know, make sure the vitamin D level is optimized and everything else may still be a independent factor for vascular risk. I don't doubt that. I'm not saying that's not the case. That if you just control blood pressure and cholesterol and weight in someone with chronic psoriasis, then there's no more problem. It doesn't matter anymore. No, I would say that I'm willing to buy that this inflammatory state could contribute independently to vascular risk. So extra care there. Celiac disease even more interesting in the sense that have been found to have higher cardiovascular risk despite having lower conventional risk factors. So by all means researchers did. Yes, that was a. That's another topic. Gluten free diets. Don't. I won't get started here. We'll talk about them one on one if you wish. But the bottom line is that people with celiac disease may have controlled risk factors but still be at elevated risk. So you might want to help them control what they can control even better beyond what they really need, which is gluten free. They absolutely need gluten free eating. That is where death can ensue without. But they again have to be ready. And keep in mind at the end of all of these KPIs key performance indicators we talk about this is what people want the most. Which is why I really recommend one of the top questions you ask anyone that comes in to see you that's ready for lifestyle change is what is your why? Why do you value health? What is it about what we're going to partner on here that drives you? Oh, I just want to get off all these pills. Yeah, but why? That's not quite a why and you might not even know what your why is. I my why is not complicated. As I said earlier, I'm almost 55, I've got a five and a seven year old and I'm just going to be brutally honest. I'm not going to be a frail 65 year old welcoming 16 year old muscular kids into my house, boyfriends and my daughter. Not going to happen. Sorry. So I'm joking aside, I really want to spend as many years as I can with my kids later in life father so that's my why. But I'm heard whys from I want to have great sex till I'm 90 to I want to walk the Great Wall of China when I'm 80 to a number of things. So what your patient's why is will be very important for you and them to know and can really help drive decisions that they make over time to average towards longevity. Even if they take some occasional calculated risks whether it's food wise or jumping out of planes with parachutes or whatever. That's just part of life and the spice of life if you will. It's another occasion of a very smart educator. Wayne State University Ricardo MBA attorney just could not get his metabolic health under control. Now he's got better insulin levels than me which kind of irritates me but he himself is also maintaining a over 100 pound loss for I think now almost seven years with some recurrence over the pandemic. And then he put his principles, his five keys if you will principles back into the game and frankly a little bit of semaglutide and I'll be happy to talk about that offline as well but not here. Another case remain uncontrolled type 2 diabetes on insulin. Again no issue with I've managed many bariatric surgery patients these are not Romaine is still maintaining Now a almost 200 pound weight loss and a much better life. She could barely get out of a couch and now you see her here on a cruise with her husband. But all these people were ready but then you had to manage that readiness well. So let me tell you about the Bolivian Tsimane. I was fascinated with this discussion. I had a chance to interview on noted you heard about that. If you go to truehealthinitiative.org nonprofit you will see in a drop down the noted interviews news of the day if you will and I had a chance to interview Professor Michael Girvin University of California about him his study on this large Bolivian tribe in the Amazon that weren't hunter gatherers. That's not the right term. He would say semi modern horticulturalists. But remarkably very high HSCRP levels. And after boating hundreds of them down the Amazon to a hospital to get coronary calcium scores, dramatically low coronary calcium scores. I mean, events are almost unheard of in terms of cardiovascular events. These people, of course, eat a plant predominant eating pattern. The flesh that they do eat is fish or bush meat. And it's complemented, of course, with a lot of minimally processed plants. They still, they have a little bit of crap because they've got a boat, they can bring a bunch of candy. And probably maybe about 5%, like blue zones of their calorie intake comes from crap. So it's a dose that is not at the poison level. Hence the 5% fun zone concept. Although I'll admit that when I explain to patients what 5% fun zone really means, the working definition of moderation. In other words, it's whatever amount you need of whatever to not want to kill me until the next time we talk. Because you're the pilot. I'm not, but I'm giving you information. I can give you risk, but I won't tell you what you're doing is good or bad. So a rather impressive evidence that despite high inflammation from what? Intestinal infections, because they're drinking out of rivers, lots of bug bites, things that have nothing to do with cardiovascular inflammation, high HSCRP. I asked if they did lipoprotein phospholipase, a 2 or other more specific. They did not. But nevertheless, very high HSCRP. But lifetime, low LDL blood pressure, insulin parameters, BMI, physical activity, 10 to 20,000 steps per day. I don't think you really need that much, to be honest with you. I mean, if we could just go from 5,000 to 7,000 or 8,000 steps per day on average in the US we would have, I think, huge benefits. From the reflections of the cardio study and others, you have low cardiovascular risk. So just remember what the big players are when it comes to cardiovascular inflammation. So what, I'll end with here and you have the slides and you can review them. I'm happy to talk about them, is what I would say when I look at patients. Would be really nice to say, you know, sort of jumping out of a plane without a parachute or texting while driving. These numbers are what I'd love to see. Resting blood pressure, as we've talked about, less than 120 over 80 heart rate less than 80. 80. Fasting insulin. Not just a fasting glucose, less than 100, but combined with a fasting insulin of less than 5. Because if your fasting insulin is high and your fasting glucose is normal, your pancreas is overworking. It's just kicking the can down the road. It'll burn out eventually, more than likely. Or you might succumb to hyperinsulinemic issues. Prior we've talked about non hdl. That's not bad. If you have access though, and almost everyone does. Check an APOB, that's an LDL particle number less than 100. If it's cardiovascular disease patient maybe even less than 80. And fasting triglycerides we discussed, as well as all of the rest. The ones on the right I'm happy to discuss. We won't be able to get into the cases today, but I'm happy to discuss any of these as we progress in the event here. And you can find me and catch me. I'm happy to talk about it, but at the very least I hope you've gotten a glimpse into the contribution I have for you and the relationship between inflammation and cardiovascular disease. And I can't thank you enough for the opportunity. Have a great rest of the conference.