Transcript
Giovanni Campanile: Hello to everyone.
My name is Giovanni Campanile. I’m a cardiologist. I work with David with Hardy and I do a lot of anti-aging work and that sort of thing.
So, I am going to talk about things that are related to the prevention and reversal of heart disease and that’s the focus of my practice. I’m going to be giving, this is a modification of a talk that I’m going to be giving at IHS in February in New York. So, this is going to be about how to assess and a little bit of lipidology, a little bit about what to do, and some newer technology about how we assess and treat heart disease in terms of prevention and reversal.
So, first of all, heart disease is very much associated with the advanced life expectancy over the past 200 years, which has increased dramatically. And this has increased life expectancy and has created a situation where age-related diseases have become somewhat of epidemic proportions. And that’s because up to recently, we weren’t living long enough to have age-related diseases. Prevention is key, but also reversal of established heart disease and established disease is becoming a big deal in medicine and in anti-aging medicine.
So, the heart disease far and away is the number one cause of problems and death in the western world. It’s a very much a lifestyle disease because in many countries where they don’t have a western lifestyle, heart disease doesn’t even exist. And when we say heart disease, we’re mainly talking about coronary artery disease. And coronary artery disease is a, it’s in Papua New Guinea for instance a team from Harvard went there to look for people with coronary disease and couldn’t find anybody. And while in United States you pick anybody off the street and they probably have heart disease and that was shown by in certain studies like in the Vietnam War the young men who got killed like 18-year-old boys that had autopsies. All of them 100% had some degree of coronary disease, like fatty streaks or something that sort of while the Vietnamese boys had none. And so, and then other studies looking at people that died of auto accidents or suicide, because that’s sort of shown the young people in the United States all have some degree of coronary disease.
The reason for this is that lipids are a major cause, but lipids is a final common pathway of all types of problems. We have traditional risk factors and non-traditional risk factors and all these things come together to increase heart disease, but through via the increase of lipids. Having high lipids is abnormal. A lot of people if you go to these other countries and modern hunter gatherers, their LDL cholesterol 20. Well, the average in America is like a 100/20. So, it’s abnormal to have elevated lipids and this is because lipids respond to things in our environment like smoking, diabetes, and also other things like these non-traditional risk factors and things that are not here are like pollutants and that sort of thing. All increased cholesterol all.
So, aging is very much connected to heart disease, and Hallmarks of Aging as we all know are epigenetic changes, metabolic dysregulation, mitochondrial disease, and inflammation and many other factors. But aging is all these factors of aging also relate to heart disease.
And if you look at the reason at the biomarkers that are related to heart disease. ApoB, if you’re going to look at one biomarker, look at apoB. ApoB is really the number one and if the little blue part of this is the apoB and you can see that the ApoB is really a great marker not only of particles that cause damage but also of the number of particles. ApoB is a factor that goes hand in hand with the LDL particle number and the greater number of particles the greater chance of atherosclerosis.
The way cholesterol comes into our body is there’s an endogenous pathway where LDL’s is formed in the liver. There’s exogenous pathway and that’s through hyperabsorption receptor in the gut. And then there’s a reverse cholesterol transport that removes cholesterol. So, the balance of lipids in our bodies is from these three different pathways. We have ways of measuring if patients have an ability to hyper absorb or hyper produce cholesterol, and that’s very important. Because that treatment especially lifestyle change treatments are very much connected to whether someone is a hyper producer or a hyper absorber of cholesterol. And if you’re a hyper absorber, it’s not only what you ingest. It’s also what’s produced in the liver. There’s an arthropathic circulation where the lipids go back into the gut. They get repicked up and circulates several times before it’s eliminated in the stool. So, it’s not diet but it’s also connected to the production of liver.
So, this is a graph showing the balance. I trained up in Boston in Mass General and the lipidology department there where we looked at mostly are is the apoB, apoA1 ratio and that’s because apoB is a factor that results in atherosclerosis. ApoA1 is a better marker of reverse cholesterol Transport than just looking at HDL cholesterol. And so, if you look at that very tall red line to the right and the back that’s where people have a high apoB, ApoA1 ratio. That’s probably the number one factor if you don’t look at one thing in terms of cardiovascular risk. And the reason why we look at all these different advanced biomarkers is to predict risk better than with just looking at total cholesterol or HDL cholesterol and LDL cholesterol. So, one of the best marks we have is ApoB, apoA1 ratio.
And then we look at inflammation. Inflammation is very important because what inflammation is as we all know is a reaction to injury. But chronic inflammation is a problem because these different cells like dendritic cells, mass cells, macrophages, fibroid, they all create inflammation substances that over time can create disease.
Then this is why we look at these advanced inflammatory markers and I’ll show you some other indications of this. But oxidized LDL, HSCRP, micro album, myeloperoxidase, LP, PLA2, and especially oxPL apoB which is the Oxidized Phospholipid. Very specific markers for worsening atherosclerosis. Because as the atherosclerosis becomes more complex, these inflammatory markers spew out of the atheroma and it’s a marker of disease.
And this is the PL apoB which is very specific for coronary or arterial inflammation. And as is the OxPL apoB. OxPL apoB which I think the way to measure that is through Boston Heart and I measure this quite frequently and very much connected to unstable disease. So, OxPL apoB is not only a sign of coronary disease but also a sign of impending strokes and that sort of thing.
Then the other issue is the LP-Lipoprotein-A or LP(a), which is magnifies or multiplies the risk of the apoB. So, if someone and this is a genetic factor that if someone has this, the way we approach this since we don’t have any good outcomes data for lowering apoB yet, although it’s being looked into, we and it’s a risk factor for atherosclerosis, for thrombosis, and aortic stenosis, what we normally do is just are a little bit more aggressive with the lowering of apoB. Like if someone has LP(a) we try to get the spoB down below, if that they don’t have it we try to get the apoB down below seventy. If they do have apoA then we try to get even lower like 40 or 30.
And then endothelial function is also, the first thing that really happens in arterial disease is endothelial dysfunction and risk factors for coronary disease also affect systemic endothelial function, and this results in coronary disease, kidney disease, eye disease, and also cerebral vascular. So, endothelial disease is really the first thing that happens and actually now we know there’s the glycocalyx, which I’ll show you is also probably even before the endothelial disease begins.
So, Falk is a major researcher in “Atherosclerosis” and he describes as a multifocal smoldering immunoinflammatory disease of medium size and large arteries fueled by lipids.
So, in order to understand this, you need to understand lipidology to a certain extent. This is the schematic of an artery the middle part. Did you see my cursor? Can you see that. Okay, so this is the endothelium and the endothelium is a single cell layer that protects the artery. And then as the apoB goes up, you could see that the apoB is a marker of the number of particles that are accumulating. The higher those numbers, the more likely they are to get between the endothelial cells and get into the sub-endothelium and start causing problems.
And this is when they become modified and oxidized and this is when you start measuring oxidized LDL. That’s when the real problems starts happening. The endothelial cells then start changing. They become defensive and they start spewing out selectins and cellular adhesion molecules and then monocytes start attacking the endothelium cells. And this is when you start seeing IL6 going, and this goes to the liver and then C reactive protein goes up. We know that IL6 is a major marker of inflammation of the arteries, and the CANTOS trial showed by lowering it whatever way you do to lower the IL6, you lower cardiovascular risk. And then monocytes start going inside the artery, the wall, and they start eating up these oxidized LDLs and then foam cells develop. These foam cells become highly inflammatory.
And then these HDL particles, they try to eat this up. The HDL particles or the apoA1, APT1 unlipidated apoA1, if the disease is minor, they can clean this up but if it’s significant, it gets overwhelmed by the system. So, reverse cholesterol transport is overwhelmed by too much atherosclerosis. And then as these foam cells enlarge, they start becoming more inflamed and nitric oxide starts decreasing and Angiotensin II and ATP1 receptors get stimulated and that results in constriction of the artery, hypertension and further progression of the atherosclerosis. And then Collagen fibers start forming and starting trying to heal the artery, but what happens is they become thrombogenic and you can get blood clot formation. This is what causes myocardial fortune is that these collagen fibers open up to the arteries and they start adhering platelets and other and coagulation cascade.
So, this is a normal vessel over here and as we get this diffuse interval thickening, we can measure this with things like CIMT. Then we get endothelial activation which we can measure with reduced endothelial function like with the vendees or endopath, foamy cell formation, early atheroma, and then a complicated plaque. This is really what we want to measure and I’ll show you some newer technology that we can see where we are with the atheroma. Like the clearly artificial intelligence overread of CCTAs.
Some people say that the only people that really understand atherosclerosis are pathologists, because pathologists see what really happens to people after they die unfortunately. So, this is a slide of an atheroma and this happens to be a circumflex artery with a branch artery, and in this branch artery you can see the collagen and calcium but also this red is the thrombosis. It’s the rupture of the plaque and the thrombosis. This is what causes unstable symptom and this is a magnification of this which you can see the thrombosis and this can either heal and then become an atheroma and a blockage or it can rupture more and cause – and this is what we’re trying to avoid.
The goal is to avoid a heart attack. We know we all have a heart attack, but as anti-aging doctors, we want to have heart attacks when we’re 99 in our bed or 100 and but you don’t want to have a heart attack when you’re 60 or 70. Because this as you can see as you lose heart function, this is what really affects quality of life and reduces health span is this big myocardial infection that reduces heart function. You get heart failure, you get it’s atherogenic, further atherogenic because of the particles it creates and also, it’s arrhythmogenic. So, it causes abnormal heartbeats, sudden death, you need defibrillators, many medicines. So, this is something we really want to avoid. So, prevention is key and reverse established heart disease is also key.
So, this is why we look at apoB, it’s apoB is much more predictive of bad outcomes than is non-HDL cholesterol or just LDL cholesterol. So, when we look at these advanced lipid markers, the reason why we do that is not just to do more testing, it’s just because they’re more predictive of bad outcomes.
And then we look at things like ADMA which is indirect measure of endothelial dysfunction and reduced nitric oxide. So, this is something we can measure in the blood ADMA and SDMA and which indicates that there’s low amounts of nitric oxide and an abnormal endothelial function.
The other markers we look at that are very much connected to heart disease and can be changed with lifestyle change is TMAO. TMAO is a novel biomarker. It’s connected to consumption of any meat but mostly red meat and dairy and due to increased amounts of Carnitine, Betaine, Choline and it affect, the reason why it goes up it affects the gut microbiota in a way that the organisms that produce TMAO increase. And this TMAO can be atherogenic. So, it’s something to look at and if someone has a diet, let’s say they’re on a carnivore diet and the TMAO levels up and maybe a reason to have them reduce it. Reduce their meat intake or their dairy intake. This is a way to affect their lifestyle.
Now this is the glycocalyx. This is a photo of a glycocalyx. And glycocalyx is a is a newer finding in arterial disease that and we can see, and the purpose of the glycocalyx is for it mechanical senses things like and it causes either vasal dilatation or vasal constriction of the artery. It also is a blocker of the space between the cells, so it helps prevent things that don’t need to get through, get through, and it’s a selective permeability. The glycocalyx is very important. It’s probably the first thing that gets disrupted before we get endothelial dysfunction and before we get atherosclerosis.
There’s a new test called the Glycocheck, which is very interesting test that can measure through the underneath the tongue, it’s a rheology test that looks at the blood flow of the red cells. And if the glycocalyx is normal, the red cells flow in a certain way and if it’s abnormal, they flow in an abnormal way. So, this is a very easy test to do in the office that you can tell if the glycocalyx is abnormal or normal and then, whatever treatments you give, you can see if they’re working or not working. So, it’s a good way to really check early on if there’s a problem with the arteries.
Other than lifestyle change, diet, and things like that. We can treat these abnormalities with certain medicines. And they work by either decreasing cholesterol by decreasing the cholesterol pool, decreasing cholesterol synthesis, decreasing absorption. Like the PCS canine inhibitors are novel and they decrease the reduction of the LDL receptor. The LDL receptor is very important for removing cholesterol from the body. So, and that was the PCSK9 inhibitors were discovered by looking a group of people that have genetic aberration and they don’t have the PCSK9 receptor. And those people had a very low LDL cholesterol like 20 and almost none of them have heart disease. That’s how the whole PCSK9 receptor blocker was discovered.
As a functional cardiologist, I do use Statins when they’re necessary if I see people with dangerous non-obstructive disease and bad areas, like their left main or their proximally D. I will use statins and one of the things that is in common misconception is that statins always cause side effects. And the actuality of that is that the only 3-to-5% of patients get side effects. This has been very well studied and there’s a nocebo effect which is the opposite of a placebo effect with statins because everyone knows statins cause problems. So, a good amount of patients will get symptoms when they’re on a Statin. And this has been studied by, studies that have looked at have used placebo statins and then the people on the placebo were told they were on a statin but they actually weren’t and they start developing symptoms. So, we know that it’s very unlikely and only 3-to-5% of patients get statin induced myopathy although it’s a real problem. And I think that even if people just like a placebo effect is important, most people has to be taken seriously. If someone feels like they’re getting symptoms, then we have to take them seriously and maybe make some changes.
And the other part of statins is that there’s some Pleotropic effects of statins. That means is that there’s good side effects. Increased nitric oxide inhibition of LVL oxidation, up regulation of endothelial progenitor cells. So, there’s I’m sorry. There’s a lot of good things. In fact, during COVID it was seen in some very well-done studies that people on statins that developed COVID did not die of the lung disease because there’s such strong anti-inflammatory agents. I don’t like using medicines unless I absolutely have to. But I do use the quite a bit.
This is how the PCSK9 inhibitors work. Really remarkable drugs, good outcome data on the furrier trial. And so, this is what happens when the PCSK9 attaches to this blue thing which is the LDL receptor, it what doesn’t degrades the LDL receptor. So, the more PCSK9 you have the more degradation of the LDL receptor and the less removal of LDL you have in the body or the aboB. And what the monoclonal antibody of the PCSK9 does, it attaches to the PCSK9. And so, it doesn’t attach to the receptor. So, you don’t get as much removal of the LDL receptor and that’s basically how it works and it’s quite effective. I use this quite a bit and we get remarkable reductions in apoB.
This is a schematic of a Niemann-Pick receptor and Niemann-Pick receptor resides in the colon and they account for hyper absorption of cholesterol. So, this part of the Niemann-Pick receptor is in the lumen of the colon, and if you have many of these then you tend to hyper absorb saturated fats and cholesterol.
And inactivating the Niemann-Pick receptor has been shown in meta-analysis to be very effective in reducing not only LDL cholesterol but also risk of coronary artery disease.
And then this is the reduction in apoB and LDL cholesterol by the various drugs. Repatha, Inclisiran which is an mRNA, it’s a new drug. You get injected twice a year and it also is a PCSK 9 inhibitor. Not yet widely used but it’s also very effective. Bempedoic acid which also reduces LDL cholesterol and Ezetimibe. So, you can see that the Repatha reduces cholesterol quite significantly or almost 80% reduction.
One of the areas in anti-aging and Neer Barzilai is a friend of mine and he’s doing the TAME trial, and we interviewed him for our podcast. I have a book my wife and I wrote. She’s a physician and we have a podcast and we interviewed Neer and he’s doing the tame trial. Metformin is a very interesting drug because it’s a – that attacks many different areas of aging. The stem cells, cellulose in essence, telomeres, epigenetic effects. So, it’s anti-aging.
And the TAME trial is really interesting trial because it’s really not to test but form it. Through the test to see if the FDA will approve a drug for anti-aging. So very important for anyone who’s in anti-aging to follow this is, because this is the first time this has ever been done. Usually, drugs are targeted for single effects like lowering cholesterol or lowering blood sugar or something that this is multiple different pathways to see if one drug can reduce cancer, can reduce heart disease, improve cognition, decrease mortality.
So, and then if the TAME trial is positive, then this opens the door to other anti-aging drugs which are very much connected to heart disease like SGLT2 inhibitors, ACE inhibitors for anti-aging, not for blood pressure reduction, methylene blue, endospheric. So, all these, so the TAME trial will open the door for many different trials of this kind.
So, one of the things that I like to emphasize to referring doctors and the patients is that a lot of patients say, you get my lipid, you get my cholesterol, my LDL cholesterol down to 20 is not going to affect my brain. It’s going to affect my steroid hormone production and no, the answer is no. because what we measure in the blood does not correlate with what’s going on in the cell membrane, what’s going on in steroid hormones, in the brain, they don’t correlate, because cholesterol is so vitally important for those processes. Each and every one of our cells is able to make the cholesterol it needs. So, the total blood cholesterol is not a big percentage of the total body cholesterol. So, even if you get the cholesterol in half, it’s not really affecting the total body cholesterol in any big way. So, that’s a somewhat of a myth or a misconception about lowering cholesterol too much because and again, you go back to where we should be with cholesterol and we should be much lower than we are. Cholesterol in Americans is very high and it’s one of the reasons why we have such an epidemic of heart disease.
So, this is the slide I show when I give these talks is the top picture is a picture of Hawaii. Things are good. Nothing’s happening. So, you don’t have to worry. Why test if nothing’s happening. On the other hand, if you had ways of knowing that you were going to be attack like a Pearl Harbor like way before it happened, you would want to do those tests. So, this is one of the reasons why we do the testing we do is to see what’s coming, what’s around the corner.
And this is important because this study which was done in 2018 showed that a lot of problems like heart attacks are missed and we don’t have, and they’re missed because we don’t have good ways of determining what’s happening. We depend on emergency room doctors and other doctors looking at things and maybe not seeing things that are there. For instance, in EKGs now we have artificial intelligence looking at EKGs or looking at EEGs which can predict myocardial fractions and strokes and that sort of thing in a much better way.
So real time EKG monitoring with AI overread is much more accurate in determining the risk of heart disease than having people just look at an EKG.
And this goes for EEGs also. EEG with artificial intelligence overread, the probability of determining a stroke is much higher because strokes just like heart attacks are missed quite a bit.
And this is what’s fascinating about AI EKG which is becoming a big area in in cardiology is that AI EKGs can predict problems and I’ll show you a recent study can predict let’s say atrial fibrillation, before it happens much more accurately than a chat scores some other way, we look at this. And also, it predicts chronological age better than any other age measure we have. What’s interesting is that AI EKG can even tell us if the patient is male or female. It’s quite remarkable things that cardiologist can’t see. We can’t interpret but the AI can.
So, deep learning electrocardiograms, this is a recent study just published in Jama showed that it predicts atrial fibrillation. Just looking at a rest in EKG in a normal patient, no atrial fibrillation. You get AI EKG; you look at it and it predicts with 80% accuracy within 31 days whether someone’s going to get an episode of atrial fibrillation. So, it’s probably going to become the best way we have of predicting that and as you know, atrial fibrillation is a major risk factor for strokes and other problems.
So, this is example of a Boston Heart. If you haven’t seen this, this is the advanced lipid marker. The three best are Berkeley, Cleveland, and Boston. I train in Boston. I train with Schaefer, the guy who started the company. I think it’s a very high-quality company and it and it shows this thing. Again, the reason why we look at this sort of thing is just sort of predict problems better. If someone had a very low risk advanced lipid panel, then we don’t have to go crazy with treatment or risk factor changes or changing their diet. On the other hand, if this shows what we call atherogenic dyslipidemia and that means like elevated apoB, elevated LDL particle number, if the LP(a) is elevated, apoB, apoA1 ratio, and then inflammatory markers, then this top right panel is the quality of the HDL. It tells us if the HDL is doing the reverse cholesterol transport because we don’t have a good way to measure reverse cholesterol transport.
So, this tells us if the reverse cholesterol transport is happening or not happening to a higher percent. And then the balance test tells us where the cholesterol’s coming from. Like the two top markers are liver production markers and the two bottom markers are absorption from the gut. Somewhat of an indirect marker of those Niemann-Pick receptors. And then the genetics, the specific genetics for heart disease like statin-induced myopathy sort of predicts if they’re going to have –, if a patient can have a problem with statins, Plavix or clopidogrel, apoB, and then factor two and factor five. These are all simple but important genetic markers.
Then, the endothelial Function. Like I said previously, we can measure blood tests like ADMA and SDMA, but this endopath or vendees or ways to measure endothelial function. And when you use this in addition to scores like the syntax score, it increases the prediction of problems significantly. 25% increase prediction rate.
So, this is a CIMT and we use this quite a bit. We use this on most of our patients and it’s a intimae media thickness test to see if there’s atherosclerosis starting in the intimate. This is the where it starts to begin with. So, it’s a very good test to determine if there’s the beginnings of atherosclerosis and also to follow patients because this is noninvasive. It’s just ultrasound. You can do this on a yearly basis and see. And we have many patients that have either progression of disease or regression of disease and this is the way we do it.
This is the typical read out of a CIMT and it gives you an arterial age which is important. It’s also important from a motivating factor for the patients. When they see their arterial age may be little bit too high. It motivates them to do what we tell them to do.
Now obesity is very important but more important is the type of fat there is. Visceral adipose tissue is highly inflammation and we really want to know if the patient has a significant amount of visceral adipose tissue because this is connected to a whole lot of problems.
Obesity, some people say it’s not a disease. We can’t call it a disease but it is a disease. It’s connected to many different things. Hypertension, erectile dysfunction, NAFL-D, osteoporosis, it is a disease.
And fatty liver is also a big problem. It’s important to know if your patient has fatty liver because it’s connected to a lot of downstream problems like insulin resistance, problems with lipids, it’s thrombogenic, and so it affects many different things. So, knowing if your patient has NAFL-D or non-alcoholic fatty liver disease is very important.
And this is, we have in our office the 770 in body and we can measure the visceral fat area which is very important. Not only can it measure the percent body fat, skeletal muscle mass, the extracellular water, the total body water ratio which is an indirect measure of inflammation. But it also measures the visceral fat which is very important. The other way to do this is with a DexaScan. DexaScan has a little bit of radiation but it’s a little bit better in a way, because you can see where the visceral fat is. This gives you a total visceral fat area. The DexaScan tells you exactly where it is. But we use this quite a bit. We follow this to make sure whatever we tell the patient to do, whatever way they’re losing weight, because we don’t want patients to lose skeletal muscle mass. Because sarcopenia metabolically is not a good thing and we measure the amount of, so we want to balance the visceral fat loss to the skeletal muscle mass and we use this on every patient every time we see them.
So, this is the Holy Grail of anti-aging cardiology is identifying a vulnerable plaque. And what a vulnerable plaque means is if we have stable atherosclerosis, really doesn’t usually do anything unless it’s obstructing the artery and causing angina or chest pain. But a vulnerable plaque is very dangerous because it can rupture. It can cause heart attacks and unstable angina or acute coronary syndrome.
So, one of the ways we have is by doing Calcium Scores and calcium score is helpful. It inexpensive and very low radiation and it gives us some idea and I think the only benefit of a calcium score to me is if it’s negative, it’s zero. If it any amount of calcium increases the patient’s risk and there’s no real reason to follow calcium scores on a serial basis. And if you look at this with a Calcium Score of zero, the risk is low and then, as any amount of calcium goes up, the risk goes up. But more importantly, what you wanna know and the Calcium Score doesn’t tell you this is that you have non-calcified plaque and we have newer technology that can show us that.
And this shows a plaque, as only a small percentage of the plaque is calcium. The rest of it is inflammatory cells lipid rich core of necrotic cells and fibrous tissues. So, just looking at calcium alone may not tell you the whole story and I do the newer clear test quite a bit and I’m seeing a growing number of patients that have Calcium Scores of zero and have significant non-calcified plaque.
And this is the newer technology clearly, which is a CAT scan a CCTA which is a coronary CTA with contrast and then with artificial intelligence overread. It can differentiate non-calcified plaque into inflamed and non-inflamed plaque and you really want to know if the patient has a good amount of non-inflamed plaque. I mean, inflamed plaque because inflamed plaque is really what poses problems. So, again, I’m seeing and this is being born out in the literature. There’s a not an insignificant number of patients with CT coronary calcium scores of zero that have significant non-calcified plaque.
The other thing we see is heart rate variability, that is the difference in the timing between QRS complexes on an EKG and it’s imperceptible to the human eye. I mean you have to have two sophisticated machineries; you have some sort of machinery to measure this and it’s a risk factor. If it’s low, if you have what you want is a lot of variability between heartbeats. If there’s a low amount of like metronomically perfectly that’s not good. You want it to be variable the and that variability is a sign of dysautonomia or autonomic dysfunction. It’s one of the measures of parasympathetic versus sympathetic nervous system. So, it’s related to a lot of different things, not just the heart, but it is a risk factor for heart disease and cardiac side and death. Exercise, diet, connection with others and stress management all help this. I use heart math quite a bit for biofeedback and biofeedback helps this to a great extent.
The other thing that we look at is metabolic disease and CGMs have become more common. And we’re finding that people are, they develop these things called Glucotypes depending on their CGM findings and depending on what they respond to what they don’t respond to. And it’s a way to monitor your personalized effects of food on you. My wife and I did us together and we had completely different responses to some foods. Mine went up, for hers didn’t. So, it helps you personalize your own diet because we never know in patients, we have patients that had I mean, I had a patient that he was eating salmon and his blood sugar go up and then he was eating at a restaurant. And what he found out was this topping or sauce they were using was making the blood sugar go up. So, he realized that he should not do that, do something a little different. So, it helps you modify your diet in a good way.
So, this is just to show, these are stents. We don’t like using stents. I used to put in a lot of stents. I used to be in Lennox Hill. I put in 500, 600 stents a year. This is I think a failure of preventive cardiology but very effective in certain sittings. We know stents do not prevent heart attacks and they’re not to be used unless someone has heart attack, unstable angina, or acute coronary syndrome, or if they’re having angina that is not responding to treatment like medicines and that sort of thing. Other than that, when I first started doing stents, we used to see a blockage and put a stent in. We thought that was the right thing to do. It made intuitive sense. It’s not correct. You don’t want to have this ocular stenotic reflux. You want to treat, patients get treated better with lifestyle change, some supplements, and that sort of thing rather than using stents unless it’s used in the proper setting.
And this is Bypass surgery. Another, I call it failure preventive medicine for endocardiology. It’s but very effective. As David knows for surgery is life saving and patients that need surgery, we’re lucky we have this. In America, we’re lucky we have the system we have because if you have a heart attack, you want to be in America. Even though we’re at the highest risk of having heart attacks and that’s probably why we have the best treatment. Almost every hospital, I set up the interventional program in Key West, Florida. It’s the most remote cardiac Cath lab in the country. And only in America would they even think about setting up an interventional stenting program in such a remote location, but even in Alaska, anywhere in the country if you have a heart attack in America, it’s the best place to be. What we like to do as anti-aging doctors is prevent this.
So, this is the CANTOS trial which showed lowering inflammation with anti-inflammatory medication decrease events and that’s cardiac events significantly as significantly as lowering lipids or maybe even more. So, this was a randomized controlled trial that showed that inflammation reduction is very important.
As is this trial looking at Colchicine, which is a gout medication was also anti-inflammatory and it showed a significant reduction in cardiovascular events. And that maybe why statins work. Statins may not work only because they lower cholesterol. They probably work more because they’re pleiotropic effects and their inflammatory reduction more than their cholesterol lowering.
So, one of the problems in America is that we have terrible, terrible diets. Since the 1950s we’ve been trying to tell the public about things, but we’ve been eating worse and worse and worse and this contributes significantly to the problem.
This is an egg-McMuffin and with a study looking at nuclear factor kappaB and F-kappaB and if you look at the timeline on the bottom, after eating this, the NF-kappaB goes up and stays up for hours. So, if you’re eating this sort of diet on a regular, if you eat this every once in a while, your body can deal with this but if you’re doing this every day, twice a day kind of thing. It’s a major risk factor and NF-kabppB as one example of problematic molecules, it causes a lot of problems with tumor cell proliferation, cellular metabolism androgenesis. So, extension of tumors that’s pro-inflammatory and a lot of cardiovascular arterial problems.
And one of the problems we have is our food supply is depleted, because of a whole flu of factors. We look at food like organic food is being healthy. But that only tells us that it doesn’t have pesticides. The quality of the food comes from the soil. And our soil is depleted. My son he went to medical school for 2 years, hated it. And now is a regenerative farm in North Carolina and he’s been trying to create great soil for years and it takes time. So, factory farms, they don’t do it. Because if you look at a at a plant that roots of a plant the roots go down normally naturally like 6 or 7-feet into the ground. If you only have like a few inches of soil with artificial fertilizers, your food is not going to be rich in nutrients.
In fact, many studies have shown this. If you look at food from 1950s versus more modern foods, the amount of nutrients is 25 times less. Scientific American did a whole study in this on those types of foods because they did a study in 1950. They know what the content was and they know what content is today. So, this is one of the reasons I tell my patients we sometimes need supplements in addition to food, because the food may not be good enough.
So, we know that there’s all types of good diets. A prudent diet or versus like a Mediterranean diet is usually what I recommend. My wife and I wrote a book about the Mediterranean diet from Sicily, but the Mediterranean diet is simply a good diet. It’s a sensible diet. It’s an omnivore diet. You’d eat everything, but you eat saturated fats in low quantities, carbohydrates in low quantities. And what’s super important about this is the effect on the microbiome, because of the high fiber content, the variety of fibers and the and the microbiome is healthy, versus American diet or SAD diet, a Standard American Diet is unhealthy in a lot of ways. High in sugar, high in fat and affects the microbiome in a bad way.
The microbiome, which is the mixed of good bacteria, viruses, fungi in our gut are very important for all sorts of issues in our body and we’re at the very beginning of knowledge about this. But we know now that it’s related to TMAO production, lipopolysaccharide production and all sorts of things that can decrease health and also affect aging. This is a very big issue in anti-aging. My wife and I did a study of centenarians and super-centenarians in Sicily. And some people we didn’t do this, but some other people looked at their stool testing and they have a very good mix of bacteria in their stools.
And then, we know that diet is related to not only obesity but also a slew of problems like inflammation, oxidative stress, mitochondrial dysfunction, all related to depression. Our mental status is directly related to our diet and our microbiome and our mental status or either depression or anxiety can increase cardiovascular risk. In fact, there’s a study looking at people that were depressed after a myocardial fortune at a six-fold increase in sudden death versus people that were not depressed. So, it’s very important to have the mental status part of this in line with good health.
So, there are several randomized controlled trials looking at diet and the very first one or one of the very first ones was the Lyon Diet-Heart Study. This looked at a Mediterranean diet as opposed to the American Heart Association Diet at that time. And there was a significant decrease and these are the patients in this trial were all patients at high risk. They all had an either a heart attack or some kind of heart procedure. And it showed a significant decrease in outcomes with the Mediterranean diet. What was interesting about this trials that enrolled patients I think up to age 85 or 87, and even in the 80s there was a change with changing the diet. So, it just goes to show epigenetically we’re always able to change and then the PREDIMED trial also showed a significant decrease in cardiovascular events mostly strokes with a Mediterranean style diet with olive oil and nuts. And this was the interesting thing about this trial was done in Spain and the Spanish population already has a semi, most of them have a Mediterranean diet. So, this was just a show the beneficial effects in a population that already was on Mediterranean diet.
So, Mediterranean diets and inflammation, there’s meta-analysis showed a significant decrease in multiple studies of various inflammatory markers. Cancer, again, meta-analysis of different types of cancer showed a significant decrease in cancers and all sorts of chronic diseases. Heart disease, stroke, type 2 diabetes, and this is another meta-analysis of chronic diseases.
So, fish oil or Omega-3 fatty acid has been in the news, it’s a little controversial and I think the reason for that is that the studies are not done properly. I think the study should be done with an Omega-3 fatty acid index to determine, because everyone has an absorption that absorbs fatty acids differently. And this is a meta-analysis of fish oils on cardiovascular outcomes and it shows a significant improvement with people that are on good amounts of fish oil.
So, the other thing that a lot of people don’t realize is that lifestyle change is changing your diet, exercise can impact tremendously on outcomes. This is a study by Ornish looking at a significant stenosis and the bottom one is a PET-scan which is probably the best study that’s why we have a measure of blood flow and patients are put on a lifestyle change program. Improved diet, exercise, reduced stress, connection with others and within a short period of time, there was a significant improvement not only in the blood flow. I think there was a 300-fold increase in blood flow but also an improvement of the blockage itself.
And Telomere Lengths also change up the front of your just lifestyle change. So, lifestyle change can make is very impactful. Changing your diet, changing your exercise parameters. Now, we’re learning more and more about what type of exercise is best.
And this is Elissa Epel with Elizabeth Blackburn. Elizabeth Blackburn won the Nobel Prize for telomeres and showing that mindfulness meditation can actually have an effect on telomeres which is remarkable. There’s a lot of studies looking at mindfulness and meditation on things like blood sugar and hypertension. So, these things have a significant effect on cognitive stress.
Sleep, we’re learning more and more about sleep. Now we know about the mechanism of detoxification of the brain through the lymphatics that only happens in deep sleep. So, you need to get a certain amount of sleep to have that happen because if that doesn’t happen, there’s a significant amount of stress on the body including the heart. So, both short and long sleep durations increase the risk of mortality, where the sweet spots probably 7-to-8 hours where you get the greatest amount of sleep. I have a lot of patients that use Oura rings to measure the quality of the sleep. And the benefit of an Oura ring whatever wearable is that you can change things you do. Like let’s say you have a glass of wine right before you go to bed, that affects sleep. So, you can change things you do to get the optimal amount of sleep.
And exercise as we know has a significant amount. One of the best things you can do for anti-aging is exercise and one of the things we discovered when we did our studies of patients that are centenarians in Sicily was none of them stayed still all day. None of them really went to gyms or did any excessive exercise, but they never sat in front of a TV or computer for any length of time. So, exercise, for a variety of reasons on the peripheral nervous system. It affects the blood system, the bone and cartilage, the liver, the mitochondria. And both resistance, aerobic, high-intensity interval training, weight training, all these things are important. So, I usually recommend to my patients to do them all. Stretch, yoga, something that sort. Aerobic or zone 2 training for two or three times a week, and then high intensity info training where you do episode zone 5. You go up need as much as you can go and go down. Tabata was the guy in Japan who really discovered this and his recommendation is 20 seconds, 10 seconds, but there’s all sorts of ways you can do this. And then some resistance, both for the bones and the muscles.
So, physical activity again has been shown to reduce all-cause mortality by good studies by a significant degree in this meta-analysis by 33%, which is significant.
And then for the glycocalyx, we have different things we can do. Medications that affected actually statins is not on this list but statins help with the glycocalyx positively. Nitric oxide, hydrocortisone, N-acetylcysteine, Metformin and then there’s these other supplements that have either Ramanan in it or chondroitin sulfate or glucosamine sulfate. The arterosil is widely marketed and I think it’s very effective, but it’s the dosage of this Ramanan is not high in the arterisil. And so, from a cost-effective standpoint, you can get things with chondroitin and glucosamine which help at a much, if it’s an issue for the patients at a much more reasonable a cost.
So, Nattokinase is also very effective especially patients with LP little A elevation because LP little A is like plasminogen. It’s very similar to plasminogen. It’s very thrombogenic. So, Nattokinase which is a fibrinolytic and anti-thrombotic agent helps, but also lowers lipids. So, I use this quite frequently and I almost always use it in patients with significant LP(a) elevation.
Now, SGLT2 inhibitors, this have been shown to significantly help the aging process and helps cardiovascular disease and it reduces cardiovascular oxidative stress, and it helps the endothelium significantly with endothelial markers.
There’s this study just came out on their Med journal. I think it just came out this week and patients with cardiovascular disease without diabetes which is interesting but they’re obese, it improves cardiovascular outcomes non-fatal myocardial functions and non-fatal strokes –. So, Semaglutide and SGLT2 inhibitors you know are very useful in patients that are obese not only make them lose weight but it lowers their cardiovascular and stroke risk.
A lot of patients ask me about Niacin. Niacin has never really been proven to help outcomes. It can reduce actually can help it reduces LP(a) and it reduces lipids, but it doesn’t have an outcome, there’s no good outcomes data on niacin. So, I tend not to use it because of that. We don’t and as I tell my patients, I don’t really care about your cholesterol. I care about your outcomes. What’s going to happen to you. And if there’s no good outcomes data then I don’t see a reason to use it.
Bergamot is an interesting derivative from a citrus brand from originally from Calabria, Calabria Italy owned in Italy. And it’s a very effective natural way to affect lipids. It lowers LDL, total cholesterol, triglycerides, and increases HDL. So, it’s bergamot. I use usually if I see a patient, I do a clearly test on them. I do a Boston heart and if they’re risk is not elevated, not significantly elevated. I usually start out with dietary changes, supplements like bergamot, and then as a last resort medications.
Berberine is also a very interesting molecule. It helps many different things and for cholesterol, it can act as a PCSK9 inhibitor. So, not everyone responds to berberine but the people that do respond, respond really well. It actually helps atherosclerosis. It can help cardiac injury after myocardial infraction and it can help reduce regress atherosclerosis.
Rapamycin is an interesting molecule. We use these types of drugs in drug eluding stents. The drug is rapamycin or one of these types of medications, and it affects the smooth muscle proliferation in the arteries, but rapamycin is an anti-aging drug used and it’s being studied in dogs. There’s a big dog study going on to see if dogs live long with rapamycin and it also helps heart failure. And in this study, the number of myocytes with rapamycin was significantly improved as compared to the non-rapamycin arm of the study. So, it affects mTOR and also helps this remodeling factor in heart failure in and may help people recover from myocardial functions.
So, this is red light therapy and Vielight is one of these companies that has this red-light therapy but we use red light therapy externally for a lot of reasons. But red-light therapy is also been shown for heart failure and increasing myocytes. There’re all types of novel ways to implement this and the Vielight uses a nasal probe and because of the aeration of the face, it affects arteries and has a systemic effect. So, it’s a new area of research and there’s not a lot of great data on it, but there’s some interesting data coming out about red-light therapy and heart disease.
Sauna, is incredibly well studied in Finland of course because in Finland everyone has a Sauna. So, the cardiologist that the universities there study this quite a bit. And Sauna therapy has been shown to really affect cardiovascular risk in a good way. It decreases inflammation. It’s an antioxidant, increases, it helps you relieve toxin, and it augments well markers of exercise like markers of exercise, heat shock proteins that go up with exercise also go up with Sauna. So, one of the ways that sauna is used is that you use it right after exercise. You take nitric oxide before you exercise, stop exercise and then use Sauna. And that combination seems to be quite effective to increase all the markers of exercise including heat shock proteins, and it’s detoxifies. So, it’s a good thing to add into your armamentum, your tools of anti-aging and helping your heart.
Cryotherapy also is anti-inflammatory; plaque has been looked at and markers of plaque instability have improved with cryotherapy. So, cryotherapy or any kind of cold exposure is good the way. I know I don’t have a cryotherapy machine in my house. What I do is after I exercise, I fill the bathtub with ice, water, and lion it for 5 minutes including my head and I feel great. I think my dopamine levels go way up.
Hyperbaric oxygen has also been shown to help a number of things including heart disease. It suppresses cellular senescence. It’s an anti-inflammatory it helps androgenesis and it’s a significant antioxidant. So, hyperbaric oxygen is a newer way to affect the anti-aging and heart disease.
Intermittent fasting, I also interviewed Valter Longo is a friend. He’s the one of the preeminent authorities on fasting. He’s the guy who developed pro on and he’s at San Francisco, University of San Francisco. So, fasting and there’s different ways of doing it in different terminology. There’s time restricted eating where you stop eating at a certain hour and you don’t eat for 3 hours before you go to bed and then you eat again 14-to-6 hours later. That’s time restricted eating. Intermittent fasting is when don’t eat for a day or two during the week or you do fasting mimicking diet where five days you do a restricted caloric diet. 1,000 calories day-1, 700-800 calories day 2, 3, 4 & 5. And this has been shown to all these things have been shown to improve markers of aging including ATP productional, mitochondrial biogenesis, BDNF in the brain, brain derived neurotropic factor. So, it’s a very good thing to do on a regular basis.
Now we have all sorts of wearables that we use. We use the Withthings Smart Scale. I think David uses this in Hardy and there’s all sorts of watches and blood pressure and continuous blood sugar monitors, micro sampling. So, all these things are growing way for patients to monitor their own health and these things are now becoming they communicate with each other. So, we’re being able to see on a community-wide basis what’s happening with health.
So, this is the book I wrote with my wife. My practice is “FunctionalHeart.com” and hopefully this information has been helpful and I’ll be happy to answer questions now or anytime about any of this. Thank you. Thank you.
Dr. David Luu: Job, job you can have a glass of water now. Wow. That was amazing.
Giovanni Campanile: Oh, thank you.
Dr. David Luu: Thank you. Thank you so much. Like Salome said, the bar is high now.
Giovanni Campanile: Yeah.
Dr. David Luu: Okay, let’s go to your question. Wherever is going to the conference. Amy, you want to start?
Amy: Yeah, I have a question. That was so good. Thank you. I took a 1000-notes.
Giovanni Campanile: Thank you.
Amy: Are we able the AI EKG? Are those is that something that’s available currently and if so, how would we get our hands on that?
Giovanni Campanile: No, it’s research only right now.
Amy: Alright.
Giovanni Campanile: I want to get my hands on it myself, but I can’t.
Amy: Okay.
Dr. David Luu: Apple will buy it soon enough. Throw it in the Apple and we’ll have troubles.
Giovanni Campanile: Absolutely. I’m sure there’ll be a wearable version of it very soon. I just, this morning I did conference call with a company that does remote monitoring for cardiac rehabilitation. So, that’s a growing area also doing cardiac rehab remotely in the patient’s home. Dean Ornish is also a friend of mine. He does a home intensive cardiac rehab program. They actually send food to the patient’s house. They have one of the nurses connect with the patient and they do exercises. They actually send the patient a machine to exercise on which gives feedback back to them. It’s doing all this at home, out of the hospital, out of offices is probably the biggest shift in things that we we’re doing.
Amy: I have one more question. I’ve been doing a lot of reading lately because I have, I do a lot of hormone education and interest in hormones. I’ve been reading a lot and seeing there’s several articles that show that different types of oral estrogen actually decrease LP(a). And I’m just wondering if that’s something that you’ve actually seen in your practice at all.
Giovanni Campanile: We have, my anti-aging practice is CorAeon and we in New York and we work. My partner is a compound pharmacist who’s an expert in hormones. And we use hormones quite a bit and we’ve seen not only, we’ve seen LP(a) go down in patients that are on estrogen. And I think estrogen is probably one of the best molecules for postmenopausal women for reduction of heart risk. And I think that there’s a misconception as we all know that the studies that have been done about this are weren’t done well. So, women have a fear, an unfounded fear of estrogen. I think it works quite well. We see reductions and we actually see endothelial function improve. We see body composition improve. All sorts of things. So, I think that, I’m a big fan of using estrogen for cardiovascular risk reductions.
Amy: Have you seen, sorry I don’t mean to hog that, this is my last question I promise. Have you and the studies that I’ve read as far as cardiovascular risk disease. It looks like the transdermal estrogens don’t actually have as much effect. It really does look like the oral and the first pass effect is important. But I know a lot of doctors transdermal is very common especially in the functional medicine world. Have you seen a difference in the type of estrogen that’s been administered as far as not just lipids but cardio disease?
Giovanni Campanile: Well, there’s been a trend, we haven’t been using oral until recently and I’ve seen a difference in the patients. My focus is not hormones but I see these patients because we see them together and I’ve seen a difference with the oral. So, I think that and I don’t know of any good studies because it’s too new, but I think there is a difference. I think it affects them in a better way.
Amy: Great. Thank you so much.
Giovanni Campanile: Oh, sure.
Joseph Raffaele: I have a couple questions if you have time. Tour to force really an excellent presentation, but I just want to focus on the PCSK9 inhibitors. It’s such a potent reduction in LDL cholesterol. You talk about the genetic model where they have a deficiency of PCSK9. Are those individuals that they have other health issues? I mean, PCSK9 exist for a reason and so knocking it out genetically like a knockout basically. Is that have any off-target adverse effects? They don’t have cardiovascular disease, because if doesn’t then why wouldn’t we all be on PCSK9 inhibitors and drop our LDL down or apoB down to 30. Even not worrying about the whole concept of number needed to treat, even if you are low risk if it adds 10 more years from your 90 to 100 or 100-110. And so, what’s the downside and with statins there’s issues with myopathy if you’re one of those people also there’s also concern about blood sugar control issues. So, my question is…
Giovanni Campanile: There’re the same concerns with PCSK9. They cause myopathies. They cause blood sugar issues. So, it’s not without risk and the genetic patients don’t seem to have those problems. I think that’s an effect of the drug more than the genetic, pleiotropy. It’s more of a drug effect and these are relatively new drugs and again, as any new drug we find out more and more and more what the problems are. But in patients that I only use these drugs in patients that actually need them and if they have, this is why clearly has really changed preventive cardiology because before, we really never knew if patients had high-risk atherosclerosis.
As I showed you that the vulnerable plaque is really the thing we want to know about. If you don’t have a vulnerable plaque, you don’t have to be super aggressive in getting your down. But if you do, it’s a good way. I mean, there are risks but those risks are worth it.
Joseph Raffaele: That’s a great answer. I think I wasn’t aware that there was myopathy and blood sugar issues with the PCSK9 inhibitors.
Giovanni Campanile: Yeah, there are. I mean, we haven’t seen it yet quite a bit, but it is reported.
Joseph Raffaele: I guess getting to…
Giovanni Campanile: I’m sorry, I have seen myopathy. I’m sorry. I have one patient. She developed significant myopathy with Repatha, but one patient.
Joseph Raffaele: And my question, I do I’ve done about a dozen or so clearly analysis and what number, let’s say and I’ve had patients with zero calcium. What number of millimeters cubed of soft plaque would you consider significant?
Giovanni Campanile: Well, any amount is that normal, but over 100 millimeters cubed of total plaque volume I think is when I start getting worried.
Joseph Raffaele: Right. So, similar to the coronary calcium is just it could be plaque, soft plaque or calcified plaque basically.
Giovanni Campanile: Right. But again, if you have, a lot of my patients are high risk, they have family history, they have lipid issues, and they have a zero Calcium Score and I still, I don’t know in those patients what their real risk is unless they do it clearly. The problem clearly, of course, is that it’s expensive and patients don’t always want to do it but I think if the cost is not an issue, the radiation is about the same for a calcium score and a clearly test. In fact, the radiation in our center is about 1.5-to-2 MERS, which it’s not that much. It’s worth the information. I think that the risks with radiation is clearly outweighed by the risk of atherosclerosis. So, it’s a worthwhile price to pay, I think.
Joseph Raffaele: I totally agree with you and I’m finding most patients aren’t that resistant to it really certainly my practice, and it just brings me to the question of the carotid intima-media thickness. They do them all the time and first instruments back in the late 90s and then got a Panasonic Cardio Health which is very advanced and I think a really good instrument. But I saw a lot of discordance between CIMT and coronary calcium scores. And people with established known Atheros, I have guys with CIMT that’s 0.6, 0.7 in coronary calcium score of 3,000. Likewise, I have patients that have a CIMT that shows significant thinking coming up on one millimeter, but zero calcium and zero clearly analysis.
I mean maybe 8 millimeters or something like that. So actually, when Panasonics stopped supporting and making the machines, I stopped using it and I was just wondering why you see that discordance. And does that mean anything in a person with a clearly analysis that’s is effectively zero, but a CIMT of one.
Giovanni Campanile: I think the problem with CIMT and I agree with you to a certain extent is that it is There’s a lot of variability between imagers, one and the other. So, the way we do it which is like a little bit difficult to do. We have a technician; he comes from Colorado. It’s always the same guy. He comes in, he does the same study on the same way on the patients. And so, it’s more reliable that way, but I agree with you. If you have like a CIMT done in one center than you do in another, it’s not, there’s a lot of variability between the person, because the way you read it depends on the angle of the probe. So, it can be read wrong. It’s just all like echocardiogram is the same thing. I mean the technician that does the echo, if they do the probe on a doppler echo in the wrong way you’re going to get a completely different reading than some other echo. So, that’s why the person doing the study is very important.
Joseph Raffaele: And I agree with that in follow up that all is true, but let’s assume you have great technician and they’re doing a great job and this is like a perfect CIMT. Are we seeing and it seems some sort of a different path physiological process that’s going on that’s causing thickening? Is it even earlier warner warning sign in the carotid artery that we’re not picking up in the coronary arteries with a very sensitive test like the clearly analysis? And if we are, does it make you uncomfortable to see somebody with CIMT of one with no heterogeneity of the image to look for that shows sort of actual plaque, but meeting that plaque sort of number at one millimeter thickness? Is that something you want to treat or worry about even if they’re clearly now in the corn areas is still zero? They used to say it was like a 95% concordance between the crowded CIMT and the coronaries, but I just wasn’t seeing that in my practice, and I wonder whether is this like a like a glycocalyx issue or I mean obviously it’s not the glycocalyx isn’t that thick? But do you want to try to stop that process and is it a different sort of thing that you want some sort of different theological process.
Giovanni Campanile: The way we use CIMT is serially over time.
Joseph Raffaele: Right. Yeah, sure. The change, right?
And if we see a CIMT like we do it every year on every one of our patients. So, we see, it correlates pretty well year to year and we can see if there’s a trend to worsening or improvement. And I think that’s where it really helps is that what trend is it more than the actual number on that one image. I think it is important even if something like clearly is completely negative because clearly, I think you have to have a little bit more advanced disease than in CIMT.
Joseph Raffaele: That’s my question. Okay.
Giovanni Campanile: I think the CIMT, earlier disease. So, if you have someone that has you know, let’s say they’re a hyper absorber and their CIMT is borderline and they’re clearly as negative, then, I would say to them change your diet or change your lifestyle in a way that we can measure next year to see if your CIMT is improving. If it’s significantly abnormal, then that leads to other testing. But it’s a way to also motivate the patient. If the patient has risk factors and we’re trying to help them along, it’s one way to show them this is this is happening. We think this is means that you’re starting to build a plaque. You know, you really want to prevent this. So, I think the CIMT is very helpful for very early plaque protection.
Joseph Raffaele: Great, thank you.
Dr. David Luu: Regarding your question about the PSCK9, you can read about Verve Therapidex. I don’t know if you know this company.
Giovanni Campanile: No.
Dr. David Luu: So, Verve Therapidex is basically a gene editing and they are they published data I think few days ago. And they had in their core they had two deaths, right? So, we don’t know if it’s related to the PCSK9 inhibition or not probably they were like sick patient obviously, but then you can investigate and look a little bit…
Giovanni Campanile: Crisper, that’s the crisper technology.
Dr. David Luu: That’s a crisper. Yeah.
Giovanni Campanile: It’s a lifelong therapy.
Dr. David Luu: It’s like a vaccine, right? That’s going to be like one injection and then you’re done.
Giovanni Campanile: I know the guys up at the Brigham that are involved with that study. So, it’s yeah, fascinating. But I think we’re a little bit a long way somewhat of a long way off before it’s used in patients, because we don’t know the long, you don’t want a lifelong therapy that made effects but it may be amazing. So, you don’t have to take medicines. I think what will happen with that technology is that someone comes in with an MI, a heart attack, or acute coronary syndrome. They get one injection of that and they’re done with lipid management. But sounds like a great thing, but I think we have to see what the side effect profile is in terms of gene manipulation long term.
Dr. David Luu: That’s only the beginning but I guess this is, we are.
Giovanni Campanile: In animals it’s amazing. The results, I’ve read about the animal studies in pigs and things. It’s really fascinating and really no side effects in animals.
Dr. David Luu: Do you have questions? Dave or Salome?
David Lipman: I’ll let Salome go but otherwise I just have. You mentioned primary prevention with Niacin and as a sort of there’s not a lot of outcome data in that stuff. I’m just interested in like primary prevention that it seems really mechanically makes a ton of sense lowering things like apoB and that. Like do we have any data on what’s best for in a primary prevention setting? Like you mentioned or maybe your take might be that it’s secondary prevention if we have a positive clearly, right? If you’ve got suggestive clearly then perhaps it’s not primary prevention, it’s a secondary prevention situation already.
Giovanni Campanile: Well, I think in most Americans it’s secondary prevent. That’s the problem. It’s a lot of people in the western, that’s why there’s 20 million deaths from heart disease in the western world is that our lifestyle is such that it leads to disease and its usually secondary prevention. Even though from a diagnosis standpoint secondary prevention is only when you’ve had an MI or you’ve had a stent. I don’t believe that. I think secondary prevent and that’s where something like clearly comes in. If you even have a mild or moderate amount of plague, I think I always look at it from secondary prevention standpoint.
So, I think if someone doesn’t tolerate anything and they don’t really want to be on any they only want to be on natural you know I have patients that say I’m not taking any medicines under any circumstances. In that case, then I do use Niacin sometimes in those cases or red yeast rice or these other supplements that lower risk. We don’t know like even in red yeast rice, we don’t know if they lower outcomes, but if diet’s not doing it and that and lifestyle changes not doing it, then we have to use, we sort of tend to use something.
Dr. David Luu: But you said it was lowering LP(a), right?
Giovanni Campanile: Yeah, LP(a). But that’s the thing about LP(a) is that all the studies that have looked at drugs that lower them. First of all, drugs are not safe. But when you lower LP(a) with drugs, so far there’s no outcomes improvement. So, again we don’t know if it’s worth it to do that.
David Layman: The only other question I had, you mentioned a few times sort of reversal and that really interested me like I was under the impression that was not something that really was that possible. Can you talk a little bit about reversal you’re seeing? Are you seeing changes?
Giovanni Campanile: Yeah, no reversal is not, when they say it’s not possible what they mean what people are talking about is calcified plaque. And calcified plaque is probably irreversible. Although there’s some data showing that maybe a little bit reversible, but the non-calcified plaque is reversible. We see this all the time. We’ve seen this quite a bit and like I and I’ve showed you the Orange Data shows a significant amount of reversal disease. His program is something that a lot of my patients don’t want to do you know it’s a 10% fat vegetarian diet and I do use that sort of thing like – in patients let’s say come to us, they’re on the verge of needing bypass surgery, right? They’ve triple vessel we want to do something like an intervention and you could do that for a year or two and then that I usually liberalize the diet to adding in fish and doing more like a Mediterranean style diet. But it does work. I mean we do see someone changes their lifestyle significantly loses their visceral adipose tissue, endothelial function improves. So, it does, it’s quite effective in the short term.
David Layman: Awesome. Thank you.
Dr. David Luu: And they’re working as well on some drugs reversing calcified plaque right now. So, there is some companies working on that.
Giovanni Campanile: Yeah, that’s the data where they’re working on that sort of thing. I haven’t seen anything super convincing, but I think it’s an area. I mean calcified plaque is stable. So, the non-calcified plaque what we, it can go in either direction. It can go either reverse and go away or come calcified. Either way, that’s a stabilizing effect. You see that quite a bit in patients that have a calcium score, they go on a statin and then their calcium score goes up and they say, why is my calcium score going up. And that’s because the non-calcified plaque is becoming calcified and that’s the natural friend of plaque is that it’s first starts out non calcified, then it becomes calcified.
So, once it becomes calcified, it usually doesn’t rupture. It usually is stable. So, it doesn’t cause a heart attack or acute coronary syndrome. So, in an optimal world, we don’t want any calcium but it’s better than the low density non-calcified plaque which is inflamed and prone to rupture. So, if you’re to and you can’t really direct which way it goes. So, you do your management and the plaque, the non-calcified plaque can go in either direction. So, you can see sometimes increasing calcification. That’s why it’s not that helpful to do repeat calcium score because it, even if it goes up, what does that mean? It doesn’t really mean much.
Dr. David Luu: Alright. Thank you so much. I think we’re going to end this amazing lecture and going to meet in the next time.
Giovanni Campanile: Well, thank you. Thank you.
Joseph Raffaele: Thanks very much. It was great.
Amy: Thank you.
