Nehal N. Mehta, MD, joins Georgia Heart Institute as a Cardiovascular Grand Rounds speaker during the CME lectures for 2022. Dr. Mehta is the chief of the Lab of Inflammation and Cardiometabolic Diseases at the National Heart Lung and Blood Institute as well as a Clinical Professor of Medicine at George Washington University. Dr. Mehta discusses cardiometabolic disease and coronary risk stratification. To receive CME credit for this presentation, please visit the survey link. [https://www.surveymonkey.com/r/XZRVZTM]
Good morning and welcome to Georgia heart grand rounds. This program is provided by Georgia Heart institute. With support from our industry partners. The planners have disclosed no relevant financial relationships with commercial interests. The presenter receives grant and research support from NIH Nvs Celgene and Abbvie and is a consultant for NBS Abbvie and Amgen. These relationships do not influence today's presentation to claim cmI credits today answer the survey evaluation. The link will be put into the chat. If you have a question for the presenter please type it into the Q. And a section and I will read it at the end. And now Dr SAM OD, president of Georgia Heart will introduce dr Mehta. Well good morning everyone. It's it's a huge honor and a privilege to present this morning's grand round cardiovascular speaker at the Georgia Heart institute. Um This morning speakers. Dr Nihal Mehta who's currently Lasker senior investigator and chief of lab of inflammation, cardio metabolic disease at the N. H. L. B. I. Um Dr Maeda attended an accelerated seven year biomedical program um at the Universe at George Washington University where he um received his B. A. With honors in 1997. Um and then his M. D. In 2001. Um He subsequently uh went to the University of pennsylvania and in 2009 received a. M. S. C. E. And genetic epidemiology. He then stayed at at penn to do um internship residency and chief medical residency followed by um cardiovascular disease, nuclear and preventive cardiology fellowships. After all this training, he decided to do a postdoctoral fellowship in genetic epidemiology with focus on inflammation and lipoproteins at the um renowned University of Pennsylvania Center of Clinical epidemiology and biostatistics as well as the Institute of Translational Medicine and Therapeutics. In 2009 Dr Mehta joined the faculty in the cardiovascular division of the University of Pennsylvania. Um and remained a associate scholar at the clinical epidemiology and biostatistics unit. In 2012 he was recruited to the National Institute of Health as the inaugural Lasker clinical research scholar um joining the NHL B. I's cardiovascular and pulmonary branch. In addition to the Lasker scholarship doctor made I received has received numerous local and national awards including being named fellow of the American College of Physicians in the American Heart Association. He's actively involved in several foundations and organizations um and he's got leadership opportunities and capacities that the american Heart Association as well as the National psoriasis Foundation. As you here today he's leading some of the work and understanding cardiovascular aspects of psoriasis. Nihal is also editor of the section of cardiovascular metabolic and lipoprotein translation in the journal of translational Medicine and serves um as a reviewer on several international grants um As well as by medical journal. So you can see that um we are absolutely privileged and honored to have dr Mehta join us to give cardiovascular grand rounds this morning on C. C. T. A. For risk stratification and why it may be the future. Ni hao welcome to Georgia Heart Institute cardiovascular grand rounds. Thank you so much. It is such a pleasure to be here. Doctor Samadi. And you know it's interesting. I have been thinking a lot about uh risk stratification. We're just at the heels of the C. R. T. Meeting and I've been keeping up on updates and I'm going to spend some time today going through how we have looked at cardio metabolic diseases from a different lens and using that as a springboard for risk stratification across different populations. So I left some time for questions at the end. I know virtual talks are a little bit difficult to interrupt and ask questions. So please do put them in the chat as they come up. It makes for a more lively Q. And a um dr Samadi and I have had a long history of collaboration that I will end the talk with. But before we get there and get to some very exciting CCT A. Data I would like to start with some basics so that we're all on the same page. So good morning my name is Nate or Metta. And you know doctor Samadi gave me such a nice introduction. I don't have many many things to add except I want to remind you I am a cardiologist because what gives what gives the impression of me being a dermatologist by the middle of the talk. I want to just remind you that I'm a cardiologist because I will I will talk about some of those um cardiac risk stratification issues. So cardio metabolic diseases. Let's get started. We used to call them metabolic syndrome, the deadly quartet. Uh But what we've learned is that not all five or four will run together in the same person. So about maybe 10 years ago, uh they changed they being the endocrine society and others changed the term to cardio metabolic diseases. And what is that? So its presence of any atherosclerosis, insulin resistance, obesity or high cholesterol. So you could look at any patient who has treated with a statin and you can say you have cardio metabolic disease. And I think this is very important. I'm going to go through a case. So I run a few practices around the country uh inflammatory risk stratification for cardiovascular diseases. And here's the case. It's a 44 year old female. She comes in with borderline hypertension, untreated psoriasis. And it turns out that she came in for the evaluation because her longtime friend had stents placed a couple weeks ago. I think it woke up a little bit in her. She's on no medications. Mom had type two diabetes. My dad had a myocardial infarction at 50 for both of those increase the likelihood of her having one of those by about 25%. Her social history was significant for tobacco use about half a pack per day. She had no general medical complaints. Her physical exam demonstrated. You could see it highlighted in red here. Her physical exam demonstrated that she had um diastolic hypertension, blood pressure of 1 44/89 body mass index of 32. Which most of us may say it's average. Especially in your part of the country. This might be average but it's not okay. It's obese. Anything over 30 is obese um waist to hip ratio. You know, holding a lot in the middle there apple shaped, not pear shaped um And then 9% of the body covered with psoriasis. So look at your palm right now. Your palm is a great thing. It gives you the size of about four ounces of meat. So if you're trying to figure out how much meat to eat or protein to eat, look at your palm. Um It also tells you 1% of your body surface area. So this is 9% This woman has plaques on her body. So a solid moderate psoriasis. Her labs for our american counterparts are on the left. Our european counterparts, if we have any are on the right total cholesterol of 2 10 LDL of 1 59 triglycerides of 200. Um HDL of 40. And the fasting sugar at 44 1 16. I mean this screams metabolic Disl epidemiology. I hope you see that basically a an increase in a probie lipoproteins which is LDL and triglycerides with the suppression of a pro a lipoproteins which is HDL. So in classic chief resident form a case summary 40 for untreated moderate psoriasis. She's smoking. She has a history of C. A. D. In her family, she has high blood pressure, she's obese, she's got a glucose of 1 16 consistent with prediabetes. What is our problem with this patient? Her cardiovascular risk which is driven by her age, turns out to be fairly low. I'm gonna go through one algorithm. I used this slide just because it's so great for illustration that even 30 years ago we were onto the concept that listen you look at their risk factors age, lipids, diabetes and smoking and you predict a 10 year risk when you look at someone like this. This is purely cookbook medicine. The slide is old on purpose because it still tells you for Framingham risk score by LDL is 9% 9% puts her right in that low risk category. We all know that a patient who's 44 has some smoking history, family history um obesity, insulin resistance. All that stuff flies under the radar. So what I'm here to do today is talk about inflammatory diseases and why do I talk about inflammatory diseases? Because I do believe they're the sixth risk factor in heart disease were not able to detect it readily. So I'm going to talk about some image guided therapy and image guidance risk stratification that I'd like to point out first we have to get on the same page. That inflammation is important Data here show that in the women's health study, those healthy women who had an elevated crp had a single fourfold risk of having future cardiovascular events. So why psoriasis? Well, psoriasis is a common inflammatory skin disease. Very undiagnosed. So someone may statistically have it. Who's watching this? And if you look at the upper right, I don't know if my mouse will show, but you'll see here. This is approximately 10 Palms just on his trunk. So this is severe cutaneous psoriasis affecting the trunk and in that person there's over one billion immune cells activated in that person. What my lab did in the clinical Center for Epidemiology and biostatistics partnering with Dr Joel gelfand is we did a series of epidemiological studies which started in 4006 and ended when I went to the NIH in 2012. And in those six years we found three things. Number one people with psoriasis die faster. Okay, They died five years faster and the five years faster is due to cardiovascular disease infection and cancer. And the immune system is involved in all three. What we took to the bank, if you will is that a young patient with Psoriasis has a twofold risk of having a heart attack. So that's called the statistical age interaction. And that age interaction was what was reported in this paper in Jama seminal paper in 2006. Finally, the third finding on this slide is that when you look at what these adjusted abnormalities are for hazard ratios, it's anywhere between 43 58% in fully adjusted models. Therefore, the single diagnosis of psoriasis portends an increased risk of cardio metabolic diseases and in this case cardiovascular disease. Therefore, I remind you I'm a cardiologist but I'm utilizing this disease to understand the immune footprint, the systemic inflammation and the lipoprotein dysfunction. Which lead to this tombstone myocardial infarction on the right, That myocardial infarction on the right has a 58% of regulation in those with psoriasis. So there is something that we're missing here. Well what is it? So I was grateful to the Lasker Foundation of the National Heart, lung and Blood Institute and the National Institutes of Health In 2012. DR Collins welcomed me here as the first Lasker clinical scholar and I started a giant cohort study. So the first thing I did is I I put together a five year now, 10 year thanks to, you know, the funding patterns, we have a 10 year cohort study on following patients with psoriasis and we compare them to the protocol below. So I remind you hear how things work at the intramural program at the NIH. I do not give out money. People are always very nice to me thinking I'm going to be a grant funder. I do not give out money, I'm actually an intramural scientist who takes the same grant money that others do. And here there are two such protocols. This is the equivalent of two R. O. Ones. The first one basically take psoriasis and those are followed with imaging visits in green. And then by four years we have three serial images and they're all deeply phenotype. We get pet ct pet M. R. I. Coronary CT A. In all of these people. And the psoriasis data is compared during a flare and then its treatment. So I'm going to show you some treatment effects of storms of inflammation. Protocol too is healthy diabetics and coronary disease. And we compare Protocol one to Protocol two and we get the same amount of deep phenotype ng another good piece of news. Just this last month we've been approved to have longitudinal enrollment of protocol too. So we'll have 0 to 1 year data and we'll have 0 to 4 year data. Very exciting. There's very few studies in the world. There's actually none that will allow you to scan repeatedly patients with subclinical atherosclerosis. But we have made enough of an understanding of a throw progression that we've been able to do these studies and I'm going to share some of that data with you today First I'd like to point out that psoriasis is as inflamed as an acute coronary syndrome. So shown here is 100 and 20 psoriasis patients walking in to my clinic comparing them to patients who have a proven a CS in my er compared to those who came in with chest pain without E. K. G. Changes in proponents. So we have a control group on the right, a real group of a CS in the middle. That dr samadi probably would open up the cath lab for in most cases. And then psoriasis that our walkie talkie in the Naples clinic. Look at the TNF alpha and I own one beta levels astounding five times higher I. 01 data levels in psoriasis nine times higher levels of TNF alpha and psoriasis. These are people who are walking and talking and they are having inflammation on a daily basis that resembles an acute coronary syndrome. Secondly, I've spent my last three years of my postdoctoral fellowship studying lipids because I thought that lipids would interact with in immunology and and and create this milieu of accelerated atherosclerosis. Imagine you took a light and you shined it through a tube of blood. Okay. And that's NMR spectroscopy and what this shows you is is that there's a normal pattern of lipid e mia here. The intermediate dense lipoproteins are on the left and then you'll see that the right side here is the high density lipoproteins in psoriasis compared to controls there's this Appleby shift. So remember I had shown you our patient has more triglycerides and more LDL. And that LDL is small and dense. We know that small dense LDL is bad from diabetics. And we've now extrapolated that into chronic inflammatory populations. Third, imagine your body had a way of reversing the cholesterol out of it. Well it does. And that's HDL. HDL performance of reverse cholesterol transport starts when the nation HDL finds its way to a lipid loaded macrophage using an abc A one transporter. It? S terrifies it into a mature HDL and then by going back into the liver using an sRB one scavenger receptor pathway. It poops it out into the bile. So our body has a way of taking the cholesterol out. Imagine that this custodial system was aberrant. Well, that's what we first discovered in psoriasis in 2012, I wondered if this whole disease was a constipation of the cholesterol that it is handling in the body. And shown here, I would usually laugh at a grad student for trying to make a story of something like this, right? You're gonna talk about 78% differences. 78% every day of their lives. I eat an egg 80 80 mg of cholesterol. My body will excrete probably 79.5 mg of that cholesterol maybe more. A patient with psoriasis will hold on to six mg of that cholesterol deposited in the skin deposited in the bone marrow and this is not unique to psoriasis and why? Because it retards HDL function so HDL dysfunction apo b lipoproteins and a lot of systemic inflammation Makes for a very terrible milieu for a three genesis. So what I've done in this first maybe 15 to 20 minutes of the talk is I've hopefully convinced you I'm a cardiologist that studies psoriasis as a model to understand inflammatory pathogenesis. It has a waxing and waning course. They develop CBD at a young age. Why wait for the event? Why wait for the event? You know, really bothers me that we haven't changed that paradigm yet. And then finally there's a broad range of therapies that are FDA approved that allow me to use this as a human experiment if you will when they get their clinical treatment. So I'm going to talk about that last bullet which I think has thrusted our program. In fact, that's how Habib and I got to know each other was we shared a podium at the C. R. T. Together. Okay now let's get to some fun. We're talking about multimodal imaging. Okay so I started the program in 12 doing the studies on the right F. D. G. Pet cT and F. D. G. P. M. R. If if you're familiar with F. D. G. You might know it from the oncology world basically we give radioactive glucose and it goes to metabolically active tissues. I discovered in 2006 that you can look at the area of vascular inflammation in the aorta and it correlated very well to one's general cardiovascular health. We then fused it to a. C. T. And we were able to check out whether there is distance ability issues and other things that M. R. Allows. But my favorite attending at Penn just retired. His name was Irvin Hurley. And he taught me on on cardiology rounds on our rounds for fellowship. Now. How do you know who Willie Sutton is? And I used to laugh. I'm like Willie Sutton. Yes I do. It was a bank robber. Willie Sutton. Sutton's favorite quote was why would you rob a convenience store where you could go to where the money is? Go rob a bank. Right. So I got to the NIH and I realized why not go to the coronaries and might not go to where we think the myocardial infarction are actually starting and ending with path of physiology. So we incorporated the C. C. T. A. Which is what I'm going to focus most of the rest of my talk on. And that will give us before an event a plaque burden which I'm going to show you how to do that. But before I do that I want to show you a few images that along our journey to 2017 in 2011 this was the world's first image we compared psoriasis to non psoriasis. And this defined psoriasis as a serious autoimmune disease. Okay what you'll see here on right is a on left is a healthy control woman um kidneys and bladder homogeneous uptake. What you'll see in the patient with psoriasis a male. Um Just for illustrative purposes is for findings, you'll see uptake in the joints when this person doesn't have psoriatic arthritis. You'll see uptake in the skin where there's psoriatic lesions. You'll see there's a heavy amount of hepatic uptake. We'll call that the story attic liver and then finally we'll see this area of the aorta which just lights up this area of vascular inflammation. Now I just joined twitter about a year ago but this was 2015. I didn't have twitter but I did learn that this image on the right generated a lot of tweets why? For the first time patients with psoriasis found that what was seen on the outside of their body in a pasi score on the X axis was mirrored by vascular inflammation on the Y axis. So for the first time patients with psoriasis used to say when I look bad on the outside, I'm feeling bad on the inside. Well so is your aorta. Look at your aorta here, right. I mean I've never seen this amount of uptake in an aortic wall. I'm not going to have time to go over it but that aortic uptake directly relates to coronary plaque burden. So is at this time never published this because I wasn't sure what to make of it. But we had our post my studies coming in and boy did that vascular inflammation look just as though someone just had an M. I. So they look like psoriasis. They looked like an M. I. And it was this year around 2015 that we asked this question. It's psoriasis in fact shares inflammatory pathways with coronary disease. Might the coronaries be affected? So it took us three years to get the right number of patients. I'm gonna see if this plays. We're very blessed and I will tell you I love collaborating. Habib knows that and if anybody would like to at the end I'll put all of my info up. Just buzz me if there's something that I show you here that interests you just reach out to me. I I highly recommend working through the data. That's you know, hours if you will. So C. C. T. A. Upper left. We have two such scanners. We can do these scans in an order of magnitude lower than other radiation studies on the bottom left. This is I'm running low on battery. Let me just get a charger one second if you don't mind. Excuse me back to our lady. Give me one second. Sorry guys all right back to the L. A. D. So subtract the ashes structure to practice. Myocardial structures were left with an A. C. C. H. A. 17 segment model of coronary disease blows my mind that we took this long to get here. Why look right and look at my finger front side, back medial. You get four views. You see inner and outer contours you get what's called a coronary plaque burden there's a mixed calcified plaque goes down. We stop and distal prune at the spatial resolution of the software as well as the machine. What do we get? So on the bottom if you care about the techniques, if you're a method person um at the top if you just want to know what's going on, we use software called Q. N. G. O. From the Netherlands. We basically are able to pacify the lumen so cracked out it and left with what the coronary wall thickness that coronary wall thickness has been dubbed the plaque volume. I look at it as a coronary wall thickness and I've gotten questions about the spatial resolution. It's absolutely correlated to O. C. T. It's correlated very well to what we see later on when these rupture and geographically um We have a few cases about 11 events that we've had in the cohort. Um And then finally we have different lengths of segments. So we normalize that to when it gets down to the distal pruning of the vessel. And we get something called a plaque index. It's been published in the european Heart journal Jama cardiology circulation and cardiovascular research. We felt like we did the gamut of all four because we felt that people needed to understand that this is a continuous outcome that you can follow before somebody develops a plaque or an M. I I'm going to show you some of that data. Okay. First hand. So I told you I'd get you to 2017. We saw five years of journey left. So in 2017 the first seminal finding was that when you took an age and gender matched control compared to psoriasis patient, you had about a 15 to 16% up regulation of their total plaque burden of which the majority was non calcified. And when you look at those differences, they held up even accounting for age, sex, blood pressure, lipids, glucose, current smoking and lipid treatment. So if you took your smartphone, this is the time where I was in person. I would love to be in person. Um I hold up my smartphone and I show you that. Did you know that if you turn your smartphone to the side it turns into a scientific calculator. I really hope you did. And if you didn't that's okay you don't have to tell me. Then you put 0.15 in there and then you hit E. To the X. Wow, What does that give you? It gives you a bastardized odds ratio of 1.16. So you have a 16% chance of having a non calcified plaque elevation. Just sheerly with having psoriasis. This was any all comers of Psoriasis not just severe. Why do I care as a cardiologist? I think dr samadi and all of you who are in the crowd taking care of these vascular patients know the most common cause of acute myocardial infarction is a non calcified plaque And we need to do something about this now that we have found now it was 2017 and moto Yama put this article out on not all blacks are created equal. And I agree that if we were in a room that was small and you guys were all willing and ready to stand outside the door that'd be a standing room only because there's not enough room in the room right here the vessel does the same thing. It's standing room only and it pooches out that in my opinion is one of the most high risk high risk black features is positive remodeling. Okay. And there's a remodeling index that's been published. I'm not going to go over it but it's there secondly if you have a bunch of lipid what did we say psoriasis is constipated of lipids. So what if you have a bunch of lipids? Guess what it's gonna do? Metastatic lipid. Oh sis I just I just made that up. But it's gonna be lipids everywhere, lipids in the brain, lipids in the bone marrow lipids in the vessels. You get these low attenuation plaques and they're not good. So then in 17. Very clever. You know student now who's a I think he's a cardiologist to do um basically asked well can you find these plaques in a psoriasis patient with psoriasis. And boy oh boy that year unfortunately this 38 year old had an R. P. L. Ruptured plaque at baseline. He was fine and then a year one. He had the event in between. And so we went back to his baseline scan. Hey we're learning as we go there was high risk plaque features. He continued to not treat his psoriasis. He had severe cutaneous disease and he had a heart attack. Not only that we then use that as a springboard to publish that patients with psoriasis have high risk plaques. And not only are they high risk They're about a third of them that have it. And they come on 14 years sooner than the Bethesda worried. Well so this is a group of 60 year olds who come in for uh new statin therapy and they get a C. C. T. A. So they have this lymphedema and we're just checking to see what their coronaries look like. And what you'll find here is 14 years sooner. You're getting the same amount of high risk plaque wow. By my slides earlier. That was about when those patients were having that spike in their age interaction curve. So we're we're finding that the action in this disease is between 40 and 50 whereas in general population it's between 50 and 60 and in women 60 and 70. So we're catching this earlier drift of age And it was at that time yet in 2017 still around that same time we got a call from Marcus chan in R. C. T. Reading room. Who said hey nao what are you doing up there that plaque is gone. And I usually don't like to say regression. They always worried me to say regression. But here I actually saw a 30% shaggy non calcified plaque Go in one year. And this happened about 13 times before we looked into it. We had a clever medical student who said dr meta if we really looked at those starting biologic therapy and compared them to those who chose not to. Would we be able to see if the coronaries changed? Okay let's take a look. So luckily by this time now it's 2019 I promised you we'd get through up until 2021. Um it's 2019. And we asked if you started biologic therapy 90 of you And let's say there's 30 of you who didn't and there's people who choose not to use severe psoriasis treatment. It rather just treated naturally. And the baseline CTS were compared after one year of therapy for those who got it compared to those who didn't get it. They just got another scam. And these data are very important. I'm gonna pause on this slide because what would you think would happen with biologic therapy? I would think that inflammation would go down and I wouldn't know if any of the risk factors for heart disease would change. And in fact they didn't here we saw a reduction in crp very significantly. Um And then we also started the people on the right on one of these three biologics. And if you care about biologics, that's basically anti TNF anti 12 23 anti isle 17. So most commonly new mera Stelara and cost sentence. Okay, this astounded me in 2019. We received an NIH Director's award in 18 for this work from Francis Collins um for the first in human evidence that treating remote inflammation improves vascular health. Okay, so we treated systemically but we saw an improvement in the vasculature. So these are patients getting treated for a skin disease with a biologic. They're found to have high risk plaque. And then when we're treating their psoriasis, we're watching their coronaries and what do we find? So a is pre treatment be as post treatment and this is somebody who received anti aisle 17 therapy. So cosmetics, their skin went down by about 90% improvement. It went from a 13 to nearly a one. They almost saw 100% improvement. And from baseline, what you'll see is there's this large red lipid rich new product for which then goes away. Never had seen that before in my life. And you see this blooming this increase of calcium which actually when the body heals it doesn't know what else to do. So it sends in its army of calcified macrophages as well as a smooth muscle cells and fibroblasts. Right? And then finally you saw this light green area of fiber fatty burden decrease. Now look, don't ever let anyone sell you a bridge, Right. Don't ever do qualitative analysis alone, do some quantitative. So here the data from the paper, I'm going to go through these rather quickly. Because the point is is that when you're on biologic therapy you get a reduction in your non calcified plaque that equivalent to about a statin. And we've used this before that when you treat the systemic disease, you're actually gaining benefit that of of approximately a statin. That that that really again imagine if you had the person on a statin as well. Um All right. And then when they weren't on therapy, you actually saw these things go up at non statistically significant. This is by far the most impactful slide when you think of the things that kill people lipid rich necrotic cores and things, they went down by over half in this patient population. Whereas those not on biologic therapy, I actually saw a massive, massive improve uh worsening of these to a point where when I took these data to our I. R. B. This was the reason why we got approval to scan our healthy volunteers at different decades. How do you contextualize this? Is this what happens to untreated psoriasis? This is where I I then now at most talks will very very I think fervently say that unopposed inflammation is a dangerous thing to blood vessels finally people ask me, well, what about the different types of therapies? The most prominent was anti TNF in terms of, sorry, prevalent, not prominent. Um and there was a reduction, non statistically significant and these are subgroups. These are post hoc subgroup. So I didn't expect them to be significant. But look at anti isle 17 therapy. Whoa right. 16% reduction, 12% reduction. And the thought here is that there is probably a steep withdrawal and inflammation with an improvement in HDL function. We're working on those data now. Okay, a few other modalities. And then I'll talk about our collaboration with dr samadi, which is probably the most exciting going through our phenotype. Ng there's also a way of looking at diffuse coronary inflammation and so shown here is something called the fat attenuation. And next this is out of christo diagnostics at Oxford and we got our whole cohort completed just this past week. This is the 1st 100 patients which was published a few years ago when you take those same patients who went on biologic therapy versus not and you did the same 90 versus 30. You found that when they went on biologic therapy, their coronary inflammation went down, their coronary inflammation actually decreased and it went to a point where it almost became normal okay, when you look across the board, every type of therapy reduced coronary inflammation except for those who are on systemic and biologic treatment and didn't have any therapy they did not improve. Now, what this is the most, I think this is the most sophisticated phenotype ng that we are able to complete without flaying open someone's vessel. So I'm gonna spend a few minutes on this data. Again, everything that I show you are part of collaborative studies that are non paid. I am not a consultant anywhere. I don't sit on any boards. So again, I am Switzerland when I am presenting data to you on different imaging modalities. So, I guess I can't say that anymore. I am neutral. Okay. Because I guess that's not fair to say. And what's the current environment so vast you cap is a history pathologic imaging application and shown on the left of a coronary artery with a lipid rich necrotic core. And shown on the right is it's correlate on this software. It was initially developed in the carrots. I saw its elusive bio imaging from massachusetts. I saw it and I grabbed it to put it into the coronaries. And you'll see here that their software takes very nice images. They will segment out where they see the lipid rich necrotic core and we will get its area. All right. So, what does this look like? Well, I promised you we'd get to 2020 and 2021. This is 2020. So in certain imaging just last year we took that same 90 versus 30. But then of course certain imaging said we need more. So we went and we finished up the entire cohort. So I think that total paper had about 270 scans in it. And here is that same person who dropped their coronary inflammation on that prior scan with aisle 17 therapy. This is a person on aisle 17 therapy. And what's found here is that their lipid rich necrotic core which is delineated here with some calcium actually dissipates at one year with this increase in calcification. I am just shocked at the amount of time that this healed it. This was one year. I mean if we look sooner would it be healing sooner? I don't know. We came up with one year at the I. R. B. For a reason it was safe yearly study. But there are colleagues of mine In Oxford who are scanning every 4-6 months. Another study going on that I'm involved in. That does every 4-6 months. When you're doing low doses of radiation, one millisievert or something like that. Clearly you can do these in series. Okay, so before I move over to our collaboration, I want to remind you at this stage, before I learned about Dr. Samadi is work. And what we were doing with the wall shear stress, I wanted to remind you that we have 300. Now we have 400. These are a little bit old. These are about three months old. Out of 400 patients, we have followed we have a ton of dis lipid e mia disc lycee mia and it's modifiable. We had an abstract th a couple of years back that when patients actually listen to what our dietitians and our exercise physiologist said the disease actually got better their psoriasis as well as their vascular disease. However this is our patient who I showed you earlier. I'm just gonna let you look at it for a second rough. Right. I hate these to be my coronaries. 44 big thick calcified plaques. Proximal L. A. D. Mid L. A. D. And we don't stop at a calcium score right? We are able to get not only the calcium score but we also get lumen ah graffiti. And so here I want to just move over to the concept before I get to the guidelines and our data That here if we had this image it would have been so much easier to counsel this patient. It would have been easier to say you have an ulcerated 70% you know plaque. You have a 40% plaque down here and gosh you're only 40 years of age like this is really you know something you need to take on. So that's when is right at that time when I had given this talk and I'd shown these data that dr Samadi had I hope you remember this Habib. We were at the C. R. T. Meeting and we were sharing a panel together and you had said hey Stone had just spoken and you had said hey I really think that some of the non calcified plaques that you're showing even if there's no plaques there's going to be abnormal shear stress forces in the wall. Now I'm not going to give these data the the the the justice that they deserve. I know dr Samadi and and and his team will be better. But what I've done is I've taken slides from that collaboration um and I've shown some images that are characteristic of what I'd like to show. So looking down these areas where there are plaques of course there's going to be an increase in wall shear stress. The magnitude of the eddies around that wall. But the point of showing these are that when you do look at the wall shear stress, my sense is that they are out of proportion to the degree of stenosis. And so as I go through these slides what I'm doing is I'm looking at areas where I seek stenosis but then I also do not. But I see that the turbulence and the shear stress forces are high in that patient. And what I'm going to do is I'm gonna go through a smattering of cases. These are cases that had plaque. We have given the team plaque cases. And now what we're doing is as we're seeing even when there's no plaque there's still an increase here in the proximal portion of this wall shear stress one may say well what how can that be if there's nothing going on? How can that be if there's no plaque, why is there abnormal flow? Well, the answer is fairly straightforward to me. There's endothelial activation in these patients and that endothelial activation is causing an expression of chemokines and cytokine receptors. It's bringing many many abnormal cell types to the vascular wall. And what's happening is you're getting a lot of changes in the flow. Remember denuded end ophelia can only be treated when you treat the endothelial inflammation. So in 2018 I go back a year in 2018. Right as I had put this collaboration together with DR Samadi, I had reminded everybody that psoriasis just made the guidelines that look, we finally did enough work over these 10 years that people recognized it to be a risk factor for early statin initiation. This was a very momentous occasion for our lab. But why did I tie that together with the wall shear stress? Well, because when one has wall shear stress, there has been rich data that statin therapy will comment a filial inflammation. The question is, will those with statins on board have different wall shear stress. So we're doing that analysis now with Dr Somalis group as well. I want to remind you that the guidelines both in cardiology which I've shown you here and dermatology and rheumatology? All site that patients who have severe disease need more care. But cv risk assessment should be done every single time you see a psoriasis patient. So as I close I close out an infographic and I remind you that psoriasis is an inflammatory disease. It's a systemic inflammatory disease. Treatment may impact the, you know, sort of systemic inflammation. But my take home here is really using image guided diagnostics To uncover what's under and what lies beneath. So, I always end with this picture and I may I published this just this past year. I promised you I'd end in 2020. But I'm actually getting you out to 2021. And what this is showing you here is psoriasis is a systemic disease. It's got co morbid disease all over the place. And if you look from the top of the infographic down, you'll see that it's a common disease here. The treatment goals here, the signs and symptoms. In fact, you have topical therapies, photo therapies and then you have biologic therapies which we've talked about. When you look at psoriasis, it's a hypercar a tonic disease rooted in systemic inflammation. And if you look at the co morbid diseases that are associated with it, look in the roots, you'll see that there's a person with a beer belly, right? So there's diabesity here, diabetes and obesity. You'll see that the central nervous system itself, there's a there's a predisposition to anxiety and depression. You'll see here. There's a hand. This is psoriatic arthritis. One in three of our patients will get psoriatic arthritis and then finally what I've spoken to you about the heart, there's the leading cause of heart attack and stroke. In those without risk factors are chronic inflammatory diseases. We must take the imaging that I've shown you and start applying it to see what lies beneath and to diagnose it. And I've ended at 7 45 to leave 15 minutes for questions. Um I do love getting questions on email. I also can be followed on twitter at Nihal Mehta, MD. I will answer my D M's but I've left time for a question and answer session mainly because I believe that most of our impact has been with me giving these types of educational lectures to providers and those providers, really taking it back to their patients and their ecosystems and reminding them that psoriasis is a whole body disease and that it impacts the vasculature, treating the primary disease will actually impact the vasculature. And now we're on our 10 year follow ups, we're going to see if treatment impacts 10 year after progression. So with that I'll stop and I'll say thank you and I'll take any questions. Uh well, dr Mehta, That was absolutely fabulous. And as are many um cardiologists and vascular surgeons, cardiac surgeons and nurses have joined. Um They can all appreciate that they're there, you know, there's some brilliant scientists out there. Um but there there are others that are not only really innovative in their work. Um but also are unbelievable and communicating extremely complex concepts. Um and and I do want to thank you for that fabulous presentation. Um And and I I also love the fact that you loved some time for questions. So um let me encourage our audience to come in via chat. Um and obviously if there's some questions, Suzanne McNeil um will um will let us know, do you already have some sense? Okay, well let me do this. Let me just briefly um maybe just pose one question because as you've just taught us in patients with active psoriasis, they seem to have at least 12% more plaque, Most of that soft plaque. Um they get increase in calcium over time with therapy with biologics. They get regression of the plaque in a way that over a year that really is impossible to imagine. Um And I learned a lot about the biologics, right? It was the anti I. L. 17, that was the most impactful in your studies and your really leveraging the latest and uh imaging and software technologies to understand this and definitely appreciate our collaboration where we're bringing together the wall shear stress which really has mechanized biologic links to a lot of the work you're doing. So extremely exciting and you know, as most cardiologists they say, well, wonderful. You're using psoriasis as a model to understand inflammation And I guess the implications of this are not only in patients with psoriasis but potentially on patients without psoriasis who have implicated who have implemented. So I know that this is kind of going through the minds of our audience and with that said I'm going to pass it over to Suzanne to see Suzanne what specific questions we have and from who? So the first one we have a comment questions. Thank you for an excellent talk and for your dedication to improving the standard of care in practice. Do you have a systematic approach that you have adopted for identifying and implementing interventions with patients in the clinic and at what age would you suggest that a patient with psoriasis? See a cardiologist given the established connection with cmd. And then the question is oh holly jones is director of research here. Wonderful. Well holly has three exceptional questions that she's posted that I would like to clump into a single answer because I really do appreciate the questions holly. Um The first one I will say is yes I I feel badly in cutting my talk and adding in the collaborative, I did leave three slides out at the end that would have answered your first question and just to go through it, I call them the meta three B's. It's basically body mass index blood pressure and blood for glucose and cholesterol. So it doesn't even have to be fasting anymore holly. If you have a story attic patient who's gotten their first diagnosis. I get them treat I get them diagnosed. I get them their body mass index, their blood pressure and their blood for glucose and cholesterol, those three will reveal their cardio metabolic status. So that's the standard of care that I should not being the first person telling the patient they're obese. I should not be the first person diagnosing them with hypertension but I frequently am and then finally they should not have their blood's never checked for glucose and cholesterol. And you may ask when to do this first diagnosis of psoriasis. Um There's no doubt that it picks up disease. Okay that's number one. Number two. When do you start biologics was another question that came in there in terms of you know the second one was when do you recommend seeing a cardiologist? In fact you don't have to see a cardiologist. We have a few clinics around the country we've set up that they just see a healthcare provider. Could be a P. A. And P. Uh internist. It could be down to getting the M. A. To just get all the vitals and handing them to a care provider. Um We've used minute clinics we used a few hagi machines so it doesn't matter who does it? You just need the three B's answered is my thing blood blood pressure, body mass index and the blood for glucose and cholesterol. Now your question on when to start biologic therapy is a great one. I say if it's indicated you started. So what are the indications um genital disease disease greater than 10% psoriatic arthritis. So if any of those three or facial disease, excuse me. So its face genitals or sensitive areas, anything greater than 10% of the whole body and I would start it right away. Look, they're safe. I know people worry about side effects and covid and all that. I've seen worse psoriasis with these covid holidays because of this. Okay, so I would say when you can start a biologic do it, the last question that holly raises is a great one. Which are what are some of the best practices that can be implemented to see results with patients in reducing obesity and increasing exercise in a population community. I'm so glad you think that I'm qualified to answer that question and I'm so glad you asked it. Um I actually sit down with the patient and ask for their level of seriousness. I'm like, do you really want to do this? And if they say yes, my best strategy grades five times a day rather than eat three meals. Keep a time restricted eating window. I only eat from 11 a.m. To six p.m. Every day, I have a 17 7 break. If I'm really getting kind of, you know tired, I might break that a little bit. Um exercise is not have to be, you know, rigorous 150 minutes. In fact what I tell my patients is is if you can get some sort of a wearable device, get 10,000 steps in a day and make sure you're standing at least half of your work hours. So I have a standing desk. My patients actually listen to me because I level with them and I'm like, look, you're gonna quit smoking if you don't want to, let's talk about it next time I tend not to ever push and I don't guilt, there's no guilt in my world, I don't judge. So I say, hey look, let's do this and what patients feel the best one. We had one visit to our dietician and I promise you £5 off in a month and it worked in 98% of my patients. My dietician basically gives them a sheet of things that are safe foods. Sounds very weight watcher is um, but it worked and I'll tell you if you have any patients you want to send up here from Georgia, either tweet me or email me, I will get them up here and we can do the £5 challenge. It works every time. Um and if they're really thin, they may not lose £5 and in that case I'll say you'll lose, you know, 3% of your body mass. Um and it works well, I hope I answered those questions for you holly. Yeah, you did. I and holly obviously is on the chat. Um Suzanne maybe as you pull up our next question. Just a couple of things to those. Those are great great tips and tricks and pointers. Um We we do have a you know center for wellness and prevention and cardio metabolic diseases. That's led by um doctors. Dave okay dr Burkle as well as uh dr Ramesh and dr when others here. So um do keep your patients here in Georgia. But um but I think some of the um the lessons you mentioned are are incredible I think does does a diagnosis of psoriasis warrants some sort of cardiovascular phenotype ng or the three B's that you mentioned sufficient. That's exactly right. So those three B's. But honestly it starts with an H. And P. It starts with a good cardiovascular history. Um And then it starts with getting the three B's. But honestly Habibi I have to say I'm now throwing in a ct calcium score for every patient above 40. And in fact I actually offer them a C. C. T. A. Because we have access to them. But most of my patients in the community we do image guided therapy for. So I will phenotype. Either their carrots get an I. M. T. Um or all three types of coronaries and I will find very high amounts of prevalence of vascular disease. Suzanne. And the other question. Yes we do. This is from an you dr is one of our cardiologists? Wonderful. And I love the question based on your presentation. Do you see a specific roles for hyper lipid E. Mia or you just think there'll be a paradigm shift from from statins? I do think I knew that statins are here to stay. Um they're definitely a cornerstone in therapy. I see. And you love I love that you asked that because in the middle of my talk I even said imagine that person were on a statin to uh you know we're working on that now. We've just gotten funding from a foundation and really nice lump of money to start a trial to randomize not excuse me not randomize. Uh give rheumatologists and dermatologists the opportunity to prescribe statins rather than sending them out. So this this is the CP three trial and we're rolling it out in july and it may be coming to a theater near you if we come to Atlanta and find out that we're working with you guys. I'd love to speak with you about this. But we're asking Durham's and rooms hey if you've got the meta three B's why not just take the step out of it. Go to a care coordinator and start the statin. So I think a new statins are here to stay. Fantastic. Suzanne. We have a question from dr Scully any data on infection rates when inflammatory disease caused C. A. D. Is treated with I. L. And other anti inflammatory prescription. Dr Scully I don't know you but that is a very smart question. You should look at the appendix of the cantos trial. There's a little bit up regulation in non significant infections which is why the FDA wanted a separate trial for Novartis. In fact I'll one beta therapy did not get the FDA approval it had hoped for because of some of the non significant safety issues. It doesn't mean the game's over at all. It means that we just have some more to learn on what the therapy is and how often to dose it. So just on that note and and I think if if you had to distill the primary lesson of your talk Nihal is you know inflammation as others and yourself and others have taught us is a very very key part of atherosclerosis and treating inflammation appears to regress plaques and psoriasis? So my question to you kind of following up on Dr Scully's question is that I know that paul Ridker and others have looked at treating inflammation perhaps using you know crp or other biomarkers as a surrogate endpoint with things like methotrexate and and other therapies. Um You know if you put your crystal ball in front of you and look at it you know do you think 35, 10 years down the line um beyond the anti inflammatory effects of the statins. Are we going to move towards biologics and specific anti inflammatory therapies in our armamentarium against non story attic at 100% no doubt. We are at the point where I've just with the three big societies put together, what's wrong with us? Why aren't we using culture seem more like seriously? What's wrong with us? Because Ludovico, one Ludovico to Kolkata one. I don't know how many other acronyms that have Ceo and that we need before we see there's something magical about low dose culture scene. Now do I say go and put it in everyone's water? No, I don't because I believe there's a specific patient we need to phenotype and that goes into Greg Julia. I don't know how to say his last name but his his question comes up with Giuliano. Thank you very much. That question is awesome. Which is it's this collaboration of bringing in advance to identifying vulnerable plaques. But then also thinking that what is a vulnerable plaque made of a bunch of inflammatory cells that guess what are treated by culture scene, why did methotrexate fail? We chose the wrong population. I think that I feel badly that we ended up doing the blanking on the trial. And we we we we we messed it up. We needed a better way of seeing whether people crp pathways they're aisle six dribbling in inflammation was high and activated. Instead. It used medicine as a criteria that such a heterogeneous group so certain unfortunately got tested and and and sub shoved aside um Interleukin one beta therapy I do think is going to be coming back if they dropped the cost. Um polaris was $64,000 a year or something. That's ridiculous. Um And then with culture scene I think what's going to be needed is just large prospective randomized trials and going out of the post. M. I. ST fantastic Susanne. Um By the way, Greg Giuliano just joined us from bay ST and he trained at the Brigham as our director of inpatient cardiology, awesome. Go ahead. There's one question I'd like to, you know who I owe parasite is because they've brought up Lps at penn with Murdoch Riley and and Sean Heffron. Can somebody tell me who I o para si Yeah. Yeah. So Doctor Yanni parasitic fetus is our director of cardiovascular imaging. And I say you know PhD and vascular biology, may I answer you honest, may I answer your question with a there's definitely different variants of C. A. D. Presentation. I'm so sorry, it's long. So just bear with me. Um do you believe that inflammation starts first and LDL oxidation follows in the space? I do, yes. And is C. A. D. The same for all people or are there different variants of C. A. D. With different presentation and severity? Um Yes, chronic inflammatory diseases do predispose to what I call and renew Vermont now agrees. Excuse me. Diffuse intimacy thickening and it just thickens the whole into MMA and it's probably because of endothelial itis and that is in contradistinction to narrowing of a focal stenosis. Um And we're working on that because we do see that indians as well as other high risk subgroups do get um diffuse coronary disease rather than focal narrowing and we just don't understand why that's the case right now. Um Somebody else, there's two that I can lump up here. I think from Clifton's Hastings, he's asked do other data indicate inflammatory states have the same amount of impact. Yes. In short I. B. D. Just got published in A. S. P. C. That it has an up regulation of coronary disease in its fifties. R. A. Has a trial out called target to treat because there's pretty good evidence that there's a lot of coronary disease in our a and all of them recommend screening and treating aggressively. I would um you know take dr Iqbal has just asked me a question, would you actually start anything if this if the three B's are within normal limits. It's a great question, it's hard because some of my psoriasis were patients with psoriasis actually do still start it knowing that they're going to end up there. But I don't recommend that I wait until their LDL are spiked. Um And usually I mean that's over 100. So unless your patient has an LDL under 100 I would probably still, you know, move towards starting it. You could say you're being a little crazy 1 30 is the absolute highest. I'll let them go. Um I do use a lot of red yeast rice and a lot of other alternative based statin therapies as well. If those are um if those are not uh you know possible as we as we approach the top of the hour here. Um I do wanna maybe for you to comment briefly on the recent cardiovascular guidelines with respect to C. T. Being used as a you know as a test to stratify patients. Right? So for patients with intermediate are disease immediate risk of disease. CTE has become a one. A recommendation has followed the british and the european guidelines. Could you make a couple of comments about where you see garden variety imaging and screening for cardiovascular disease? Where is it today? What should we be doing? Yeah patient. And also and I just yes and I just answered a question. Habib on somebody and I feel bad because I just hit type answer and now it's gone. But with that person and I were just saying was so and said if the cat if the cat score was negative would you still pursue a. C. C. T. A. What I'd like you guys all to hear is that imaging is better than none. And the best imaging would be lumen ah graffiti insurance companies aren't paying for it yet. We're working on that. The european guidelines suggest if you're a moderate risk patient with chest pain. You deserve a C. C. T. A. We put it in through your p phi we get coronary inflammation and we risk stratify you for your 10 year risk. I would urge you to look up that work. It's from Harris Antonetti's group Charalambos Antoniades group at Oxford. But I would say the easiest way to think about this is image ng is necessary, imaging is necessary here. You're not going to be able to get blood borne biomarkers and phenotype without knowing imaging. So adapting the nice guidelines from europe I would say that you have the ability for a moderate risk patient with chest pain to fight for a. C. C. T. A. Most insurance carriers now with a simple phone call and a mention of a paper will get their C. C. T. A. Paid for with inflammatory diseases if they have chest pain. Right? And I think that what we've seen is that the insurance carriers as well as with the guidelines coming down the U. S. And the end of 2021. Or moving in the direction of incentivizing imaging with C. C. T. A. And actually maybe making it even a little harder to do more standard nuclear imaging and requiring pre certification. Well wow what a what a whirlwind what an incredible talk. Um We've we've had obviously as witnessed by the wonderful questions you know real engagement. So um I wanna thank you so much for a wonderful cardiovascular grand rounds at Georgia heart institute. Um I also want to let everyone know that dr Meadows talk was recorded um and will be available like the other cardiovascular grand rounds in addition to that, um he and I will now spend a few minutes doing a short interview so that he can distill in a maybe a 10 minute Q. And a. Some of the key lessons um that we should take away from this talk and want to thank um Suzanne, McNeil and Robby and Billy for organizing this incredible venue. Um and look forward to seeing you all next month. Thank you very much for joining. Thank you for having me, Doctor Samadi.
