Chapters Transcript Video Residual Risk Assessment: Cardiologist Use of Cardiometabolic Drugs Dr. Michael Blaha from Johns Hopkins Medicine discusses preventive cardiology with a focus on cardiometabolic medications. Perfect. Thank you very much for the kind invitation and thank you very much for that introduction, yeah. The only thing I'll add, I guess the introduction relevant to this morning is I'm also for our Cicarroni Center for the Prevention of Heart Disease. I'm the director of our cardio metabolic clinic. We'll talk about cardio metabolic clinics later in this talk. That's been something that's going on here for about 5 years, and it is one of the fads in the field, but thinking about do we need a home for our patients with cardio metabolic disease. So that's in the backdrop as we talked today about risk assessment, residual risk assessment. And cardiologist use of cardio metabolic drugs. I specifically want to talk about risk today and talk about not just what can we do with drugs, but what specifically can cardiologists do or should do with cardio metabolic drugs. All right, here are my disclosures. I thought I'd start with just a definition of risk. Uh, I feel like sometimes in clinical practice we use this term residual risk, but we don't talk as much about what actually we mean. It actually is a term that comes from processing engineering fields, um, thinking about large systems and how to to de-risk systems. So really residual risk is the the term that means the risk that remains after efforts to identify and eliminate some or all types of risks have been made. So residual risk is the risk that's left over after basic security controls or these process improvements have been applied. So there's some inherent risk. Um, we do something to mitigate that risk, and the residual risk is what's left over in the auto industry, this is talked about like, for example, when you put a seatbelt on. Some residual risk to the driver. And I think in the context of clinical medicine and cardiology patients we usually talk about residual risk after basic mitigation strategies have been applied, maybe aspirin, statin, and blood pressure control. So for the purpose of talk, I'm gonna be talking about risk that exists after basic risk factor control and how we're gonna be having many choices in the future about how to proceed next, and I'm gonna make an argument about that cardio metabolic disease should be at the center of that decision making. Slide that's usually shown when we talk about residual rest. This shows the 12 of the major statin trials, and then the light blue shows the vet rate in the placebo group and the dark blue shows the vet rate in the statin group and shows that even though statins reduce risk well, there's still a significant amount of risk in the dark bar that remains. So this was the kind of the construct of residual risk for a long time. It was a cholesterol phenomenon. Patient has residual risk after having a statin, they need more LDL lowering or they need HDL to go up or their triglycerides to go down. But of course now we construe residual risk to be much broader than just lipid-based risk. So how does estimating the mechanism of an individual patient's residual risk play into a clinician's approach to treatment beyond the basics like statins? This is a slide that's been shown now in many settings. This came from Paul Ridker and his group at the Brigham, saying that, well, once upon a time, it was as simple as a patient was high risk, let's give statin. Now that we have lots of choices, lots of choices to mitigate risk further in our primary and secondary prevention patients. And he thinks, and I agree. So we're moving towards a world where we're gonna be looking at patients and saying, well, what's the driver of risk in this patient? And let's treat that patient specifically with something that mitigates that risk. And you can see on the screen there's many options now for reducing risk in our ASCBD patients. There's residual cholesterol risk, as I mentioned DLR the AOB is still high, and we have evidence for many therapies in that space. Maybe the patient has inflammation, as residual inflammatory risk. We know now that we could target inflammatory risk with things like colchicine or other, many other going down the pipeline, and maybe that is a big bucket of risk that we need to be thinking about. What residual thrombotic risk in our stable secondary prevention patients, things like a low dose rivaroxaban have excellent data from the COMPASS trial that we can reduce risk further. however, residual triglyceride risk, we've just had the approval of a new, uh, AOC3 inhibitor triglyceride drug. It's for FCS right now, but soon it will be, uh, fully tested for cardiovascular disease. That's another bucket of risk residual LPA risk. In 2025, hopefully maybe early 2026, we'll know the results of the Horizon trial with Pella Carson, and anti-sens of like a nucleotide to APOA. So we'll better treat that And on the right, this says residual diabetes risk and of course many of you are familiar now with the data behind SGL-2 inhibitors and GOP-1 receptor agonists, which we'll talk about. But what's not shown on this slide is even more fundamental. We'll talk about today, the risk that comes from obesity and the risk that comes from early metabolic changes for obesity even before a patient has diabetes. So I would argue that this slide isn't even complete. There's other buckets of risk that we need to think about. So let's use this uh case as a jumping point for today. So let's think about the categories of residual risk in this very standard outpatient that you'll see today in your clinic, someone like this. So this is a 64 year old man. Is a relatively sedentary lifestyle. He has a history of hypertension, sleep apnea, osteoarthritis, and he had an anterior MI 4 years ago, and he had needed a couple additional stents 3 years prior. His BMI is 36, putting him in the class 2 obesity zone. His blood pressure is still, uh, not optimal, his ejection fraction is a little low in the 45 to 50% range. His hemoglobin A1C is 6.4%, not quite in the diabetes range. The LDL is 75%, a little bit above goal. His HDL is low, his triglycerides are high, and his LPLA is high as well. Both based on his age as well as his risk factors, his GFR is 56, putting him in the stage 3A CKD zone, and he's got mild microalbuuria. And if you measure a CRP, it's elevated too. He's a former smoker, 1 or 2 glasses of wine several days a week. He only gets about 6000 steps a day, and he doesn't exercise, and currently he's on an aspirin, a statin, a beta-blocker, and lisinopril. So hopefully you recognize this patient in your practice. Of course we see these patients time. And I think you'd recognize that there's many buckets of residual risk in this patient, and one of the concerns we have nowadays is that depending on who of you all he sees, or maybe he sees me or someone else, he could be treated drastically differently with all the different choices. So all types of residual risks are present in this patient? Well, clearly he has residual lifestyle risk. He could emphasize lifestyle coaching in that visit. He has residual cholesterol or LDL risk. You could add azeamide, PCSK9 inhibitor or beadoic acid. triglycerides are high, you could try to lower that with something like a cost of ethyl. LPA is high, we don't have those drugs yet, but hopefully soon we'll haveelloarin, but you could lower the LPO away with like a PCSK9 inhibitor, for example. Certainly he's got glycemic and diabetes risk, probably would benefit from a GOP one or an. He's in the uh zone where he probably is at risk for HA and certainly kidney disease development or SCL 2 inhibitors and phennerinone have strong data. It could be a consideration for odus rivaroxaban. Also, he could treat his inflammation with something like colchicine or an upcoming drug like seltadecommab. So you can see there's so many ways of approaching this patient, and this is the problem now, this is data from the Copenhagen Heart Study looking at patients with known ischemic heart disease or NMI and if you actually look at 4 classes of drugs. LDL drugs, inflammatory drugs, diabetes drugs, and so forth. Actually, most of our patients qualify for many clinical trial proven therapies. In fact, in this particular study in patients with a prior MI, 80% of the patients qualified for four separate drug classes based on recent clinical trial data. Which raised that difficult question of well what do we do next for this patient and how do we do it in a way that's evidence based and relatively consistent across the. So this is the this particular paper that showed that how many drugs and these new therapies that these patients with ASCBD are eligible for, and it said the study raises questions for the cardiovascular community about access to these potentially expensive therapies, including strategies for prioritizing their use. I think we'd all agree if you look at the guidelines, the guidelines are commonly risk factor based. You could look at the cholesterol section, you could look at the inflammation section and get recommendations. And when goes up, you could treat the patient with many, many new therapies and current ASCBD guidelines provide very little guidance on the order of therapies or the priority of therapies. So my thesis number one for this talk is that most physicians are willing to prescribe one or two sort of new and very expensive drugs to their patients, but not more. We have too many physicians out there that are willing to say, well, let's start 4 new expensive therapies for you. They're probably going to select one or two they think that are the most likely to benefit this patient. So I guess the question is how would you approach his care? You heard his case by thinking of what they would do, but there's no doubt that the perspective on this patient depends on your background. Your training, maybe your interests or your tolerance for cost. Right, so he could go to one clinic and have an emphasis on blood pressure, one clinic can get a PCSK9 inhibitor. One clinic and maybe get a GOP 1 receptor agonist. So my thesis number 2 for this talk is that the most impactful strategies that don't just treat a single risk factor. But those that fundamentally alter the pathophysiology of the totality of the cardiovascular risk for the patient. And I think this in in this sense, strate these strategies could fundamentally alter our perception of what it even means to have residual risk. So hopefully in the future we're not going to be looking at just these things in isolation. Well, what will be good for your blood pressure, what will be good for your cholesterol? What will be good for your inflammation. Let's think about what's driving the risk in this patient, and clearly I think everyone would agree that this patient is metabolic patient. cardio metabolic disease is driving this patient's risk. So what is cardio metabolic medicine? Well, I think we sort of all know what cardio metabolic medicine is, but at least we know where we're headed with it. And a crew is driven by obesity and lifestyle choices. So here this is a slide that looks at as you go down the page, the prevalence of obesity in the United States projected up to 2030. And what's really remarkable, this is just how, of course, how much obesity there is, but how much severe obesity we have now. So now the most common, um, the most common BMI zone for a patient is to be, um, at least overweight if not obese. By 2030, greater than 50% of all patients will have obesity. And remarkably 1 in 10 patients will have a BMI above 40, will have class 3 obesity, and we can see in that heat map there, especially in the um. Uh, in the in the South, or even in the Midwest, we're starting to see states that have upwards of 50 to 60% levels of obesity, 1 in 4 patients with a BMI above 35, and it's really a completely new phenomenon from the obesity of the past. Where we'd say, well, the BMI is 31 or 32. Now a common clinical scenario is running into a BMI of 35 to 40 or even greater than 40. We see it every day. We're almost used to it by now. So just as the Uh, trends in obesity are taking up, of course, trends in diabetes are taking up too. In fact, if you look at them, they're co-located in areas where there's increased obesity, there's increased diabetes. In fact, the uptick in obesity and diabetes is similar over a time period, of course, linking those two, and this is a worldwide phenomenon. If we think it's bad in the United States, we've maybe already had some of our worst rises in obesity. We are expected to have about a 33% increase in obesity over the next 20 years. In North Africa, 100%, Southeast Asia 74%. Africa 143% increased projection in diabetes by 2050. So this is a worldwide epidemic of cardio metabolic disease. And really, of course, right now we're not doing a whole lot about it, and the costs of diabetes and cardiovascular disease are staggering. If you really add up both the direct costs as well as the cost to society based on the loss of productivity, it's clearly over $1 trillion. an expensive, expensive phenomenon that we're really not getting to the root of. So of course, cardio metabolic disease is more than just uh atherosclerotic cardiovascular disease or even um uh hypertension or diabetes, sleep apnea. It's a folder nowadays called MASH metabolic associated steal hepatitis, chronic kidney disease. Heart failure, particularly half pep, atrial fibrillation, and even dementia is closely linked to obesity and cardio metabolic disease. So where we used to have A thought about diabetes. Well, diabetes is a disease, of course, of high blood sugars. Of course, now we recognize that the pathophysiology of diabetes is far more complicated, uh, rooted in adipocyte biology. Adipocytes, inflammation, the liver, insulin resistance, and of course uh prothrombotic pathways as well. Well, likewise, we recognize that obesity is way more complicated than we used to appreciate too. There used to be things like this. Can you say skinny without willpower or well, It's just what you eat. You need to eat better. Now we recognize that BC is far more complicated than we appreciated before with peripheral signals, but most importantly central signals that really are addictive in nature, that really speak to the the linkage between the modern diet, the modern way of life and addiction in a way that leads to perpetuation of obesity. So what I want to talk about in the rest of this talk is the cardiologists' use of what we used to think of as diabetes or cardio metabolic medicines and what the role of the cardiologist is and are we well suited to deliver on stemming what is the greatest epidemic of cardiovascular cardio metabolic medicine. Well, I think you all probably have heard this story, but it's useful to remember again that the regulatory history of diabetes drugs in this country. It used to be that therapies could get access to the market with as little as 250 patient years of exposure and just demonstrating a sustained reduction in hemoglobin A1C. And if it weren't for the FDA changing their approach to approving these drugs, we may be still in the same place we had been a long time lowering the A1C, lowering the LDL. at the root causes. Of course, in 2008, the FDA issued new regulatory guidance that to expand the market to have access to the market, diabetes therapies and by extension, obesity therapies. Had to demonstrate at least cardiovascular cardiovascular outcome study to exclude a 30% hazard for increased mace because of course we've seen some risk with earlier diabetes therapies and several obesity therapies too. And what this led to is an explosion of clinical trials for both SGO2 inhibitors. And GOP 1 receptor agonist, this is just up until 2020. So many of which changed the game in terms of thinking about lowering cardiovascular risk via so-called diabetes drugs. The SCL-2 inhibitors, um, of course, starting with mace moving to heart failure and kidney disease, and we'll talk about the GOP1 receptor agonists quite a bit, right? And these drugs are complementary. GOP one receptor agonists probably have a little bit more of an antigenic um mechanism. SCO22 inhibitor is probably more of a hemodynamic mechanism. But clearly they both do both, and they're both and they are both additive in their mechanisms, but what I want to talk about today. Is GOP1 receptor agonists, and I'm gonna posit that GOP 1 receptor agonists are probably the drugs that are gonna overhaul thinking about cardiovascular disease, or at least the overall cardio metabolic health for our patients more than any other therapy since the statin class of medications that the select trial, which I'll talk about in a second, is the most important trial in preventive cardiology since the early statin trials. So GOP receptor agonists are remarkable, right? It's remarkable that we now have cardiologists talking about this pathophysiology here on the screen and this biology. But of course GOP1 receptor agonists are in Cretin-based therapies, the therapies that replicate. The fed and satiated signal that we get from the gastrointestinal tract after we eat, it's what we miss when we eat ultra prosthetics or sugar sweetened beverage, we create no satiety signals. It is really the problem of the modern society. But when we eat a normal meal, we have this signal. We have GOP one that's dumped into the bloodstream. It feeds back uh to the, to the pancreas to increase the secretion of insulin, and gastrointestinal tract, of course, itself to slow gastric emptying and increase emphasis on digestion and absorption, and of course, importantly feeds back on the brain. To reduce signals of hunger, to reduce reward mechanisms type signaling. And of course, ultimate reduce energy balance, reduce the need for energy intake, and it's amazing that these therapies have have gone so far to to be so much weight loss and potential cardiovascular benefit, which we'll talk about. So let's talk about the STEP trials real quick. So the STEP trial, um, step 4 in particular we'll talk about with the magnetag really changed the game of thinking about weight loss. As you know, this is a therapy that you subcutaneous weekly, you titrate it up over the course of 4 or 5 months to the max dose. And you see weight loss that we hadn't seen with any therapies prior, the mean weight loss loss doses magnetite is about 14 to 15% or, or so, with half of patients getting at least 15% weight loss and a third of patients getting at least 20% weight loss. So this is meaningful, meaningful weight loss, far outstripping what we saw with other weight loss therapies in the past. So the question was, though, would this translate to cardiovascular benefit? So I made reference to the fact that the select trial I thought was the most important trial in preventive cardiology in the last 15 years. So let's dive into that trial real quick. As you probably know, the select trial was a trial that took patients with existing atherosclerotic cardiovascular disease. In a BMI above 27, at least in the overweight zone, most patients were obese. But they didn't have diabetes. The patients were excluded if they had diabetes, and they were randomized to a dose titration scheduled to get up to the weight loss dose of someagottide. or placebo and follow it in an event driven way for 3 point mace, 3 point cards. And we know that about 10% weight loss was achieved in this study and about a 20% reduction in 3 point makes with this strategy. remarkably we are taking a therapy. It works in the gastrointestin in the brain in the peripheral endocrine tissue. We're getting meaningful weight loss and meaningful cardiovascular risk reduction in patients that weren't even eligible for this a few years ago because of the lack of the diabetes indication. Not only that but these signals for other benefit in the Select trial and others, of course a signal for benefit in heart failure, signal for benefit in kidney disease. We've seen from other publications a reduction in all cause hospitalizations. And potentially other signals that we'll talk about. And of course, even more remarkable is the fact that the reduction in cardiovascular events was seemingly independent of the baseline BMI. Even patients in the overweight zone. Particularly patients in the class 1 obesity zone that we see every day. Got a substantial benefit from the weight loss doses some maetite similar to the patients that had severe class 3 obesity. And in the select trial, treatment with weight loss dose of simagottide reduced cholesterol, or cholesterol, increased HDL cholesterol, decreased the LDL cholesterol, decreased triglycerides by 15%, and decreased C-reactive protein by up to 40%. So to me that's the definition of a cardio metabolic therapy, something that's improving. Across the board, even with just a modest weight loss achieved in this study. Really making us think hard about our patients saying, well, hmm. Maybe it doesn't make as much sense to just to work on, let's say inflammation individually or or or work on LDL and we can give a therapy that does so many things. So this is a study that we did recently from all of us, which is from the Precision medicine Initiative from the NIH. We looked at 16 health outcomes associated with obesity. We're really talking about therapies now that have benefits well beyond just even the cardiovascular system. So we looked at outcomes like obstructive sleep apnea, asthma, pulmonary embolism, gastroesophageal reflux disease, of course, liver disease, biliary disease, osteoarthritis, gout, DVT, and of course the cardiovascular diseases that you see. It's remarkable is that obesity, but particularly severe obesity, particularly Class 2 and class 3 obesity, which is really the emphasis of my talk here. was strongly linked to all of these 16 conditions but with varying degrees of point estimates. What you see on the right is a summary of the findings. This is kind of a multi-dimensional figure that shows the population attributable on the Y axis of these diseases to obesity and then the size of the circle, how common these diseases are. And on the uh the x-axis here or the at least the color axis would be the strength of the hazard ratio between. In one of these conditions, so it's remarkable when you look at this is actually ASCBD is probably the condition that's least associated with obesity. Population attributable fraction for ASCBD from obesity is only about 10%. But if you look at things like sleep apnea, fatty liver disease, gout, biliary disease, but particularly heart failure and atrial fibrillation. You see a stronger link between obesity and in these conditions. So really I think that select trial is just the tip of the ice. When you think about what the benefits to our patients are when you treat um the energy imbalance, uh, that's that's uh characteristic of this cardio metabolic disease, so let's talk about the explosion of GOP one receptor agonist trial data over the last few years will be to come. Not gonna talk about any of these trials in detail because I want to get to the end of my talk where I talk about cardio metabolic clinics, but I'm sure you're all familiar with the HEPA outcomes with GOP1 receptor agonists from the SEEPE trials, there's a recent summit trial with urzepatide. On the left, uh, the results of the SEEF trial showing remarkable improvements in symptomatology over just one year, and patients, um, treated with the weight loss dose of imagottide in people with. Including those with with and without diabetes. And on the right, the recent results of the summit trial. trazepatide, which actually showed reduction in heart failure, hospitalizations and urgent heart failure visits on top of the symptomatic improvement in patients with he back with trazepatide, which is even more potent weight loss therapy. So from HPA we go to sleep apnea, this recent surmount OSA trial. Showed that treatment with tzepatide markedly improvedaptic episodes in patients with sleep apnea. With downstream effects on risk factors. On the right we have the MASH trial, synergy Nash, in essence with the simagottide and terzeotide. Showing a marked reduction in fatty as well as liver fibrosis. Um, which is the the steps towards liver failure. In these patients with cardio metabolic disease. On the left is the flow trial. His patients with type 2 diabetes, CKD treated with sagottine, showed a marked renal benefit. In the Faux trial and on the right step 9 trial with the magnet time showing an improvement in Uh, and sleep apnea, again, um, oh sorry, I'm sorry, the 9 on the right is this is the, this I got it wrong, this is the osteoarthritis trial, patients with knee arthritis and obesity treated with weight loss, uh, dose of magnetite, marked benefit on functional status and pain and so forth in patients with osteoarthritis. So a benefit across many of these same diseases that we see linked to obesity and and epidemiologic studies. So the question then goes back to patient care. So how does physician training in our roles, particularly as cardiologists, affect our approach to cardio metabolic risk? We've been monitoring this for a while. This is an older study now. This is only up to 2020, but the the story remains the same, which is that cardiologists are lacking in their prescription of STL-2 inhibitors, but particularly GOP1 receptor agonists for patients bowel disease. As of this year 2020, less than 1% of all prescriptions for SGO2 inhibitors are GOP 1 receptor agonists were by cardiologists, particularly, they were having an uptick in SGL2 inhibitor use but not so much GOP1 receptor agonist use. So I think this study is instructive. This came from Neha Papadi at Duke and said, what are the perceived barriers to prescribing cardio metabolic therapies amongst endocrinologists, primary care doctors, and cardiologists, and are they different? So in this oranges endocrinologists, blue is primary care doctors, and green is cardiologists say, well, what are the barriers? Why aren't we delivering on the amazing data that we're seeing in the cardio metabolic space? Particularly on the left, let's look at GOP1 receptor agonists for simplicity for SGO2 inhibitors are similar. What cost? Are the costs too high? Well, primary care doctors and endocrinologists said yes, cost is a major barrier from using these medications, but cardiologists say no, we're used to using expensive therapies. Cost really isn't a big barrier. How prior authorization clearly a barrier, but more of a barrier for primary care than for cardiology. But as we move down the page, what about it's not my responsibility to prescribe diabetes medications as a cardiologist. I don't want to introduce confusion to the existing diabetes or cardio metabolic care plan. It's too difficult to communicate with PCPs and endocrinologists on diabetes care plans, but I don't know enough about these medications to actually use them. That was the predominant answer from cardiologists, don't want to get involved, don't think it's our space. Don't wanna confuse the picture or don't know enough to to use them, and maybe that's a problem too. So this was looking at the knowledge gaps, um, as opposed to primary care and endocrinologist said 3 of the time not comfortable at all with these therapies or another 13 of the patients, another 3 of the cardiologist said really only slightly comfortable using these therapies. My clinic is really isn't set up for this kind of thing. So what are the solutions delivering on What I think is going to be the next. Big paradigm shift in cardiovascular disease, which is cardiologists thinking about cardio metabolic disease as well. Well, here I think the evolution. We're going to see incorporation of these data into guidelines which we're seeing now. I think we're going to start having comprehensive cardio metabolic clinics within our cardiology practice like I practice here. It's a dedicated place to refer patients within the cardiology practice to patients physicians with expertise in cardio metabolic. I'll introduce something that we're thinking a lot about here which is actually planning on uh educating the next generation of cardio metabolic physicians and potentially even a new specialty of internal medicine called cardio metabolic medicine. OK, but these are some older slides, mainly looking at diabetes, but just illustrative that these are working their way into cardiology guidelines, right? Here's the ESC guidelines from 2019. Once upon a time, the ESC really wasn't writing diabetes and obesity guidelines, but here it says, clearly in a patient with type 2 diabetes, naive. Who has ASCBD or as high risk of ASCBD. The first drug you should start is an SCO2 inhibitor or a GOP-1 receptor agonist, with metformin being only second line. This was cardiology leading the way actually, well before the ADA even updated their guidelines to prioritize SGL-2 inhibitors and GOP-1 receptor agonists, and even said, well, you can use my other interest, calcium scoring, you can use cardiac CT to identify patients who otherwise wouldn't have thought were high risk, but you've now determined to be high risk based on their high calcium scores. You can use that as a justification for prioritizing SDL 2 inhibitor or GOP1 use, and there will be a new paper out this week about prioritizing obesity therapy based on subclinical disease measures. Just a class 2A recommendation, the cardiology guidelines for metformin, class 1 recommendation for SDL-2s and GLP-1s. You should probably know the 2020 ACC, uh, expert consensus decision pathway and diabetes also pushed the envelope a little bit. So in patients with diabetes. Who have a CBD or heart failure or kidney disease or just who have multiple risk factors, which is basically everyone. The first drug should be an SDL-2 inhibitor or a GOP-1 receptor agonist, and if further risk reduction or A1C reduction is needed, you should select the other drug, an explicit recommendation for combination therapy in these patients. And of course the ADA has filed suit. Multiple other organizations have followed suit with the first drug. Or cardio metabolic disease, particularly diabetes, being an SCO2 inhibitor or a GOP-1 receptor agonist. So why aren't we achieving better real world results? Well, I think this is one of the main problems that I alluded to. Which is our siloed approach to these patients, right? A patient like the one we talked about maybe a recent myocardial infarction, maybe sees the cardiologist first after discharge, then a primary care doctor, and he has to wait a few months to see an endocrinologist. Upon discharge, they see the cardiologist who talks about do you want the platelet therapy, maybe rehab, maybe some quick issues surrounding lifestyle. Doesn't really get around to starting a cardio metabolic therapy because there's so many other things to do. Patient sees the primary care doctor where some issues uh surrounding the copays are discussed, uh, your blood pressure is addressed. It says, well, the cardiologist will probably deal with all the drugs that lower cardiovascular risk. I'm just gonna deal with the other issues. The patient sees the endocrinologist where the new diabetes is discussed, um, maybe finger sticks and, and continuous glucose are discussed, um. Maybe metformin has started and they said, well, I'll defer to the cardiologist to start the SCO2 inhibitor GOP 1 receptor agonist. The patient goes around and around and despite no bad intentions because of therapeutic inertia. Evidence-based therapy is never started. It's such a common scenario and everyone says, well, I thought someone else was going to do it, particularly the cardiologist says, well, I thought the endocrinologist, the primary care doctor, would take care of that. And The do each of us play and I would say it's the role of the cardiologist to think about whatever we can do to lower cardiovascular risk. So the solution that many institutions are going to that we've tried here is this so-called cardio metabolic. The cardio metabolic clinic is potentially a solution uh within a large cardiology practice to have a dedicated clinic where patients can be referred for addressing their cardio metabolic disease risk. They can either then stay in that clinic for a while or get right back to their cardiologist. To go about the rest of their care, having updated their cardio metabolic um uh therapies or diagnoses. So this is what we do here. I'm taking referrals from cardiologists but also internists. Cardiologist within our campus or outside of our campus. And getting them on GOP receptor agonist or SCO2 inhibitors, diagnosing their sleep apnea or fatty liver disease, and getting them shipped back. So I really think we can make the biggest difference doing this. So we've been doing this for about 5 years now, and I think we've had tremendous results with our patients. It's something that once again more centers are adopting, but it really is the answer to when we're busy, when we're too busy to to really maybe engage in these evidence-based practices, they have a specialized center who can help out and can help teach locally best practices in cardio metabolic therapy use, sort of like the old lipid clinic. So this is a poll on the American College of Cardiology website. Do we need a new pathway for clinical training in medicine? Just 15% of all cardiologists said that the current training model is adequate. Most said, I didn't really get any treat any, uh, teaching about obesity in medical school, really not that much about diabetes even, uh, really spent my time in the cath lab or the EP lab, but really didn't get a chance to really even get exposed that much to lifestyle medicine. 85% of cardiologists said, Well, we need some new model for training in cardio metabolic medicine. So my friend Bob Who is a luminary from Colorado and I've been thinking for a while about what the future of training is. Now of course it starts with things like training our medical students and fellows about cardio metabolic medicine. We're starting to think about the future, and is the future actually having a new draining track in internal medicine in in cardio metabolic disease? The reason why we've been thinking about this is that Bob Echel is an endocrinologist by training, but he practices in a cardiology practice. He was the president of the American Heart Association. time ago was in endocrinology, but then I decided to go into cardiology clearly in between these spaces. Um, And it really points to just the relatively few people who are really trying to bridge this gap and the more training that we need for our coming generation of physicians to feel comfortable talking about cardio metabolic disease. So we've moved forward with this a little bit. We've gotten the American Society of Preventive Cardiology to sponsor a fellowship training program in cardio metabolic medicine. We have our first cardio metabolic fellow at ASPC right now, and this is something that'll be they'll spread to more institutions, uh, to train hopefully the next generation of cardio metabolic physicians. So how have cardio metabolic medicines, get back to our original topic, how have these cardio patients redefined these concepts of residual risk? And how will they change practice in the next 3 to 5 years? This is an editorial actually a couple of years ago that I wrote in Jack saying that type 2 diabetes is now in the cardiology and I know a lot of cardiologists sort of recoil when they hear this, they say, well, that's not, that's not a cardiology thing, but. You know, we have to think about therapies that lower cardiovascular risk in our patients, and here's what I wrote. I said, thankfully, the era of large cardiovascular outcomes trials for therapy has placed the treatment of type 2 diabetes directly in the cardiologist's wheelhouse. Historically, cardiologists have been, I think, appropriately hesitant to get involved in treatments that don't reduce cardiovascular disease. I think that's actually reasonable. Cardiologists really shouldn't do anything outside of something that doesn't lower cardiovascular disease. Examples of this would have been diabetes before the year 2015 are now obesity before the year 2023. However, with several cardiovascular outcomes trials showing cardiovascular risk reduction with GOP1 receptor agonists in the early treatment of cardiovascular disease should now be a part of every cardiology practice, and I believe that. I said in summary data like the recent trial data I was referring to remind us that we've entered an era where metabolic disease must be a part of cardiologists education practice, but I'm very optimistic about this. I said, fortunately we are quite confident the cardiologists will rise to the challenge. We are a very evidence-based specialty that embraces new strategies that have been conclusively proven to reduce CBD just like a long time ago, statins were thought to be outside the cardiology space. Now we own them. So we've adopted to hypertension management cardiology practice to lipidd management, cardiology practice, even to think about smoking cessation. And now we must adapt to team-based treatment of obesity and early manifestations of type 2 diabetes. That's where I think we're headed. So getting back to this original slide that I showed about how once you've done the basics for a patient, looking at those bins of residual risk and deciding what treatment to pursue next, but I think this whole paradigm could be overhauled. I think even what we consider. What is risk residual to what will change? I think treating cardio metabolic disease upstream will be considered something that's foundational to these patients. It'll have to be treated with something like an aspirin, a statin, maybe blood pressure, and some sort of a cardio metabolic treatment before we get on to these more expensive therapies that we'll see in the future like antibodies to IL-6 to anti-sensoli and nucleotides to LPLA, things like downstream of. Of first treating cardio metabolic disease, so I'll close with another case. 59-year-old man, stage 2 obesity, advanced subclinical CAD, hypertension, sleep apnea, paroxysmal atrial fibrillation, prediabetes, LVH, grade 2 diastolic dysfunction. That's a lot of things, but I think you'll see this patient every day in practice, and I think hopefully. We knew this before the lecture, but even more after this secture, hopefully you look at these patients instantly say that's a cardio. This patient's probably subclinical CBD, sleep apnea, Afib, um, diastolic dysfunction, and emerging HA are all linked to underlying. Um, stage 2 obesity and disease and basically fat mass is really what we're talking about, uh, although we use BMI clinically as our measurement, we're really talking about fat mass. This patient has too much fat mass. This patient works from home, is sedentary. He's already on an aspirin and the statin, has a, a blood pressure that's 146/88 and has lower extremity edema. an A1C of 5.9%, LDL of 99%, and creatinine of 1.3. Once again, you can go a lot of different directions for this patient, but what I'd have you consider. After hearing this talk is what drug class is most likely to make the biggest and most fundamental impact on this patient's lifetime, disability, morbidity, and mortality. It's me right now, I think that's a GOP1 or C cretin-based weight loss therapy, but, as we see from clinical trial data, improve the sleep apnea. symptomatic improvement in health. Reduce atheroscritic cardiovascular events, at least in patients with existing AS CBD, the AF data is upcoming. That we'll see soon as well as really has things like, um, and of course the kidney disease almost sure has uh fatty liver as well. So let me summarize this talk. It tries to kind of get more cardiologists thinking about the cardio metabolic space by saying that residual that's evolving. Residual to what? And I would say that cardio metabolic disease is taking its place amongst the uh foundational therapies of patients like this, and preventive cardiology is now booming with an array of options to treat the risk in a way that we never before and that cardio metabolic disease is the fundamental epidemic medications like concretein-based therapies are the most impactful innovation in preventive cardiology in the last 15 years. But at present, I think the clinical education or practice patterns are poorly suited. For the have assessed this residual risk, and we need to rethink the future of cardio metabolic medicine training and care delivery. I think this starts with training our next generation of physicians around these therapies. I think this, uh, uh, starts thinking about maybe specific trainings, um, and specific clinics within, uh, like your institution, my institution. And these clinics can serve as referral areas for patients like this, teaching areas, as well as most commonly what happens in our clinic is a physician for a patient in, there are several patients in for GOP-1 receptor agonist initiation. We do the teaching, we start the therapy. So we notice that physicians are not referring to patients anymore and we ask why and they say, Well, you know what, I realized I can do this myself. All you're doing is prescribing GOP 1s and teaching. I can do that, so it serves as a trickle down effect for improved practice patterns across an institution. Published January 23, 2025 Created by