Episode Transcript
[00:00:01] Speaker A: Welcome to Obesity a Disease, the official Obesity Medicine association podcast exploring the many facets of the disease of Obesity A Disease podcast is brought to you by the Obesity Medicine Association, a clinical leader in obesity medicine.
[00:00:28] Speaker B: A 48 year old male presented for a routine physical exam. His BMI was 32, blood pressure 144 86, and laboratory results included a lipid panel that revealed a triglyceride level greater than 2500 and an HDL of 25.
He had no history of pancreatitis or mace and was otherwise healthy. He initiated an intensive physical activity program which included biking up to 100 miles per week as well as dietary changes to reduce sugar and saturated fat. He was able to bring his triglyceride level down to 180 and HDL up to 42. He lost 15 pounds. The story provides a prime example of how powerful lifestyle changes can be towards improving cardiometabolic health. Hi, I'm Dr. Nick Pennings, professor of Family Medicine at the Campbell University School of Osteopathic Medicine and Director of Clinical Education for the Obesity Medicine Association. With me on the podcast today is Chadiya Ndumile, MD, who practices general and preventive cardiology at the University of Pennsylvania. Dr. Ndimli, tell us some more about yourself.
[00:01:34] Speaker C: First of all, thank you so much for having me and it's going to be exciting to have the chance to discuss these issues with you and your audience.
I am, as you mentioned, a preventive cardiologist and an epidemiologist.
I have recently just been the Chair of the Council on Lifestyle and Cardiometabolic Health for the American Heart association. And I've had the great privilege of chairing the American Heart association and American College of Cardiology's work on the CKM Syndrome initiative, including the Presidential Advisory and Scientific Statement that introduced this concept in 2023, and then the most recent AHA ACC ADA ASM clinical practice guidelines around CKM Syndrome that came out just in June of 2026. So it's great to have the chance to talk with you today.
[00:02:29] Speaker B: And it's great to talk with you today too. You've clearly been such a key player in the deep dive into cardiometabolic disease. So tell us more about what cardiovascular kidney metabolic syndrome is.
[00:02:46] Speaker C: Yeah, so cardiovascular kidney metabolic syndrome, or CKM syndrome, is a condition that reflects the close pathophysiologic interrelatedness of obesity or excess adiposity with diabetes, diabetes, chronic kidney disease, and the cardiovascular system. So metabolic factors, kidney factors, and cardiovascular disease. It's a progressive condition that's reflected by the stages of CKM syndrome, and it's associated with a greater likelihood of earlier cardiovascular disease and most notably, premature mortality.
The cardiovascular kidney metabolic construct is meant to reflect the fact that these factors are not isolated conditions. Despite that, that's how we often treat them in clinical practice. But they're rather very closely interconnected conditions that each one impacts the other. And it's increasingly the case that CKM is what we are seeing in clinical practice as the growing phenotype of cardiovascular disease risk. So understanding this interplay and addressing these interrelated challenges are really going to be key to improving cardiovascular health for the population.
[00:03:59] Speaker B: And so historically, we've kind of seen cardiovascular disease be associated with hypertension, hyperlipidemia and smoking, but we're now seeing different drivers of cardiometabolic disease, is that right?
[00:04:12] Speaker C: Yeah, that is true. I mean, it's not to diminish the importance of hypertension and of hyperlipidemia or dyslipidemia. Those are still very important and fundamental targets for. For modifying risk and reducing the likelihood of going to cardiovascular disease. But what the case is, just to your very great point, is that we're increasingly seeing that individuals are not coming in with those isolated conditions alone anymore. They're not just coming in with hypertension or dyslipidemia as their primary phenotype of risk. We're increasingly seeing that individuals are coming in with obesity and diabetes and chronic kidney disease. Now, that may be overlaid with hypertension, that may be overlaid with some dyslipidemia. But is that clustering of conditions that's increasingly driving risk in the population, and
[00:05:01] Speaker B: that how does that trigger disease processes? What are the underlying factors like insulin resistance, inflammation? Are those big factors in this.
[00:05:11] Speaker C: Yes, you're absolutely right. So there's some central factors that are really kind of associated with the progression of all of these inflated metabolic kidney and cardiovascular clusters. And central factors certainly include inflammation, which is closely linked to insulin resistance. So those two, we see a lot in the way of oxidative stress that causes a lot of multivascular injury across various vascular beds. We see a resultant good amount of vascular dysfunction. We see all of these processes contributing to the development of metabolic risk factors to chronic kidney disease and really to all forms of cardiovascular disease. Those are some of those central pathophysiologic unifying tenets that we see across these different conditions. But it really underscores the importance of not thinking about these as isolated conditions, but rather understanding their collective interrelations and addressing them collectively.
[00:06:06] Speaker B: And so how do these CKM guide syndrome guidelines kind of address those issues?
[00:06:15] Speaker C: Yeah, so I think there's a lot of different things that come up as a result of the CKM syndrome guidelines. So one is just the general recognition. And this is something for clinicians to understand and for us to be able to communicate to people in the lay public that we are seeing these interrelations between these conditions. When you see sometimes, like the case you just demonstrated here, which is a really great case, by the way, the impact of lifestyle. And we'll talk more about staging and CKM regression later. But this is a really great example of that. But you see the individual who has some obesity, who has clearly what we call atherogenic dyslipidemia and has hypertension. Those are all. And has some evidence of likely some early insulin resistance. Those are all interrelated. So I think being able to describe to somebody that's not bad luck, that that's because these are so closely intertwined is an important starting point. I think what these guidelines also do is help us to not only conceptualize that interrelatedness, but to understand the progressive risk over time associated with the CKM syndrome. This is a great case that you just demonstrated here, because awareness of the risk allowed somebody to make changes and avert progression to what could have been a much more concerning clinical state. And there is these stages of CKM syndrome that are very predictable. We kind of go along a very kind of predictable trajectory. But understanding those, these are windows of opportunity to progression to those later stages, I think. Third. Go ahead. Sorry.
[00:07:46] Speaker B: Oh, I was going to ask you to tell some more about those staging systems. What are they? How do we apply them clinically?
[00:07:53] Speaker C: Yeah.
So the stages are a concept that are really meant to reflect the traditional pathophysiologic progression of CKM syndrome. And it's really to support a greater focus on prevention across the life course.
I want to emphasize that these factors that we're seeing, this is not just unfortunately happening in adults. We see historic levels of obesity, of course, and diabetes among adults, but we're also seeing historic levels among youth as well. As we all know, youth risk factors lead to adult risk factors, just more severe with additional consequences.
The stages really reflect the progression. So we start with stage zero, which is actually not part of CKM syndrome.
That is actually individuals who have fairly ideal cardiovascular health. Everything is going well, and we want to emphasize and support staying in that state for as long as possible, or getting back to that state if possible, as well. Stage one is really the Entryway most of the time to CKM syndrome. And that's really excess or dysfunctional adiposity, which is defined by either BMI by your waist circumference, because central adiposity around the waist is really what drives a lot of this metabolic risk.
And also by prediabetes, which we can actually even see in some people who don't have overtly excess weight. Stage two, which usually follows from stage one, is the emergence of metabolic risk factors or chronic kidney disease. And that includes things like diabetes, type 2 diabetes, hypertension, the dyslipidemia. Like we see in this case, it includes chronic kidney disease or a clustering that's like metabolic syndrome, where this individual also meets criteria for. And that is typically these days, the precursor to stage three, which is the development of subclinical cardiovascular disease. Early changes in the vascular wall or early changes in the heart function, or very high predicted risk.
We have a prevent calculator that everybody can use to describe their risk.
A prevent score greater than or equal to 20% is a very high risk population. That's a risk equivalent for these other subclinical measures or very high risk. Chronic kidney disease is also a risk equivalent for this as then that's the precursor to stage four, which is clinical cardiovascular disease, overlapping with these metabolic risk factors or chronic kidney disease.
Each of these represent an opportunity to understand risk, prevent risk, and help people not get those later stages. It's not just preventing progression like in this case here. We can see with substantial lifestyle change or with substantial weight loss, we can see actually regression. So basically losing the criteria for stages and going backwards, which in my experience as well, helping people understand the modifiability of this and the fact that this is not inevitable, we can actually see a lot of people going that other direction.
But it also helps us call attention to those individuals who are very high risk or have these risk factors before they progress to those later stages by implementing appropriate therapies as well.
All of this is really to support prevention across the life course for people in the population for what's increasingly the cause of cardiovascular disease and mortality.
[00:11:05] Speaker B: I think that's always been a big focus of us as obesity medicine specialists is really identifying those patients early on. It's not just about losing weight. It's about improving cardiometabolic health. It is about helping people get healthy. And those early interventions really are a key part of this, as you describe. But also what I take from this is as you move along this progression, it's not additive, really, it's Almost exponential in terms of, as you develop multiple, multiple complications from ckm, that your risk and mortality goes up dramatically. Is that right?
[00:11:43] Speaker C: Yeah. So you definitely, as you get clusters of conditions, you can see a synergistic impact on mortality, particularly when you see the emergence of diabetes and chronic kidney disease, which unfortunately are common partners. We often see these happening together.
We definitely see a synergistic increase in mortality that can result from those conditions. So this, again, highlights the importance of trying to get involved early. But then, even for these individuals who already have some of these conditions in the later CKM stages, it's often the case that they're unrecognized or unaddressed. And I think a big part of this approach is not only starting some of these changes from a lifestyle standpoint and a weight management standpoint, but it's also greater recognition of these conditions. So that all of us are looking for the kidney disease, all of us are looking for the fatty liver disease, all of us are looking for the diabetes and the hypertension, but all of us are just paying attention to these issues and helping to characterize risk for our patients and supporting better prevention.
[00:12:52] Speaker B: So what are some of the metrics that obesity medicine specialists should be looking at when evaluating their patients and assessing them for CKM risk?
[00:13:02] Speaker C: Yeah, so I think that there are complementary approaches, qualitative approaches to assessing risk, and quantitative approaches to assessing risk. But it all starts with the same initial piece, which is basically getting the assessments. So I think, first of all, from an anthropometric standpoint, BMI is pretty standard. So we get that everywhere. But as all of us know, BMI doesn't really reflect body composition and that central adiposity is important. So assessing that waist circumference and helping people understand that when that waist circumference is more elevated, we're going to see that that's where we're going to see the greatest urgency for needing to change that lifestyle and change that adiposity trajectory. I think it's really important. And additionally, assessing for metabolic risk factors or assessing for the lipids, like you have in this case, assessing for glycemia, assessing for blood pressure, all of these are the kind of metabolic consequences we see of visceral adiposity. And then we also want to make sure we're looking for chronic kidney disease. As I've said, it's a risk multiplier for cardiovascular disease. We actually now have a lot of therapies that target it directly, including the GLP1 agents.
But we want to identify that in a timely fashion and people who are higher risk. We want to use both EGFR estimated GFR and UACR urine album creatin ratio. But these are important metrics to be incorporating into practice. And then additional things to look at are fatty liver disease or metabolic dysfunction associated. Steatotic liver disease is exceptionally common here. We know it's threefold higher likelihood in individuals who have overweight and obesity. Actually along the spectrum when you start getting inflammatory liver disease, steatohepatitis, we see that in about 70% of individuals with type 2 diabetes. So we want to be assessing for that. There's a very simple algorithm called the Fib 4 index that just includes AST, ALT, age and platelets. That's it, very simple things. But you calculate the fib4 index and that can tell you should you be worried or should you not be worried and needing further testing to look for fatty liver disease. These are some of the core things that we need to be doing in our patient population to make sure we're regularly characterizing their risk. Those metrics I just discussed can put people into their CKM stages, but it can also help us to calculate that prevent score. That prevent score kind of aggregates all these factors, all these CKM factors together and tells you your global risk for total cardiovascular disease for heart failure or atherosclerotic cardiovascular disease over 10 or 30 years for younger and middle aged adults.
[00:15:36] Speaker B: And there's a couple of different components that you can plug into the Prevent score, like a 1C and urine albumin ratio. Yeah, BMI. Which ones are the most important? Should you be incorporating all of those?
[00:15:50] Speaker C: Yeah, it's a great question, BMI standard. But we have these add on variables and I would say adding them on where they're clinically indicated is helpful. It helps to increase the accuracy of how we predict risk risk with using the prevent calculator. So if you're measuring your A1C for somebody who has overweight or obesity or has diabetes, that's going to add predictive value. If you're measuring the urine album creatinine ratio for somebody with diabetes or hypertension or chronic kidney disease, that's going to add additional predictive value that we'd be missing otherwise. And the third add on measure is social deprivation index. So we know that the likelihood of developing CKM syndrome, but also the complications of CKM syndrome is much higher. For those individuals who have more adverse social factors, who are basically having a harder time with a healthy diet or exercise, or have more stress or difficulty with Transportation. We know these issues increase the likelihood of progressing along this spectrum of CKM syndrome. So it's an important part of the CARE model. But in the predictor, the social deprivation index is a measure that you can use to basically identify to help further refine risk estimation because your risk differs substantially, unfortunately, by your zip code in the United States. States.
[00:17:04] Speaker B: And I think putting those things together really are an important part of obesity treatment because it shifts that focus away from just being about how much weight you lose to how can you improve your cardiometabolic health. And when patients hit plateaus or they don't lose as much as they expect, but their cardiovascular health parameters are improving, I think that's important messaging that we should be delivering to our patients.
[00:17:29] Speaker A: Yeah.
[00:17:29] Speaker C: And I think one thing that I will say that's important about this, I agree completely with what you're describing. And I think there's two things I want to highlight. One is that, you know, it is, I think obesity medicine, physicians have been doing this for some time, but some others would think of some of these things as all isolated conditions. And we need to be thinking about obesity as a centerpiece that's increasingly deriving cardiovascular, kidney, metabolic health.
When we see that individual, we need to be doing this broader assessment to really fully characterize their risk. But then there's a progressive nature to this staging that we also see here. And the main metric that we're focusing on in this staging construct that's different from others is cardiovascular disease. It's all centrally tied to what is the risk of cardiovascular disease, because that's the leading cause of mortality. That's what's making individuals die prematurely in the context of obesity. So that's this. And it ties directly to prevent staging and also their approaches to prevent cardiovascular disease.
[00:18:28] Speaker B: When we're looking at trying to prevent the cardiovascular disease, what percentage of weight loss seems to be meaningful to be able to create significant improvements in cardiometabolic health?
[00:18:40] Speaker C: Yeah, it's a very good question. So all weight loss, that's intentional and it's related to healthy lifestyle change or intentional therapy is going to be good. Good. So that's the first thing and should be encouraged. But we know that when we get to 5% weight loss, then we start to see some movement. Most of the time, 3 to 5%, but 5% most reliably in this CCAM risk factor profile. So we'll start to see the blood pressure and the lipids and inflammation and the glycemia all kind of moving in the right direction. Even album Neuroscience improving as well.
We don't have definitive data on exactly where we start to see cardiovascular benefit, but the data suggests the clinical trials have not been positive for cardiovascular outcomes thus far. But post hoc analyses of lifestyle changes in clinical trials seem to suggest that above 10% we're likely is where we're going to start seeing potentially some impact on cardiovascular disease events. So that's a good framework to think about where you might move beyond seeing just improvements in the risk profiles and start to see some actual outcome benefits in the 15 to 20% range. We're now likely exceeding that, seeing even more improvements in risk profiles, getting off of therapies, and we're seeing CKM regression. So now we're probably seeing individuals being able to lose criteria and going into regression for conditions like diabetes or like hypertension and lose the need for medications. So basically, I think we see a stepwise improvement in each of these outcomes as we get greater and greater intentional weight loss.
And I think those are all good metrics to go for. I will make a point though that the GLP1 medications, which we obviously increasingly use as an adjunctive therapy for weight loss, the benefits we see from a cardiovascular standpoint with those obviously weight is one component of that, but it also seems to have a weight independent component as well, because even in the clinical trials we started seeing cardiovascular risk reduction below these levels of weight loss that I'm talking about here. So below that 10% level of weight loss and regardless of the degree of weight loss achieved in the clinical trials. So the GLP one seemed to have some additional cardiovascular benefits above and beyond that weight benefit. It But I will say that these are the metrics to be looking for when we think about lifestyle and thinking about weight loss in general.
[00:21:15] Speaker B: Yeah. And I think some of the post hoc analysis in the select trial showed some of that benefit to be not necessarily tied to weight and to be independent of some of that weight loss,
[00:21:25] Speaker C: which is exactly right.
[00:21:26] Speaker B: Very interesting. And, and with future studies with these agents, do you think we'll see more of a focus on improvements in cardiometabolic health rather than just on weight loss, which has been a big factor in the past?
[00:21:40] Speaker C: Yeah, I certainly hope so. I think that weight loss is one important metric, but I think that what we really care about is improving overall health, quality of life and cardiometabolic health. And I am hopeful that more and more studies will focus more and more on those as the kind of main focus rather than just the numbers on the scale.
[00:22:04] Speaker B: And I think that has always been the focus of obesity medicine specialists that been involved with the OMA that really is. It is about creating health, not just losing weight.
So what are some of the most important takeaways from these guidelines for clinicians who are not cardiologists?
What kind of things should they be focusing on in their practice?
[00:22:26] Speaker C: So I think the first thing is something we talked about earlier, which is that we make sure we are assessing risk at each of these stages and really helping individuals understand where they are along this CKM spectrum. So that includes assessments of anthropometrics, that includes these metabolic assessments for blood pressure and lipids and glycemia, and that also includes assessments for chronic kidney disease.
And this is kind of key for helping people understand where they are, motivating change like we saw in this situation, and giving appropriate therapies to the right individuals. I also think the prevent score estimation is allowed as made possible by these assessments. So I think that's an important part and very complementary in terms of helping people understand their risk. I think the second thing that we need to be doing in practice is when we see individuals and help them understand where they are and the interrelatedness of any condition, conditions that are present, really supporting and motivating lifestyle change. I think that that is one of the things that's a key tenet here, I think, as we have a lot of new therapies that are very effective, which I'll say something about in a moment. But I think lifestyle modification is an essential component of what we're dealing with. And actually there's certain components, some of those pathophysiologic things we talked about, like the insulin resistance and the vascular dysfunction and the this hyperthrombosis, a bunch of pathophysiologic things that get better with lifestyle, that's going to be necessary, not just treating the risk factors like hypertension or high lipids.
Then additionally, I think we now have a lot of tools to target improving CKM health for individuals. Obviously, we've talked about lifestyle. We also have bariatric surgery for people who have a need for very substantial weight loss. But then we have these GLP1 receptor agonists that have demonstrated benefits for cardiovascular outcomes in obesity and heart failure with preserved ejection fraction in atherosclerotic cardiovascular disease like select, and then also in patients with diabetes, we have other agents that we know are really effective like the SGLT2 inhibitors. And there's nonsteroidal mineralocorticoid receptor antagonist pineranone. Now, we're not all going to be reaching for all those therapies, but it's just helpful to understand that there's going to be things that we have at our disposal to help individuals who have these conditions, but calling attention to them is the first step. I think that that's going to be really key for everybody to be doing and then we can all collectively work to improve outcomes for this patient population.
[00:24:59] Speaker B: Well, I think that's an awesome summary on the approach to the treatment of cardiovascular kidney metabolic syndrome. I really like to thank you for being with us today and sharing your thoughts and knowledge and insights on this chronic condition that is affecting so many people in the United States and around the world.
[00:25:18] Speaker C: Well, thank you. I mean, obviously the Obesity Medicine association has been doing such tremendous work in this space for some time. It's great to be able to partner on this discussion and excited for what the future holds in terms of improving cardiovascular kidney metabolic health for the population.
[00:25:32] Speaker B: All right, thank you for being here today and if you like this podcast, please share it with a friend or colleague and help the OMA as we strive to advance clinician understanding of the disease of obesity. Obesity
[00:25:46] Speaker A: thank you for listening to this episode of Obesity a Disease. For more information about obesity medicine, podcasts and other valuable resources from the clinical leaders in obesity Medicine, please visit www. Obesitymedicine.org podcasts. If you enjoyed this episode and want to listen regularly, head over to itunes where you can subscribe, rate and leave us a much appreciated review.
The views expressed in this episode are those of the host and guest and do not necessarily represent the opinions, beliefs or policies of the Obesity Medicine association or its members. Please join us again for our next episode of Obesity A Disease.
