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Formulate an early, comprehensive plan of action for adults with CKD, T2D or CVD based on the interrelated
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Featured
Presentation
Dr. Wright: Hello and thanks for joining us! I'm Dr. Eugene Wright, Consulting Associate in the Department of Medicine at Duke University Medical Center. I also serve as the Medical Director for Performance Improvement at the Charlotte Area Health Education Center. The title of today's talk is Understanding the Interconnectivity of the Cardiovascular, Renal, and Metabolic Systems. We'll be discussing the dynamics of cardiovascular, renal, and metabolic diseases, as well as how they impact patient care across different medical disciplines. Joining me for this discussion are two of my colleagues, Dr. Leigh Perreault and Dr. Dan Bensimhon. Leigh, would you care to introduce yourself first?
Dr. Perreault: Sure, Gene. I'm Dr. Leigh Perreault. I am an Endocrinologist and Associate Professor of Medicine at the University of Colorado.
Dr. Bensimhon: And I'm Dr. Dan Bensimhon, the Medical Director of the Advanced Heart Failure, Mechanical Circulatory Support Program at Moses Cone Hospital in Greensboro, North Carolina.
Dr. Wright: Thank you, Leigh and Dan, and thanks for being here. It's always exciting to be able to gain perspective from clinicians in other specialties, and I'm sure it will make for a robust discussion. So without further ado, let's get started.
Dr. Wright: This presentation is supported by and made on behalf of Boehringer Ingelheim Pharmaceuticals, Inc. and Lilly USA, LLC. Presentation content has been reviewed for consistency with FDA guidelines and is not approved for continuing medical education credit. This is a disease state awareness education presentation. As such, we will not be discussing or answering questions about specific products or classes of products.
Dr. Bensimhon: Thanks, Gene. Once again, today we'll be discussing the intricate link among the CV, renal, and metabolic systems and the implications of this link on our approach to patient care.
I think we all realize that changes in one of these systems can lead to profound changes in the others—either for the better or for the worse. We are quite used to this idea in the cardiology field, where the significant overlap between CV disease, diabetes, and chronic kidney disease can make our jobs tricky at times. Leigh and Gene, is this something you see in your practices as well?
Dr. Perreault: Absolutely, many of my patients with diabetes have cardiovascular disease and/or renal disease. These are the leading causes of death in patients with diabetes so, as an endocrinologist, it ends up being something I'm concerned with for all of my patients with diabetes.
Dr. Wright: This has also been my experience in primary care, Leigh. These diseases go hand-in-hand for so many of my patients. So when I see one, I know to look for the others.
Dr. Wright: It seems that our own observations are consistent with the notion that these diseases are interconnected. Now, let's spend a little time talking about the multisystem effects of this interconnectivity.
Dr. Wright: When we look at how many people are affected by heart failure, chronic kidney disease, and diabetes, the numbers are staggering. Over 6 million adults in this country have heart failure, 37 million have chronic kidney disease, and 34 million have diabetes. This equates to a prevalence of 2.2%, 15%, and 10.2%, respectively.
And, as we're all aware, these numbers continue to increase. By 2030, just 10 years from now, the prevalence of heart failure, chronic kidney disease, and diabetes are predicted to increase by 35%, 11%, and 36%, respectively.
Dr. Wright: And the overlap we see in our own patients generally reflects population statistics. A quarter of patients with heart failure have diabetes. 60% of patients with heart failure have renal disease. And 37% of patients with diabetes have chronic kidney disease. Of course, cardiovascular risk is also a major issue for patients with diabetes. Nearly a third of them have cardiovascular disease, and the risk of hospitalization for heart failure is twofold greater in patients with diabetes compared to those without.
Dr. Perreault: And you know Gene, one reason we see these diseases overlap so frequently is that they share common risk factors. Older age, high blood pressure, obesity, coronary artery disease, and a history of myocardial infarction are all risk factors for diabetes, heart failure, and chronic kidney disease. I know that these are things we probably all look for, but hypertension and obesity certainly stand out to me as an endocrinologist. I rarely see a patient with diabetes who doesn't have at least one of these risk factors.
And for patients with overt diabetes, heart failure, or chronic kidney disease, each condition acts as a prognostic risk factor for the other two, something I think can be attributed to the interconnected mechanisms underlying these diseases. Dan, would you like to expand a bit more on the shared pathophysiology?
Dr. Bensimhon: Sure, Leigh. Looking at the rightmost side of this figure, going from the heart to the kidneys, we see that heart failure can worsen kidney disease by activating the RAAS system and decreasing renal perfusion. This relationship also works in the opposite direction, since decreased renal perfusion can disrupt the release of vasoactive hormones and make heart failure more difficult to care for.
On the left side of the figure, we can see that loss of cardiac output can activate the sympathetic nervous system, causing increased lipolysis and promoting insulin resistance, which in turn leads to worsening diabetic control and hyperglycemia. Persistent hyperglycemia can then have a direct impact on kidney function by causing damage to the microvasculature over time. It can certainly be complex, and we probably don't understand all of the connections, but those of us who care for these patients on a daily basis clearly realize that problems with one system can throw off the other systems and really put a patient at risk.
Dr. Wright: Thanks, Dan. Looking at the results shown here, we can see that the physiologic link you just described is exactly what is investigated in this study. In a large-scale analysis of more than one million adults, there was a direct linear relationship between decreasing renal function and the prevalence of heart failure or diabetes.
The severity of renal impairment is also associated with poorer outcomes in patients with heart failure. In the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity, or the CHARM study, which consisted of 3 trials that enrolled over 2000 patients with symptomatic congestive heart failure, the cumulative incidence of cardiovascular death or hospitalization for worsening heart failure increased as the eGFR decreased. So, for patients with moderate renal impairment, early intervention not only helps to preserve kidney function, but also reduces the multisystem burden that can lead to poor outcomes.
Dr. Wright: It is important to remember, however, that the interconnectivity of these diseases is also exemplified by the multisystem benefits that can result from improvements in individual systems, and this is something that really informs my approach to patient care. It means that when a patient comes to me looking for help managing their diabetes, I need to take a holistic approach that accounts for the link between diabetes and cardiovascular and renal systems. So, Dan, what do you think about that?
Dr. Bensimhon: Well, Gene, apart from the fact that my patients usually come to me seeking help with CV issues rather than diabetes, I think my approach is very similar to the one you've just described. As clinicians, we need to be continually reminding ourselves how interventions that affect one system are likely to affect the rest of the body. We can see a clear example of this when we consider how improvements in renal function can reduce cardiovascular risk. The study we're looking at here evaluated the effect of changes in albuminuria on incident heart failure in over 1500 patients with type 2 diabetes and nephropathy. For these patients, the risk for incident heart failure decreased linearly with reductions in albuminuria. In fact, among all available baseline risk markers, albuminuria reduction was the strongest predictor of long-term protection from cardiovascular events.
There's also an association between improvements in glycemic control and renal outcomes, something I know Leigh is very familiar with.
Dr. Perreault: Yup, I sure do, Dan. There is a well-established relationship between glycemic control and microvascular risk in patients with type 2 diabetes. It was the landmark UK Prospective Diabetes Study, or UKPDS, that first established the association between intensive glucose lowering and a reduced risk for microvascular complications in patients with type 2 diabetes. Similarly, the Veterans Affairs Diabetes Trial which we're looking at here found that intensive glycemic control was associated with a significant reduction in the risk for worsening renal function in patients with type 2 diabetes. What's interesting about these data is they show an enduring renal benefit for more than a decade post-randomization, even after differences in glycemic control between the study groups had disappeared. You'll sometimes hear this referred to as the "legacy effect."
Dr. Perreault: There's also some evidence linking improved cardiac function with improvements in glycemic control. In this small retrospective study of 15 patients with diabetes and chronic heart failure, a statistically significant reduction in A1C was observed after restoration of normal cardiac output following the implantation of a left ventricular assist device.
Now, the inverse of this—the effect of glycemic control on cardiovascular risk—remains unclear. Despite being evaluated in several large-scale studies, the data from these studies do not show any positive effects during the intervention phase, but some long-term follow-up studies have shown a modest benefit for macrovascular disease.
Dr. Wright: Now let's discuss how all of this information influences our approach to patient care in the context of two hypothetical patient case studies. The idea here is that we share our perspectives on how we manage patients affected by cardiovascular, renal, and metabolic conditions, and examine how our different approaches may reflect the similarities and differences that exist across different medical disciplines. Leigh, can you tell us about the first patient we'll be discussing?
Dr. Perreault: Yeah, I'd be happy to, Gene. So, she's a 62-year-old woman diagnosed with type 2 diabetes 2 years ago. Her A1C is currently 7.8%. She also has mild renal impairment with albuminuria. She has high blood pressure and she's overweight.
To start us off, as an endocrinologist, I frequently see patients with a similar presentation. I'd say most of my patients actually have overweight or obesity, their blood pressure is rarely perfectly controlled, and they frequently have either high lipids and/or microalbuminuria. So this is a classic patient that I would see in my practice. We're already seeing signs of kidney disease so I'd prioritize getting her A1C under control to reduce the risk of worsening renal function, but I'd want to approach this in a way that simultaneously addresses her cardiovascular risk. Diabetes alone puts her at an increased risk for cardiovascular disease, so I'd also prioritize getting her weight, blood pressure, and lipids under control to try to reduce that risk.
Dr. Wright: I'd say that reflects my own approach to managing this patient, Leigh. A1C reduction is definitely a priority here, with the goal of reducing her risk for worsening renal function now, while she's still fairly early in disease progression. However, we're already seeing renal dysfunction, so it's possible that she developed diabetes some time before receiving a formal diagnosis; that's not uncommon. In this case, it would be even more important to act early to prevent further microvascular damage from persistent hyperglycemia.
Dr. Bensimhon: I agree with that approach, Gene. Similar to what we see when managing patients with hypertension, cardiovascular risk grows over time and the damage is progressive. The combination of diabetes, renal disease, and traditional cardiovascular risk factors multiply this patient's cardiovascular risk. This patient may already have undetected cardiovascular disease, in fact, so getting things like a coronary calcium score may help us understand her CV risk even better. That said, people often don't get to a cardiologist for an evaluation until they've had an event like a heart attack or another cardiac event. So we often find that patients like this have significant, underlying asymptomatic atherosclerotic disease. If we're going to reduce her risk and not just address these individual risk factors and events, we need to encourage our partners in primary care and endocrinology to take a comprehensive approach to her care that focuses on preventing symptomatic, or even deadly, cardiovascular disease before it happens.
Dr. Wright: Great point, Dan. We know that patients with diabetes and cardiovascular disease tend to have a lot more interactions with cardiologists compared with other specialists, but for a patient like this we can't necessarily assume that to be the case. This just reinforces why we need to take a holistic view on risk reduction every time a patient comes into our office.
Dr. Bensimhon: Let's take a look at our second patient. Now, this looks more like a patient who is likely to walk through my door at the Heart Failure Clinic. He's a 74-year-old male with all the fixin's: he's had known CV disease with a heart attack 2 years ago, and now he has diastolic heart failure; he has been living with type 2 diabetes for 12 years and his hemoglobin A1C is 8.4%; and he also has stage III/IV renal impairment, with an eGFR of 31. This is really someone who requires us to look at the whole picture. And by the way, he's also obese, so we can't forget about that diet and exercise are key elements of comprehensive patient care. Gene, what do you think?
Dr. Wright: I absolutely agree, Dan. Diabetes, obesity, and hypertension are very common in the patients that we see. As we all know, diet and exercise are the cornerstones of type 2 diabetes management. When I look at this patient, I see an example of the compounding effect of cardiovascular, renal, and metabolic diseases on one another, and the resulting need for multisystem risk reduction.
Dr. Perreault: Yeah, I agree, and I'm so glad this conversation's really been around a multisystem approach and multispecialty approach. And to put it plainly, the need for comprehensive care in this case is to reduce the risk of dying from cardiovascular or renal disease. What he really needs is a multifactorial approach to get that risk under control. The longer he goes on like this, the more his risk is going to increase, and the more his life is going to be in danger. His A1C, his eGFR, and long duration of diabetes are real causes for concern, but I'm particularly struck by his urinary albumin-creatinine ratio. With respect to his kidneys, we've been focusing primarily on the eGFR, but it's worth noting that his urine albumin can give us some additional context on the status of his kidneys. We also know that albuminuria is an important prognostic factor for other systems, especially the heart and macrovasculature.
Dr. Wright: Now, having looked at those two patients, it seems that we're all in agreement that we need to act early to address multisystem risk in patients with cardiovascular, renal, and metabolic diseases. I think it's worth noting that, despite our different areas of concentration, we all agreed on the best approach to patient care. Perhaps we can attribute this to the fact that, as healthcare providers, we ultimately share the same goal: to ensure the best possible outcomes for our patients.
Dr. Perreault: Yeah, that nicely summarizes the key takeaway from our discussion today, Gene. The interconnectivity of the cardiovascular, renal, and metabolic systems underscores the urgency for an integrated approach to patient care, one that addresses the whole patient rather than individual diseases in isolation.
Dr. Bensimhon: Thanks Leigh, and thank you both for the discussion today. It has been great. I really think it's important that we continue to share our perspectives as physicians with similar goals for our patients, and despite the fact that our primary foci may be different, I think regardless of our specialty, each of us needs to be looking at our patients' health in a comprehensive way. We need to remain mindful of the inextricable link between these systems to make sure that our patient gets the very best care possible.
Dr. Wright: Yes, thank you both, and thanks to everyone who joined us today for this discussion. We hope you've found it as informative and enriching as we have.
PC-US-116977
Understanding the Interconnectivity of the Cardiovascular, Renal, and Metabolic Systems
Dr. Eugene Wright leads a discussion about the dynamics of cardiovascular, renal, and metabolic diseases, plus how they impact patient care across different medical disciplines. 18 minutes
Featuring
Dr. Eugene Wright
Consulting Associate in the Department of Medicine at Duke University Medical Center; Medical Director for Performance Improvement at the Charlotte Area Health Education Center
Dr. Dan Bensimhon
Medical Director of the Advanced Heart Failure & Mechanical Circulatory Support Program at Moses Cone Hospital in Greensboro, North Carolina
Dr. Leigh Perreault
Endocrinologist and Associate Professor of Medicine at the University of Colorado
Panel
Discussions
CV, Renal, and Metabolic System Interconnectivity
Dr. Eugene Wright and a guest panel comprised of an endocrinologist, a cardiologist, and a nephrologist discuss the interconnectivity of the cardiovascular, renal, and metabolic systems. 11 minutes
Dr. Wright: Hello! Thank you for taking the time to join us. I'm Dr. Eugene Wright, Medical Director for Performance Improvement at the Charlotte Area Health Education Center and Consulting Associate in the Department of Medicine at Duke University Medical Center. Our discussion today is going to focus on the interconnectivity of the cardiovascular, renal, and metabolic systems, an important topic for health care providers across multiple specialties and one that has substantial implications for patients.
In my experience as a primary care physician, conditions like diabetes, cardiovascular disease, and kidney disease rarely exist in isolation. More often than not, my patients with diabetes also have cardiovascular diseases or multiple cardiovascular risk factors, and patients with cardiovascular disease often present with some degree of renal impairment. So, when it comes to cardiovascular, renal, and metabolic diseases, it's becoming increasingly difficult to classify patients into discrete categories. As we'll be discussing today, this emphasizes the importance of taking a holistic approach to patient care, one that addresses the interconnectivity of these conditions.
On that note, I'm glad to be joined today by several colleagues to discuss the implications of cardiovascular, renal, and metabolic dynamics for patient care. They are here representing the different specialties most impacted by this issue. We have with us cardiologist Dr. Pam Taub, endocrinologist Dr. Rosemarie Lajara, and nephrologist Dr. Matthew Weir. Pam, would you care to introduce yourself first?
Dr. Taub: It's great to be here today. I'm Pam Taub. I'm a cardiologist and Associate Professor of Medicine at University of California, San Diego.
Dr. Lajara: Hi. I'm Dr. Rosemarie Lajara, an endocrinologist in Dallas, Texas.
Dr. Weir: My name is Dr. Matthew Weir. I'm a Professor of Medicine and Chief of Nephrology at the University of Maryland School of Medicine in Baltimore, Maryland.
Dr. Wright: Now, as specialists, you can share with us your experiences in managing patients with overlapping conditions. Why don't we start with you, Pam?
Dr. Taub: Thanks, Gene. I'm happy to be joining you today to discuss this really important topic. Your observations in primary care definitely resemble what I see in my own practice as a cardiologist. Cardiovascular disease, kidney disease, and type 2 diabetes share many of the same risk factors, and I think that's one reason why so many of my patients are affected by more than one of these diseases. This means that, even as a cardiologist, I'm concerned with managing risks associated with multiple organs, not just the heart.
Dr. Weir: I agree, Pam, and this is also consistent with what I see as a nephrologist. Patients with renal impairment have an increased risk for both cardiovascular disease and diabetes. Close to two-thirds of patients with heart failure have renal disease, and we see a direct linear increase in the prevalence of cardiovascular events as renal function decreases. So, similar to the way you view your role as a cardiologist, as a nephrologist I also need to be taking a comprehensive approach to patient care, one that accounts for the effects of renal impairment on the other organ systems.
Dr. Wright: What about you, Rosemarie? What has been your experience as an endocrinologist?
Dr. Lajara: Unfortunately, so many of my patients with diabetes are affected by cardiovascular and renal disease, but I'm equally concerned about patients who don't necessarily have a formal diagnosis of cardiovascular or kidney disease because diabetes increases their risk for both conditions. As Pam noted, much of the overlap we're seeing can be attributed to shared risk factors like hypertension and obesity, and most of my patients have at least one of these risk factors.
Dr. Wright: Thanks, Rosemarie. It's interesting that, despite our different areas of concentration, our patients have a great deal in common, which is just another example of why a comprehensive approach to patient care is so important.
Dr. Lajara: I agree, Gene. As an endocrinologist, cardiovascular risk and renal risk are major factors in my approach to caring for patients. I need to consider that the mechanisms underlying each of these diseases have a compounding effect. So, not only does diabetes increase the risk of developing cardiovascular disease, it's also associated with worse outcomes. The risk of heart failure hospitalization is twofold higher in patients with diabetes compared to those without, something I'm sure Pam is well aware of.
Dr. Taub: That's right, Rosemarie, diabetes is a predictor of poorer outcomes in patients with cardiovascular disease. That statistic you mention is really alarming when you consider that heart failure is the leading cause of hospitalization in the United States, and the risk of death in patients with heart failure increases with each hospitalization.
Dr. Weir: As you are all aware, diabetes is also associated with poor renal outcomes. It's the leading cause of end-stage renal disease in this country. We know that in patients with longstanding diabetes, the microvascular damage caused by persistent hyperglycemia over long periods of time ultimately impairs the ability of the kidneys to function normally.
Dr. Taub: And, of course, kidney function can have a substantial impact on cardiovascular outcomes. In heart failure patients, we see a direct increase in the risk of hospitalization or cardiovascular death as eGFR decreases.
Dr. Weir: That certainly makes sense given that the underlying mechanisms of heart failure and renal disease are so intertwined that it's difficult to tease them apart. For example, we have reduced cardiac output in heart failure leading to decreased renal perfusion, and decreased renal perfusion, in turn, disrupting cardiac function. So, the onset of dysfunction in one system can set off a vicious cycle.
Dr. Wright: We should also mention that the interconnectivity of the cardiovascular, renal, and metabolic systems works both ways. You've all mentioned how dysfunction in one system has a compounding effect on the other systems, but there's also evidence demonstrating that improving the function of one system can improve the function of the others.
Dr. Weir: That's a great point, Gene. In fact, I recently read about a study in which cardiac function improved in late-stage CKD patients that had undergone kidney transplant. And when it comes to patients with diabetes, we know that intensive glycemic control has a positive impact on kidney disease progression. Rosemarie, can you discuss that further? Can you speak to that from an endocrinologist's perspective?
Dr. Lajara: That's right, Matthew. Multiple studies have shown an association between glycemic control and a reduced risk for microvascular outcomes, including nephropathy, although the association between glycemic control and cardiovascular risk in patients with diabetes isn't quite as clear.
Dr. Wright: I think all this evidence that the cardiovascular, renal, and metabolic systems can work together synergistically to improve outcomes really emphasizes the importance of us—as primary care specialists, endocrinologists, cardiologists, and nephrologists—working together to help improve the lives of our patients.
Dr. Lajara: I couldn't agree more, Gene, and this means addressing multisystem risk early in the course of disease progression, instead of managing individual diseases in isolation as they arise. My patients may come to me thinking that I'm solely focused on managing their diabetes, but if I want to do what's best for them, I need to be thinking about their cardiovascular and renal health as well.
Dr. Taub: Well said. I think it's great that, as providers of different specialties, we're coming together and recognizing how the link between these systems affects all of us in similar ways. As the body of knowledge around this topic continues to grow, I expect that we'll see more and more conversations among healthcare providers on how to integrate it into patient care.
Dr. Wright: Great point, Pam, I certainly hope that recognition will come as this idea becomes more prevalent. In the meantime, it's going to be up to us to spark reform at an individual patient level by recognizing how these systems are interconnected and, most importantly, by integrating that knowledge into our daily practice.
Unfortunately, we're running out of time, but I'll try to summarize our discussion with a few takeaways.
- First, the cardiovascular, renal, and metabolic systems are tightly linked, something exemplified by the frequent overlap of diseases affecting these systems
- Second, cardiovascular disease, kidney disease, and diabetes have a deleterious effect on one another, and, conversely, improvements in one condition can have a positive impact on the others
- Finally, all of this reminds us that we need to be adopting a comprehensive approach to patient care—early—and to help address the risk associated with these interconnected conditions. Not only will this help our patients, it will also allow us, as physicians across specialties, to work together toward our shared goal of optimizing care
With that, I want to thank Dr. Pam Taub, Dr. Rosemarie Lajara, and Dr. Matthew Weir for joining me today.
Dr. Lajara: And thank you, Gene, for leading us through this discussion.
Dr. Weir: Yes, thank you, Gene. I think it's really important for us, as clinicians with our different areas of expertise, to share our perspectives.
Dr. Taub: I agree, Matthew. And thank you, Gene. I enjoyed this discussion.
Dr. Wright: I did as well. Thank you again everyone and thank you to our viewers who took the time today to join us.
PC-US-116994
Featuring
Dr. Eugene Wright
Consulting Associate in the Department of Medicine at Duke University Medical Center; Medical Director for Performance Improvement at the Charlotte Area Health Education Center
Dr. Pam Taub
Cardiologist and Associate Professor of Medicine at the University of California, San Diego
Dr. Rosemarie Lajara
Endocrinologist in Dallas, Texas
Dr. Matthew Weir
Professor of Medicine and Chief of Nephrology at the University of Maryland School of Medicine in Baltimore, Maryland
Adopting Integrated Care Strategies
Dr. Eugene Wright speaks with the panel about how clinicians are being called upon to adopt integrated care strategies. 13 minutes
Dr. Wright: Hello and thank you for joining us. I'm Dr. Eugene Wright, Consulting Associate in the Department of Medicine at Duke University Medical Center. I also serve as the Medical Director for Performance Improvement at the Charlotte Area Health Education Center.
Our discussion today is going to focus on shared risk factors among the cardiovascular, renal, and metabolic systems. As many healthcare providers know, there is an ever-growing body of clinical data showing that diseases affecting one of these systems often exert a negative effect on the others. As a result, we as clinicians are being increasingly called to adopt integrated care strategies—ones that account for comorbidities and risk factors across all 3 systems—rather than manage single conditions in isolation. Understanding how to recognize and address early markers of disease can help us do just that.
I'm joined today by a panel of experts who have agreed to lend us their perspectives on this topic. We have with us cardiologist Dr. Robert Mentz, endocrinologist Dr. Leigh Perreault, and nephrologist Dr. Christian Mende. Rob, would you care to introduce yourself first?
Dr. Mentz: Sure thing, Gene. I'm Dr. Robert Mentz. I'm a cardiologist and Associate Professor at Duke University and I also serve as Chief of our Heart Failure Section here.
Dr. Perreault: Hello, I'm Dr. Leigh Perreault. I am an endocrinologist and Associate Professor of Medicine at the University of Colorado.
Dr. Mende: And I'm Dr. Christian Mende. I'm a nephrologist and a Clinical Professor of Medicine at the University of California in San Diego.
Dr. Wright: Thank you all, and thanks for being here to help us delve deeper into this important topic. Now, can each of you start by speaking just a bit about how cardiovascular, renal, and metabolic interconnectivity manifests in your practice? Namely, what sort of multisystem risk factors do you observe most often, and how do they influence your clinical approach?
Dr. Perreault: Well Gene, as an endocrinologist, I see metabolic disease in the form of obesity, prediabetes, and diabetes, all of which are extremely common. When a patient comes to me, I view my role as one mostly of prevention, so educating patients about their risk of end-organ complications and making suggestions on how to avoid them is my main priority. Some of the things I make sure to talk about are the increased risks for cardiovascular and renal disease, as well as the importance of healthy lifestyle choices in helping to reduce those risks. Unfortunately, it isn't always that easy and most people require medical management. In those cases, it's often necessary to enlist the help of a cardiologist or a nephrologist!
Dr. Mentz: Well, Leigh, while I bring the cardiologist perspective to this discussion, the data support that the cardiovascular system greatly affects, and is affected by, the rest of the body. Case in point: a large proportion of my patients with cardiovascular disease also have diabetes, and many of them are already starting to experience complications by the time they see me. This is a common clinical picture that can't be resolved by looking at the heart in isolation, so it's critical for me to factor in the health of the metabolic and renal systems to make sure my patients are getting the best outcomes they can. And when you consider the complex, progressive, and heterogenous nature of entities like heart failure and atherosclerotic disease, you can appreciate why early and accurate risk stratification is so important. This is a major unmet need for patients with heart failure, and there's actually some parallels with renal disease in that way too. Christian, would you agree?
Dr. Mende: Absolutely, Rob. The progressive renal damage associated with conditions like chronic kidney disease is a lot like what we see in patients with heart disease, atherosclerosis, and other kinds of cardiovascular disease, in that we can usually preserve organ function to a greater degree when we address the problem early. However, issues like chronic kidney disease tend to be silent until the kidneys are badly damaged, so early detection is both a challenge and a major unmet need. And when we consider that declining kidney function has serious implications for volume status, hormone production, and glucose homeostasis, it's easy to recognize that the relationship between cardiovascular and renal disease is very much a two-way street.
Dr. Wright: That's consistent with what I see in my patients with diabetes as well. It seems we have ample evidence to suggest that progressive damage to any one of these systems eventually impacts the others. I'm sure this isn't groundbreaking news for any of you, nor for most of our listeners, but it's important to keep this at the front of our minds so that when we see patients with multiple risk factors, we can adopt a comprehensive approach as early as possible.
Dr. Mentz: I couldn't agree more, Gene. But even though this is a pretty foundational concept, that's not to say that the connections between these systems aren't complex. And really on the contrary, there's a lot we don't know about how they influence one another, particularly in an individual patient. However, examining the interplay of these shared risk factors across these systems can give us some clues as to what's going on. Obesity is a great example that really illustrates this point, since it has so many different ramifications throughout the body. Leigh, I'm sure that's something that comes up in your work quite a bit.
Dr. Perreault: All the time! As people become overweight and obese, they fill up their fat cells until the triglycerides spill over into other tissues like the skeletal muscle, liver, and heart. Those organs were never meant to store fat and they don't like it! A major inflammatory response ensues, causing insulin resistance, and the resultant diabetes then further exacerbates the whole-body inflammation.
Dr. Mende: To that point, many of those same inflammatory processes also have implications for the kidneys, with the potential to cause direct renal damage via oxidative stress and RAAS activation. And once established, renal disease itself can contribute further to a chronic inflammatory state. So even though obesity is a common precipitating factor, you could go one layer deeper and say that chronic inflammation is one of the primary threads tying these issues together. And that touches on another important point, too, because a lot of those same processes can contribute to the development and progression of hypertension, something that's well-known to be hazardous to the microvasculature of the kidneys. Plus, it has been repeatedly associated with insulin resistance.
Dr. Perreault: Many experts believe that insulin resistance is the fertile ground that leads to all the diseases we are discussing today. It has been linked to hypertension, diabetes, atherosclerotic cardiovascular disease, congestive heart failure and chronic kidney disease. Of course, each of those diseases compels its own inflammatory responses that then feeds back and makes the insulin resistance worse. There is no way to truly unlink the cardiovascular, renal, and metabolic axis because it is so interrelated.
Dr. Mentz: Exactly. Take the relationships you just described, Leigh. In the absence of proper care, those kinds of vicious circles are bound to worsen over time, greatly increasing the risk for cardiovascular diseases like heart failure and coronary artery disease. The cycle doesn't end there either, because overt cardiovascular disease itself is a major risk factor for CKD and diabetes. In fact, that really captures a critical point that can't be overstated: disease in any one of these systems can act as a prognostic risk factor for the others. That's why we as clinicians need to look at these issues from a holistic standpoint rather than trying to manage single conditions in isolation.
Dr. Wright: That's so true, Rob. If you all wouldn't mind joining me in a quick exercise, perhaps we can illustrate this point further by examining a hypothetical patient case.
Let's say that a 65-year-old woman has come into your office as a new patient. She was diagnosed with diabetes 3 years ago and also has Stage 2 chronic kidney disease with albuminuria. She's hypertensive, overweight, and has dyslipidemia. On top of all that, she recently received a diagnosis of coronary artery disease, roughly 3 months ago. Given that information, how would you go about caring for this patient, and what would be at the forefront of your minds throughout the process?
Dr. Perreault: Gosh, she already has complications of diabetes, so my guess is that she must have been living with it for a while before she was finally diagnosed. Undiagnosed diabetes remains a major issue in the U.S. That said, if this patient came to me, I would indeed address her diabetes—meaning her hyperglycemia—but you need to do that in a way that's safe to use in someone with compromised renal function and hopefully will prevent further decline of her eGFR. This would be a busy clinic visit!
Dr. Mentz: You won't be surprised to hear this from me, but I would spend much of my time primarily on reducing her cardiovascular risk. Even though she hasn't yet experienced a cardiac event, her coronary artery disease still raises some red flags with regards to CKD progression and worsening insulin resistance. So I view this as a critical point around communication, implementing strategies across the multisystems of care. So it's the cardiologist working with the endocrinologist and primary care physician, as well as with the patient and their family to bring all of these multisystem components together.
Dr. Mende: Well, looking at this patient from a nephrologist's perspective, halting the decline in her kidney function would have to be a top priority for me. Getting her blood pressure down to at least 140/90 or, if possible, to 130/80 would be one of my first concerns. With that, I'd also prioritize getting her LDL below 70 mg/dL and her A1C below 7%, although 6.5% would be a more ideal target. I would also speak to her about her current lifestyle practices and look for areas where we could improve those. Reducing her salt intake to less than 5 grams per day, limiting her protein intake to 0.8g/kg per day, and encouraging weight loss would be the main priorities.
Dr. Wright: All good points, Christian. As you just touched upon, one thing that really can't be overemphasized for a patient like this is the importance of lifestyle interventions. Encouraging healthy habits such as eating well, increased physical activity, and smoking cessation are foundational to a successful care plan.
I think it's fair to say that, even though we're approaching care from a different perspective, we're seeing more commonalities than differences in the way we would prioritize multisystem risk in this patient. I think that reflects our shared goal of optimizing outcomes for our patients. And perhaps most importantly, it shows just how inextricable the link between the cardiovascular, renal, and metabolic systems really is.
Unfortunately, we're running out of time, but I'll try to summarize our discussion with a few key takeaways:
- First, the interconnected nature of the cardiovascular, renal, and metabolic systems is evidenced by the presence of shared risk factors, many of which stem from common pathophysiologic mechanisms
- Second, these shared risk factors can serve as important prognostic tools to help us recognize and address progressive diseases as early as possible
- Third, as physicians, we need to prioritize cardiovascular, renal, and metabolic health by adopting comprehensive care strategies that simultaneously address risk across multiple systems
I want to thank Dr. Leigh Perreault, Dr. Robert Mentz, and Dr. Christian Mende for joining me today and lending their expertise on this topic.
Dr. Mentz: Thanks very much, Gene, and thank you for leading the discussion.
Dr. Perreault: Thanks, everybody!
Dr. Mende: Thanks for having me, I've enjoyed speaking with all of you.
PC-US-116995
Featuring
Dr. Eugene Wright
Consulting Associate in the Department of Medicine at Duke University Medical Center; Medical Director for Performance Improvement at the Charlotte Area Health Education Center
Dr. Christian Mende
Clinical Professor of Medicine at the University of California, San Diego
Dr. Robert Mentz
Cardiologist and Associate Professor at Duke University; Chief of the Heart Failure Section at the Duke Cardiology Clinic
Dr. Leigh Perreault
Endocrinologist and Associate Professor of Medicine at the University of Colorado
Cardio-Renal-Metabolic
Map
Shared Risk Factors Compound the Impact of Cardio-Renal-Metabolic Conditions
The interactive map provides insight into the impact of cardio-renal-metabolic conditions in the Medicare population in the United States. Use it to investigate the prevalence of these conditions at the state-, county- and congressional district-level, explore the health burden associated with these diseases, and learn about their economic impact.
Intervene early using a comprehensive approach that prioritizes patients' overall cardiovascular-renal-metabolic health.
CKD=chronic kidney disease; CV=cardiovascular; CVD=cardiovascular disease; HbA1c=hemoglobin A1C; T2D=type 2 diabetes; PCP=primary care professional; HF=heart failure; C-R-M=cardio-renal-metabolic.
References
1. Braunwald E. Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog Cardiovasc Dis. 2019;62(4):298-302. 2. Ndumele CE, Neeland IJ, Tuttle KR, et al. A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American Heart Association. Circulation. 2023;148:1636-1664. 3. Palladino R, Tabak AG, Khunti K, et al. Association between pre-diabetes and microvascular and macrovascular disease in newly diagnosed type 2 diabetes. BMJ Open Diabetes Res Care. 2020;8(1):e001061. 4. Marassi M, Fadini GP. The cardio-renal-metabolic connection: a review of the evidence. Cardiovasc Diabetol. 2023;22(1):195. 5. Vijay K, Neuen BL, Lerma EV. Heart failure in patients with diabetes and chronic kidney disease: challenges and opportunities. Cardiorenal Med. 2022;12(1):1-10.