How Patients Benefit from Growing Intersectionality of Renal and Cardiovascular Diseases

Cardiometabolic health, as both a concept and a field, has undergone a revolution in recent years as the community strives to develop a better understanding of the intersectionality of nephrology and cardiology.

The results of this fervor are evident in both the research and clinical development programs, with revelations surrounding SGLT2 reshaping their traditional role as glucose-lowering agents leading the charge and the advent of newer, effective agents bringing forth finerenone, sotagliflozin, and other agents.

There is no better showcase of this growing emphasis on intersectionality than at the American College of Cardiology (ACC)’s 2023 Annual Scientific Session Together With the World Congress of Cardiology, which featured a session with the specific goal of providing clinicians with practical tips for integrating newer therapies into clinical practice.

As part of our coverage at ACC 23, our editorial team sat down with a pair of experts in cardiometabolic health to understand their perspectives on this growing intersectionality and the impact this recognition is having on the field.

HCPLive: As a member of an FDA advisory committee, how have you seen this growing recognition reflected in research

Steve Nissen, MD
Courtesy: American College of Cardiology

Steve Nissen, MD: Well, these are very good questions. I can tell you that more and more of our clinical trials are including both cardiovascular and renal outcomes. We are in the middle of launching a very large obesity trial with a very powerful weight loss agent, where we're going to measure not just cardiovascular outcomes, but renal outcomes as well. There's also an interest in the intersection of heart disease and liver disease.

All of our organ systems are interconnected and we're moving past the idea that you can take on isolate one organ system and say, "Well, we got a drug that does this to this organ system". Actually, think we're entering an era when we really want to know what drugs do to all of the organ systems and all of the disorders that are all interrelated. This is the future.

HCPLive: What do you make of the growing emphasis on the intersectionality between nephrology and cardiology? How have you seen this impact patient care?

Clyde Yancy, MD
Courtesy: Twitter

Clyde Yancy, MD: So, I like the conversation about the cardiometabolic space and I enjoy thinking about the intersectionality of diseases like heart disease and kidney disease, but I also like to think about the universality of risk. It was always a thought process of convenience to assume that high blood pressure was predominantly affecting the heart, or to presume that dyslipidemia was predominantly affecting the vasculature. Diabetes was having this portfolio effect, but we would mostly see it with the kidneys and with the heart.

Now, we recognize that we have to accept this universality of risk and that a phenomenon, like obesity, has a whole portfolio of consequences. We can't then separate those consequences and deal with them singularly. So, we are now thinking about the heart, the kidney, and the liver. We begin to realize that there are disease processes that, though the manifestation in front of us might be heart disease, there's also kidney involvement, there is liver involvement, and there is lung involvement. So, opening up this brand-new frontier, if you will, where the exploration, and this is what's exciting, is no longer about treating heart failure, or chronic kidney disease, and you begin to think “is it possible that we can have an intervention that will have an influence in multiple organ systems?”.

The first real expression of that is probably the SGLT2 inhibitors, but that can't be the only compound that would have that sort of portfolio effect. The really fascinating thing about the SGLT2s to celebrate, and I've written about the influence in the heart, and we appreciate and we're fully aware of the influence in the kidney but think about what it means in terms of our understanding of biology.

We have an agent that works for heart failure—whether it's reduced EF, mid-range EF, or preserved EF and that is pretty startling. Even today, that's pretty startling. The biology is what fascinates me. Trying to understand that biology and say, if the SGLT to inhibitor is manipulating a biology that influences all iterations of heart failure plus kidney disease, is there another way to influence that biology? Because as SGLT2 inhibitors are we saw very impressive relative risk reductions. But we still saw events, events persistent.

So, even though we have an intervention that works, that intervention works imperfectly, because it doesn't completely remove the risk. That's why I'm saying the biology is so important, because if we understood the biology and it was a way to even more deliberately manipulate that biology without harm, and reduce events even further, as people would say, “Now you're talking”. It's great to have something at our disposal right now. That's terrific. But the way I'm wired, okay, if we could do this much now, couldn't we do more if we knew exactly what systems more upregulated or downregulated?

I mean, we don't even know that. There are a lot of wonderful theories and I'm fascinated with quite a few of them, but none of them proven to be the definitive approach. But when we do find something that informs that biology, it would be great. Now I've got colleagues that say, well, “Clyde, we don't really know how ACE inhibitors work, and we think we know how beta blockers work, maybe. So why do you insist that we need to continue to press to understand how the SGLT two inhibitors work?”. It is precisely because of the ubiquity of the effect. These drugs are doing something that we've never been able to get to before I think in this case, we need to know what that is.