The Immune System’s Role in Cardiovascular Disease

Podcast Transcript

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Welcome to Love Your Heart, brought to you by Cleveland Clinic's, Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute. This podcast will explore disease prevention, testing, medical and surgical treatments, new innovations and more. Enjoy.

Samir Kapadia, MD:

Thank you, again. Today is a great day for us because we are going to talk about the new initiative that we are doing at Cleveland Clinic, which is a cardioimmunology center. This is unique, not just to Cleveland Clinic, but probably nowhere in the world they have a cardioimmunology center of the magnitude that we are planning to have. We have been able to recruit one of the leaders in cardioimmunology, Dr. David Zidar.

He's an interventional cardiologist, but also an extremely well-trained immunologist. His basic interest is to understand how immunology affects cardiovascular diseases.

I'm Samir Kapadia, I'm the chairman of cardiology here at Cleveland Clinic, and we are going to talk about the different areas. Th heart is [made up of] the muscle of the heart, the arteries of the heart, the pericardium, the valves, all these different things could be affected by immunology. How immune reaction or your body's reaction to that ,or external insults that can start the immune reaction. How do you put it all together to say why immunology study is important for cardiovascular diseases?

David Zidar, MD, PhD:

Thank you very much, Dr. Kapadia. As one of the premier early immunocardiologists, it's quite an honor to be here, and I'm thrilled. I think that it probably helps to frame three major areas. There are certainly situations where the body's immune system gets activated, even for a variety of reasons potentially unrelated to the heart, where the heart is a bystander, but it gets affected by certain cytokines or activation pathways, some of which you've described.

Samir Kapadia, MD:

Right. The cytokines, meaning that these are the proteins that are released by the cells to communicate with each other, and these are the chemicals that may affect the heart.

David Zidar, MD, PhD:

Yes. Those, in general, are good reactive pathways that then protect the body. We don't necessarily want to stop inflammation. That's one way, where the heart can be affected by these systemic pathways. What we know is that that probably tweaks the heart to become weaker and certainly not to perform in a reliable way.

The second thing that can happen then is that that inflammation can lead to fibrosis. That then is remodeling of heart tissue for basically scar tissue. That we don't want. We know that that's associated with worse outcomes. People are very different in how they become inflamed and in how they form fibrosis. We want to understand better who's at risk and how we can mitigate that risk. So, that's one big way.

The second, interestingly, very important way in which the body's immune system can affect the heart is, that whenever the heart gets activated or when the body's immune system gets activated, it typically also tells the body to start forming blood clots. That can lead to heart attacks. So, completely independent of the first framework is this understanding that when patients, for instance, have influenza, they're at really a six-fold, probably increased risk of having a heart attack several days after.

Samir Kapadia, MD:

Same with COVID and things.

David Zidar, MD, PhD:

Yeah. So, there are these relationships between immune activation, which is good, and blood clotting, which can be very adverse, certainly in the heart.

Then the third way is that we know usually when patients get very sick acutely, their blood pressure goes down. The body's immune system interacts, then, with the blood vessels systemically, and that can put a strain on the heart. It can make the heart have to do more work than it can be capable of. We know that that can be very difficult to manage in many of our patients.

So, there's really a number of different, distinct, separable areas where we'd like to understand and help patients.

Samir Kapadia, MD:

Now, there is also an autoimmunity, meaning that the body tries to reject your own self or whatever the immune system is. It's like having, say, lupus or rheumatoid arthritis or any other of those diseases. Similarly, in the heart, sometimes people get pericarditis that could be an autoimmune kind of a reaction or immune reaction, or myocarditis.

Is there some way that you connect stress also to the immunologic reaction? Because when people are super stressed, they get more infections, for example, because their immunity is less. Are there similar things that can correlate cardiac problems that happen with stress, with immunologic reactions?

David Zidar, MD, PhD:

Absolutely, yes. These are kind of different “flavors”, if you will. Patients who have rheumatoid arthritis or any disease where there's chronic inflammation, we know that they have more heart attacks and they have more heart failure. That's also an area where there's probably opportunity, because there are more and more drugs now coming out that are FDA approved to specifically inhibit different pathways of the immune system. How that interacts with heart disease will be very important for us to understand. It's one area.

The second area that you spoke to a little bit is that the body can react in an autoimmune way and develop antibodies against the heart. Sometimes the adrenergic receptors, in fact. That's where other researchers here at the Cleveland Clinic have begun to understand how this can alter the performance of the heart.

Then the third way is, in all of us, when we have the fight or flight response, catecholamines and adrenaline responses, they not only impact the heart and the blood vessels, but they really do interact with immunologic cells through just the same receptors. These same pathways are active in lymphocytes that are active in the heart.

That's really what brought me into this area. I trained with Dr. Bob Lefkowitz, who has won the Nobel Prize for understanding how the adrenergic receptors really regulate cells. It turns out that those same pathways also regulate immune function. So, there is this kind of synergy between these lines of investigation, where cardiologists have traditionally done very good work in understanding how the heart works. Now we can kind of begin to apply that as to how the immune system works.

Samir Kapadia, MD:

It just reminds me that even this time, the Nobel Prize was given to the autoimmune disease recognition of how the T-cells work. What do you understand from the most recent Nobel Prize? Why is it so important to understand? Is there any relation to the cardiovascular diseases that we can currently link to?

David Zidar, MD, PhD:

Absolutely. I think that what this Nobel Prize illustrates is really a common theme in immunology, which is that there's an equal and opposite reaction to any action. The body is certainly triggered to become activated. It also then has, through T regulatory cells, the subject of this Nobel Prize award, there are counterbalances. You can't just go in and hope to just alter the immune function without sort of understanding all of these balances.

It's much like the blood pressure, where you can't have the blood pressure get too low, you don't want it to be too high. It's much like most things that are physiologic in nature, where there's, I think, really a need to deeply understand and rigorously test a lot of these hypotheses because there's just so many more unknowns than we know about even right now.

Samir Kapadia, MD:

We are also studying these mutations in the peripheral blood, the CHIP areas [clonal hematopoiesis of indeterminate potential]. Do you think that there are also immunologic parameters that we can study, similarly, in the blood to say what are the ways that somebody is healthier than the other, and if you do some intervention, you can correct or you can monitor how to measure the immunologic response?

David Zidar, MD, PhD:

So this is a great topic, great point where I think that in order to understand the large population level issues, it may help us to really drill down into very specific populations, such as people who have clonal hematopoiesis, which is where as we age, we can have some immune cells that out-compete others, and those are not always the best behaved cells. Those monocytes do tend to do behaviors that are adverse to the heart and to the blood vessels through immunologic pathways that are pretty well described and probably pretty active in many of us.

By really understanding this small niche of patients, we can hope to then understand larger concepts that are applicable to all of us.

Samir Kapadia, MD:

My point to people is that, if you are wanting to be a healthy person and be healthy at heart, currently we monitor the cholesterol, we try to do exercise, we are doing all this blood pressure, other things. The reason why my personal interest is also in this field is to say that if you want to be healthier, there may be more than one way to monitor. The whole body has to be immunologically well-regulated so that if that is an adverse event or something happens, body can fight it.

So, is it a reasonable thing to say that with all these efforts that we are putting together, we can identify people who are at higher risk, using these novel pathways and novel systems, and make them healthier in the future if we can regulate this thing in an appropriate way?

David Zidar, MD, PhD:

Yes, and that's what drives me to want to pursue this. I do think it is practical. I think that there are ways to discover patient populations, nowadays certainly, where so much of our information is electronic and can be processed in large volumes. That would be the idea, I think, to try and use the immune system, not just as a potential enemy of the heart, but to use the immune system as the proverbial canary in the coal mine. Where the immune system is always surveying tissues and we can see that activity level play out in certain blood markers. That lends itself well to discovering which patients are at highest risk before they have an adverse event by understanding their immunologic signs and symptoms before something happens that may lead to larger damage down the line.

Samir Kapadia, MD:

Exactly. The point that I think is that, if anybody who has heart problems or wants to prevent heart problems, these are a few of the things that they can try to understand. Or if there is an undiagnosed heart problem that they are trying to figure out that what exactly is the cause or how is it related, this center for cardioimmunology can be very helpful. This is the reason for our efforts to make that available.

At Cleveland Clinic, of course, we are very, very much geared towards the care of people. We are taking care of their acute problems, we are taking care of their chronic problems, and we are trying to prevent problems from happening, preventive care. So, from a cardiovascular standpoint, we are well poised to take care of all these different problems. But this particular effort adds a very unique dimension to our patient care where we can not only understand the cause of the problem, but also try to prevent the problem that may happen in the future and identify patients who are at very high risk of having problems in the near future. This is a great effort, and we are very fortunate to have the expertise at Cleveland Clinic.

David Zidar, MD, PhD:

Thank you for listening to Love Your Heart.

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