Coronary Artery Disease in the Athlete with Dr Paul Thompson

Although exercise usually provides a cardiovascular benefit, there is some data that points to an increase in event rates in extreme endurance athletes.  In this episode, Dr. Thomas Nero and Dr. Paul Thompson discuss the surprising findings regarding coronary calcium, cardiac troponins and atrial fibrillation in the endurance athlete and some thoughts about ideas to pursue in future research.

Transcript

  Future Pulse,  investigating innovative cardiovascular research and the intersection of academic theory and clinical practice. I'm Dr. Thomas Niro, interventional cardiologist and director of cardiovascular research at CAFC. 

This is Dr. Thomas Nero and this is part three of our interview with Dr. Paul Thompson.  Dr. Thompson is the Professor emeritus of cardiology and the chief of cardiology emeritus at Hartford Hospital, and today we'll be discussing.  coronary artery disease and the athlete.  Talking a little more about athletes and making sort of a small segue here.

We talk about exercise, how important exercise is. We talk about how important dietary changes, especially after coronary events and the statins. But one of the things that we know is that. Exercise and high amounts of exercise can actually maybe be detrimental that there's a number of studies and runners that, you know, getting off their after keysters will decrease their cardiac event rates by 25%.

But after somewhere around 3000 kilocalories of exercise a week. that their event rates start going up again, and we certainly don't know the answer to that yet.  You know, it is one of those things that really sort of gives everyone pause, and it's one of those things where I would love to hear your take on, can exercise actually hurt the heart? 

So, you know, that's a great topic, and it's something I'm actually working on right now. I spent today in my semi retirement writing a paper, a requested review article, Can the heart get an overuse sports injury? And I'm not sure, but I think it might. So let me go through it. First of all, you know, way back, I mentioned the 15 physicians who ran the Boston Marathon and they had big increases in CK.

That was back when CK was used to measure whether you had a myocardial infarction. They subsequently repeated the study using CK MB and that went up after the marathon race as well, but all pretty well dismissed. when they did biopsies of the gastrocnemius muscle in a bunch of Boston marathon runners.

And they found that the muscle had double the CKMB of sedentary people's muscles. So what happens with exercise training is you actually change the metabolic milieu of your skeletal muscle and you make the CK look more like heart. So I dismissed the whole thing. Okay, just, yeah, yeah, it's just the skeletal muscle.

And then along comes troponin.  Now, I was surprised when some of my friends measured troponin levels in the London Marathon and found that about 50 percent of those individuals had troponin T values the day after the race in the area you diagnose a myocardial infarction because troponin is excreted in the kidneys and we see it up in people with renal failure and all that sort of stuff, so I dismissed it to some extent.

But then we've started looking at troponin I, and we measured troponin I in 71 participants in the 2011 Boston Marathon. Every single one of them raised their troponin I,  physiologic benign response. I was lucky enough to have a fellow named Thijs IJsvogels from the Netherlands come and work with me for two years.

They did that data from the Boston Marathon in the Troponin elevations, and we've gone along together using data from the Netherlands to really look at a group of runners and see what happens to them. So what Thijs did is he measured troponin eye levels using high sensitivity troponins in, uh, let me think, I think it was 420 men who were walking these marches that they have in the Netherlands called the Nijmegen marches.

And the Nijmegen marches, my understanding is, are to commemorate the American paratroopers who jumped into the Netherlands and a lot of them drowned. Because the Germans had flooded these fields. So the Nijmegen marchers are, um, quite long. I think they're between 45 kilometers and like 60 kilometers. He measured troponin I levels in individuals and 9 percent of the individuals increased their troponin I levels after the race above the 99th percentile.

So diagnosis of myocardial injury. Then he followed those individuals over the next 44 months. And those who raised their troponin eyes with exercise had three times the rate of cardiac events as those that didn't. We don't know what happens. It may be that the skeletal muscle during exercise can release little blebs.

You know, the membrane forms these little, these little balloons and they go off into the circulation.  carry messages to other parts of the body, you know, to, I don't know, the hormone system or whatever, to tell the body how to adapt to exercise training. It's likely that the heart does the same thing, so it may be that the heart is releasing these troponins  We don't think from irreversible injury, but as some sort of a sign of something, whether it's inflammation or whatever, we don't know.

The other thing is this, troponin I has never been shown to develop in skeletal muscle. In fact, there's a study in Jack within the, in 2019, I think, that looked at 74 people who had skeletal muscle disease. Nearly all of them had an elevation in troponin T. And four out of those 74 had an elevation in troponin I.

So we think that it's probably from the heart and it means something, but we don't know much. So number one, clinicians out there need to know that troponin levels, troponin eye levels go up after exercise. So you don't over-diagnose a myocardial infarction in somebody who ran a marathon the day before or something like that. 

Now, what about the heart? What happens to the heart when you do long endurance exercise? Well, it's really interesting. Way back in 1990, Pam Douglas, who was at that time was at the Beth Israel, did echoes on there was 40 men who were competing in the Hawaiian triathlon. You know, like a 2. 3 mile swim, a 110 mile bike ride, and then a 26 mile run.

And what she found is that the left ventricle looked like it squeezed fine, the atria looked like they squeezed fine, but the right ventricle got sluggish. The right ventricle looked like it dilated and the right ventricular ejection fraction was not as good. And that finding has been repeated. It looks like the right ventricle gets dilated.

what she called cardiac fatigue from prolonged exercise. Now, why? Well, remember the at rest, your right ventricle is facing relatively low pressures. With exercise, however, the change in the pulmonary pressure, the relative change compared to rest, is much greater than the relative change in the systemic blood pressure.

You can vasodilate your leg muscles to take a lot more blood, so the pressure doesn't go up. The work on the left heart isn't as high. But you can't dilate your pulmonary vasculature. to anywhere the same amount, and it's contained in this small chest cavity, and the right ventricular wall is thin. A friend of mine, Andrew LaGuerre from Australia, what he postulates is that the right ventricle suffers with exercise, and we now know, for example, that people with right ventricular cardiomyopathy, or right ventricular dysplasia, or what you can call it, arrhythmogenic right ventricular cardiomyopathy.

Those people present earlier if they were varsity athletes. If they've repetitively stressed their right ventricle, their desmosomes don't work as well. Now, desmosomes are these little discs that keep the heart muscles attached. They're both electrically important. But they're also contraction important because you can't contract the heart well if you pull apart.

So these people with right ventricular cardiomyopathy have desmosomal gene defects. When they exercise and stretch that heart, they get more disruption of those discs. And you know, here's the very interesting thing. It seems to affect the best athletes the most. Why would affect the best athletes the most?

Because they have the biggest stroke volumes. They put the most size stretch on the right ventricle. So along with this is the finding that lifelong endurance athletes have increased late gadoleum enhancement. They have some more fibrosis than you'd expect. Where is the fibrosis? the intraventricular septum, not always, but most times, the intraventricular septum, and interestingly, where the septum inserts, the insertion point, so where the left and right ventricles kind of attach to each other at the top or the bottom of the septum.

So what's the point? The point is you exercise, you do an endurance event, puts a lot of increased relative stress on the right side, increased compared to the left, stretches or does something to the right ventricle, which results in this fibrosis. And it's just interesting that the, the, the best athletes seem to get the problem.

Clinically, it's important if you take care of anybody with right ventricular cardiomyopathy, you don't want them exercising like crazy. I think there are three studies that have confirmed the original finding that came out of Calkinson's group, but it's very interesting. So let's switch a little bit. I talked about these troponin coming out of the cardiac muscle during exercise, at least what we think, from some changes in permeability.

We don't think it's necrosis. You know, we don't think it's apoptosis, you know, the planned cell death. So it's probably the release of those little packages. But the other interesting thing that's come along is that lifelong endurance athletes seem to have more coronary calcification than expected. What?

Exercise is supposed to reduce the risk of atherosclerotic events, and yet these athletes have more calcium than you expect. Clarence Damar won the Boston Marathon seven times. ran up until he, just about the time he died. I think he died at 71 and he died of colon cancer. But after he died, Paul Dudley White, the famous mass general cardiologist, convinced Clarence's wife to let him autopsy Clarence and examine his heart.

If you read the report 1965, Cullens, C U L L E N S and White in the New England Journal of Medicine, it says that it was hard to examine the heart because of the trocar.  insertion. So in other words, Clarence had already been embalmed by the time, uh, by the time Paul Dudley White got his hands on his heart.

But Clarence had tons of atherosclerosis. They've got a picture in the New England Journal of Medical Article that says this is the left main and it's got considerable atherosclerosis and the arteries were very big. So it's not totally a new concept. It's just that, you know, we kind of all dismiss Clarence's.

calcification because it was Clarence and we knew he was good and all that sort of stuff. But now it turns out that we're finding a lot of calcification more than expected for the risk factors in athletes. So what's the clinical importance? The clinical importance is, first of all, you got to be able to reassure these athletes because, you know, you don't want to jump in out the seventh floor window.

They get very dysphoric about this thing.  I treat them very aggressively with statins. It may be due to the exercise, but I want to hedge my breaths, so I try to get their lipid levels low. I almost always do an exercise stress test on them just to make sure they're not hiding symptoms for me. I almost never do a cath or a CTA.

The CTA is somebody with a lot of calcium. I always check a parathyroid hormone level and a calcium, and we'll just report within the next month or so in the American Journal of Cardiology, two distance runners who came to me with very high coronary artery calcification scores. Good reason, right?

They're distance runners, lifelong distance runners. both hyperparathyroid, and so, you know, you need to think about it. Now, remember, as your calcium score goes up, as your coronary calcium score goes up, your risk of a cardiovascular event goes up. But as the density of that calcium score goes up, your risk goes down.

And I'm seeing athletes with calcium scores of Get ready, 2, 3, 000, 900, one winner of the Boston Marathon who I take care of has a calcium score of 900. He lets me use his name, but I'm not going to do it. So there's a lot of calcification in these individuals, and so you have to reassure them and tell them you don't know what it is.

I check a parathyroid hormone level, I do a stress test, I reassure them. So far, all but one have done quite well. What's the mechanism? Don't know. Could those little blebs being released with troponin packets carry other things that stimulate atherosclerosis? We do know that exercise acutely raises parathyroid hormone levels.

Two hours of a bicycle ride among competitive cyclists raised their parathyroid hormone level twofold. So that's a possibility. And also remember these are calcified lesions, so they may be safe. But here's the rub.  There's a letter in Jack about 10 people who ran the race across America. It's basically 10 people who had CTAs done before the start of this race.

They ran across the United States. They ran six days out of seven. And eight finished, so I'm going to talk about those eight. Four of the eight had some atherosclerosis on their CTA at the beginning. Every single one of them increased the amount of atherosclerosis by the end of the race, and it was all soft plaque.

One person didn't increase their soft plaque very much. That person was on atorvastatin, the only one of the four that was on atorvastatin. So, I'm bothered by that. I've thought this is just calcification, good thing, nothing to worry about.  It may not be true. So let me finish with two things. I want to talk about AFib.

AFib is more common in endurance athletes. I tried to write that up in 2007, couldn't get anybody to take the paper, circulation, everybody, okay. I finally published it, 2009, British Journal of Sports Medicine. Now, everybody kind of accepts that in endurance, men have more atrial fibrillation because it hasn't been shown in women.

The best studies come out of the Swedish group who studied runners in the Vesalopet, which is a series of races. It used to just be a 54 mile cross country ski race, but now it's a bunch of races. And what they've shown is that there's more atrial fibrillation in the skiers than there is in control groups.

And here we go again. The best skiers get the most atrial fibrillation. The fastest finishers get more atrial fibrillation. The people that have been doing it the longest get more atrial fibrillation. Why? What's the mechanism? Is it inflammation? Is it the adrenaline of the race? Is it the high vagal tone that comes from training?

I think it's big hearts. Remember, if you're good, you have to have a good stroke volume because you got to have a good cardiac output. And heart rate is determined by other stuff. Stroke volume can be manipulated a fair amount by exercise training. So we think you get a big left atrium for lots of exercise training, you stretch the sucker, and you get atrial fibrillation, at least in men.

Now, it's a J shaped curve, because if you look at people that are very sedentary, they have more atrial fibrillation than people that do some exercise.  But they have less, some, the group doing some exercise has less atrial fibrillation than the group doing tons of exercise. And let me finish with just the aorta.

You know, about three years ago, Andrew Laguerche, my friend from Australia, asked me to help him with an editorial that found big ascending aortas in Australian rugby players. And I did, wrote the editorial with him and he asked me because we had done a meta analysis of aortic size in athletes. years ago and reported that the aorta was only slightly bigger in the athletes, uh, strength athletes, endurance athletes was only slightly bigger.

But these were people who'd played rugby for a long period of time and they had increased aortas. And then the group at Mass General that I work with now has come out showing that the endurance athletes tend to have bigger ascending aortas than we would expect. So I think this bears watching. So, let's go back to the beginning again.

First of all, exercise is good for you.  You get the most benefit when you go from little to some. The 2018 Physical Activity Guidelines recommend the following.  Move more, sit less. That's their big recommendation. Move more, sit less, because most Americans are nearly totally sedentary. They recommend between 150 and 300 minutes a week of moderate exercise.

That is like fast walking. 150 to 300. 150 is 22 minutes a day. So, nearly everybody can do that. If it's vigorous exercise, they recommend 75 minutes. to 150 per week. So 150 to 300 minutes of brisk walking or 75 to 150 minutes of something like jogging more vigorous. And they also recommend some weightlifting.

The studies all show big reductions with small increases with exercise. But as you pointed out at the start, Tom, there are now a bunch of studies that look like there's a little curve up, a little twist up, a far right of those curves, a little increase in risk. Hard to know because in this country, our public health problem is not people getting too much exercise.

Our public health problem is people doing absolutely nothing and getting very heavy and all that sort of stuff. So I don't want you to get the wrong message. What do I think about this? I think that this is really interesting and I think it should be used as a way to understand mechanisms. What's happening with atherosclerosis?

What do those troponin blebs mean if they're coming out of the myocardium? So I view it as something I need to know about clinically because I take care of patients and I want to be able to tell them what's going on and I want to be able to reassure them. But also,  I think it's something that keeps me interested in the game.

It is absolutely fascinating. I, you know, you and I have, have the same kind of approach to this because we both take care of a lot of athletes. I have a fairly large athletic clinic, partially because having been a triathlete myself for a while, and when I talk to them, one of the messages I try to give them is.

Yes, we have some data that something happens at the end. We have no idea why yet, but we have to know why we're doing it. If you're doing it because you're going to be crazy if you don't get out and run every day,  go out and run every day. But you have to know what you're training for and you have to know why you're doing it.

And then let that lead you. So if you're happier because you're doing more exercise and every study that showed that looked at exercise had a graded curve that didn't drop off at the end, that people who exercise more were happier. And so I use that as sort of the flip side of this conversation. You know, I agree.

I think a lot of physicians don't appreciate that with people. I don't think that these athletes are manic depressive. That's not what I'm saying, but all of us have high points in our lives in down points in our lives. And one of the nice things about exercise, it kind of removes the down for a lot of people.

If they don't do it, they become slightly dysphoric. And so, I let them do it. I just try to control, like, my people with right ventricular cardiomyopathy. I let them do brisk walking and stuff, but I try not to get them to be the varsity athlete that they once were.  On a slightly separate topic, I just want to know if you had two or three thoughts about the use of cardiopulmonary exercise testing and how you currently use it and what your thoughts are on using it in the future, both for You know, we tend to use it a lot for patients with heart failure, but for our general cardiology patients. 

So, I don't think I'm your world's expert on cardiopulmonary exercise testing. I do a fair amount of it, but I often do it in athletes because they want to have it done. I don't think I necessarily need it in the athletes to know what's going on with them. I do find it useful when it's, when you're having trouble differentiating pulmonary from cardiac disease, you can watch their ventilation slope, etc. 

Possibly. And this frequently happens to me. I use things less frequently when I don't understand it as well as I probably should. So I'm probably not your best person. You know, so let's talk about exercise in general. I think stress testing is underutilized in terms of what it can tell you. And what I do is I refer to it as two things.

I refer to it as the external workload, how far the person went, How much exercise they did. That, believe it or not, is a surrogate for stroke volume. If you're a good athlete, if you have great exercise performance, a good oxygen uptake, you gotta have a good stroke volume. So it gives me a sense as to where the external work rate is, gives me a sense of stroke volume.

And then I refer to it, the internal work rate. The internal work rate is what heart rate you got because heart rate's the primary determinant of myocardial oxygen demand. So now I've got the external oxygen demand, I've got the internal oxygen demand. That gives you a very good look at what's going on with people.

Now I didn't invent that. Ezra Amsterdam from the University of Davis way back in I think the article was in Jack in  1976, referred to the internal external work rate and I've used it and I cite them ever since then. And I do think that we need to sort of go back to our primary teaching that, you know, doing just exercise treadmill stress testing gives us so much information on what the patient can do and that there's a graded curve just based on what they're able to achieve.

Uh, you know, patients that can only achieve Bruce one don't do as well as Bruce two or three. That's right. I always say that if you've got good exercise performance, you've got a good heart. Well, Dr. Thompson, I can't thank you enough for taking the time and going over these topics. You have been a mentor to me and you are a guiding light in the research and shown us both by what you do physically, actively, as well as your excitement and enthusiasm towards research that really shines bright and gives us all something to aspire to in the future.

So I thank you. And before we sign off, do you have any other thoughts of things that you just would like to put out there?  No, thank you very much for the kind words. I mean, I, I really feel it's been a privilege to work with people, take care of people. And, you know, I think we all forget that, you know, if we can make people feel better, that really, it's a wonderful thing to do in the world, but also it's really been my pleasure.

Thank you again, and have a great evening.