Professor Andre La Gerche is a sports cardiologist and chair of the Heart Exercise and Research Trials Lab at St. Vincent's Institute in Melbourne, Australia. Dr. Srikanth Krishnan is an advanced imaging fellow at Harbor-UCLA. The following is an edited summary of an interview conducted by Dr. Krishnan with Dr. La Gerche on his approach to the athlete with elevated CAC score.

Krishnan: What do we know about the mechanism behind athletes developing CAC?

La Gerche: Truthfully, we don't understand the mechanism. One of the most prominent ideas revolves around the concept of sheer stress. Exercise can spike central blood pressure (BP) significantly, even in healthy athletes. It's common to see BP shoot past 200 mmHg during intense workouts, which could indicate the impact of sheer stress and microtrauma.

Another avenue to explore is transient inflammation. We measured cytokine levels after high-intensity exercise. Cytokine levels are low during rest periods and several cytokines, including interleukin 6 and interleukin 8, rise and fall dramatically with exercise. What's intriguing is that even though athletic activity fosters an environment that is anti-inflammatory in nature, there are these flushes of inflammation after big bouts of exercise.

Diet often comes under scrutiny as a potential factor. While some suggest athletes might offset poor diets with intense exercise, from my observation their diets, though not flawless, are generally better than the average person's. In our studies, we did not control for diet, which is hard to do. I'm skeptical diet alone would explain the excessive atherosclerotic disease we're observing.

Both athletes and non-athletes share common factors, such as genetics. Since these don't significantly vary between the two groups, the distinguishing element likely lies in the athletics. What catches my attention are the changes in hemodynamics and the way sheer stress influences arteries as well as transient inflammation.

Another intriguing, albeit speculative, theory is calcium leaching from non-weight-bearing bones to be deposited in arteries. It's an avenue worth investigating, although it does feel a bit simplistic.

Krishnan: What do we know about the risk or prevalence of cardiac events in athletes who have CAC?

La Gerche: Athletes seem to be at lower risk of stroke and myocardial infarction,¹ so it's completely paradoxical that there might be increased atherosclerotic burden. Another point to consider is why many studies indicate plaques are more calcified. I believe exercise acts as an anti-inflammatory for arteries, much like a statin. This might clarify the disparity between higher CAC levels and reduced event rates. There's quite good data suggesting that increased fitness corresponds with lower event rates for any given coronary calcium.

Krishnan: Have researchers investigated how distinct types of exercise, like high volume versus high intensity or static versus dynamic exercise, affect CAC?

La Gerche: There's probably not a heap of evidence to base this. However, there's a study by Vincent Aengevaeren et al² from the Netherlands linking amount of exercise to coronary plaque presence. They identified a correlation between MET-hours,* which combine intensity and duration, and coronary plaque. While exercise types affect arteries distinctly, intensity and duration remain central. The challenge in our literature is the lack of precise exercise quantification, largely relying on questionnaires. Interestingly, with activity watches and devices, we're approaching more accurate measurement methods. As for specific sports, I tell my trainees that the heart can't see what shoes you're wearing, only the hemodynamic stimulus. Whether running or cycling, it ultimately responds to intensity, duration, pressure, and volume load.

Krishnan: Besides exercise, are there specific clinical demographics that differentiate athletes who develop CAC from those who don't?

La Gerche: That's one of the great mysteries, and I don't have a good sense for which of my athletes is going to have coronary calcium. Even athletes who do everything right can end up with high calcium scores and you're left thinking how could this be? While the differentiating factors or demographics aren't clear, clinical risk scores and elements like lipoprotein (a) might have a role. But it's complex, and we're still trying to figure out the key players here. Clinically, I discuss potential outcomes with every athlete before testing. It's crucial to anticipate that despite doing all the right things, results might be abnormal, leading to disappointment and fear. You have to be able to anticipate that.

Krishnan: Speaking of demographics, what about gender differences? Do they play a role in athletes' CAC?

La Gerche: Gender is a fascinating aspect because, like so much sports cardiology, we have not done this justice. There's some nice work by Sanjay Sharma et al³ where he had a good cohort of female athletes and there didn't seem to be even a hint that they had the same phenomenon. So at the moment research suggests that women athletes seem to be somewhat protected – they don't exhibit the same degree of exercise-related calcium deposition and plaque buildup. However, there's a huge caveat because we said the same for ages with atrial fibrillation (AF) and then two trials have just come out that suggest women athletes indeed have an increased rate of AF.⁴ Similarly, we have some women who develop profound athletic remodeling of the heart, and they look just as influenced by exercise as do their male counterparts. So my concern is that we might not have done this justice, and it's possible that our understanding might evolve with more comprehensive studies.