MASTER@HEART: Long-term Endurance Athletes Not Immune to Atherosclerosis

NEW ORLEANS, LA—(UPDATED) Avid older athletes who participate in large amounts of physical activity, particularly those who have been active their entire lives, have a higher burden of atherosclerotic plaque compared with healthy controls, as well as those who are equally active but who came to sports later in life, according to results from the MASTER@HEART study.

That endurance athletes can have a higher plaque burden than less-active controls is not a novel finding—other studies have demonstrated this group tends to have more coronary artery calcium (CAC), for example, although the clinical importance of this remains unclear.

Also debated is whether duration of high-intensity activity over the lifetime leads to different patterns of atherosclerosis than in athletes who engage in endurance sports for shorter time spans.

As lead investigator Ruben De Bosscher, MD, PhD (University Hospitals Leuven, Belgium), put the question: “Is lifelong endurance exercise associated with more coronary atherosclerosis than the standard of care?” Here, the standard of care refers to roughly 3 hours per week of moderate-intensity exercise as recommended in CVD prevention guidelines. “Our answer,” he said, “would have to be yes.”

In their analysis, lifelong endurance athletes had consistently higher coronary plaque burden, including more calcified, noncalcified, and mixed plaques, as well as more plaque in a proximal segment and more plaques with a 50% stenosis, said De Bosscher.  

MASTER@HEART was presented earlier this week during a featured clinical research session at the American College of Cardiology/World Congress of Cardiology (ACC/WCC) 2023 meeting and published simultaneously in the European Heart Journal.  

Elite Endurance Athlete Paradox

Previous studies have documented the higher prevalence of coronary atherosclerotic plaques among highly trained endurance athletes compared with nonathletes. Back in 2008, investigators showed that 108 male marathon runners had a higher CAC score than a healthy control group. Subsequent studies have also pointed to a higher prevalence of atherosclerotic plaque or CAC scores in older athletes.

The higher prevalence of atherosclerotic plaque, coupled with the increased longevity and lower incidence of CVD in elite athletes, represents a bit of a paradox, said De Bosscher. One of the hypotheses is that while athletes might have a higher plaque burden, they tend to have a more benign plaque composition with a higher percentage of stable plaque.

The worst thing you can do is nothing at all, [where] your only relationship with exercise is watching it on TV or from the grandstand while eating junk food. Ruben De Bosscher

The Master@Heart study investigators wanted to better understand the upper range of the dose-response relationship between exercise and atherosclerosis in older athletes (mean age 55 years). To do so, they looked at 191 lifelong endurance athletes, 191 endurance athletes who started later in life, and 176 nonathletic but healthy controls.

Like many of these types of studies, all the participants were male, which is a limitation. Athletes were defined as those who cycled 8 or more hours per week or ran 6 or more hours per week (or participated in triathlon, a multisport that includes swimming, cycling, or running, for 8 or more hours weekly). Lifelong participation was defined as someone who started regular endurance training before age 30. The control group engaged in 3 or less hours per week of physical activity.  

On average, the lifelong and late-onset athletes exercised for 11 and 10 hours per week, which was significantly higher than the controls (1 hour per week). The lifelong athletes had 36 years of endurance exercise under their belts, on average, whereas the late-onset group had 14 years. Overall, the athletes had a higher VO₂ max than the control group, as well as less body fat and lower body mass index. The other cardiovascular risk factors were similar in all three groups, although the athletes had higher HDL levels.

There was no significant difference in the CAC score between the three groups, although there was a trend toward more calcification in lifelong athletes followed by the late-onset group. Corrected for age and CVD risk factors, however, lifelong athletes were in a higher CAC percentile compared with the control group.  

Overall, lifelong athletes had a significantly higher plaque burden when compared with the control group. The lifelong athletes also had a higher prevalence of stenotic plaques (> 50%) compared with late starters.  

When researchers looked specifically at plaque types, there was no significant difference in the distribution between the three groups—they all had a similar percentage of calcified, noncalcified, and mixed plaque, with calcified plaque the predominant type.

With respect to the more stable lesions, the lifelong athletes were more likely to have one or more calcified plaques and calcified proximal plaques than the nonathletes. However, the long-term exercisers also had a higher prevalence of one or more noncalcified or noncalcified proximal plaques compared with the control group, and a higher prevalence of stenotic noncalcified plaque compared with the late-onset group. Additionally, the lifelong group had a higher prevalence of one or more mixed lesions compared with controls.

The researchers also looked at other plaque features, noting that lifelong athletes had less vulnerable plaques than the healthy control group, although the incidence of vulnerable plaque was very infrequent in the study.

What’s the Clinical Message?   

Michael Emery, MD (Cleveland Clinic, OH), one of the discussants during the ACC/WCC session, applauded the researchers for the trial, noting that it’s difficult to assess lifelong exercise habits in such a large group of athletes. However, he pointed out that the study might be subject to recall bias, noting that some athletes were going back more than 30 years to recollect their exercise habits.

To TCTMD, Emery said the development of atherosclerosis in endurance athletes is a controversial topic but noted that no study has demonstrated athletes are at higher risk of death, MI, or other hard outcomes. He highlighted an analysis from the Cooper Center Longitudinal Study showing that while CVD risk increased with higher CAC scores, cardiorespiratory fitness attenuated that relationship. Fitness still matters regardless of calcium score, so don’t stop exercising, Emery said in email.   

Regardless of those benefits, the study also “nicely illustrates that exercise does not make you immune from heart disease—which is a message a lot of athletes need to hear, honestly,” he added.

The more important issue, though, is just what physicians, as well as the general public, should make of the results. He worries about the wrong take-home message being sent that too much exercise will do more harm than good. “If we know that exercise improves outcomes—even at the extremes, with data from Tour de France riders showing much improved mortality—how do we translate this clinically?” asked Emery. “What public health message do you want to send the general public, and potentially the media, of how to translate this study?”

De Bosscher said the message is relatively straightforward: nobody is granted immunity from coronary atherosclerosis, not even highly trained endurance athletes. Also, just a little exercise can go a long way.  

“If we take all of the information we have to date, we suggest a dose-response relationship with regard to exercise and coronary atherosclerosis,” he said. “The worst thing you can do is nothing at all, [where] your only relationship with exercise is watching it on TV or from the grandstand while eating junk food. But as soon as you do a little bit of exercise, whether its walking or jogging up to 3 hours, it seems you get the most benefit. As you increase your exercise dose, we tend to see an increase in coronary plaque burden.”

He agreed that endurance athletes have much better survival and CVD outcomes than the general public, but pointed out that the general population, as a whole, isn’t particularly active or healthy.

“If you were, for example, to completely ignore the general population and only look at people who exercise with a varying dose, then this is a discussion that we’re having more and more in sports cardiology,” De Bosscher said. “Do we still see the same relationship, with less events in elite athletes? There might be a point of diminished returns where an increased risk is seen in elite and endurance athletes.”