No Excuses: Routine, High-Volume Exercise in Men Not Associated With Increased Mortality

A high level of physical activity equivalent to running more than four miles per day at a pace of 10 minutes per mile is associated with slightly higher levels of coronary artery calcium (CAC) in men, according to the results of a new study. But even in the presence of clinically significant calcium, such high levels of activity are not associated with an increased risk of all-cause or cardiovascular mortality.

After a decade of follow-up, men who engaged in high-volume physical activity—defined as 3,000 MET-minutes per week or roughly 5 to 6 hours of weekly endurance exercise—had an 11% higher risk of having CAC levels of 100 Agatston units (AU) or greater compared with individuals who were less active. For those with CAC scores above that threshold, though, high-volume exercise was not associated with an increased risk of death compared with those who didn’t exercise as much.     

“If you’re an athlete and have calcification, does that mean you’re at greater risk than if you were a sedentary person with calcification?” asked senior investigator Benjamin Levine, MD (UT Southwestern Medical Center, Dallas, TX), in an interview with TCTMD. “The answer to that is clearly no.”

The results, from an analysis of 21,758 men in the Cooper Center Longitudinal Study (CCLS) published online January 30, 2019, ahead of print in JAMA Cardiology, are reassuring for highly active individuals, said Levine.

“As someone who now takes care of lots of masters athletes who come to me after having a coronary artery calcium scan asking what they do now, I tell them, ‘Look, you clearly have some atherosclerosis and we need to address your risk factors as best as possible, but it’s not the running that’s the problem. In fact, your running, and your exercise, is going to be protective for you,’” said Levine. “I don’t tell patients they need to stop marathon running.”

Aaron Baggish, MD (Massachusetts General Hospital, Boston), who was not involved in the study, said the potential harms of long-distance endurance exercise, particularly with respect to coronary calcification, have been a hot topic for several years now, but the new research should alleviate such concerns.

“The coronary calcium story in the general population is pretty clear-cut,” he told TCTMD. “The higher your calcium, the higher the risk of something bad happening to you. But, at the same time, it’s also a classic example of trying to apply a principle learned in one population to a very different population. Those of us who take care of athletes have seen coronary calcium many, many times in people who are otherwise healthy and have had a long athletic lifestyle. We know that these people tend to live longer and have less cardiac events independent of the calcium.”

Exercise is Protective, Not Harmful

Concerns about the risks of high-volume/high-intensity physical activity, such as long-distance running, cycling, or triathlons, among other sports, emerged several years back when German researchers studied 108 healthy male marathon runners in the Heinz Nixdorf Recall study. In the initial analysis, the athletes had similar distributions of CAC when compared with age-matched controls, but when the runners were matched with healthy controls with the same burden of CVD risk factors, the marathon runners had a higher degree of calcification.

To TCTMD, Levine said it’s difficult to know from retrospective analyses whether individuals began running to overcome decades of unhealthy lifestyles, thus making it difficult to determine whether the marathon running was the cause of the increased calcification. Since the German publication, however, a number of published papers have suggested similar findings, including a 2017 study showing that the plaque in male masters athletes is highly calcified.

“It’s not the calcium we worry about—the calcium is just a footprint of atherosclerosis,” said Levine. “Calcified plaques are quite stable and don’t rupture. It never goes away. You put someone on a statin, for example, and their non-calcified plaque resolves, but the calcium never goes away. So it’s a sign of the underlying atherosclerotic process. If more of the [athletes’ plaques] are calcified, it could actually be a good thing. Nobody really knows.”

For that reason, Levine, along with lead researcher Laura DeFina, MD (UT Southwestern Medical Center), and colleagues, analyzed data from the CCLS to determine whether CAC in athletes was associated with an increased risk of clinical outcomes. In their cohort, those who engaged in at least 3,000 MET-minutes per week were more likely to have CAC, but Levine stressed that nearly 75% of individuals in the study, regardless of physical activity level, had low levels of CAC (< 100 AU).           

In the men who had a CAC score < 100 AU, those who engaged in high-volume physical activity had a 48% lower risk of all-cause mortality compared with men who accumulated less than 1,500 MET-minutes per week. For those with CAC score ≥ 100, there were trends toward a lower risk of all-cause and cardiovascular mortality among the high-volume athletes compared with those who exercised less, but the benefit wasn’t significant given the small number of deaths.

“I think we can be reassured that while there might be a small increased risk of calcification, mortality, both overall and cardiovascular, was actually lower,” said Levine. “We can all agree that it certainly wasn’t higher.”

To TCTMD, Baggish said the presence of coronary calcification “simply means a different thing” in athletes as opposed to the general population. “It’s not associated with the same poor outcomes as it would be in people who would develop calcium for other reasons.” Over years of endurance activity, it’s possible there is a small degree of damage done to the arterial wall but the calcification is a form of repair that acts as a scaffolding, which would make these individuals less susceptible to plaque rupture as might happen in an active plaque, said Baggish.

Levine said that while 3,000 MET-minutes per week was used in the study as the cutoff, those classified as high-volume exercisers were active for roughly 8 hours per week. That type of volume far exceeds the daily recommended physical activity guidelines for health promotion, but he noted that anybody who engages in that type of volume/intensity is doing so because they enjoy it, or for performance, and not necessarily for health reasons.

Use of CAC For Risk Stratification

In an editorial, Carl Lavie, MD (John Ochsner Heart and Vascular Institute, New Orleans, LA), Ulrik Wisløff, PhD (Norwegian University of Science and Technology, Trondheim, Norway), and Roger Blumenthal, MD (Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD), write that while high-volume physical activity appears to promote calcific coronary atherosclerosis, “it appears to still be associated with safety and possibly lower mortality risks.”

Moreover, from a societal perspective, not getting enough physical activity is a much bigger concern than individuals who are involved in high-volume endurance sports, they add.

Regarding the clinical guidelines advocating for use of CAC screening in selected patients, such as those at intermediate risk of CVD, Lavie, Wisløff, and Blumenthal believe it remains a useful tool even in high-volume exercisers. “High CAC scores were still associated with higher risk at any given physical activity level in this study, which is why CAC assessment is being promoted to help risk assessment and intensify preventive therapies, such as vigorous lipid treatment,” they write.