Exercise Intensity, Not Volume, Linked to Atherosclerosis Progression in Men

For middle-aged and older men, new data suggest that it’s how hard they exercise, not how much, that may be contributing to the paradoxical increase in coronary atherosclerosis seen in athletes.  

Very-vigorous-intensity exercise, such as running, rowing, or water polo, was associated with increasing coronary artery calcium (CAC) during 6 years of follow-up, while vigorous activity, such as cycling, soccer, or hockey, was also associated with CAC progression but to a lesser extent, report investigators. Exercise volume, on the other hand, had no impact on the development of atherosclerosis.

The new study, which was published this week in Circulation, is not intended to scare middle-aged athletes out of their Nikes, however.  

“To be honest, one of the problems with the paper is that we don’t yet know the clinical relevance associated with the coronary calcification in those athletes,” lead investigator Vincent L. Aengevaeren, MD, PhD (Radboud University Medical Center, Nijmegen, the Netherlands), told TCTMD. “What I think is very interesting is that in those who do very-vigorous-intensity exercise we found an increase in coronary artery calcification, but we also saw more calcified plaque progression. It’s possible that we see increased plaque calcification that’s also seen when individuals start with statins.”

In some statin studies, said Aengevaeren, use of the LDL-lowering drugs increased plaque progression but decreased atheroma volume and cardiovascular risk.

Benjamin Levine, MD (The University of Texas Southwestern Medical Center, Dallas), an expert in sports cardiology, said the present study confirms what is known among physicians who care for patients the world over, namely that coronary artery disease progresses.

“Of course, the key question is whether such progression is associated with events, which this small study can't tell us,” Levine told TCTMD via email.

He said that a clear distinction between vigorous and very-vigorous activity is challenging because most participants are likely to engage in both types of exercise. Levine also pointed out that the total progression of coronary atherosclerosis was relatively modest, noting that statin use, which also increases CAC, increased threefold over the 6 years of follow-up in the Dutch study.

Of note, the current analysis is focused only on male athletes. To TCTMD, Aengevaeren said almost all of the research related to exercise volume/intensity and progression of atherosclerosis to date has been performed in men. As such, the results may not be directly applicable to women participating in the same types of activities, given that the association between exercise and CAC/coronary plaque may be different for women. 

Wide Range of Male Athletes

While physical activity and exercise are associated with a significantly lower risk of cardiovascular disease, there is a growing body of evidence showing that athletes do have higher CAC scores than the general population. However, as Aengevaeren pointed out, the clinical relevance of higher CAC scores in this group is not fully understood. CAC is an indicator of coronary artery plaque burden and is associated with future cardiovascular risk, but that data is derived from the general population. In these US derivation cohorts, very few people are exercising regularly, said Aengevaeren.

Measuring Athletes’ Risk of Cardiovascular Events 2 (MARC-2) is a follow-up study of 287 healthy, middle-aged, amateur male athletes who underwent CT imaging in MARC-1 to investigate the presence of subclinical atherosclerosis. The average follow-up between the CT scans was 6.3 years, and during this time average blood pressure and use of antihypertensive and statin medications increased. Total cholesterol levels, on the other hand, remained steady during follow-up.

In MARC-1, participants exercised for 41 MET hours/week, of which 44% was done at a vigorous intensity and 34% done at a very-vigorous intensity. For the study, intensity was classified as the proportion of exercise MET hours/per week in the range of light (< 3 METs), moderate (3 to 6 METs), vigorous (6 to 9 METs), and very-vigorous (≥ 9 METs) activity. For the follow-up, the men were not directed to follow any prescribed exercise pattern, but rather to participate as they saw fit.  

“It’s a very heterogenous group of active males of middle to older age,” said Aengevaeren. “We have triathletes who do an enormous amounts of exercise, but we also have men who are on the bike now and then, or those playing soccer or hockey. It’s a wide distribution. I would say the average is a cyclist who rides a couple hours three times or week or the runner who is out there three times a week for 1.5 hours [total].” 

At baseline, CAC was present in 52% of men but increased to 71% at follow-up. Overall, the median CAC score increased from 1 to 31. The percentage of CAC scores ≥ 100 increased from 15% to 31% while the percentage of scores ≥ 400 increased from 6% to 13%. The percentage of CAC scores ≥ 1000 also increased, from 1% to 6%. Three-quarters of the men had a rise in the total number of coronary atherosclerotic plaques, including 52% who had an increase in the number of calcified plaques. Additionally, half had an increase in the number of mixed plaques and 36% showed evidence of increased noncalcified plaques.

Exercise volume had no impact on CAC or plaque progression in multivariable-adjusted and regression analyses.

For Aengevaeren, the association between intensity and CAC, but not volume, is one of the most interesting aspects of the new study. As for why, the researchers speculate that intense physical exercise produces higher catecholamine levels. While relatively stable at lower-intensity exercise, higher catecholamine levels increase heart rate and blood pressure, leading to increased coronary mechanical stress and disrupted laminar flow. Higher levels have also been shown to result in long-lasting proinflammatory changes in monocytes.

Some Reassurances Out There

In terms of clinical implications, there are some data that suggest active people might not have to worry as much about higher CAC scores than those who are inactive. 

For example, Aengevaeren pointed to the large Cooper Center Longitudinal Study that included nearly 22,000 individuals without prevalent cardiovascular disease who underwent CAC imaging. Those who did the most exercise had a higher CAC score, but the higher score did not have any impact on all-cause or cardiovascular mortality. In fact, among those with a CAC score of less than 100, those who did at least 3,000 MET-min/week of exercise were 48% less likely to die over a 10-year follow-up period compared with those who did less than 1,500 MET-min/week of exercise. Even in those with CAC scores greater than 100, which is clinically significant, there was a nonsignificant trend toward lower mortality risk among those who did the most exercise compared with those who did the least.

That study, he said, provided reassurances as it showed that athletes weren’t at higher risk than those who exercised less, even with a higher CAC score.

“At this point, I wouldn’t recommend athletes change their exercise regimen based on this study,” said Aengevaeren. “It’s a bit too early, but it does trigger follow-up research to figure this out. In the end, that’s the idea, to figure out the clinical relevance and to possibly change exercise recommendations to get the optimal benefits for coronary atherosclerosis prevention.”