Does a higher exercise volume and intensity worsen the progression of atherosclerosis? Original paper

Physical activity dramatically reduces the risk for cardiovascular disease (CVD) morbidity and mortality. However, some studies have found that athletes who participate in high amounts of exercise may have elevated levels of coronary artery calcification (CAC) — an established risk factor for CVD — but these associations need to be confirmed with longitudinal data.^[1]

This prospective cohort study included 291 middle-aged and older male amateur athletes (average age of 60, 99% Caucasian) who were part of the Measuring Athletes’ Risk of Cardiovascular Events (MARC) study. This study, MARC 2, was a follow-up on baseline data collected during the MARC 1 study.

All participants provided information about their exercise participation, which was used to calculate their weekly volume of exercise in metabolic equivalent of task (MET) hours per week (MET hours/week) and time spent in low, moderate, vigorous, and very vigorous intensity exercise as a percentage of their total exercise volume.

The primary study outcomes were CAC and plaque progression and plaque characteristics, including the presence of calcified, noncalcified, or mixed/partially calcified plaques. The outcomes were measured an average of 6.3 years after the participants’ baseline assessment.

There was no association between exercise volumes and CAC or plaque progression.

There was a negative correlation between vigorous-intensity exercise and CAC progression, but not plaque progression. Participants who spent the most time in vigorous-intensity exercise (as a percentage of total exercise volume) had less CAC progression compared to those who spent the least time in vigorous-intensity exercise.

How do exercise volume and intensity affect CAC progression?

In contrast, there was a positive association between the proportion of time spent in very vigorous intensity exercise and the progression of CAC and plaque. The latter was characterized mainly by an increase in calcified plaque.

Most of the athletes in this study were cyclists and runners, so there was little representation from other sports, which is why the contribution of different types of exercise to CAC and plaque progression could not be investigated in this study.

The MARC 1 study was published in 2017^[1] and included the same cohort that was studied in the current analysis. In MARC 1, it was observed that athletes with higher volumes of lifelong exercise were more likely to have a CAC score greater than 0, indicating the presence of coronary artery calcification. The most active group also had a greater prevalence of any type of plaque compared to the least active group. However, most of these plaques were of the calcified type as opposed to the noncalcified or mixed/partially calcified types. In addition, lifelong very vigorous exercise was associated with the presence of CAC and plaques, while lifelong moderate intensity and vigorous intensity exercise had no such association.

Thus, some of the findings from MARC 1 are consistent with those in MARC 2, specifically, that participating in more very vigorous intensity exercise increases the risk of CAC and plaque presence and/or progression. However, in MARC 1, exercise volume was also related to CAC, while in MARC 2, exercise volume did not influence CAC or plaque progression. This difference may be due to the study designs: MARC 1 assessed lifelong physical activity levels (40 years), whereas MARC 2 assessed activity levels between the baseline and follow-up assessment only (6.5 years).

The results of both studies can be interpreted to suggest that having a high exercise volume may make athletes more likely to have — but not influence the progression of — CAC and plaque.

Interestingly, between the baseline and follow-up visits, the participants increased their exercise levels from 3 to 5 hours per week (25 MET hours/week at baseline to 40 MET hours/week at follow-up). As they got older, they engaged in more — and seemingly more intense — exercise. And though CAC and plaque progression were observed in the entire cohort during the follow-up, it’s difficult to determine whether aging, exercise, or a combination of the two contributed to these processes. Indeed, participants’ blood pressure also increased during the follow-up period, from 129/80 at baseline to 139/82 at follow-up.

How do exercise volume and intensity affect plaque progression?

Other studies on CAC risk in athletes have been published, with similar findings. A study from 2017 found that, compared to sedentary and age-matched controls, masters endurance athletes had a higher prevalence of elevated CAC and coronary plaques.^[2] Most of these plaques were calcified, in contrast to the plaques in the control group, which were more likely to be of a mixed morphology. A 2020 study also provided evidence that the total volume of exercise is not related to the progression of CAC in middle-aged endurance athletes.^[3] However, a study of over 25,000 adults with no health conditions found that those who engaged in higher levels of physical activity were more likely to have CAC and a worse CAC progression compared to the least-active group.^[4]

While some of these results may seem like a warning against doing too much (or too intense) exercise, the findings of a higher CAC burden in heavy exercisers must be reconciled with the fact that there is a well-known dose-response relationship between moderate and vigorous intensity exercise. Higher levels of each are associated with a lower CVD and all-cause mortality.^[5] Studies also indicate that elite and professional athletes live longer than the general population and have a 27% and 40% lower risk of CVD and cancer mortality, respectively.^[6]

What could explain these somewhat conflicting data? Although CAC is a significant CVD risk factor, the type of plaque may be important in determining risk. Though the athletes in this and other studies have more CAC and plaque, they more often have a greater proportion of or only calcified plaques, for which the risk of CVD and CVD events is lower than that for noncalcified or mixed plaque.^[7] Calcified plaques are more stable and thus less likely to rupture and cause a myocardial infarction (heart attack) or other major cardiac event, which could explain this seeming paradox.

Furthermore, exercise, in particular aerobic exercise training, promotes beneficial cardiovascular adaptations, including improved endothelial function, reduced blood pressure, and enhanced coronary blood flow. These mechanisms may provide protection for athletes even in the presence of elevated levels of CAC.

The reasons why high levels of very vigorous intensity exercise may be related to more CAC could involve the greater physiological stress that is associated with this type of activity. During high-intensity exercise, blood pressure and heart rate increase, there is a greater mechanical stress on the heart and arteries, blood flow rates are disturbed, and there is an increased production of inflammatory cytokines. Each of these mechanisms could promote cardiac damage, leading to the development of scarring (fibrosis) and calcification in the heart and arteries, resulting in a higher risk of atherosclerosis. However, there is little research dedicated to examining the direct effects of exercise on atherosclerosis development in humans. More studies are needed to determine the exact contribution of each to promoting CAC and plaque development.^[8]

The biggest limitation of this study might be its lack of diversity. Almost all (99%) of the men in this study were Caucasian (the term used by the study authors), and no women were included. For this reason, these findings cannot be generalized to women or to other racial and ethnic groups. This limitation indicates the need for more longitudinal data in these populations to build a more complete understanding of how long-term exercise affects cardiovascular health and disease risk. In the meantime, unless an individual is at the extreme end of an exercise habit — either doing way too little or way too much — the evidence is overwhelmingly in support of the benefits of exercise for heart health.