Most active athletics present most frequently with CAC, but have a more beneficial plaque composition

18-7-2017 • Aengevaeren VL, et al, Circulation 2017  

The Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes

Aengevaeren VL, Mosterd A, Braber TL, et al.
Circulation. 2017;136:138-148


Coronary artery calcification (CAC) is a measure of atherosclerotic plaque burden in the coronaries. In addition to this, coronary angiography (CTCA) allows determination of plaque composition, which is predominantly important for cardiovascular disease (CVD) risk prediction [1,2].
There is a lot of disagreement in relation to the dose-response relationship of exercise and CVD outcomes [3,4] and whether a high volume of exercise accelerates atherosclerosis [5,6].
This analysis of the Measuring Athlete’s Risk of Cardiovascular Events (MARC) study was conducted to assess whether extreme exercise is related to accelerated development of coronary artery atherosclerosis and calcification, using cardiac CT to calculate CAC, followed by CTCA. The analysis included 284 asymptomatic men free of known CVD and aged ≥45 years that participated in competitive or recreation leisure sports.

Main results

  • 53% of participants had CAC and the median score was 35.8 (95%CI 9.3-145.8). Average lifetime exercise volume was 2.9 hours/week (95%CI 1.9-4.4), resulting in 1356 MET-min/week (95%CI 851-2030).
  • Only very vigorous exercise was associated with CAC presence: OR 1.03 (95%CI 0.80-1.32, P=0.81), 1.13 (95%CI 0.97-1.31, P=0.12) and 1.47, 95% CI 1.14-1.91, P=0.003) for those who perform moderate, vigorous or very vigorous intensity exercise, respectively.
  • Comparing participants >2000 MET-min/week with those <1000 MET-min/week showed that CAC frequency >0 was higher in the >2000 group (68 vs 43%), as were CAC scores (9.4, 95%CI 0-60.9 vs 0, 95%CI 0-43.5, P=0.019), CAC area (4.3, 95%CI 0-20.3 vs 0, 95%CI 0-16.8, P=0.025) and number of regions of interest (2, 95%CI 2-5 vs 0, 95%CI 0-3, P=0.014). 
  • CAC scores increased with exercise volume group (P=0.006): OR 1.62 (95%CI 0.88-2.97, P=0.12) and 3.20 (95%CI 1.56-6.57, P=0.001) for those with 1000-2000 and >2000 MET-min/week, respectively, compared with <1000 MET-min/week.
  • Analysis of coronary atherosclerosis characteristics showed significantly higher plaque prevalence (either calcified, non-calcified or mixed) with OR of 3.35 (95%CI 1.57-7.14, P=0.002) when comparing >2000 MET-min/week with <1000 MET-min/week.
  • Prevalence of plaque appears to be specifically associated with hours of very vigorous intensity exercise (OR 1.56, 95%CI 1.17-2.08, P=0.002), which did not apply to moderate and vigorous intensity exercise.
  • In participants with coronary atherosclerosis, a lower prevalence of mixed plaques was observed in most active versus least active group (48 vs 69).
  • The most active people more often showed calcified plaque as dominant type (OR compared to the least active group 3.57, 95%CI 1.28-9.97). Other types of dominant plaque did not differ across exercise groups.


Participants with >2000 MET-min/week had a higher prevalence of CAC and atherosclerotic plaques. However, most active group did have a more benign composition of plaques. These observations may explain the increase longevity typical of endurance athletes, despite presence of more coronary atherosclerosis in most active participants.

Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile

In the same issue of Circulation, Merghani et al. publish the findings of their study into subclinical coronary artery disease in 152 master endurance athletes (cyclists and runners, with on average 31 years experience, an a median of 13 marathon runs per athlete) with a low atherosclerotic risk profile, who were compared with 92 age-, sex- and Framingham risk score-matched controls who engaged in exercise concordant with physical activity recommendations. CAC score was measured.
  • Most athletes (60%) and controls (63%) had normal CAC score (females more often than males). No differences were seen in the proportion with CAC=0 or CAC >70th percentile between athletes and controls.
  • Male athletes more often showed atherosclerotic plaque of any luminal irregularity (44.3% vs. 22.2%) than control males, and athletes more often had multiple plaques (21.7% vs. 3.7%). Only male athletes showed CAC ≥300 Agatston units (11.3%) and luminal stenosis ≥50% (7.5%). No differences in CAC score were seen between the female groups.
  • Male athletes showed predominantly calcified plaques (72.7% vs. 30.8% in controls) rather than mixed plaques (23.2 % vs. 61.5%). Plaque morphology did not differ between female groups.
The authors concluded that while most lifelong endurance athletes with low atherosclerotic risk profile have normal CAC score, they are more likely to have CAC score >300 Agatston units or coronary plaques as compared with males with a similar risk profile. The difference in plaque morphology indicates potentially different pathophysiology underlying plaque formation between athletic vs. control men. While coronary plaques were more abundant in athletes, they seemed more stable.
Editorial comment

Coronary Artery Calcification Among Endurance Athletes- “Hearts of Stone”

Baggish and Levine discuss these two studies in an editorial comment in the same issue. They summarise as “data from these studies suggest that a significant minority of long-term endurance athletes will develop CAC and predominantly calcific plaques that cannot be explained by typical mediators of coronary artery disease.” They consider the data an important contribution to sports cardiology literature, but the findings also raise questions, partly due to the limitation inherent to cross-sectional data, the potential influence of unmeasured confounders and the absence of clinical outcomes. Underlying mechanisms leading to the possibly unexpectedly high amounts of CAC remain unclear to date. It is also interesting to consider what differentiates athletes with calcified plaques from those without. While both studies attempted to adjust for traditional atherosclerotic risk factors, this may not have been sufficient. “For example, many endurance athletes engage in relatively unhealthy, proatherogenic dietary patterns that go underappreciated in both clinical and research settings because of the athlete’s ability to maintain lean body profiles attributable to high caloric expenditure.” Also selection bias towards recruiting preferentially those athletes who might be particularly worried about their CV health, is imaginable.  
The complete lack of clinical outcome data in these studies is perhaps most important. The authors note that “Although CAC in sedentary and/or normally active cohorts has been associated with adverse cardiovascular outcomes, no similar data are available for highly active individuals. We urge caution against the reflex generalization of data derived from nonathletic populations in this setting”. The authors conclude with several considerations on the relevance of noninvasive coronary artery morphology assessment that emerge from their work as directors of high-volume sports cardiology programs, in which they express reluctance to use such testing methods. “We have much to learn about coronary artery physiology among people that push the body to its limits and beyond. But, as we continue this journey and diagnostic technology advances in parallel, it remains prudent to minimize the application of testing with uncertain relevance.”

Find the article by Aengevaren et al. online at Circulation
Find the article by Merghani et al. online at Circulation
Find the editorial online at Circulation


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2. Hou ZH, Lu B, Gao Y, Jiang SL, Wang Y, Li W and Budoff MJ. Prognostic value of coronary CT angiography and calcium score for major adverse cardiac events in outpatients. JACC Cardiovasc Imaging. 2012;5:990-999. doi: 10.1016/j.jcmg.2012.06.006.
3. Eijsvogels TM, Molossi S, Lee DC, Emery MS and Thompson PD. Exercise at the Extremes: The Amount of Exercise to Reduce Cardiovascular Events. J Am Coll Cardiol. 2016;67:316-329. doi: 10.1016/j.jacc.2015.11.034.
4. Lee DC, Lavie CJ, Sui X and Blair SN. Running and Mortality: Is More Actually Worse? Mayo Clin Proc. 2016;91:534-536. doi: 10.1016/j.mayocp.2016.01.013.
5. Sharma S, Merghani A and Mont L. Exercise and the heart: the good, the bad, and the ugly. Eur Heart J. 2015;36:1445-1453. doi: 10.1093/eurheartj/ehv090.
6. Aengevaeren VL, Hopman MT and Eijsvogels TM. Fitness and Coronary Artery Calcification. JAMA Intern Med. 2016;176:716. doi: 10.1001/jamainternmed.2016.0898.

atheroscleroticathleticsCACexerciseMARCplaqueplaque compositionSports

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