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Cardiac CT in asymptomatic - The MARC study

Philips CT Clinical Science Philips Healthcare • USA

Prof. Birgitta Velthuis

University Medical Center

Room E01.132

Heidelberglaan 100

3584 CX Utrecht

The Netherlands


Regular physical activity helps to prevent cardiovascular disease (CVD). The European Society of Cardiology (ESC) recommends 150 minutes of moderate-intensity, or 75 minutes of vigorous-intensity, aerobic exercise per week for overall cardiovascular health.1 There is a rapidly growing group of middle-aged athletes, such as marathon runners and cyclists. Vigorous exercise is associated with a transient increased risk of exercise-related cardiovascular events in persons with (un)known CVD. Most exercise-related cardiac arrests occur in men aged ≥45 years and are caused by coronary artery disease (CAD). Traditional cardiovascular risk scores, like the Framingham Heart Study risk score (FRS) and the ESC Systematic COronary Risk Evaluation (SCORE), a resting ECG and exercise testing form the basis of both the European and U.S. recommendations for the cardiovascular evaluation of middle-aged and seniors athletes,2 however they do not reliably identify CAD.3,4


Non-contrast cardiac CT assessment of coronary artery calcium (CAC) score provides an easily obtainable measure of coronary atherosclerosis and is an independent predictor of CAD and cardiovascular events in an asymptomatic population, with additional value to all risk factor-based scores.5 Although currently only advised in asymptomatic persons with intermediate to high risk,1 CAC scoring can have additional value in individuals with few or no risk factors.5 The majority of long-term asymptomatic athletes with a low risk score have zero CAC score, which is associated with a very low risk of future cardiovascular events. A CAC score ≥300 Agatston units or ≥75th percentile for age, sex and ethnicity is considered to indicate increased CV risk.1 However, a higher cardiovascular event rate is also seen in asymptomatic people with CAC score ≥100.6 The standard radiation exposure of CAC score is ±1 mSv, but can be lowered using model-based iterative reconstruction.7


The Measuring Athlete’s Risk of Cardiovascular events (MARC) study evaluated the additional value of CAC score and coronary CT angiography (CCTA) to a routine normal sport medical evaluation (SME), including resting and exercise electrocardiography, in 318 asymptomatic sportsmen aged 45 years and older without known cardiovascular disease.3 Most participants (96%) had a low ESC risk score. Nearly one in five (19%) of these asymptomatic sportsmen had significant CAD (either CAC score >100 and/or stenosis >50%), and 16% were reclassified to a higher risk category based on CAC score >100. Follow-up data is not yet available. A study of middleaged marathon runners in Germany also found higher than expected CAC scores, with 36% having a CAC score ≥100 AU compared to 22% of FRS matched controls.4 Most events occurred in the group with a CAC score >100.


Several recent studies have shown that very active longterm male athletes have more overall coronary plaque with more calcified plaque components on CCTA than their less active or sedentary counterparts.8,9 The significance of this is unclear but the predominantly calcific morphology of coronary plaques in male athletes might imply that different pathophysiological mechanisms play a role in plaque formation in athletic versus more sedentary men. The more abundant calcific plaques probably carry less risk of plaque rupture and acute myocardial infarction than mixed plaques. No significant differences were seen between female athletes and matched sedentary controls; however, the numbers are small.9


Not every >50% coronary artery stenosis is hemodynamically significant. Ischemia detection and/or fractional flow reserve (FFR) measurement are used to determine the hemodynamic significance of a stenosis. CT derived fractional flow reserve (CT-FFR) measurements compare well to invasive coronary angiography (ICA) measurement for detecting a flow-limiting coronary artery stenosis.10 Demand ischemia, an imbalance between myocardial oxygen supply and demand, is thought to be a more common cause of cardiovascular events than plaque rupture during prolonged exercise in sportsmen.


A normal cardiac CT indicates a low risk of cardiovascular events, but does not guarantee that exercise-related events will not take place. Recent influenza remains a relative contraindication for sports due to the risk of myocarditis, and unknown cardiomyopathies or an anomalous coronary artery can still reveal themselves at middle-age.


In conclusion, a non-contrast CAC score can be a valuable addition to the routine screening of middle-aged asymptomatic male athletes, even those with a low risk score and despite the fact that long-term master athletes may have more calcific plaque. There is still insufficient evidence to support CAC scoring in older sportswomen. CCTA is of value for assessment of plaque burden, plaque morphology and detection of a flow-limiting stenosis.


49 year old asymptomatic male has a coronary calcium score of 2.5 (not shown), at the 64th MESA percentile. Coronary CT angiography (Figure A) shows a solitary mixed plaque with >50% stenosis (arrow) in the left anterior descending (LAD) artery. This was confirmed by invasive coronary angiography (arrow in Figure B) with a FFR of 0.79. No ischemia could be detected.



  1. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice. Eur Heart J 2016;37(29):2315-81.
  2. Borjesson M, Urhausen A, Kouidi E, et al. Cardiovascular evaluation of middle-aged/ senior individuals engaged in leisure-time sport activities: Position stand from the sections of exercise physiology and sports cardiology of the European Association of Cardiovascular Prevention and Rehabilitation. Eur J Cardiovasc Prev Rehabil 2011;18(3):446-58.
  3. Braber TL, Mosterd A, Prakken NH, et al. Occult coronary artery disease in middle-aged sportsmen with a low cardiovascular risk score: The Measuring Athlete's Risk of Cardiovascular Events (MARC) study. Eur J Prev Cardiol 2016;23(15):1677-84.
  4. Mohlenkamp S, Lehmann N, Breuckmann F, et al. Running: the risk of coronary events: Prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J 2008;29(15):1903-10.
  5. Silverman MG, Blaha MJ, Krumholz HM, et al. Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis. Eur Heart J 2014;35(33):2232-41.
  6. Blaha MJ, Budoff MJ, DeFilippis AP, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: Implications for the JUPITER population from MESA, a population-based cohort study. Lancet 2011;378(9792):684-92.
  7. den Harder AM, Wolterink JM, Willemink MJ, et al. Submillisievert coronary calcium quantification using model-based iterative reconstruction: A within-patient analysis. Eur J Radiol 2016 Nov;85(11):2152-59.
  8. Aengevaeren VL, Mosterd A, Braber TL, et al. The relationship between lifelong exercise volume and coronary atherosclerosis in athletes. Circulation 2017 Jul 11;136(2):138-48.
  9. Merghani A, Maestrini V, Rosmini S, et al. Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile. Circulation 2017 Jul 11;136(2):126-37.
  10. Budoff MJ, Nakazato R, Mancini GB, et al. CT Angiography for the prediction of hemodynamic significance in intermediate and severe lesions: Head-to-head comparison with quantitative coronary angiography using Fractional Flow Reserve as the reference standard. JACC Cardiovasc Imaging 2016 May;9(5):559-64.

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Nov 2, 2017

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atherosclerosis, calcified plaque, calcium score, Cardiac, coronary angiography, coronary arteries, coronary artery disease, IMR, iterative model reconstruction, LAD, non-contrast, stenosis, Vascular

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