An observational study in Coronary Artery Disease and Atherosclerosis, sponsored by Radboud University Medical Center. Enrolling by invitation at 2 sites in Netherlands. Open to male participants aged 45 Years and older. Per ClinicalTrials.gov, last updated 2026-08-13.
Sponsored by Radboud University Medical Center · Observational
Regular endurance exercise is widely known to improve cardiovascular health and reduce the risk of heart disease. Yet several imaging studies have shown that male endurance athletes have a higher prevalence of coronary artery calcification (CAC) and calcified plaque than less active individuals. It remains unclear whether this represents harmful progression of coronary artery disease or a more benign, stable form of atherosclerosis. Understanding this distinction is essential, because coronary atherosclerosis is the leading cause of exercise-related cardiac events in athletes >35 years.
The MARC-3 study is the second long-term follow-up of the original Measuring Athlete's Risk of Cardiovascular Events (MARC) cohort and aims to clarify how lifelong exercise training influences coronary artery health.
The study will:
Our working hypothesis is that endurance exercise predominantly leads to more stable, calcified plaque, and that mechanisms such as exercise-induced hypertension, inflammation, lipid regulation, and genetic background may provide an explanation for the unexpected results observed in previous studies.
For a detailed description, please see the attached study protocol under 'Documents'.
4,857 studies on the registry are indexed under Coronary Artery Disease; 890 are open to participants now.
This study's planned enrollment of 250 is below the median of 320 across 1,687 observational studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →Radboud University Medical Center is the lead sponsor of 986 studies on the registry; 136 are open to participants now.
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Participants are invited from the established MARC cohort, which originally included 318 Caucasian, middle-aged (≥45 years) male amateur athletes recruited between 2012 and 2014. At baseline, athletes were eligible if they engaged in regular endurance exercise and were free of known cardiovascular disease. All participants underwent a comprehensive sports medical evaluation without abnormalities prior to enrollment. The initial exclusion criteria included inability to provide informed consent and medical conditions precluding participation in exercise testing or CT imaging.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
- Previous participation in the original MARC study (enrolled between 2012-2014).
Exclusion Criteria:
Additional exclusion criteria for CCTA:
Additional exclusion criteria for maximal exercise testing:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this cohort are the surviving and traceable members of the original MARC study, which enrolled 318 middle-aged male amateur endurance athletes between 2012 and 2014. In the first follow-up (MARC-2), 291 participants were successfully re-examined. All participants have a lifelong history of regular endurance exercise. In MARC-3, they undergo repeat evaluation of coronary atherosclerosis, cardiopulmonary fitness, exercise exposure, biomarkers, and genetic factors approximately 12.5 years after baseline.
Coronary Artery Calcium (CAC) Score
Total CACS (AU) AU: Agatston units
Time frame: Baseline
Coronary stenosis and plaque characteristics
Determine the characteristics (burden, composition, risk features)
Time frame: Baseline
Quantitative Plaque Phenotype and Burden
Total plaque volume (mm³); calcified, mixed, non-calcified and low-attenuation plaque (mm³); remodeling index.
Time frame: Baseline
Pericoronary Adipose Tissue Attenuation (PCATa)
CCTA-derived PCAT attenuation around proximal coronary arteries (Hounsfield Units, HU).
Time frame: Baseline
Peripheral Atherosclerosis and Vascular Function
Carotid artery intima-media thickness (IMT, mm)
Time frame: Baseline
Long-Term Clinical Outcomes
All-cause mortality and major adverse cardiac events (MACE)
Time frame: Through current study baseline, approximately 13 years after initial cohort enrollment
Plan to share: Yes — Pseudonymised individual participant data underlying published results may be made available to qualified researchers upon reasonable request. Data access will be subject to approval by the study group leaders, compatibility with participant consent, institutional privacy/legal review, and execution of a data sharing agreement. Only data necessary for the approved research question will be shared.
Started May 2026 (actual). Primary completion is estimated for Dec 2027, 19 months after the start.
How these figures are worked out, and which studies are left out of them.
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