Measuring Athlete's Risk of Cardiovascular Events 3 (MARC-3)
Netherlands250 participantsStarted 2026-05-31
Plain-language summary
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:
1. examine how long-term exercise patterns relate to the progression of coronary atherosclerosis;
2. assess plaque characteristics using artificial-intelligence based quantitative coronary CT angiography (AI-QCT);
3. identify biological markers that may link exercise to plaque development; and
4. evaluate long-term clinical outcomes, including all-cause mortality and major adverse cardiovascular events (MACE).
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.
Who can participate
Age range
45 Years
Sex
MALE
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
\- Previous participation in the original MARC study (enrolled between 2012-2014).
Exclusion Criteria:
* Inability to provide written informed consent.
* Not willing to receive information about potential incidental CT findings.
* Concurrent participation in an interventional study targeting cardiovascular health.
Additional exclusion criteria for CCTA:
* Not willing to undergo CCTA with intravenous contrast.
* History of severe allergic reaction to iodinated contrast agents.
* Renal dysfunction (eGFR \< 30 mL/min/1.73 m²).
Additional exclusion criteria for maximal exercise testing:
* Absolute contraindications to maximal exercise testing as defined by institutional SOPs, including but not limited to:
* Recent acute myocardial infarction (3-5 days)
* Unstable angina
* Uncontrolled arrhythmias with symptoms or hemodynamic compromise
* Syncope
* Active endocarditis
* Acute myocarditis or pericarditis
* Uncontrolled heart failure
* Acute pulmonary embolus or pulmonary infarction
* Lower extremity thrombosis
* Suspected aortic dissection
* Uncontrolled asthma
* Pulmonary edema
* Resting room-air oxygen saturation ≤ 85 percent
* Respiratory failure
* Acute non-cardiopulmonary disorders that impair or are aggravated by exercise (e.g., infection, renal failure, thyrotoxicosis)
* Mental impairment preventing cooperation
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.