Long-term follow-up of how lifelong exercise affects heart artery health in athletes
Follows male endurance athletes to see how exercise affects plaque in heart arteries.
Plain-language title generated from the registry record
Registry title: Measuring Athlete's Risk of Cardiovascular Events 3 (MARC-3)
Key facts
- Where
- Nijmegen and Utrecht, NetherlandsSee the 2 sites
Where in Netherlands
- Radboud University Medical CenterNijmegen, NetherlandsNo longer taking part
- University Medical Center UtrechtUtrecht, NetherlandsNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Radboud University Medical Center
- Trial code
- NCT07625488
- Record updated
- 13 August 2026
- Original description
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.Read full original descriptionShow less
Measuring Athlete's Risk of Cardiovascular Events 3 (MARC-3)
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.
Inclusion: Previous participation in the original MARC study (enrolled between 2012-2014).
Exclusion: Concurrent participation in an interventional study targeting cardiovascular health; Additional exclusion criteria for CCTA:; History of severe allergic reaction to iodinated contrast agents; Recent acute myocardial infarction (3-5 days); Unstable angina; Uncontrolled arrhythmias with symptoms or hemodynamic compromise; Uncontrolled heart failure; Lower extremity thrombosis; Respiratory failure; Acute non-cardiopulmonary disorders that impair or are aggravated by exercise (e.g., infection, renal failure, thyrotoxicosis); Mental impairment preventing cooperation; Renal dysfunction (eGFR < 30 mL/min/1.73 m²); Additional exclusion criteria for maximal exercise testing:; Inability to provide written informed consent; Not willing to receive information about potential incidental CT findings; Not willing to undergo CCTA with intravenous contrast; Absolute contraindications to maximal exercise testing as defined by institutional SOPs, including but not limited to:; Syncope; Active endocarditis; Acute myocarditis or pericarditis; Acute pulmonary embolus or pulmonary infarction; Suspected aortic dissection; Uncontrolled asthma; Pulmonary edema; Resting room-air oxygen saturation ≤ 85 percent.