Measuring Athlete's Risk of Cardiovascular Events 3 (MARC-3)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Enrollment
- 250
- Locations
- 2
- Primary Endpoint
- Coronary Artery Calcium (CAC) Score
Study Overview
Brief 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:
- examine how long-term exercise patterns relate to the progression of coronary atherosclerosis;
- assess plaque characteristics using artificial-intelligence based quantitative coronary CT angiography (AI-QCT);
- identify biological markers that may link exercise to plaque development; and
- 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.
Detailed Description
For a detailed description, please see the attached study protocol under 'Documents'.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 45 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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
- •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
Arms & Interventions
MARC-3 cohort
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.
Outcomes
Primary Outcomes
Coronary Artery Calcium (CAC) Score
Time Frame: Baseline
Total CACS (AU) AU: Agatston units
Coronary stenosis and plaque characteristics
Time Frame: Baseline
Determine the characteristics (burden, composition, risk features)
Secondary Outcomes
- Peripheral Atherosclerosis and Vascular Function(Baseline)
- Quantitative Plaque Phenotype and Burden(Baseline)
- Pericoronary Adipose Tissue Attenuation (PCATa)(Baseline)
- Long-Term Clinical Outcomes(Through current study baseline, approximately 13 years after initial cohort enrollment)