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.
For a detailed description, please see the attached study protocol under 'Documents'.
Study Type
OBSERVATIONAL
Enrollment
250
Radboud University Medical Center
Nijmegen, Netherlands
University Medical Center Utrecht
Utrecht, Netherlands
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
Carotid and femoral intima-media thickness (IMT, mm) and degree of stenosis (%).
Time frame: Baseline
Biomarker Profile
Lipid profile (mmol/L); HbA1c (%); inflammatory markers (e.g., hsCRP, mg/L); hair cortisol (pg/mg); immunophenotyping (cell subsets, % and absolute counts); polygenic risk score.
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
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