Atherosclerosis, Coronary Artery Disease
Conditions
Keywords
Exercise, Physical Activity, Coronary Artery Calcification, Plaque, Atherosclerotic, Coronary Computed Tomography Angiography, AI-based Quantitative Computed Tomography, Pericoronary Adipose Tissue Attenuation, Vascular Inflammation, Biomarkers, Genetic Predisposition to Disease, Polygenic Risk Score, Major Adverse Cardiovascular Events
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: 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.
Detailed description
For a detailed description, please see the attached study protocol under 'Documents'.
Interventions
None listed
Sponsors
Radboud University Medical Center
Collaborators within FIT-HEART consortium (e.g. UMC Utrecht, Amsterdam UMC)
Cleerly, Inc.
Caristo Ltd.
Philips Healthcare
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Artery Calcium (CAC) Score | Baseline | Total CACS (AU) AU: Agatston units |
| Coronary stenosis and plaque characteristics | Baseline | Determine the characteristics (burden, composition, risk features) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Plaque Phenotype and Burden | Baseline | Total plaque volume (mm³); calcified, mixed, non-calcified and low-attenuation plaque (mm³); remodeling index. |
| Pericoronary Adipose Tissue Attenuation (PCATa) | Baseline | CCTA-derived PCAT attenuation around proximal coronary arteries (Hounsfield Units, HU). |
| Peripheral Atherosclerosis and Vascular Function | Baseline | Carotid artery intima-media thickness (IMT, mm) |
| Long-Term Clinical Outcomes | Through current study baseline, approximately 13 years after initial cohort enrollment | All-cause mortality and major adverse cardiac events (MACE) |
Countries
Netherlands
Outcome results
None listed