Measuring Athlete's Risk of Cardiovascular Events 3 (MARC-3)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Coronary Artery Disease, Atherosclerosis. Basic parameters: from 45 years · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Netherlands
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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'.
Primary outcome measures
- Coronary Artery Calcium (CAC) Score [Time frame: Baseline]
- Coronary stenosis and plaque characteristics [Time frame: Baseline]
Secondary outcome measures (4)
- Quantitative Plaque Phenotype and Burden [Time frame: Baseline]
- Pericoronary Adipose Tissue Attenuation (PCATa) [Time frame: Baseline]
- Peripheral Atherosclerosis and Vascular Function [Time frame: Baseline]
- Long-Term Clinical Outcomes [Time frame: Through current study baseline, approximately 13 years after initial cohort enrollment]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Study design
- Observational model
- Cohort
Study locations
Netherlands · 2 centers
- Radboud University Medical Center — Nijmegen
- University Medical Center Utrecht — Utrecht
Publications
- Braber TL, Mosterd A, Prakken NH, Doevendans PA, Mali WP, Backx FJ, Grobbee DE, Rienks R, Nathoe HM, Bots ML, Velthuis BK. Rationale and design of the Measuring Athlete's Risk of Cardiovascular events (MARC) study : The role of coronary CT in the cardiovascular evaluation of middle-aged sportsmen. Neth Heart J. 2015 Feb;23(2):133-8. doi: 10.1007/s12471-014-0630-0. PMID 25410576
- Braber TL, Prakken NH, Mosterd A, Mali WP, Doevendans PA, Bots ML, Velthuis BK. Identifying Coronary Artery Disease in Asymptomatic Middle-Aged Sportsmen: The Additional Value of Pulse Wave Velocity. PLoS One. 2015 Jul 6;10(7):e0131895. doi: 10.1371/journal.pone.0131895. eCollection 2015. PMID 26147752
- Braber TL, Mosterd A, Prakken NH, Rienks R, Nathoe HM, Mali WP, Doevendans PA, Backx FJ, Bots ML, Grobbee DE, Velthuis BK. Occult coronary artery disease in middle-aged sportsmen with a low cardiovascular risk score: The Measuring Athlete's Risk of Cardiovascular Events (MARC) study. Eur J Prev Cardiol. 2016 Oct;23(15):1677-84. doi: 10.1177/2047487316651825. Epub 2016 May 24. PMID 27222386
- Schurink MM, Braber TL, Prakken NH, Doevendans PA, Backx FJ, Grobbee DE, Rienks R, Nathoe HM, Bots ML, Velthuis BK, Mosterd A. No psychological distress in sportsmen aged 45 years and older after cardiovascular screening, including cardiac CT: The Measuring Athlete's Risk of Cardiovascular events (MARC) study. Neth Heart J. 2017 Apr;25(4):271-277. doi: 10.1007/s12471-017-0948-5. PMID 28144819
- Aengevaeren VL, Mosterd A, Braber TL, Prakken NHJ, Doevendans PA, Grobbee DE, Thompson PD, Eijsvogels TMH, Velthuis BK. Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes. Circulation. 2017 Jul 11;136(2):138-148. doi: 10.1161/CIRCULATIONAHA.117.027834. Epub 2017 Apr 27. PMID 28450347
- Aengevaeren VL, Mosterd A, Sharma S, Braber TL, Thompson PD, Velthuis BK, Eijsvogels TMH. Coronary Atherosclerosis in Athletes: Exploring the Role of Sporting Discipline. JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 1):1587-1589. doi: 10.1016/j.jcmg.2019.01.002. Epub 2019 Feb 13. No abstract available. PMID 30772217
- Berge K, Aengevaeren VL, Mosterd A, Velthuis BK, Lyngbakken MN, Omland T, Schalkwijk CG, Eijsvogels TMH. Plasma Advanced Glycation End Products and Dicarbonyl Compounds Are Not Associated with Coronary Atherosclerosis in Athletes. Med Sci Sports Exerc. 2023 Jul 1;55(7):1143-1150. doi: 10.1249/MSS.0000000000003152. Epub 2023 Apr 4. PMID 36849122
- Janssen SLJE, de Vries F, Mingels AMA, Kleinnibbelink G, Hopman MTE, Mosterd A, Velthuis BK, Aengevaeren VL, Eijsvogels TMH. Exercise-induced cardiac troponin release in athletes with versus without coronary atherosclerosis. Am J Physiol Heart Circ Physiol. 2024 Apr 1;326(4):H1045-H1052. doi: 10.1152/ajpheart.00021.2024. Epub 2024 Feb 16. PMID 38363583
Identifiers
NCT: NCT07625488 · MARC-3 · #01-001-2024-0621 · 4334294-1093118-PG