Measuring Athlete's Risk of Cardiovascular Events 3 (MARC-3) (MARC-3)
28 de mayo de 2026 actualizado por: Radboud University Medical Center
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.
Descripción general del estudio
Estado
Inscripción por invitación
Condiciones
Descripción detallada
For a detailed description, please see the attached study protocol under 'Documents'.
Tipo de estudio
De observación
Inscripción (Estimado)
250
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Nijmegen, Países Bajos, 6525 GA
- Radboud University Medical Center
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Utrecht, Países Bajos, 3584 CX
- University Medical Center Utrecht
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
N/A
Método de muestreo
Muestra no probabilística
Población de estudio
Participants are invited from the established MARC cohort, which originally included 318 Caucasian, middle-aged (≥45 years) male amateur athletes recruited between 2012 and 2014.
At baseline, athletes were eligible if they engaged in regular endurance exercise and were free of known cardiovascular disease.
All participants underwent a comprehensive sports medical evaluation without abnormalities prior to enrollment.
The initial exclusion criteria included inability to provide informed consent and medical conditions precluding participation in exercise testing or CT imaging.
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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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.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Coronary Artery Calcium (CAC) Score
Periodo de tiempo: Baseline
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Total CACS (AU) AU: Agatston units |
Baseline
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Coronary stenosis and plaque characteristics
Periodo de tiempo: Baseline
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Determine the characteristics (burden, composition, risk features)
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Baseline
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Quantitative Plaque Phenotype and Burden
Periodo de tiempo: Baseline
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Total plaque volume (mm³); calcified, mixed, non-calcified and low-attenuation plaque (mm³); remodeling index.
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Baseline
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Pericoronary Adipose Tissue Attenuation (PCATa)
Periodo de tiempo: Baseline
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CCTA-derived PCAT attenuation around proximal coronary arteries (Hounsfield Units, HU).
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Baseline
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Peripheral Atherosclerosis
Periodo de tiempo: Baseline
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Carotid and femoral intima-media thickness (IMT, mm) and degree of stenosis (%).
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Baseline
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Biomarker Profile
Periodo de tiempo: Baseline
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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.
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Baseline
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Long-Term Clinical Outcomes
Periodo de tiempo: Through current study baseline, approximately 13 years after initial cohort enrollment
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All-cause mortality and major adverse cardiac events (MACE)
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Through current study baseline, approximately 13 years after initial cohort enrollment
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Berge K, Janssen SLJE, Velthuis BK, Myhre PL, Mosterd A, Omland T, Eijsvogels TMH, Aengevaeren VL. Predictors of coronary atherosclerosis in middle-aged and older athletes: the MARC-2 study. Eur Heart J Cardiovasc Imaging. 2025 Mar 3;26(3):461-470. doi: 10.1093/ehjci/jeae317.
- Janssen SLJE, Aengevaeren VL, DE Vries F, Kleinnibbelink G, Mingels AMA, Hopman MTE, Mosterd A, Velthuis BK, Riksen NP, Eijsvogels TMH. Exercise-Induced Changes in Hemodynamics, Hormones, Electrolytes, and Inflammatory Markers in Veteran Athletes with and without Coronary Atherosclerosis. Med Sci Sports Exerc. 2025 Jul 1;57(7):1297-1308. doi: 10.1249/MSS.0000000000003674. Epub 2025 Feb 17.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Estimado)
31 de mayo de 2026
Finalización primaria (Estimado)
31 de diciembre de 2027
Finalización del estudio (Estimado)
31 de diciembre de 2027
Fechas de registro del estudio
Enviado por primera vez
20 de mayo de 2026
Primero enviado que cumplió con los criterios de control de calidad
28 de mayo de 2026
Publicado por primera vez (Actual)
4 de junio de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
4 de junio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
28 de mayo de 2026
Última verificación
1 de mayo de 2026
Más información
Términos relacionados con este estudio
Palabras clave
- Actividad física
- Ejercicio
- Biomarcadores
- Inflamación Vascular
- Eventos cardiovasculares adversos mayores
- Calcificación de la arteria coronaria
- Angiografía por tomografía computarizada coronaria
- Puntaje de riesgo poligénico
- Predisposición genética a la enfermedad
- Placa Aterosclerótica
- AI-based Quantitative Computed Tomography
- Pericoronary Adipose Tissue Attenuation
Términos MeSH relevantes adicionales
- Enfermedades Vasculares
- Enfermedades cardiovasculares
- Procesos Patológicos
- Condiciones Patológicas, Anatómicas
- Enfermedades cardíacas
- Atributos de la enfermedad
- Arteriosclerosis
- Enfermedades arteriales oclusivas
- Enfermedad coronaria
- Isquemia miocardica
- Susceptibilidad a la enfermedad
- Condiciones Patológicas, Signos y Síntomas
- Comportamiento
- Puntuación de riesgo genético
- Enfermedad de la arteria coronaria
- Placa Aterosclerótica
- Aterosclerosis
- Predisposición genética a la enfermedad
- Actividad del motor
Otros números de identificación del estudio
- MARC-3
- #01-001-2024-0621 (Otro número de subvención/financiamiento: Dutch Heart Foundation (FIT-HEART consortium))
- 4334294-1093118-PG (Otro identificador: Dutch Health Council)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
Pseudonymised individual participant data underlying published results may be made available to qualified researchers upon reasonable request.
Data access will be subject to approval by the study group leaders, compatibility with participant consent, institutional privacy/legal review, and execution of a data sharing agreement.
Only data necessary for the approved research question will be shared.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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