Measuring Athlete's Risk of Cardiovascular Events 3 (MARC-3)

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.

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