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.