Bio-Epidemiology of Fitness and Cardiovascular disease From Society to Molecules and back again

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Large-scale epidemiological studies demonstrate that aerobic fitness, measured as maximal oxygen uptake, is the single best predictor for future cardiovascular mortality in healthy individuals and in patients with cardiovascular disease. We hypothesise th at both intrinsic and acquired low level of maximal oxygen uptake initiate detrimental cardiovascular signalling pathways, and that diagnostic as well as therapeutic strategies must be specifically targeted to those pathways. Identification of new biomark ers and detrimental and positive (through exercise training) cardiovascular signalling pathways will bring forward a potential to establish original and novel diagnostic and therapeutic tools and strategies for cardiovascular disease, including prevention strategies to avoid progression to cardiovascular diseases, thus contributing to reduce the burden of cardiovascular and life-style related diseases. We will improve the mechanistic understanding of how low level of maximal oxygen uptake, intrinsic or ac quired, influence upon cardiovascular signalling, and how exercise training programs may influence upon this regulation by combining animal models, cell biology, human myocardium, large population and patient cohorts. The novelty of the suggested projects is the combination of studies of physical activity ranging from the largest health survey in an unselected population in the world (HUNT-1, 2, 3) "all the way down to molecules".