More than 14 million Europeans suffer from heart failure (HF), of which more than 50 % have HF with preserved left ventricular (LV) ejection fraction (EF) (HFPEF, “diastolic heart failure”). HFPEF is the only cardiovascular disease with increasing prevalence and incidence, affecting 10-20% of the elderly and contributing substantially to hospitalizations of elderly HF patients. Currently, no medical treatment has been shown to be effective and the economic, social and personal burden of HFPEF is enormous; this disease constitutes one of the most pressing unmet clinical needs. A cardinal feature of HFPEF is exercise intolerance. The pathophysiology of exercise intolerance in HFPEF depends on multiple factors in heart, endothelium and skeletal muscles. From a pathophysiological point of view, exercise could by far outweigh any pharmacological intervention in this heterogeneous syndrome, since lifestyle dependent risk factor, physical inactivity, and physical deconditioning underlay and contribute to HFPEF. OptimEx will focus on the cardiovascular effects of exercise training as primary and secondary prevention of HFPEF. We will combine in vivo and in vitro studies in man and rats in serial experiments that will advance our understanding of fundamental cellular and molecular mechanisms underpinning dose-dependent exercise-induced changes in the heart, blood vessels and skeletal muscles. This research is aimed to tackle one of the major health problems the developed world faces with its ageing societies and increasing prevalence of the HFPEF and will support sustainable health systems in EU member states through improvements in the clinical management of a common and disabling disease. The project is therefore highly relevant to improve the health of European citizens and important to promote healthy ageing and preventing disease.