Globally, cardiovascular disease is the leading cause of death, with stroke being the second most prevalent single cause. Endothelial dysfunction is a hallmark of cardiovascular disease ultimately increasing the risk of arterial thrombosis and leading to capillary rarefaction. Exercise plays an important role in both primary and secondary prevention of cardiovascular disease, however, acute exercise might increase the risk of thrombosis. The primary aim of this thesis was to evaluate the effect of aerobic exercise training and of acute exercise on thrombogenicity and factors affecting thrombogenicity in healthy and diseased cohorts. To address this aim we conduced one study in which healthy recent postmenopausal females (≤ 5 years post menopause) and late postmenopausal females (≥ 10 years post menopause) completed eight weeks of high-intensity exercise training and one study in which lacunar stroke patients and healthy elderly individuals completed one bout of acute exercise. The two studies allowed for an examination of the effect of exercise on the novel biomarker for clot microstructure, fractal dimension, and thereby the susceptibility to thrombosis. Focus in the study on the recent and late postmenopausal females was also on the impact of exercise training on properties of isolated muscle microvascular endothelial cells, vascular function and angiogenesis. The main findings of this thesis were that eight weeks of high-intensity exercise training led to reduced clot microstructure and platelet reactivity, indicating a reduced susceptibility to thrombosis, in recent postmenopausal females (Study I). In microvascular endothelial cells derived from skeletal muscle biopsies of recent postmenopausal females, glycolysis increased and the production of reactive oxygen species (ROS) per respiration decreased with exercise training
(Study I). Vascular function and skeletal muscle capillarization remained unaltered in both groups (Study I). Both lacunar stroke patients and healthy elderly individuals showed an increase in thrombogenicity in response to acute exercise, however at rest the thrombotic risk was higher in the stroke patients compared to the healthy elderly individuals (Study II). In conclusion, this thesis shows for the first time, that late postmenopausal females present less adaptation to exercise training than recent postmenopausal females for many parameters, including thrombogenicity, and endothelial cell properties. It is therefore proposed that, for the best primary prevention, exercise training should be initiated soon after menopause. Additionally, our findings imply that exercise is important in the prevention of thrombotic risk. However, given the transient increase in thrombotic risk with acute exercise, for patients at risk, including lacunar stroke patients, exercise should be prescribed with caution to prevent a cardiovascular event following exercise.