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Background: Cardiovascular disease is the leading cause of mortality worldwide. Cardiovascular risk factors, such as obesity and hypertension often manifest in childhood. Both of these cardio-vascular risk factors track into adulthood and are independent predictors for cardiovascular disease events later in life. To date there are no prospective studies on the association of microvascular health with the development of blood pressure in children. Furthermore the association of changes in physical activity behavior on microvascular and macrovascular health in childhood are poorly understood. Aims: The aims of my PhD project were four-fold: 1) to analyze the association of retinal arteriolar diameters at baseline with blood pressure development over 4 years. 2) to analyze the as-sociation of changes in physical activity and fitness with development of body mass index (BMI), blood pressure and retinal vessel diameters over 4 years. 3) to systematically sum-marize and meta-analyze the association of BMI, blood pressure, physical activity and fit-ness with large artery pulse wave velocity (PWV). 4) to analyze the association of changes in BMI, blood pressure, physical activity and fitness as well as retinal vessel diameters with large artery PWV as outcome after 4 years of follow-up. Methods: My PhD is based on the Sportcheck Follow-up study. This prospective school-based cohort study included 262 prepubertal children, who were screened for the above mentioned CV risk factors and retinal vessel diameters at baseline (aged 6-8 years) and at follow-up (aged 10-12 years) using standardized protocols. PWV was measured by an oscillometric device and implemented at follow-up. Cardiorespiratory fitness was objectively assessed by a 20m shuttle run and physical activity was assessed by use of questionnaires. To achieve my third aim, a systematic literature search through the databases PubMed, Web of Science, Embase and the Cochrane Register of Controlled Trials was conducted. Only school and population-related cross-sectional data were included. Results: Our results demonstrated that children with narrower arteriolar vessel diameters at baseline developed a higher systolic blood pressure at follow-up. Elevated blood pressure at base-line was related to narrower arteriolar vessel diameters at follow-up. Children, who achieved a higher cardiorespiratory fitness level over the 4 years reduced their weight and subsequently developed wider arteriolar vessel diameters at follow-up. An increase in sed-entary behavior from baseline to follow-up was associated with narrower arteriolar vessel diameters in children with elevated or high systolic blood pressure at baseline. The results of the meta-analysis showed that a higher BMI and blood pressure is associated with high-er PWV in children. On the other hand a higher cardiorespiratory fitness level was inversely related to PWV. Furthermore increased blood pressure and narrower arteriolar vessel di-ameters over 4 years were related to higher PWV at follow-up. In contrast, children with increased vigorous physical activity from baseline to follow-up had a lower PWV at follow-up. Conclusions: Arteriolar narrowing was predictive for accelerated blood pressure progression. In turn, a higher initial blood pressure was associated with subsequent development of microvascular impairments. The findings postulate a bivariate temporal relationship between microvascu-lar health and blood pressure. Children, who achieved an increased cardiorespiratory fit-ness performance, reduced weight and improved microvascular phenotype. A reduction in sedentary behavior by even 10 min a day can ameliorate microvascular health in children with increased systolic blood pressure. The results from the meta-analysis suggest that a higher childhood BMI and blood pressure are related to impaired arterial stiffness, whereas higher cardiorespiratory fitness performance is associated with favorable arterial stiffness. Additionally increased vigorous physical activity over 4 years seems to decelerate the pro-cess of arterial stiffness in childhood. Based on our findings, we suggest that the assess-ment of vascular biomarkers from different vascular beds can optimize cardiovascular risk stratification. Our findings also highlight the potential of promoting physical activity and fit-ness, especially in children with increased cardiovascular risk to prevent the development of small and large vessel disease.