Shared early origins of cardiovascular and respiratory development

Non-communicable diseases are often studied separately, but there is growing awareness that these diseases are closely linked. In this thesis we focused on two non-communicable diseases, cardiovascular and respiratory diseases, which form a large contribution of the total morbidity and mortality of chronic diseases. Epidemiological studies have shown that these diseases often co-exist within the same patient, independent of shared risk factors like smoking. To gain more insights into shared risks factors and the origin of the interaction between the respiratory and cardiovascular system, we performed our research in childhood, as increasing evidence suggests that these chronic diseases have their origins in early life. Adverse exposures in utero and childhood could lead to structural or functional changes in organ systems and due to tracking of these changes, it could make them more susceptible for cardiovascular or respiratory diseases in later life. In the first part of this thesis we explored whether interactions of the cardiovascular and respiratory system are already present in early life. We have shown that associations between the cardiovascular and respiratory system, as described in adulthood, are not present in healthy children. In healthy children a more favourable lung function was associated with a higher blood pressure and increased arterial stiffness, which is largely explained by anthropometry. In contrast to evidence from healthy children, in children with a disease, which is characterized by severe pulmonary problems, cystic fibrosis, we found evidence for subclinical cardiac dysfunction and increased arterial stiffness. In the second part of this thesis we focussed on determinants, which could affect both the cardiovascular and respiratory development in early life. Weight is an important modifiable risk factor for both respiratory and cardiovascular disease in adulthood. We observed a trend of reduced systolic cardiac function with increasing maternal BMI. Higher maternal weight is also associated with increased risk of wheezing illnesses in early life. The associations of maternal BMI and wheezing in the first year of life could partially be explained by neonatal lung function. At the age of 5 years, associations with consultations and prescriptions for respiratory illnesses are also present, but these could not be explained by a reduced lung function. The mechanisms underlying these associations remain unclear. Several studies have proposed that leptin, a hormone primarily produced by adipocytes, could play a role in these associations. In our cross-sectional study among 8-year-old children, we observed an association between higher leptin levels and impaired lung function. In the last part of this thesis, we studied new non-invasive measurement devices, which have the potential to evaluate cardiovascular and respiratory risk in youth. Our results suggest that it is important for future research to study the cardiovascular and respiratory system in parallel. Especially in our current health care system, in which physicians are increasingly trained to become a specialist in a particular area, it is important to gain more awareness among physicians of the shared origins and parallel development of the cardiovascular and respiratory system.