Abstract

Cardiovascular disease is the leading cause of mortality, morbidity and hospitalization worldwide, and is a major public health problem in adult populations. The developmental‐ origins hypothesis suggests that cardiovascular disease might originate from early life. Adverse exposures, acting in different periods of fetal and early postnatal life might lead to permanent adaptations in the cardiovascular system, which are beneficial for short term survival, but increase the susceptibility of cardiovascular disease in later life. This hypothesis is supported by experimental studies in animals showing that growth restriction in early life leads to developmental adaptations in cardiovascular structure and function, which leads to an increase in vulnerability to cardiovascular disease. In line with this hypothesis, large observational studies in humans have shown that fetal growth restriction and rapid infant growth are associated with cardiac and vascular changes in childhood and an increased risk of cardiovascular disease in adulthood. Also, observational studies using more detailed adverse exposures during fetal life suggested that, among other maternal factors, higher maternal blood pressure during pregnancy and the presence of gestational hypertensive disorders are associated with increased risks of fetal growth restriction and a higher blood pressure in childhood. Postnatally, suboptimal infant nutrition and increased adiposity levels throughout childhood are also shown to be associated with the development of cardiovascular disease in later life. Thus, previous research suggests that a restricted nutritional in utero environment and abundant postnatal environment may lead to cardiovascular disease in later life. The mechanisms relating adverse maternal, fetal and infant factors with an increased risk of cardiovascular diseases in later life are not fully understood. Early microvasculature adaptations, in response to adverse exposures in early life, might be part of the underlying mechanisms in the development of cardiovascular disease. Animal studies have shown that alterations in the microvascular structure and, hence, increased peripheral resistance, precede the development of hypertension. In humans, the microvasculature can non‐invasively be assessed by using retinal vascular imaging. Several longitudinal studies among adults have shown that retinal arteriolar narrowing, likely indicative of increased peripheral vascular resistance, is associated with increased risks of hypertension and stroke in later life, whereas wider retinal venular caliber is associated with an increased risk of metabolic syndrome and inflammation. Thus, these studies suggest that alterations in retinal vessel calibers can be used as early markers of cardio‐metabolic disease risk. In summary, cardiovascular disease might already originate in early life. Identifying risk factors and potential mechanisms influencing the development of cardiovascular diseases from early life onwards, is important for future preventive strategies that aim to improve cardiovascular health throughout the life course. Therefore, studies presented in this thesis were designed to identify maternal, fetal and infant factors associated with microvasculature alterations and cardiovascular health outcomes in childhood.

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V.W.V. Jaddoe (Vincent) , E.A.P. Steegers (Eric)
The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands. Organization for Health Research and Development (ZonMw), the Nether‐lands Organisation for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families. Research leading to the results described in this thesis has received funding from the European Union's Seventh Framework Programme (FP7/2007‐2013), project EarlyNutrition under grant agreement n°289346. The work presented in this thesis was conducted in the Generation R Study Group, in close collaboration with the Departments of Epidemiology, Pediatrics, Obstetrics and Gynaecology and Ophtalmology, Erasmus Medical Center, Rotterdam, the Netherlands. Publication of this thesis was kindly supported by the Department of Epidemiology, the Generation R Study Group and the Erasmus University Rotterdam. Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. Additional financial support was kindly provided by Danone Nutricia Research and AbbVie B.V.
hdl.handle.net/1765/78277
Erasmus MC: University Medical Center Rotterdam

Gishti, O. (2015, June 19). Microvasculature and Cardiovascular Risk Factors in Childhood. Retrieved from http://hdl.handle.net/1765/78277