Cardiorespiratory fitness, obesity-related cardiovascular risk factors and cognitive abilities during childhood development: the EXAMIN YOUTH follow-up study

Background
Cardiovascular diseases (CVD) are one of the leading causes of death in adults worldwide. But
cardiovascular (CV) risk factors such as hypertension and obesity originate in early life.
Elevated blood pressure (BP) and body mass index (BMI) during childhood and adolescence
are associated with subclinical vascular changes. Both CV risk factors track from childhood
into adulthood and are independent predictors of CVD in later years. Narrower retinal arteriolar
(CRAE) and wider venular diameters (CRVE), along with increased pulse wave velocity
(PWV), have been linked to an increased risk of CV risk and mortality in adults.
Objectives
The objectives of this PhD project were: 1) to analyze the association between CV risk factors
with vascular health, 2) to investigate the association between initial vascular health with
development of BP, and 3) to examine the association between cardiorespiratory fitness (CRF)
with CV risk factors, vascular health, and cognitive abilities at follow-up.
Methods
This PhD project is based on the EXAMIN Youth Study. This prospective school-based cohort
study encompassed an initial assessment of 1171 pre-pubertal children aged six to eight years.
Children were screened for anthropometry, BP, CRF, vascular health, and cognition. Four years
later, at ages ten to twelve, 749 of the same children were reexamined utilizing the same
standardized methods. Blood pressure was measured using a validated BP device for children
and adolescents, CRF was assessed using the 20m shuttle run test, and vascular health was
evaluated through static retinal vessel analysis and an oscillometric device for determining
PWV. Skin autofluorescence was used to determine advanced glycation end products (sAGEs)
levels and cognitive abilities were assessed using the Flanker Task.
Results
Our results show that children with initial increased BP had developed narrower CRAE and
higher PWV four years later. Vice versa, we also found that children with initial narrower
CRAE and higher PWV had developed significantly higher BP after four years. Higher CRF at
baseline was associated with favorable developments in BP, BMI, and vascular health.Furthermore, children with higher initial CRF displayed significantly lower levels of sAGEs
and better performance in the Flanker task at follow-up.
Conclusion
Retinal arteriolar diameter and PWV independently predict progression of childhood BP, while
initial BP is linked with development of micro- and macrovascular impairments, describing a
bivariate temporal relationship between vascular health and BP. Both diagnostic tool as a
standalone or in conjunction have the potential to improve CV risk stratification. We identified
CRF as a key modulator for the risk trajectories of BMI, BP and microvascular health in
children. Furthermore, higher CRF may help mitigate the formation of sAGEs and improve
cognitive abilities. Childhood present a window of opportunity for initiation of primary
prevention strategies, targeting at enhancing PA and CRF to contribute holistically to both CV
health and cognitive advancement.