Cardiovascular disease often develops during childhood, but the determinants of vascular health and disease in young children remain unclear. The study aimed to investigate the association of obesity and hypertension, as well as physical fitness with retinal microvascular health and large artery stiffness, in children. In this cross-sectional study, 1171 primary school children (aged 7.2±0.4 years) were screened for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters, pulse wave velocity (PWV), body mass index, blood pressure (BP), and cardiorespiratory fitness by standardized procedures for children. BP was categorized according to the reference values of the population-based German KiGGS study (Kinder- und Jugendgesundheitssurvey [Children- and Adolescents Health Survey]) and the American Academy of Pediatrics guidelines. Overweight (mean [95% CI]: CRAE, 200.5 [197.9–203.2] µm; CRVE, 231.4 [228.6–234.2] µm; PWV, 4.46 [4.41–4.52] m/s) and obese children (CRAE, 200.5 [196.4–204.7] µm; CRVE, 233.3 [229.0–237.7] µm; PWV, 4.51 [4.43–4.60] m/s) had narrower CRAE, wider CRVE, and higher PWV compared with normal-weight children (CRAE: 203.3 [202.5–204.1] µm, P <0.001; CRVE: 230.1 [229.1–230.9] µm, P =0.07; PWV: 4.33 [4.31–4.35] m/s, P <0.001). Children with high-normal BP (CRAE, 202.5 [200.0–205.0] µm; PWV, 4.44 [4.39–4.49] m/s) and BP in the hypertensive range (CRAE, 198.8 [196.7–201.0] µm; PWV, 4.56 [4.51–4.60] m/s) showed narrower CRAE, as well as higher PWV, compared with normotensive peers (CRAE: 203.7 [202.9–204.6] µm, P <0.001; PWV: 4.30 [4.28–4.32] m/s, P <0.001). With each unit increase of body mass index and systolic BP, CRAE decreased and PWV increased significantly. Children with the highest cardiorespiratory fitness had wider CRAE, narrower CRVE, and lower PWV compared with least fit children. Childhood obesity and hypertension, even at preclinical stages, are associated with microvascular and macrovascular impairments in young children. Primary prevention programs targeting physical activity behavior may have the potential to counteract development of small and large vessel disease early in life. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02853747.

CONTEXT: Retinal vessel imaging is a noninvasive diagnostic tool used to evaluate cardiovascular risk. Childhood obesity and elevated blood pressure (BP) are associated with retinal microvascular alterations. OBJECTIVE: To systematically review and meta-analyze associations between obesity, BP, and physical activity with retinal vessel diameters in children. DATA SOURCES: We conducted a literature search through the databases of PubMed, Embase, Ovid, Web of Science, and the Cochrane Register of Controlled Trials. STUDY SELECTION: School- and population-based cross-sectional data. DATA EXTRACTION: General information, study design, participants, exposure, and outcomes. RESULTS: A total of 1751 studies were found, and 30 full-text articles were analyzed for eligibility. Twenty-two articles (18 865 children and adolescents) were used for further assessment and reflection. Eleven articles were finally included in the meta-analysis. We found that a higher BMI is associated with narrower retinal arteriolar (pooled estimate effect size −0.37 [95% confidence interval (CI): −0.50 to −0.24]) and wider venular diameters (0.35 [95% CI: 0.07 to 0.63]). Systolic and diastolic BP are associated with retinal arteriolar narrowing (systolic BP: −0.63 [95% CI: −0.92 to −0.34]; diastolic BP: −0.60 [95% CI −0.95 to −0.25]). Increased physical activity and fitness are associated with favorable retinal vessel diameters. LIMITATIONS: Long-term studies are needed to substantiate the prognostic relevance of retinal vessel diameters for cardiovascular risk in children. CONCLUSIONS: Our results indicate that childhood obesity, BP, and physical inactivity are associated with retinal microvascular abnormalities. Retinal vessel diameters seem to be sensitive microvascular biomarkers for cardiovascular risk stratification in children.

Background: Cardiovascular disease (CVD) remains to be one of the most frequent causes of death worldwide. Cardiovascular (CV) risk factors such as hypertension and obesity often manifest in childhood. The study examines the associations of blood pressure, body mass index and physical activity with cardiopulmonary, metabolic, and psychosocial health of children in a systems physiology approach. Methods/Design: This cross-sectional study will be performed in a cohort of 6 to 8 year old school children (n = 1000). As a measure of vascular health, retinal microvascular diameters and large artery pulse wave velocity will be examined. Anthropometric parameters, such as weight, height, body mass index, and blood pressure will be assessed according to standardized protocols for children. Physical fitness and activity will be measured by a 20 m shuttle run, a 20 m sprint and a proxy-reported questionnaire on lifestyle behavior. Spirometry, assessment of heart rate variability and skin advanced glycation end products as well as a flanker test will be performed to determine systemic end organ alterations. Discussion: The study offers a unique integrative primary prevention concept that aims to set the grounds for a healthy and active lifestyle approach during childhood. It will help optimize CV risk stratification to identify children at risk of disease progression later in life. The study will demonstrate the importance of specific CV screening programs in children to reduce the growing burden of CV disease in adulthood. Prospective follow-up studies will have to prove the efficacy of primary prevention programs in children to achieve healthier aging as a long-term goal.