Circulating adropin concentrations in pediatric obstructive sleep apnea: potential relevance to endothelial function

Abstract

Objective: To test the hypothesis that concentrations of adropin, a recently discovered peptide that displays important metabolic and cardiovascular functions, are lower in obstructive sleep apnea (OSA), especially when associated with endothelial dysfunction.

Study design: Age-, sex-, and ethnicity-matched children (mean age, 7.2 ± 1.4 years) were included into 1 of 3 groups based on the presence of OSA in an overnight sleep study, and on the time to postocclusive maximal reperfusion (Tmax >45 seconds) with a modified hyperemic test. Plasma adropin concentrations were assayed using a commercial enzyme-linked immunosorbent assay kit.

Results: Among controls, the mean morning adropin concentration was 7.4 ng/mL (95% CI, 5.2-16.3 ng/mL). Children with OSA and abnormal endothelial function (EF) (OSA(+)/EF(+) group) had significantly lower adropin concentrations (2.7 ± 1.1 ng/mL; n = 35) compared with matched controls (7.6 ± 1.4 ng/mL; n = 35; P < .001) and children with OSA and normal EF (OSA(+)/EF(-) group; 5.8 ± 1.5 ng/mL; n = 47; P < .001). A plasma adropin concentration <4.2 ng/mL reliably predicted EF status, but individual adropin concentrations were not significantly correlated with age, body mass index z-score, obstructive apnea-hypopnea index, or nadir oxygen saturation. Mean adropin concentration measured after adenotonsillectomy in a subset of children with OSA (n = 22) showed an increase in the OSA(+)/EF(+) group (from 2.5 ± 1.4 to 6.4 ± 1.9 ng/mL; n = 14; P < .01), but essentially no change in the OSA(+)EF(-) group (from 5.7 ± 1.3 to 6.4 ± 1.1 ng/mL; n = 8; P > .05).

Conclusion: Plasma adropin concentrations are reduced in pediatric OSA when endothelial dysfunction is present, and return to within normal values after adenotonsillectomy. Assessment of circulating adropin concentrations may provide a reliable indicator of vascular injury in the context of OSA in children.

Keywords: AHI; Apnea-hypopnea index; BMI; Body mass index; EF; Endothelial function; Endothelial nitric oxide synthase; OSA; Obstructive sleep apnea; Oxygen saturation; SpO(2); T(max); TST; Time to postocclusive maximal reperfusion; Total sleep time; eNOS.

Figure 1

Drop plots showing individual changes in adropin levels before (closed symbols) and after adenotonsillectomy (open symbols) in 14 children with OSA and endothelial dysfunction (square symbols) and in 8 children with OSA and no evidence of endothelial dysfunction (circle symbols).

Figure 2

Receiver operator curves using adropin plasma concentration cut-off value of <4.2 ng/ml for prediction of endothelial dysfunction in children with OSA.