Endothelial Dysfunction in Children With Obstructive Sleep Apnea Is Associated With Elevated Lipoprotein-Associated Phospholipase A2 Plasma Activity Levels

Abstract

Background: Obstructive sleep apnea (OSA) is a highly prevalent condition, especially in obese children, and has been associated with increased risk for endothelial dysfunction and dislipidemia, which are precursors of atherosclerosis. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is recognized as an independent risk factor for cardiovascular risk and atheromatous plaque activity. We hypothesized that Lp-PLA2 levels would be elevated in children with OSA, particularly among obese children who also manifest evidence of endothelial dysfunction.

Methods and results: One hundred sixty children (mean age 7.1±2.3 years), either nonobese with (n=40) and without OSA (n=40) or obese with (n=40) and without OSA (n=40) underwent overnight polysomnographic and postocclusive reperfusion evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, Lp-PLA2 plasma activity was assessed using a commercial kit. Obese children and OSA children had significantly elevated plasma Lp-PLA2 activity levels compared to controls. Furthermore, when both obesity and OSA were concurrently present or when endothelial function was present, Lp-PLA2 activity was higher. Treatment of OSA by adenotonsillectomy resulted in reductions of Lp-PLA2 activity (n=37; P<0.001).

Conclusions: Lp-PLA2 plasma activity is increased in pediatric OSA and obesity, particularly when endothelial dysfunction is present, and exhibits decreases on OSA treatment. The short-term and long-term significance of these findings in relation to cardiovascular risk remain undefined.

Keywords: atherosclerosis; cholesterol; endothelial dysfunction; sleep apnea.

Figure 1

Scatterplots of Lp‐PLA2 plasma activity levels, BMI z‐score, obstructive apnea hypopnea index (AHI), and T_max in children with and without obesity or OSA. A, T_max vs BMI z‐score: r=0.319, P<0.001. B, Lp‐PLA2 vs BMI z‐score: r=0.350, P<0.001. C, T_max vs AHI: r=0.489, P<0.001. D, Lp‐PLA2 vs AHI: r=0.483, P<0.001. E, AHI vs BMI z‐score, not significant. F, Lp‐PLA2 vs T_max: r=0.837, P<0.001. Actual values rather than log‐transformed values were used in the linear fitting functions shown. AHI is displayed as log scale (C and D). Dotted lines indicate the cutoff used to define endothelial dysfunction, ie, T_max >45 seconds. AHI indicates apnea hypopnea index; BMI, body mass index; Lp‐PLA ₂, lipoprotein‐associated phospholipase A2; T_max, time to peak reperfusion; TST, total sleep time.

Figure 2

Individual changes in AHI (A), Lp‐PLA2 (B) and T_max (C) before and after adenotonsillectomy. AHI indicates apnea hypopnea index; Lp‐PLA2, lipoprotein‐associated phospholipase A2; T_max, time to peak reperfusion.