TREM-1 and pentraxin-3 plasma levels and their association with obstructive sleep apnea, obesity, and endothelial function in children

Background: Obstructive sleep apnea (OSA) is a common health problem in children and increases the risk of cardiovascular disease (CVD). Triggering receptor expressed on myeloid cells-1 (TREM-1) plays an important role in innate immunity and amplifies inflammatory responses. Pen-traxin- 3 is predominantly released from macrophages and vascular endothelial cells, plays an important role in atherogenesis, and has emerged as a biomarker of CVD risk. Thus, we hypothesized that plasma TREM-1 and pentraxin-3 levels would be elevated in children with OSA. Methods: One hundred six children (mean age: 8.3 ± 1.6 y) were included after they underwent overnight polysomnographic evaluation and a fasting blood sample was drawn the morning after the sleep study. Endothelial function was assessed with a modified hyperemic test after cuff-induced occlusion of the brachial artery. Plasma TREM-1 and pentraxin-3 levels were assayed using commercial enzyme-linked immunosorbent assay kits. Circulating microparticles (MPs) were assessed using flow cytometry after staining with cell-specific antibodies. Results: Children with OSA had significantly higher TREM-1 and pentraxin-3 levels (versus controls: P < 0.01, P < 0.05, respectively). Plasma TREM-1 was significantly correlated with both body mass index (BMI)-z score and the obstructive apnea-hypopnea index (AHI) in univariate models. Pentraxin-3 levels were inversely correlated with BMI-z score (r = -0.245, P < 0.01), and positively associated with endothelial MPs and platelet MPs (r = 0.230, P < 0.01 and r = 0.302, P < 0.01). Both plasma TREM-1 and pentraxin-3 levels were independently associated with AHI in multivariate models after controlling for age, sex, race, and BMI-z score (P < 0.001 for TREM-1 and P < 0.001 for pentraxin-3). However, no significant associations emerged between TREM-1, pentraxin-3, and endothelial function. Conclusions: Plasma TREM-1 and pentraxin-3 levels are elevated in pediatric OSA, and may play a role in modulating the degree of systemic inflammation. The short-term and long-term significance of elevated TREM-1 and pentraxin-3 in OSA-induced end-organ morbidity remains to be defined.