The endothelin-1 system among high-risk pregnant women with obstructive sleep apnea.

Abstract

Obstructive sleep apnea is associated with gestational hypertension. Elevated endothelin-1 is a proposed factor in the pathogenesis of gestational hypertension. However, the association between endothelin-1 and obstructive sleep apnea complicating pregnancy is unknown. In a prospective cohort of 60 pregnant patients with obesity but without confounding comorbid conditions (i.e. cardiac/pulmonary disease), plasma and placental samples were collected at delivery in 30 women with obstructive sleep apnea and 30 without. Endothelin-1 concentrations were evaluated using Western blot, quantitative real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Multivariable analyses were conducted comparing endothelin-1 levels between obstructive sleep apnea and non-obstructive sleep apnea groups. There was no significant difference in band intensity or quantitative densitometric evaluation when comparing obstructive sleep apnea-positive and -negative groups (p = 0.42). mRNA expression of endothelin-1 did not differ in placental tissues between groups (p = 0.73). There was no significant difference in endothelin-1 median plasma concentrations between groups (p = 0.95). However, there was a significant sixfold increase in the rate of endothelin-1 elevation > 90th percentile (adjusted odds ratio 5.9, 95% confidence interval 1.05-32.7) after adjusting for confounding by body mass index. Additionally, lower pre-pregnancy body mass index (< 32 kg m^-2) was associated with plasma endothelin-1 > 11 at delivery (p < 0.01), and class 3 obesity appeared protective for having elevated plasma endothelin-1 > 90th percentile (p = 0.03). Overall, in this prospective cohort of high-risk pregnant patients, obstructive sleep apnea was associated with an increased rate of markedly elevated (> 90th percentile) endothelin-1 plasma levels. Lower pre-pregnancy body mass index among patients with obesity was associated with elevated endothelin-1 plasma levels. Obstructive sleep apnea screening questionnaires focused on high body mass index may result in underestimated risk.