Patients with Obstructive Sleep Apnea Have Altered Levels of Four Cytokines Associated with Cardiovascular and Kidney Disease, but Near Normal Levels with Airways Therapy.

Abstract

IntroductionObstructive sleep apnea (OSA) results in chronic intermittent hypoxia leading to systemic inflammation, increases in pro-inflammatory cytokines TNF-Alpha and IL-6, and increased risk for a number of life threatening medical disorders such as cardiovascular and kidney disease.MethodsA BioPlex Array was used to examined the serum levels of four cytokines also expressed in endothelial cells and/or macrophages and associated with cardiovascular and kidney disease risk.ResultsRelative to untreated OSA patients, airways treated OSA patients had a 5.4-fold higher median level of MMP2 (p = 9.1x10−11), a 1.4-fold higher level of TWEAK (p = 1.8x10−7), a 1.7-fold higher level of CD163 (p = 1.4x10−6), but a 2.0-fold lower level of MMP3 (p = 7.9x10−7). Airway treatment resulted in levels more similar to or indistinguishable from control subjects. Both t-SNE or UMAP analysis of the global structure of these multi-dimensional data revealed two data clusters, one populated primarily with data for controls and most airways treated OSA patients and a second populated primarily with data for OSA patients.DiscussionWe discuss a concept in which the aberrant levels of these cytokines in untreated OSA patients may represent a chronic response after years of experiencing intermittent nightly hypoxia, which attenuated the acute response to hypoxia. A balanced therapeutic correction of the aberrant levels of these cytokines may limit the progression of CVD and kidney disease in OSA patients.