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

Introduction: Obstructive 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. Methods: A 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. Results: Relative to untreated OSA patients, airways treated OSA patients had a 5.4-fold higher median level of MMP2 (p = 9.1×10-11), a 1.4-fold higher level of TWEAK (p = 1.8×10-7), a 1.7-fold higher level of CD163 (p = 1.4×10-6), but a 2.0-fold lower level of MMP3 (p = 7.9×10-7). 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. Discussion: We 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.