• Glaucylara Reis Geovanini, Rui Wang, Jia Weng, Russell Tracy, Nancy S Jenny, Ary L Goldberger, Madalena D Costa, Yongmei Liu, Peter Libby, and Susan Redline.
• Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ggeovanini@hsph.harvard.edu.
• Int. J. Cardiol. 2018 Apr 15; 257: 318-323.

BackgroundObstructive sleep apnea (OSA) associates with increased risk of cardiovascular diseases (CVD). Immune abnormalities and surges in sympathetic activity accompany OSA and CVD. We hypothesized that OSA associates with leukocytosis partially by abnormalities in autonomic nervous system (ANS) function that would suggest a pathway linking OSA and CVD.MethodsParticipants from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort of individuals initially without overt CVD, underwent polysomnography and assays for white blood cells (WBC) and subsets. Heart rate (HR) and heart rate variability (HRV), indirect measurements of ANS, were obtained from overnight electrocardiography. A formal statistical mediation analysis tested the indirect effect that mean HR and HRV measures contribute to associations between OSA and leukocytosis.ResultsThe analytical sample consisted of 1298 participants (54% female), ages 54-93years, 14% with severe OSA (apnea-hypopnea-index, AHI≥30). Severe OSA associated with a higher prevalence of obesity, diabetes, and increased levels of WBC total and subsets. Neutrophil count associated with severe OSA after adjusting for confounders (p=0.017). Mean HR positively associated with OSA indices and neutrophils. A mediation analysis revealed an "indirect" effect of mean HR that explained an estimated 11% of the association between AHI and neutrophils. Overnight hypoxia also associated with neutrophil count (p=0.009), and mean HR explained 14% of the association between neutrophils and hypoxia.ConclusionsIn the MESA cohort, OSA measures associate with elevated neutrophil counts and increases in overnight mean HR. These data link innate immune dysregulation with OSA and provide a potential pathophysiologic pathway between CVD and OSA.Copyright © 2017 Elsevier B.V. All rights reserved.

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