Multicenter Study

. 2018 Apr 15:257:318-323.

doi: 10.1016/j.ijcard.2017.10.121.

Elevations in neutrophils with obstructive sleep apnea: The Multi-Ethnic Study of Atherosclerosis (MESA)

Affiliations

¹ 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.
² Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jweng2@bwh.harvard.edu.
⁴ Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT, USA. Electronic address: russell.tracy@med.uvm.edu.
⁵ Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA. Electronic address: nancy.jenny@med.uvm.edu.
⁶ Margret and H.A. Rey Institute for Nonlinear Dynamics in Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: agoldber@bidmc.harvard.edu.
⁷ Margret and H.A. Rey Institute for Nonlinear Dynamics in Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: mcosta3@bidmc.harvard.edu.
⁸ Wake Forest University School of Medicine, Department of Epidemiology and Prevention, Division of Public Health Sciences, Winston-Salem, NC, USA. Electronic address: yoliu@wakehealth.edu.
⁹ Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: plibby@bwh.harvard.edu.
¹⁰ Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: sredline1@rics.bwh.harvard.edu.

PMID: 29506719
PMCID: PMC5842816
DOI: 10.1016/j.ijcard.2017.10.121

Multicenter Study

Elevations in neutrophils with obstructive sleep apnea: The Multi-Ethnic Study of Atherosclerosis (MESA)

Glaucylara Reis Geovanini et al. Int J Cardiol. 2018.

. 2018 Apr 15:257:318-323.

doi: 10.1016/j.ijcard.2017.10.121.

Authors

Affiliations

¹ 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.
² Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jweng2@bwh.harvard.edu.
⁴ Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT, USA. Electronic address: russell.tracy@med.uvm.edu.
⁵ Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA. Electronic address: nancy.jenny@med.uvm.edu.
⁶ Margret and H.A. Rey Institute for Nonlinear Dynamics in Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: agoldber@bidmc.harvard.edu.
⁷ Margret and H.A. Rey Institute for Nonlinear Dynamics in Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: mcosta3@bidmc.harvard.edu.
⁸ Wake Forest University School of Medicine, Department of Epidemiology and Prevention, Division of Public Health Sciences, Winston-Salem, NC, USA. Electronic address: yoliu@wakehealth.edu.
⁹ Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: plibby@bwh.harvard.edu.
¹⁰ Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: sredline1@rics.bwh.harvard.edu.

PMID: 29506719
PMCID: PMC5842816
DOI: 10.1016/j.ijcard.2017.10.121

Abstract

Background: Obstructive 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.

Methods: Participants 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.

Results: The 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.

Conclusions: In 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.

Keywords: Granulocytes; Heart rate; Hypoxia; Neutrophils; Polymorphonuclearleukocytes; Sleep apnea.

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Conflict of interest statement

The authors report no relationships that could be construed as a conflict of interest.

Figures

**Figure 1**
Schematic Depiction Showing how mean HR Mediates the Relationship between OSA measures and Neutrophil counts.

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Elevations in neutrophils with obstructive sleep apnea: The Multi-Ethnic Study of Atherosclerosis (MESA)

Affiliations

Elevations in neutrophils with obstructive sleep apnea: The Multi-Ethnic Study of Atherosclerosis (MESA)

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