Sex-specific associations between daytime sleepiness, chronic diseases and mortality in obstructive sleep apnea

Naima Covassin; Dongmei Lu; Erik K St Louis; Anwar A Chahal; Phillip J Schulte; Meghna P Mansukhani; Jiang Xie; Melissa C Lipford; Nanfang Li; Kannan Ramar; Sean M Caples; Peter C Gay; Eric J Olson; Michael H Silber; Jingen Li; Virend K Somers

doi:10.3389/fnins.2023.1210206

Sex-specific associations between daytime sleepiness, chronic diseases and mortality in obstructive sleep apnea

Front Neurosci. 2023 Jun 23:17:1210206. doi: 10.3389/fnins.2023.1210206. eCollection 2023.

Authors

Naima Covassin¹, Dongmei Lu^{1

2}, Erik K St Louis^{3

4

5}, Anwar A Chahal¹, Phillip J Schulte⁶, Meghna P Mansukhani^{3

5

7}, Jiang Xie⁸, Melissa C Lipford^{3

4

5}, Nanfang Li⁹, Kannan Ramar^{3

5}, Sean M Caples^{3

5}, Peter C Gay^{3

5}, Eric J Olson^{3

5}, Michael H Silber^{4

5}, Jingen Li^{1

10}, Virend K Somers¹

Affiliations

¹ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States.
² Department of Respiratory and Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
³ Department of Medicine, Mayo Clinic, Rochester, MN, United States.
⁴ Department of Neurology, Mayo Clinic, Rochester, MN, United States.
⁵ Center for Sleep Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States.
⁶ Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States.
⁷ Department of Family Medicine, Mayo Clinic, Rochester, MN, United States.
⁸ Department of Respiratory and Critical Medicine of Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
⁹ Center of Hypertension of the People's Hospital of Xinjiang Uygur Autonomous Region, The Center of Diagnosis, Treatment and Research of Hypertension in Xinjiang Hypertension Institute of Xinjiang, Urumqi, China.
¹⁰ Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Abstract

Objective: Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA) and has been linked to adverse outcomes, albeit inconsistently. Furthermore, whether the prognostic impact of EDS differs as a function of sex is unclear. We aimed to assess the associations between EDS and chronic diseases and mortality in men and women with OSA.

Methods: Newly-diagnosed adult OSA patients who underwent sleep evaluation at Mayo Clinic between November 2009 and April 2017 and completed the Epworth Sleepiness Scale (ESS) for assessment of perceived sleepiness (N = 14,823) were included. Multivariable-adjusted regression models were used to investigate the relationships between sleepiness, with ESS modeled as a binary (ESS > 10) and as a continuous variable, and chronic diseases and all-cause mortality.

Results: In cross-sectional analysis, ESS > 10 was independently associated with lower risk of hypertension in male OSA patients (odds ratio [OR], 95% confidence interval [CI]: 0.76, 0.69-0.83) and with higher risk of diabetes mellitus in both OSA men (OR, 1.17, 95% CI 1.05-1.31) and women (OR 1.26, 95% CI 1.10-1.45). Sex-specific curvilinear relations between ESS score and depression and cancer were noted. After a median 6.2 (4.5-8.1) years of follow-up, the hazard ratio for all-cause death in OSA women with ESS > 10 compared to those with ESS ≤ 10 was 1.24 (95% CI 1.05-1.47), after adjusting for demographics, sleep characteristics and comorbidities at baseline. In men, sleepiness was not associated with mortality.

Conclusion: The implications of EDS for morbidity and mortality risk in OSA are sex-dependent, with hypersomnolence being independently associated with greater vulnerability to premature death only in female patients. Efforts to mitigate mortality risk and restore daytime vigilance in women with OSA should be prioritized.

Keywords: chronic disease; mortality; obstructive sleep apnea; sex differences; sleepiness.