Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Author:

Qin Hua1,Keenan Brendan T2ORCID,Mazzotti Diego R3,Vaquerizo-Villar Fernando45ORCID,Kraemer Jan F6,Wessel Niels6,Tufik Sergio7,Bittencourt Lia7,Cistulli Peter A89ORCID,de Chazal Philip8,Sutherland Kate89ORCID,Singh Bhajan1011,Pack Allan I2ORCID,Chen Ning-Hung12,Fietze Ingo1,Gislason Thorarinn1314ORCID,Holfinger Steven15,Magalang Ulysses J15,Penzel Thomas1ORCID

Affiliation:

1. Interdisciplinary Center of Sleep Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany

2. Division of Sleep Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

3. Division of Medical Informatics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS

4. Biomedical Engineering Group, Universidad de Valladolid, Valladolid, Spain

5. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain

6. Department of Physics, Humboldt Universität zu Berlin, Berlin, Germany

7. Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

8. Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney Sydney, Australia

9. Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, Australia

10. West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

11. School of Human Sciences, University of Western Australia, Crawley, WA, Australia

12. Division of Pulmonary, Critical Care Medicine and Sleep Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan

13. Department of Sleep Medicine, Landspitali University Hospital, Reykjavik, Iceland

14. Medical Faculty, University of Iceland, Reykjavik, Iceland

15. Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH

Abstract

Abstract Study Objectives Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample. Methods 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates. Results Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009). Conclusions Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients. Clinical Trial Information:  A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966

Funder

National Institutes of Health

American Academy of Sleep Medicine Foundation

Ministerio de Educación

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Neurology (clinical)

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