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Nocturnal Arrhythmias Across a Spectrum of Obstructive and Central Sleep-Disordered Breathing in Older Men: Outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study
Open accessAbstract
BACKGROUND: Rates of cardiac arrhythmias increase with age and may be associated with clinically significant morbidity. We studied the association between sleep-disordered breathing (SDB) with nocturnal atrial fibrillation or flutter (AF) and complex ventricular ectopy (CVE) in older men. METHODS: A total of 2911 participants in the Outcomes of Sleep Disorders in Older Men Study underwent unattended polysomnography. Nocturnal AF and CVE were ascertained by electrocardiogram-specific analysis of the polysomnographic data. Exposures were (1) SDB defined by respiratory disturbance index (RDI) quartile (a major index including all apneas and hypopneas), and ancillary definitions incorporating (2) obstructive events, obstructive sleep apnea (OSA; Obstructive Apnea Hypopnea Index quartile), or (3) central events, central sleep apnea (CSA; Central Apnea Index category), and (4) hypoxia (percentage of sleep time with <90% arterial oxygen percent saturation). Multivariable logistic regression analyses were performed. RESULTS: An increasing RDI quartile was associated with increased odds of AF and CVE (P values for trend, .01 and <.001, respectively). The highest RDI quartile was associated with increased odds of AF (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.19-3.89) and CVE (OR, 1.43; 95% CI, 1.12-1.82) compared with the lowest quartile. An increasing OSA quartile was significantly associated with increasing CVE (P value for trend, .01) but not AF. Central sleep apnea was more strongly associated with AF (OR, 2.69; 95% CI, 1.61-4.47) than CVE (OR, 1.27; 95% CI, 0.97-1.66). Hypoxia level was associated with CVE (P value for trend, <.001); those in the highest hypoxia category had an increased odds of CVE (OR, 1.62; 95% CI, 1.23-2.14) compared with the lowest quartile. CONCLUSIONS: In this large cohort of older men, increasing severity of SDB was associated with a progressive increase in odds of AF and CVE. When SDB was characterized according to central or obstructive subtypes, CVE was associated most strongly with OSA and hypoxia, whereas AF was most strongly associated with CSA, suggesting that different sleep-related stresses may contribute to atrial and ventricular arrhythmogenesis in older men.
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“while in the Outcomes of Sleep Disorders in Older Men Study there was a dose-dependent association of OSA with prevalent AF.720”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [720]
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Self-citationPrediction of Ventricular Tachycardia One Hour before Occurrence Using Artificial Neural Networks
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“…of SDB with prevalent AF is unclear because previous population-based studies focused only on nocturnal AF as determined during the sleep study 11 12 and the above mentioned clinic-based study failed to show any signi fi cant association between AF and apnoea hypopnoea index (AHI), the most…”
BackgroundSelf-citationObstructive sleep apnea syndrome: natural history, diagnosis, and emerging treatment options
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“and hypoxia, whereas atrial fibrillation was most strongly associated with central sleep apnea.(242)”
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Self-citationCentral Sleep-disordered Breathing Predicts Incident Atrial Fibrillation in Older Men
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“9,16,17 In addition, our study adds to the current understanding of SDB and arrhythmias in several important ways.”
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Obstructive Sleep Apnea and Atrial Fibrillation
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Obstructive Sleep Apnea and Cognition in Parkinson's disease
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“As discussed above, surges of sympathetic and parasympathetic activity are induced by OSA.42,47 The former induces a large and extended Ca++ transient and the latter markedly shortens the action potential duration and refractory period, leading to triggered firing of the PV and atrium, thereby inducing AF.60 Atrial st…”
BackgroundInfluentialSleep apnea and risk of vertigo: A nationwide population‐based cohort study
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Self-citationThe Relationship between Obstructive Sleep Apnea and Atrial Fibrillation: A Complex Interplay
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“It remains unclear whether the association is based on mutual risk factors, such as obesity and hypertension, or whether OSA is an independent risk factor and causative in nature.”
BackgroundInfluentialAssociations between sleep conditions and body composition states: results of the EPISONO study
Piovezan, R. D., Hirotsu, C., Moizinho, R., Souza, H. D. S., D’Almeida, V., Tufik, S., & Poyares, D. R. (2019) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12445 · Cited by 61
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Cardiac Arrhythmias in Obstructive Sleep Apnea (from the Akershus Sleep Apnea Project)
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“All arrhythmias were coded as dichotomous outcomes (present or absent) according to acknowledged cutoffs applied in previous communitybased studies.(4,5) Ventricular premature complexes were tudy.”
MethodSleep, sleep apnea and atrial fibrillation: Questions and answers
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Obstructive Sleep Apnea and Aging Effects on Macrovascular and Microcirculatory Function
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Research Opportunities in Autonomic Neural Mechanisms of Cardiopulmonary Regulation
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“Importantly, the presence of concomitant diseases such as obstructive sleep apnea (OSA) and central sleep apnea (CSA) may increase the prevalence, incidence, and recurrence of AF (91-98).”
BackgroundSelf-citationSleep apnea, daytime somnolence, and idiopathic dizziness—A novel association
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“This transient increase in atrial arrhythmogenesis may depend on nightly variability in SDB-severity and contribute to the temporal relationship between increased occurrence of arrhythmias during or after sleep apnea episodes [37–40].”
BackgroundVascular Dysfunction in Obstructive Sleep Apnea and Type 2 Diabetes Mellitus
Yim‐Yeh, S., Rahangdale, S., Nguyen, A. T. D., Stevenson, K. E., Novack, V., Veves, A., & Malhotra, A. (2010) · Obesity · doi:10.1038/oby.2010.116 · Cited by 52
“Recently, OSA has been associated with cardiovascular sequelae such as hypertension (13), stroke (14), ischemic heart disease, and cardiac arrhythmias (15).”
BackgroundTreatment of Cheyne‐Stokes Respiration Reduces Arrhythmic Events in Chronic Heart Failure
Bitter, T., Gutleben, K., Nölker, G., Westerheide, N., Prinz, C., Dimitriadis, Z., Horstkotte, D., Vogt, J., & Oldenburg, O. (2013) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12197 · Cited by 49
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“The Sleep Heart Health Study revealed an association between severe sleep-disordered breathing and arrhythmias, such as atrial fibrillation, non-sustained ventricular tachycardia and complex ventricular ectopy, which often occur during the nocturnal hours [17]; in addition, the incidence of atrial fibrillation and ven…”
Sanchez, A. M., Germany, R. E., Lozier, M. R., Schweitzer, M. D., Kosseifi, S. G., & Anand, R. G. (2020) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2020.100527 · Cited by 42
“Although studies are lacking on treatment options, many have identified a relationship between CSA and AF [7,9,20,22,25,38,57,84].”
BackgroundObesity as a risk factor for cardiac arrhythmias
Patel, K. H. K., Reddy, R. K., Sau, A., Sivanandarajah, P., Ardissino, M., & Ng, F. S. (2022) · BMJ Medicine · doi:10.1136/bmjmed-2022-000308 · Cited by 43
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Ventricular Arrhythmias in Patients with Obstructive Sleep Apnea
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Sleep-Disordered Breathing and Cardiac Arrhythmias
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“The difference in atrial and ventricular arrhythmias seen in OSA versus CSA was assessed in a large study of 2,911 older men (94).”
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Self-citationArrhythmogenic mechanisms of obstructive sleep apnea in heart failure patients
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Effect of Obstructive Sleep Apnea on QT Dispersion: A Potential Mechanism of Sudden Cardiac Death
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Sun, L., Yan, S. R., Wang, X., Zhao, S., Li, H., Wang, Y., Lu, S., Dong, X., Zhao, J., Yu, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14960-2 · Cited by 36
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Chen, C., Ho, C.-H., Chen, C.-L., & Yu, C.-C. (2017) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.6594 · Cited by 37
“34 As HF and CSA can also cause nocturnal hypoxia, excluding patients with underlying CSA and HF in this study might be the main reason for the different findings from aforementioned studies.”
Positionspapier „Schlafmedizin in der Kardiologie“
Podszus, T., Seevers, H., Mayer, G., & Baumann, G. (2009) · Der Kardiologe · doi:10.1007/s12181-008-0134-5 · Cited by 31
Atrial Fibrillation And Sleep Apnea: Considerations For A Dual Epidemic.
Tung, P., & Anter, E. (2016) · PubMed Central · doi:10.4022/jafib.1283 · Cited by 29
Prevalence and correlates of obstructive sleep apnoea among patients with and without HIV infection
Kunisaki, K. M., Akgün, K., Fiellin, D. A., Gibert, C., Kim, J., Rimland, D., Rodriguez‐Barradas, M., Yaggi, H. K., & Crothers, K. A. (2014) · HIV Medicine · doi:10.1111/hiv.12182 · Cited by 30
El síndrome de apneas-hipopneas durante el sueño en edades avanzadas
Martínez‐García, M. Á., Durán‐Cantolla, J., & Montserrat, J. M. (2010) · Archivos de Bronconeumología · doi:10.1016/s1579-2129(10)70116-6 · Cited by 39
“67-69 Finally, in a study conducted on 70 people (57% women) with a mean age of 74.9 years, Endershow et al. observed that the presence of an AHI > 15 was associated with an increase in the systolic and diastolic night blood pressure, 69 after adjusting the AHI for various misleading variables.”
InfluentialHypopnea definitions, determinants and dilemmas: a focused review
Shamim-Uzzaman, Q. A., Singh, S., & Chowdhuri, S. (2018) · Sleep Science and Practice · doi:10.1186/s41606-018-0023-1 · Cited by 34
Blekic, N., Bold, I., Mettay, T., & Bruyneel, M. (2022) · Nature and Science of Sleep · doi:10.2147/nss.s374572 · Cited by 33
Periodic Limb Movements during Sleep and Cardiac Arrhythmia in Older Men (MrOS Sleep)
Koo, B. B., Mehra, R., BLACKWELL, T. L., Ancoli‐Israel, S., Stone, K. L., Redline, S. S., & Osteoporotic Fractures in Men (MrOS) Study Group (2014) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.3346 · Cited by 29
“19,30 Although the relationship between PLMS and sleep disordered breathing is not clear, PLMS is common among patients with obstructive sleep apnea.”
Self-citationSleep-Disordered Breathing in Patients With the Brugada Syndrome
Macedo, P. G., Brugada, J., Leinveber, P., Benito, B., Molina, I., Kuniyoshi, F. H. S., Adachi, T., Bukartyk, J., van der Walt, C., Konečný, T., et al. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2010.10.046 · Cited by 28
Tuohy, C. V., Montez‐Rath, M. E., Turakhia, M. P., Chang, T. I., Winkelman, J. W., & Winkelmayer, W. C. (2016) · BMC Nephrology · doi:10.1186/s12882-016-0229-3 · Cited by 28
“More recently, a study of community-dwelling men over 65 years of age (Outcomes of Sleep Disorders in Older Men Study) did find an independent association between severity of SDB and incident atrial fibrillation [15].”
BackgroundPositionspapier „Schlafmedizin in der Kardiologie“
Oldenburg, O., Arzt, M. E., Bitter, T., Bonnemeier, H., Edelmann, F., Fietze, I., Podszus, T., Schäfer, T., Schöbel, C., Skobel, E. C., et al. (2015) · Der Kardiologe · doi:10.1007/s12181-015-0654-8 · Cited by 30
Ghazi, L., Bennett, A., Petrov, M. E. R., Howard, V. J., Safford, M. M., Soliman, E. Z., & Glasser, S. P. (2018) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7320 · Cited by 26
Cardiac Arrhythmias and Sleep-Disordered Breathing in Patients with Heart Failure
Grimm, W., & Koehler, U. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151018693 · Cited by 27
“Another 8 studies, however found a significantly higher prevalence of atrial fibrillation in patients with versus without CSA [1,3,6,7,12,13,19,24].”
BackgroundShikuma, C. M., Kohorn, L. B., Paul, R. H., Chow, D. C., Kallianpur, K. J., Walker, M., Souza, S. A., Gangcuangco, L. M. A., Nakamoto, B. K., Pien, F. D., et al. (2018) · HIV Clinical Trials · doi:10.1080/15284336.2018.1511348 · Cited by 27
Urbanik, D., Martynowicz, H., Mazur, G. J., Poręba, R., & Gać, P. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9030836 · Cited by 27
Mohamed, B. A., Yarlagadda, K., Self, Z., Simon, A., Rigueiro, F., Sohooli, M., Eisenschenk, S. J., & Doré, S. (2023) · Translational Stroke Research · doi:10.1007/s12975-023-01123-x · Cited by 31
Obstructive Sleep Apnea and Atrial Fibrillation
Maan, A., Mansour, M., Anter, E., Patel, V. V., Cheng, A., Refaat, M. M., Ruskin, J. N., & Heist, E. K. (2015) · Critical Pathways in Cardiology A Journal of Evidence-Based Medicine · doi:10.1097/hpc.0000000000000044 · Cited by 26
Longitudinal relationships of periodic limb movements during sleep and incident atrial fibrillation
May, A. M., BLACKWELL, T. L., Stone, K. L., Cawthon, P. M., Sauer, W. H., Varosy, P. D., Redline, S. S., Koo, B. B., & Mehra, R. (2016) · Sleep Medicine · doi:10.1016/j.sleep.2016.08.009 · Cited by 25
Self-citationNocturnal Peak in Atrial Tachyarrhythmia Occurrence as a Function of Arrhythmia Burden
Shusterman, V., Warman, E. N., London, B., & SCHWARTZMAN, D. S. (2012) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2011.02263.x · Cited by 24
May, A. M., May, R. D., Bena, J., Wang, L., Monahan, K., Stone, K. L., Barrett-Connor, E. L., Koo, B. B., Winkelman, J. W., Redline, S. S., et al. (2019) · SLEEP · doi:10.1093/sleep/zsz165 · Cited by 24
Self-citationSleep Disordered Breathing, Obesity and Atrial Fibrillation: A Mendelian Randomisation Study
Ardissino, M., Reddy, R. K., Slob, E. A. W., Patel, K. H. K., Ryan, D. K., Gill, D., & Ng, F. S. (2022) · Genes · doi:10.3390/genes13010104 · Cited by 25
Correlation Analysis between Obstructive Sleep Apnea Syndrome (OSAS) and Heart Rate Variability.
Xie, J., Yu, W., Wan, Z., Han, F., Wang, Q., & Chen, R. (2017) · Europe PMC (PubMed Central) · Cited by 24
Health Consequences of Obstructive Sleep Apnea
Espiritu, J. R. D. (2021) · Springer eBooks · doi:10.1007/978-3-030-54146-0_3 · Cited by 21
Braun, M., Stockhoff, M., Tijssen, M., Dietz-Terjung, S., Coughlin, S. R., & Schöbel, C. (2024) · Current Sleep Medicine Reports · doi:10.1007/s40675-024-00301-z · Cited by 26
Sleep-disordered breathing increases the risk of arrhythmias
Padeletti, M., Zacà, V., Mondillo, S., & Jelić, S. (2014) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000000019 · Cited by 23
Loomba, R. S., & Arora, R. R. (2010) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e3181e70c49 · Cited by 21
“Although the study did not dismiss the correlation of OSA and AF, it did find that OSA seemed to have a stronger correlation with complex ventricular ectopy, leading to the conclusion that perhaps other sleep-related stresses may contribute to AF as well.(13)”
ResultObstructive sleep apnea and cardiovascular events in elderly patients
Catalán, P., & Soler, X. (2022) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2022.2030225 · Cited by 19
“Central sleep apnea was more associated with atrial fibrillation than with extrasystole [65].”
BackgroundArrhythmia Risk Associated with Sleep Disordered Breathing in Chronic Heart Failure
Mehra, R., & Redline, S. S. (2013) · Current Heart Failure Reports · doi:10.1007/s11897-013-0171-7 · Cited by 19
Self-citationSleep-Disordered Breathing and Arrhythmia in Heart Failure Patients
Fox, H., Bitter, T., Horstkotte, D., & Oldenburg, O. (2017) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2017.01.003 · Cited by 18
“Therefore, the impact of SDB therapy for hard clinical endpoints, such as mortality, remains unclear to date, although recent data show in patients with preserved left ventricular ejection fraction may be in favor through ASV therapy treatment for a combined endpoint in a very recent randomized controlled clinical tri…”
BackgroundInfluentialChowdhuri, S., Patel, P. J., & Badr, M. S. (2017) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2017.09.003 · Cited by 20
Prevalence and Predictors of Arrhythmia in Patients with Obstructive Sleep Apnea
Almeneessier, A. S., Alasousi, N., Sharif, M. M., Pandi-Perumal, S. R., Hersi, A. S., & BaHammam, A. S. (2017) · Sleep Science · doi:10.5935/1984-0063.20170025 · Cited by 20
Hypoxia reduces mature hERG channels through calpain up‐regulation
Lamothe, S. M., Song, W., Guo, J., Li, W., Yang, T., Baranchuk, A. M., Graham, C. H., & Zhang, S. (2017) · The FASEB Journal · doi:10.1096/fj.201700255r · Cited by 18
Tschirhart, J. N., & Zhang, S. (2020) · Molecular Pharmacology · doi:10.1124/mol.119.119271 · Cited by 20
“, 2017) and prolongs QT intervals in patients (Kenigsberg et al., 2007; Mehra et al., 2009).”
BackgroundArrhythmia and sleep-disordered breathing in patients undergoing cardiac surgery
Unosawa, S., Sezai, A., Akahoshi, T., Niino, T., Shimura, K., Shiono, M., Sekino, H., & Akashiba, T. (2012) · Journal of Cardiology · doi:10.1016/j.jjcc.2012.01.012 · Cited by 18
Walking the fine line between OSA and aging
Antonaglia, C., Fabozzi, A., Steffanina, A., Ture, R., Palange, P., & Confalonieri, M. (2025) · Sleep And Breathing · doi:10.1007/s11325-025-03343-x · Cited by 17
“A recent large study demonstrated that 50% of older men had a respira - tory disturbance index > 13/h, with aging being an indepen - dent risk factor in multivariate logistic regression analyses [4 ].”
Metadata
- Authors
- Mehra, R., Stone, K. L., Varosy, P. D., Hoffman, A. R., Marcus, G. M., Blackwell, T., Ibrahim, O. A., Salem, R., & Redline, S.
- Affiliations
- Case Western Reserve University (US)
- San Francisco VA Medical Center (US)
- ORCID
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2009-06-22
- Volume
- 169
- Issue
- 12
- Pages
- 1147
- ISSN
- 0003-9926 (ISSN-L)
- PMC
- PMC2802061
- OpenAlex
- W2162509245
- Semantic Scholar
- a6e20afb1823fe86770b9901448e0c1308040351
- Cited by
- 269
- References
- 50
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 10 · 2023: 11 · 2022: 21 · 2021: 15 · 2020: 13 · 2019: 9 · 2018: 16 · 2017: 24 · 2016: 28 · 2015: 20 · 2014: 17 · 2013: 14 · 2012: 16
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (U01-AG-18197, U01AG018197, U01AG027810)
- National Heart, Lung, and Blood Institute (R01HL070847, R01HL070839, R01HL070838, R01HL070841, R01HL070848, R01HL071194, R01HL070837, R01HL070842, K23HL079114)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01AR45614, U01-AR45632, U01 AR45647, U01AR045583, U01 AR-45583, U01-AR-45654, U01AR045580, U01AR045632, U01AR045654, U01AR045614, U01AR045647, U01AR066160, U01AR45580)
- National Center for Research Resources (UL1RR024140)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Obstructive Sleep Apnea Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- obstructive sleep apnea, central sleep apnea, atrial flutter, nocturnal arrhythmia, hypoxemia, older men, respiratory disturbance index, apnea-hypopnea index, central apnea index, arrhythmia risk
- MeSH terms
- Aged, Arrhythmias, Cardiac, Circadian Rhythm, Electrocardiography, Follow-Up Studies, Heart Rate, Humans, Male, Retrospective Studies, Sleep Wake Disorders, Time Factors, United States, Prevalence, Odds Ratio, Polysomnography
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