Evidence map›Paper›PMID 30376054›Full record

ArticleEuropean heart journal2019

The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study.

Ali Azarbarzin, Scott A Sands, Katie L Stone, Luigi Taranto-Montemurro, Ludovico Messineo, Philip I Terrill, Sonia Ancoli-Israel, Kristine Ensrud, Shaun Purcell, David P White and 2 more

Erratum issued 2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European heart journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 505 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
505citing papers in PubMed, 8 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07577661 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea: A Randomized-Controlled Trial.

TypeinterventionalSponsorBrigham and Women's HospitalRan2026 to 2027Enrolled24ConditionsObstructive Sleep Apnea, Sleep-disordered BreathingArmsCombination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy), Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition, Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition, Placebo, placebo comparator condition
NCT07792746 recruitingnot on this mapstarted 2026, after this paper: background citation

Impact of Obstructive Sleep Apnea Biomarkers on Adherence to Continuous Positive Airway Pressure: Role of Pulse Wave Amplitude Drop Index, Hypoxic Burden, and Heart Rate Variability

TypeobservationalSponsorClinique du MillenaireRan2026 to 2027Enrolled200ConditionsObstructive Sleep Apnea (OSA), CPAP, Biomarkers for Prediction of OA Treatment EfficacyArmsContinuous Positive Airway Pressure
3 · Its place in the literature

Who cites it

505 citing papers in PubMed, 8 syntheses or guidelines pooled it.

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  13. Comorbid insomnia and sleep apnea is associated with worse verbal episodic memory in older females.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025
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445 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Ali AzarbarzinDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.
Scott A SandsDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.
Katie L StoneResearch Institute, California Pacific Medical Center, 550 16th Street, 2nd Floor, San Francisco, CA, USA.
Luigi Taranto-MontemurroDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.
Ludovico MessineoDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.
Philip I TerrillSchool of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia.
Sonia Ancoli-IsraelDepartment of Psychiatry, University of California San Diego, 9500 Gilman Drive La Jolla, CA, USA.
Kristine EnsrudUniversity of Minnesota and Minneapolis Veterans Affairs Health Care System, 1 Veterans Dr, Minneapolis, MN, USA.
Shaun PurcellDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.
David P WhiteDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.
Susan RedlineDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.
Andrew WellmanDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Sleep Disordered Breathing Lab, 221 Longwood Avenue, Boston, MA, USA.

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
Outcomes of Sleep Disorders in Older MenR01HL071194 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI STONE, KATIE L · 2003 to 2013
$12.2M
Osteoporotic Fractures in Men (MrOS) - San Francisco Coordinating CenterU01AR066160 · NIAMS · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON · 2013 to 2017
$9.3M
National Sleep Research Resource (NSRR)R24HL114473 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S., ZHANG, GUO-QIANG · 2013 to 2017
$7.5M
Phenotypic and Molecular Signatures for Sleep Apnea and Related MorbiditiesR35HL135818 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S. · 2017 to 2023
$7.2M
Osteoporotic Fractures in Men (MrOS) - MinneapolisU01AG042145 · NIA · UNIVERSITY OF MINNESOTA · PI ENSRUD, KRISTINE · 2013 to 2019
$5.3M
Osteporotic Fractures in Men (MrOS)- Admin CenterU01AG027810 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2006 to 2017
$5.1M
Osteoporotic Fractures in Men (MrOS) - PortlandU01AG042124 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2013 to 2019
$3.0M
Osteoporatic Fractures in Men (MrOS)U01AG042168 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KADO, DEBORAH · 2013 to 2017
$3.0M
Osteoporotic Fractures in Men (Mr. Os) Palo AltoU01AG042143 · NIA · STANFORD UNIVERSITY · PI STEFANICK, MARCIA L. · 2013 to 2017
$3.0M
Osteoporotic Fractures in Men (Mr.OS)U01AG042139 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CAULEY, JANE ANN · 2013 to 2017
$2.9M
NCATS NIH HHS UL1 TR001102NCRR NIH HHS UL1 RR025758NHLBI NIH HHS R01 HL070837NHLBI NIH HHS R01 HL070838NHLBI NIH HHS R01 HL070839NHLBI NIH HHS R01 HL070841NHLBI NIH HHS R01 HL070842NHLBI NIH HHS R01 HL070847NHLBI NIH HHS R01 HL070848NHLBI NIH HHS R01 HL071194NHLBI NIH HHS R24 HL114473NHLBI NIH HHS R35 HL135818NHLBI NIH HHS U01 HL053916NHLBI NIH HHS U01 HL053931NHLBI NIH HHS U01 HL053934NHLBI NIH HHS U01 HL053937NHLBI NIH HHS U01 HL053938NHLBI NIH HHS U01 HL053941NHLBI NIH HHS U01 HL063429NHLBI NIH HHS U01 HL063463NIAMS NIH HHS U01 AR066160NIA NIH HHS U01 AG027810NIA NIH HHS U01 AG042124NIA NIH HHS U01 AG042139NIA NIH HHS U01 AG042140NIA NIH HHS U01 AG042145NIA NIH HHS U01 AG042168
6 · The paper itself

Abstract

aimsApnoea-hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the 'hypoxic burden' would predict mortality among adults aged 40 and older. METHODS AND

resultsThe samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 [95% confidence interval (CI) 1.25-2.62] and 2.73 (95% CI 1.71-4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43).

conclusionThe 'hypoxic burden', an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.

Indexed as

Severity of Illness IndexAgedCardiovascular DiseasesCohort StudiesFemaleHumansHypoxiaMaleMiddle AgedSleep Apnea, ObstructiveUnited StatesApnoea–hypopnoea indexCVD mortalityHypoxic burdenPolysomnographySleep apnoea

Identifiers

PMID30376054
PMCPMC6451769

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.