ArticleAnnals of the American Thoracic Society2026
Associations of excessive sleepiness with sleep apnea physiological endo-phenotypes: the multi-ethnic study of atherosclerosis.
Cecilia Castro-Diehl, Raichel Alex, Ali Azarbarzin, Ying Zhang, Andrew Wellman, Tianyi Huang, Scott Sands, Susan Redline
Abstract readMulticenter Study
In one paragraphArticle in Annals of the American Thoracic Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
8 authors.
Cecilia Castro-DiehlDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Raichel AlexDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Ali AzarbarzinDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.ORCID 0000-0002-4986-4753 Ying ZhangDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.ORCID 0000-0003-3697-6702 Andrew WellmanDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Tianyi HuangLaboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Baltimore, MD, United States.ORCID 0000-0001-8420-9167 Scott SandsDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Susan RedlineDepartment of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.ORCID 0000-0002-6585-1610 Funding
SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTERN01HC95159 · NHLBI · UNIVERSITY OF WASHINGTON · PI KRONMAL, RICHARD A · 2007 to 2014
$19.6MASSOCIATION OF SLEEP DISORDERS WITH CARDIOVASCULAR HEALTH ACROSS ETHNIC GROUPSR01HL098433 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S. · 2010 to 2015
$8.2MSUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC95160 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL · 2007 to 2015
$7.7MSUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTERN01HC95164 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LIU, KIANG · 2007 to 2015
$7.0MSUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC95161 · NHLBI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SHEA, STEVEN · 2007 to 2014
$6.4MSUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC95165 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BURKE, GREGORY L · 2007 to 2014
$6.3MSUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTERN01HC95163 · NHLBI · UNIVERSITY OF MINNESOTA · PI FOLSOM, AARON R · 2007 to 2014
$6.1MTITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA)N01HC95162 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI POST, WENDY · 2007 to 2015
$6.0MSUBCLINICAL CARDIOVASCULAR DISEASE STUDYN01HC95166 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI TRACY, RUSSELL P · 2007 to 2014
$4.0MRole of ventilatory drive in obstructive sleep apnea: An avenue for precision interventionR01HL168067 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Scott A Sands · 2023 to 2026
$3.5MA Novel Pharmacological Therapy for Obstructive Sleep ApneaR01HL146697 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SANDS, SCOTT A · 2019 to 2023
$3.4MSUBCLINICAL CARDIOVASCULAR DISEASE STUDYN01HC95168 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI LIMA, JOAO · 2007 to 2015
$2.6Mcooperative agreements UL1TR000040cooperative agreements UL1TR001079cooperative agreements UL1TR001420Multi-Ethnic Study of AtherosclerosisNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01HC95159NHLBI NIH HHS N01HC95160NHLBI NIH HHS N01HC95161NHLBI NIH HHS N01HC95162NHLBI NIH HHS N01HC95163NHLBI NIH HHS N01HC95164NHLBI NIH HHS N01HC95165NHLBI NIH HHS N01HC95166NHLBI NIH HHS N01HC95167NHLBI NIH HHS N01HC95168NHLBI NIH HHS N01HC95169NHLBI NIH HHS R01HL146697NHLBI NIH HHS R01HL168067NIHNIH-NHLBI R01HL098433NIH-NIA 5R01AG070867
6 · The paper itselfAbstract
backgroundObstructive sleep apnea (OSA) is a heterogenous disease characterized by several endo-phenotypes (mechanistic traits and physiological severity metrics) and variable associations with excessive daytime sleepiness (EDS). Examining the relationship of EDS with features of OSA may identify physiological processes that drive increased risk for adverse health outcomes in patients with OSA and EDS. RESEARCH QUESTION: Do variations in physiological endo-phenotypes identified from polysomnography associate with EDS in a general population, and do such associations vary by sex? STUDY DESIGN AND
methodsParticipants in the Multi-ethnic Study of Atherosclerosis (MESA) Exam 5 Sleep Study underwent polysomnography, actigraphy, and questionnaire assessment. Among participants with an apnea-hypopnea index > 5 events/hour (n = 1783; mean, age 68.7 ± 9.1; 52% female), we examined associations between OSA endo-phenotypes including physiological severity measures (hypoxic burden, arousal intensity, event duration, heart rate response [Δ HR]), and endotypes (mechanistic traits: collapsibility, compensation, loop gain, and arousal threshold) with EDS (Epworth Sleepiness Scale, ESS > 10). Poisson regression models with robust variance were used, adjusting for demographics, smoking, and other factors.
resultsEDS was found in 14% of the sample. An interquartile increase in hypoxic burden was associated with a 28% higher prevalence ratio (PR) of EDS (PR = 1.28; 95% CI: 1.10, 1.51) in models adjusted for demographic factors and smoking. An increased adjusted PR of EDS was also associated with higher loop gain (1.26; 1.12, 1.42) and higher ΔHR (1.32; 1.01, 1.73). In sex-stratified analyses, EDS was associated with shorter respiratory event duration and higher compensation in females, and with hypoxic burden and high ΔHR in males (P value for sex interaction < .05 for event duration). Associations did not materially change with adjustment for short sleep duration.
interpretationEDS was associated with several OSA endo-phenotypes. EDS was more strongly associated with shorter event duration in females, with trends for stronger associations for hypoxic burden and ΔHR in males. The physiological correlates of EDS in people with OSA may contribute to differences in OSA outcomes across symptom groups.
Indexed as
AtherosclerosisDisorders of Excessive SomnolenceSleep Apnea, ObstructiveActigraphyAgedAged, 80 and overFemaleHumansHypoxiaMaleMiddle AgedPhenotypePolysomnographySeverity of Illness IndexSex FactorsSleep Apnea Syndromesendotype traitsepidemiological studyobstructive sleep apneasleepiness
Identifiers
PMID41955419
PMCPMC13315775
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