Year: 2022
Type: article
Abstract: Rationale Sleep apnea is the manifestation of key endotypic traits, including greater pharyngeal collapsibility, reduced dilator muscle compensation, and elevated chemoreflex loop gain. Objectives We investigated how endotypic traits vary with obesity, age, sex, and race/ethnicity to influence sleep apnea disease severity (apnea–hypopnea index [AHI]). Methods Endotypic traits were estimated from polysomnography in a diverse community-based cohort study (Multi-Ethnic Study of Atherosclerosis, N = 1,971; age range, 54–93 yr). Regression models assessed associations between each exposure (continuous variables per 2 standard deviations [SDs]) and endotypic traits (per SD) or AHI (events/h), independent of other exposures. Generalizability was assessed in two independent cohorts. Results Greater AHI was associated with obesity (+19 events/h per 11 kg/m2 [2 SD]), male sex (+13 events/h vs. female), older age (+7 events/h per 20 yr), and Chinese ancestry (+5 events/h vs. White, obesity adjusted). Obesity-related increase in AHI was best explained by elevated collapsibility (+0.40 SD) and greater loop gain (+0.38 SD; percentage mediated, 26% [95% confidence interval (CI), 20–32%]). Male-related increase in AHI was explained by elevated collapsibility (+0.86 SD) and reduced compensation (−0.40 SD; percentage mediated, 57% [95% CI, 50–66%]). Age-related AHI increase was explained by elevated collapsibility (+0.37 SD) and greater loop gain (+0.15 SD; percentage mediated, 48% [95% CI, 34–63%]). Increased AHI with Chinese ancestry was explained by collapsibility (+0.57 SD; percentage mediated, 87% [95% CI, 57–100]). Black race was associated with reduced collapsibility (−0.30 SD) and elevated loop gain (+0.29 SD). Similar patterns were observed in the other cohorts. Conclusions Different subgroups exhibit different underlying pathophysiological pathways to sleep apnea, highlighting the variability in mechanisms that could be targeted for intervention.
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1085777395, G1087732098, G1261793039, G1276754516, G1286721212, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, Outcomes of Sleep Disorders in Older Men-Minneapolis, G1409423729, G1472918012, General Clinical Research Center, ASSOCIATION OF SLEEP DISORDERS WITH CARDIOVASCULAR HEALTH ACROSS ETHNIC GROUPS, G1640378483, G1686417863, Wake Forest Clinical and Translational Science Award, G198029770, SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTER, Outcomes of Sleep Disorders in Older Men- Reading Center, G2144938473, G22458031, G2262782284, G2391309017, G2457626021, G2600980409, G2623279087, National Sleep Research Resource (NSRR), G2837638605, G290884426, G291913881, Phenotypic and Molecular Signatures for Sleep Apnea and Related Morbidities, Familial Aggregation and Natural History of Sleep Apnea, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G354191473, Sleep apnea phenotyping for personalized therapy using clinical polysomnography, G3612559655, G3639969904, G3647016462, G3687594596, G3945347839, G3966146196, G3988954801, G399481048, G4013255670, G4187977420, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G4512137732, Biometric Genetic Analysis of CardiopulmonaryDisease, G4590187187, G4824239441, G496640596, G5088122703, G5108002584, G5324596834, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G5787256936, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G6095866717, Outcomes of Sleep Disorders in Older Men-Portland, G6217957645, G6338126091, G6359107525, Institute for Clinical and Translational Research, G6466198328, G6514094751, A Novel Pharmacological Therapy for Obstructive Sleep Apnea, G6564366179, G658953780, G66341962, G6742279884, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, Outcomes of Sleep Disorders in Older Men-Palo Alto, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, Outcomes of Sleep Disorders in Older Men, G7511203839, G7595082214, Outcomes of Sleep Disorders in Older Men, G7706274302, Outcomes of Sleep Disorders in Older Men-Birmingham, G78770644, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G8031945918, Clinical and Translational Science Award, Outcomes of Sleep Disorders in Older Men - Pittsburgh, G8248489912, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, G867112777, G8887585663, G9000132197, Predicting response to non-PAP therapies in OSA using PSG-derived endotypes, Novel physiologiC prEdictors of Positive Airway Pressure effectiveness: NICE-PAP study., Yale Clinical and Translational Science Award, G91634571, G941228542, G991334795
OpenAlex ID: W4307339094