Effect of obesity on sleep apnea pathogenesis differs in women versus men: multiple mediation analyses in the...

Area of Science:

• Sleep Medicine
• Cardiorespiratory Physiology
• Obesity Research

Background:

• Obstructive sleep apnea (OSA) is a common disorder with complex underlying mechanisms.
• Classic risk factors like body mass index (BMI) and sex are known contributors to OSA, but their precise roles are not fully elucidated.
• Understanding these mechanisms is crucial for targeted interventions.

Purpose of the Study:

• To investigate how obesity (high BMI) contributes to OSA development.
• To assess whether the mechanisms linking BMI to OSA differ between men and women.
• To identify specific OSA endotypes mediating the relationship between BMI and OSA severity.

Main Methods:

• Analysis of data from the San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort, including 2,146 adult patients.
• Utilized polysomnography signals to determine OSA endotypes.
• Performed sex-stratified mediation analyses to examine how BMI influences the apnea-hypopnea index (AHI) via OSA pathophysiological traits, adjusting for covariates.

Main Results:

• BMI was significantly associated with AHI in both men and women.
• In men, BMI's effect on AHI was mediated by reduced upper airway stiffness, reduced circulatory delay, and increased arousal threshold.
• In women, BMI's effect on AHI was mediated by reduced upper airway stiffness and reduced circulatory delay.

Conclusions:

• The pathogenesis of obesity-related OSA differs significantly between sexes.
• Findings support the role of increased upper airway collapsibility and suggest reduced circulatory delay contributes to higher AHI.
• This study provides the largest sample size to date examining sex-based differences in obesity's influence on OSA pathogenesis.