The relationship between sleep apnea, metabolic dysfunction and inflammation: The gender influence

- OSA can differently affect respiratory sleep parameters according to gender.
- OSA men presented greater apnea index and lower N3 sleep stage than OSA women.
- Postmenopause was related to increased apnea-hypopnea index during REM in OSA women.
- OSA was associated with higher TNF-α in women and higher leptin levels in men.
- Sexual hormones may play a role in the inflammatory consequences associated with OSA.

Obstructive sleep apnea (OSA) has been associated with increased risk of cardiovascular morbidity and mortality. Although inflammatory markers may mediate this association, it is unknown the influence of gender in this mechanism. Thus, we aimed to evaluate the interaction effects between OSA and gender on metabolic and inflammatory profile in a population sample. This study is part of EPISONO cohort, in which 1042 participants underwent polysomnography, answered questionnaires, and had their blood collected for analysis of fasting glucose, total cholesterol and fractions, leptin, ghrelin, liver transaminases, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein. The results showed that men with OSA had higher leptin levels, shorter sleep latency and lower N3 sleep stage compared to men control (CTRL). They also presented higher apnea index and number of central apneas compared to both CTRL men and OSA women. In women, OSA was related to longer REM sleep latency, higher apnea-hypopnea index (AHI) during REM sleep and increased TNF-α levels compared to CTRL women. A multivariate model showed that male gender, ghrelin and total cholesterol were negatively associated with TNF-α, while IL-6, triglycerides and hypopnea index were positively associated (R2 = 0.21). Additionally, gender (men), body mass index, ghrelin, apnea index and smoking were positive predictors of leptin levels (R2 = 0.55). Of note, postmenopause was associated with changes observed in both TNF-α and AHI during REM sleep in women with OSA. Taken together, our study suggests that OSA consequences may differ between genders and this could indicate a need for different OSA management in women according to their reproductive life's stage.