Sleep Medicine Section, Veterans Affairs San Diego Healthcare System, San Diego, California, United States.
Division of Pulmonary, Critical Care, Sleep Medicine and Physiology, University of California, San Diego, California, United States.
J Appl Physiol (1985). 2024 Jun 1;136(6):1516-1525. doi: 10.1152/japplphysiol.00925.2023. Epub 2024 Apr 25.
There are multiple mechanisms underlying obstructive sleep apnea (OSA) development. However, how classic OSA risk factors such as body mass index (BMI) and sex portend to OSA development has not been fully described. Thus we sought to evaluate how obesity leads to OSA and assess how these mechanisms differ between men and women. The San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort includes 3,319 consecutive adults who underwent a clinical in-laboratory polysomnography at the University of California, San Diego, sleep clinic between January 2017 and December 2019. Using routine polysomnography signals, we determined OSA endotypes. We then performed mediation analyses stratified by sex to determine how BMI influenced the apnea-hypopnea index (AHI) using OSA pathophysiological traits as mediators, adjusting for age, race, and ethnicity. We included 2,146 patients of whom 919 (43%) were women and 1,227 (57%) were obese [body mass index (BMI) > 30 kg/m]. BMI was significantly associated with AHI in both women and men. In men, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (β = 0.124), a reduction in circulatory delay (β = 0.063), and an increase in arousal threshold (β = 0.029; < 0.05). In women, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (β = 0.05) and circulatory delay (β = 0.037; < 0.05). BMI-related OSA pathogenesis differs by sex. An increase in upper airway collapsibility is consistent with prior studies. A reduction in circulatory delay may lead to shorter and thus more events per hour (higher AHI), while the relationship between arousal threshold and OSA is likely complex. Our data provide important insights into obesity-related obstructive sleep apnea (OSA) pathogenesis, thereby validating, and extending, prior research findings. This is the largest sample size study to examine the relationships between obesity and gender on OSA pathogenesis. The influence of obesity on sleep apnea severity is mediated by different mechanistic traits (endotypes).
阻塞性睡眠呼吸暂停（OSA）的发病机制有多种。然而，像体重指数（BMI）和性别这样的经典 OSA 风险因素如何预示 OSA 的发展尚未得到充分描述。因此，我们试图评估肥胖如何导致 OSA，并评估这些机制在男性和女性之间有何不同。圣地亚哥多结局 OSA 表型（SNOOzzzE）队列包括 2017 年 1 月至 2019 年 12 月期间在加利福尼亚大学圣地亚哥睡眠诊所接受临床实验室多导睡眠图检查的 3319 名连续成年人。我们使用常规多导睡眠图信号确定 OSA 表型。然后，我们按性别进行中介分析，以确定 BMI 如何通过将 OSA 病理生理特征作为中介物来影响呼吸暂停低通气指数（AHI），同时调整年龄、种族和民族。我们纳入了 2146 名患者，其中 919 名（43%）为女性，1227 名（57%）为肥胖[体重指数（BMI）>30kg/m]。BMI 与男女的 AHI 均显著相关。在男性中，BMI 对 AHI 的影响通过上气道僵硬度降低（β=0.124）、循环延迟降低（β=0.063）和觉醒阈值升高（β=0.029； <0.05）部分介导。在女性中，BMI 对 AHI 的影响通过上气道僵硬度降低（β=0.05）和循环延迟降低（β=0.037； <0.05）部分介导。BMI 相关 OSA 的发病机制因性别而异。上气道塌陷性增加与既往研究一致。循环延迟的减少可能导致每小时的事件次数增加（更高的 AHI），而觉醒阈值与 OSA 之间的关系可能很复杂。我们的数据为肥胖相关阻塞性睡眠呼吸暂停（OSA）的发病机制提供了重要的见解，从而验证和扩展了先前的研究结果。这是最大的样本量研究，用于检查肥胖和性别对 OSA 发病机制的关系。肥胖对睡眠呼吸暂停严重程度的影响是通过不同的机制特征（表型）介导的。
