Obstructive sleep apnea subtyping based on apnea and hypopnea specific hypoxic burden is associated with brain aging and cardiometabolic syndrome

Conventional metrics such as the apnea-hypopnea index (AHI) may not fully capture the diverse clinical manifestations of obstructive sleep apnea (OSA). This study aims to establish a novel OSA subtype classification based on the patterns of apneic and hypopneic hypoxic burden (HB), a potential biomarker that more accurately reflects the severity and duration of respiratory events. We further examined the associations of these HB-based subtypes with cardiometabolic risk and brain health outcomes. We retrospectively analyzed polysomnography data from 1000 participants including normal, mild, moderate, and severe OSA patients. We performed hierarchical clustering based on apneic and hypopneic HB to identify OSA subtypes. We then compared the prevalence of cardiometabolic syndrome (CMS) and brain health outcomes using the brain age index (BAI) among these subtypes. Five distinct subtypes were identified: ‘good sleepers’ (subtype 1), ‘light hypopneic HB’ (subtype 2), ‘mild HB’ (subtype 3), ‘moderate HB’ (subtype 4), and ‘severe HB with marked apneic HB’ (subtype 5). The prevalence of CMS (particularly hypertension) was significantly higher in subtypes 2–5 (p < 0.001) compared to subtype 1. BAI was higher in subtypes 4 (3.2 years, p < 0.0001) and 5 (11.1 years, p < 0001) compared to subtype 1. Greater daytime sleepiness was observed in HB-based subtypes 2 and 5 compared to subtype 1 (p < 0.001), whereas no significant differences were found among groups classified by OSA severity using AHI. Our study demonstrates that the HB-based subtypes of OSA are significantly associated with various clinical features and outcomes. These insights could be utilized to improve risk stratification and guide the design of future OSA studies. • New obstructive sleep apnea subtypes identified via apneic and hypopneic hypoxic burden patterns. • Identified five distinct OSA subtypes correlating with cardiometabolic and brain health outcomes. • Apneic hypoxic burden links to brain aging, while hypopneic hypoxic burden associates more with cardiometabolic syndrome. • HB-based subtyping revealed associations not captured by traditional AHI classification. • Findings support hypoxic burden as a superior biomarker for personalized OSA management.