Abstract Introduction Obstructive sleep apnea (OSA), which is associated with a high mortality, is a heterogeneous disease that is affected by various pathophysiology. Although the severity of OSA is divided based on apnea-hypopnea index (AHI), AHI alone did not sufficiently represent these pathologies. The objective of this study is to categorize OSA using PSG data and compare the characteristics of each group including mortality. Methods 7,247 subjects were recruited at the Center for Sleep and Chronobiology, Seoul National University Hospital from June 2004 to December 2021. Demographic data, polysomnography, Sleep scale including Epworth sleepiness scale, Pittsburgh sleep quality index, Beck depression inventory, and Beck anxiety inventory were performed. After categorizing OSA using K-mean cluster analysis, Kaplan-Meir survival analysis and Cox proportional hazard regression analysis were used to evaluate all-cause mortality and hazard ratios. Results Three clusters were identified; Cluster 1 was associated with moderate OSA (mean AHI=19.28/h), high sleep efficiency and low arousal, Cluster 2 with moderate OSA (mean AHI=24.81/h), low sleep efficiency and high arousal, Cluster 3 with the most severe OSA (mean AHI=64.76/h), obese, and decreased O2 saturation. Conventional classification of OSA showed no difference in mortality between group, whereas Cluster 1 and Cluster 3 showed significant higher all-cause mortality compared to not-OSA group (Cluster 1, Log rank p=0.008; Cluster 3 Log rank p< 0.001). The risk of mortality was also significantly increased in cluster 1 (HR 2.048, 95% CI 1.265-3.317, p=0.004) and cluster 3 (HR 3.686, 95% CI 1.871-7.262, p< 0.001). These results were also observed after adjustment for sex, age, BMI and comorbid disease (Cluster 1, HR 2.053, 95% CI 1.197-3.518, p=0.009; Cluster 4, HR 2.640, 95% CI 1.230-5.666, p=0.012). Conclusion Phenotyping of OSA considered multiple variables is more appropriate to predict mortality than conventional classification based on AHI. In addition to evaluate patient with severe OSA, patients with moderate OSA who shows relatively good sleep and low arousal should be cautiously evaluated and monitored. Support (if any) This study was supported by the Technology Innovation Infrastructure program through the Korea Institute for Advancement of Technology funded by the Ministry of Trade, Industry and Energy.(study no.: P0014279, 20009210, Dr. Yu Jin Lee)
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