Mortality Patterns Associated with Central Sleep Apnea among Veterans: A Large, Retrospective, Longitudinal Report

Abstract

Rationale: Central sleep apnea (CSA) is associated with high mortality. Current knowledge stems from studies with limited sample size (fewer than 100 subjects) and in homogeneous populations such as heart failure (HF). Objectives: To address this knowledge gap, we compared the mortality pattern and time to death between the CSA and obstructive sleep apnea (OSA) patients in the large Veterans Health Administration patient population using the big data analytic approach. Methods: This is a retrospective study using national Veterans Health Administration electronic medical records from October 1, 1999, through September 30, 2020. We grouped the patients with underlying sleep disorders into CSA and OSA, using the International Classification of Diseases, Ninth and Tenth Revision codes. We applied Cox regression analysis to compare the mortality rate and hazard ratio (HR) among the two groups and adjusted HR by gender, race, body mass index (BMI), age, and Charlson Comorbidity Index. In CSA groups, a machine-learning algorithm was used to determine the most important predictor of time to death. Further subgroup analysis was also performed in patients that had comorbid HF. Results: Evaluation of patients resulted in 2,961 grouped as CSA and 1,487,353 grouped as OSA. Patients with CSA were older (61.8 ± 15.6 yr) than those with OSA (56.7 ± 13.9 yr). A higher proportion of patients with CSA (25.1%) died during the study period compared with the OSA cohort (14.9%). The adjusted HR was 1.53 (95% confidence interval [CI], 1.43-4.65). Presence of HF history of cerebrovascular disease, hemiplegia, and having a BMI less than 18.5 were among the highest predictors of mortality in CSA. The subgroup analysis revealed that the presence of HF was associated with increased mortality both in CSA (HR, 7.4; 95% CI, 6.67-8.21) and OSA (HR, 4.3; 95% CI, 4.26-4.34) groups. Conclusions: Clinically diagnosed CSA was associated with a shorter time to death from the index diagnostic date. Almost one-fifth of patients with CSA died within 5 years of diagnosis. The presence of HF, history of cerebrovascular disease and hemiplegia, male sex, and being underweight were among the highest predictors of mortality in CSA. CSA was associated with higher mortality than OSA, independent of associated comorbidity.

Keywords: central sleep apnea; electronic medical records; machine learning; obstructive sleep apnea.

Figure 1.

Kaplan-Meier curves. Comparison of survival probability of CSA and OSA. CSA = central sleep apnea; OSA = obstructive sleep apnea.

Figure 2.

Kaplan-Meier curves. Comparison of survival probability on the basis of the presence and absence of HF. *HR (95%CI) = hazard ratio 95% percent confidence intervals and ^†adjusted by gender, race, body mass index, age, and Charlson comorbidity index. aHR = adjusted hazard ratio; CI = confidence interval; CSA = central sleep apnea; HF = heart failure; IQR = interquartile range; M = mean; OSA = obstructive sleep apnea; TtoD = time to death.