Central sleep apnea linked to worse mortality outcomes than obstructive sleep apnea
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Key takeaways:
- More veterans with central vs. obstructive sleep apnea died over a shorter number of years.
- Heart failure raised the mortality hazard in both types of sleep apnea.
Compared with obstructive sleep apnea, veterans with central sleep apnea had greater mortality rates, shorter time to death and higher mortality hazard, according to study results published in Annals of the American Thoracic Society.
Further, simultaneous heart failure raised the mortality hazard in both types of sleep apnea, according to researchers.
“We observed that one-fifth of patients with central sleep apnea (CSA) died within 5 years of diagnosis, with substantially higher mortality of patients with CSA than patients with OSA,” Ritwick Agrawal, MD, assistant professor of pulmonary medicine at Baylor College of Medicine, and colleagues wrote. “The mortality hazard remained significant, even after adjusting for comorbidities.”
In a large, retrospective and longitudinal report, Agrawal and colleagues compared 2,961 patients (age, 61.8 years; 95.7% men) with CSA with 1,487,353 patients (age, 56.7 years; 93.4% men) with OSA taken from electronic health records of the Veterans Health Administration between October 1999 to September 2020 to assess mortality and time to death among both groups of patients.
Researchers evaluated mortality rates and hazard ratios, as well as hazard ratios adjusted for gender, race, BMI, age and Charlson Comorbidity Index (CCI) through an applied Cox regression analysis.
In terms of time to death predictors in those with CSA, researchers figured out these factors through a machine-learning algorithm.
Within the mean follow-up period of 5.92 years, more patients with CSA than OSA died (25.1% vs. 14.9%) and were found to have a heightened rate of mortality following adjustment for demographics and comorbidity (aHR = 1.53; 95% CI, 1.43-4.65). Patients with CSA also had a faster median time to death vs. patients with OSA (2.7 years vs. 5.1 years), with 18.7% dying within about 5 years of receiving the diagnosis, according to researchers.
Increased chances for mortality among patients with CSA was further found independent of comorbid conditions that have high mortality (HR = 1.79; 95% CI, 1.66-1.94) and after additional adjustment for the previously outlined variables (aHR = 1.38; 95% CI, 1.28-1.5).
Among patients with CSA, researchers identified four major predictors of mortality: heart failure, history of cardiovascular disease, hemiplegia and BMI of less than 18.5 kg/m2, which is considered having underweight.
When analyzing only those with comorbid heart failure (CSA, n = 470; OSA, n = 99,919), researchers observed elevated mortality in both sleep apnea types (CSA, HR = 7.4; 95% CI, 6.67-8.21; and OSA, HR = 4.3; 95% CI, 4.26-4.34). The higher hazard in both patient cohorts was still observed following adjustment (CSA, aHR = 3.66; 95% CI, 3.3-4.07; OSA, aHR = 2.2; 95% CI, 2.18-2.22).
Additionally, among those with prescriptions for opiates, patients with CSA had greater mortality hazards than patients with OSA (HR = 1.91; 95% CI, 1.69-2.16; aHR = 1.67; 95% CI, 1.48-1.89), according to researchers.
“The CSA group had a higher proportion of comorbid conditions than the OSA group, suggesting this is a sicker cohort,” Agrawal and colleagues wrote. “However, when adjusted for these comorbid conditions and demographics, results showed that patients with CSA without HF continued to have an independent 41% higher mortality hazard. These data suggest that the deaths in this subgroup may not be fully explained by the comorbidities included in CCI. Whether CSA is an independent risk for increased mortality or simply a biomarker remains unknown. These findings should be explored further in prospective studies.”
This study by Agrawal and colleagues adds to growing literature on sleep apnea’s relation to mortality, with specific divisions between the risks associated with CSA and those associated with OSA. According to an accompanying editorial by Shahrokh Javaheri, MD, of the division of pulmonary and sleep medicine at Bethesda North Hospital in Cincinnati, and colleagues, this study had several limitations, such as not separating those with preserved ejection fraction from those with heart failure with reduced ejection fraction, possible “lack of uniformity” in the interpretation of sleep testing data for diagnoses and capturing more patients with CSA who have a severe version of the condition or are more symptomatic.
“Given the detailed information contained within the VA database and electronic medical records, most if not all of the aforementioned limitations could be rectified and be the subject of a future analysis,” Javaheri and colleagues wrote. “Even so, the current study reinforces the already compelling evidence that CSA is an important factor leading to mortality in heart failure. By extending their analysis as outlined above, even more factors may be revealed that can help make treatment decisions when CSA complicates heart failure.”