In-hospital survival paradox in patients with sleep apnea-A nation-wide nested case-control study

Abstract

Background: Sleep apnea (SA) is a prevalent disorder characterized by recurrent events of nocturnal apnea originating from obstructive and/or central mechanisms. SA disrupts normal sleep and can lead to a series of complications when left untreated. SA results in intermittent hypoxia which has an impact on the cardio- and cerebrovascular system. Hospitalized patients with SA typically have a greater burden of comorbidity, a longer length of hospital stay, but may show an improvement of in-hospital mortality compared to patients without diagnosed SA. The reason for this survival benefit is controversial and we aimed to clarify this protective effect in the light of predictive factors including SA-associated comorbidities using a nation-wide hospitalization database.

Methods and findings: Data were extracted from a nation-wide hospitalization database provided by the Swiss Federal Office for Statistics. Hospitalized patients with a SA co-diagnosis were extracted from the database together with a 1:1-matched control population without SA. Overall, 212'581 patients with SA were hospitalized in Switzerland between 2002 and 2018. Compared to the controls, SA cases had a longer median length of hospital stay (7 days; 95% CI: 3 to 15 vs. 4 days; 95% CI: 2 to 10) (p < 0.001) and a higher median number of comorbidities (8 comorbidities; IQR: 5 to 11 vs. 3 comorbidities; IQR: 1 to 6) (p < 0.001). The risk of in-hospital mortality was lower in the SA cases compared to the controls (OR: 0.73; 95% CI: 0.7 to 0.76; p < 0.001). SA was associated with a survival benefit in hospitalizations related to 28 of 47 conditions with the highest rate of in-hospital death. Sixty-three comorbidities were significantly over-represented in SA cases among which obesity, hypertension and anatomic nasal deviations were associated with a significant decrease of in-hospital mortality.

Conclusions: Compared to matched controls, SA was associated with significant and relevant inpatient survival benefit in a number of most deadly conditions. Within SA-patients, associated comorbidities mostly correlated with a poorer prognosis, whereas obesity and hypertension were associated with an improved in-hospital mortality.

Fig 1. Flow diagram of the study protocol.

The study follows a nested case-control design. The cases correspond to the hospitalizations of adults patients with a SA co-diagnosis. The controls correspond to hospitalizations without coded SA in patients matching the cases 1:1 for age, gender and month of hospitalization.

Fig 2. Characteristics of SA hospitalizations in Switzerland.

The evolution of the annual number of SA hospitalizations between 2002 and 2018 is shown in panel A. The number of hospitalizations with a co-diagnosis of SA increases steadily over the years. The age distribution per gender is depicted in panel B.

Fig 3. Principal component analysis (PCA) biplot of comorbidities associated with sleep apnea.

SA hospitalization cases are reported in smoothed blue density areas, whereas comorbidities (ICD-10-GM codes) are depicted by framed labels. Comorbidities lying in the same direction are correlated. Comorbidities lying far away from the center of the plot are the most influential comorbidities. As a help for interpretation, the upper left inset represents external explanatory variables fitted to the PCA plot. The association between comorbidities and explanatory variables is given by the direction of the arrows.

Fig 4. Survival benefit of coded sleep apnea in patients hospitalized with 47 conditions with highest in-hospital mortality.

The odds-ratios (and 95% confidence intervals) comparing the in-hospital mortality between SA cases and matched controls are displayed using a forest plot. The estimates are represented by dots whose size is proportional to the prevalence of the condition. Comorbidities significantly associated with a lower rate of in-hospital mortality are shown in green. Comorbidities not significantly associated with in-hospital mortality are shown in gray. The simplified ICD-10-GM codes including 2 digits are presented.