Sudden death in individuals with obstructive sleep apnoea: a systematic review and meta-analysis

Abstract

Objectives: Over 1 billion individuals worldwide experience some form of sleep apnoea, and this number is steadily rising. Obstructive sleep apnoea (OSA) can negatively influence one's quality of life and potentially increase mortality risk. However, the association between OSA and mortality has not been reliably estimated. This meta-analysis estimates the risk of all-cause and cardiovascular mortality in individuals with OSA.

Design: Systematic review and meta-analysis.

Data sources: MEDLINE, Cochrane Library, Scopus and Joanna Briggs Institute Evidence-Based Practice databases were searched from inception through 1 January 2020.

Eligibility criteria for selecting studies: We included observational studies assessing the association of sudden deaths in individuals with and without OSA.

Data extraction and synthesis: Two independent reviewers (AES and ESH) extracted data and assessed the risk of bias using the Newcastle-Ottawa Scale quality assessment tool. Data were pooled using the random-effects models and reported as risk ratios (RRs) with 95% CIs. Heterogeneity was quantified with I² statistic.

Results: We identified 22 observational studies (n=42 099 participants). The mean age was 62 years and 64% were men. OSA was associated with all-cause sudden death (RR=1.74, 95% CI: 1.44 to 2.10, I²=72%) and cardiovascular mortality (RR=1.94, 95% CI: 1.39 to 2.70, I²=32%). A marginally significant dose-response relationship between severity of OSA and the risk of death was observed (p for interaction=0.05): mild OSA (RR=1.16, 95% CI: 0.70 to 1.93), moderate OSA (RR=1.72, 95% CI: 1.11 to 2.67) and severe OSA (RR=2.87, 95% CI: 1.70 to 4.85). Meta-regression analysis showed that older age was a significant contributing factor in the relationship between OSA and mortality. The median study methodological quality was considered high.

Conclusions: OSA is a significant risk factor for all-cause mortality and cardiac mortality. Prevention and treatment strategies to optimise survival and quality of life in individuals with OSA are urgently needed.

Prospero registration number: CRD42020164941.

Keywords: clinical epidemiology; sleep apnoea.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. JBI, Joanna Briggs Institute; OSA, obstructive sleep apnoea;EBP, Evidence-Based Practice.

Figure 2

Forest plot of pooled risk ratio for the association of OSA with all-cause sudden death. Blue squares and their corresponding lines are the point estimates and 95% CI. Maroon diamonds represent the pooled estimate (width denotes 95% CI). Heterogeneity was considered high (I²=72%). OSA, obstructive sleep apnoea.

Figure 3

Forest plot of subgroup analysis by the severity of OSA. Blue squares and their corresponding lines are the point estimates and 95% CI. Maroon diamonds represent the pooled estimate for each subgroup (width denotes 95% CI). Heterogeneity by severity of OSA: mild (I²=66%); moderate (I²=0%); severe (I²=0%); p for interaction comparing the different subgroups=0.05. OSA, obstructive sleep apnoea.

Figure 4

Forest plot of pooled risk ratio for the association of OSA and cardiovascular mortality. Blue squares and their corresponding lines are the point estimates and 95% CI. Maroon diamonds represent the pooled estimate for each subgroup (width denotes 95% CI). OSA, obstructive sleep apnoea.

Figure 5

Forest plot of subgroup analysis by study quality score. Blue squares and their corresponding lines are the point estimates and 95% CI. Maroon diamonds represent the pooled estimate for each subgroup (width denotes 95% CI). Heterogeneity by methodological quality score: high quality score (I²=64%); moderate quality score (I²=79%); p for interaction comparing the different subgroups=0.37.

Figure 6

Forest plot for subgroup analysis by the continent of the study population. Blue squares and their corresponding lines are the point estimates and 95% CI. Maroon diamonds represent the pooled estimate for each subgroup (width denotes 95% CI). Heterogeneity by continent: North America (I²=77%); Europe (I²=62%); Asia (I²=64%); South America (I² not applicable); Australia (I²=not applicable); p for interaction comparing the different subgroups=0.47.

Figure 7

Univariate meta-regression analysis. Meta-regression bubble plots using age (A) and the publication year (B) as covariates.