Obstructive sleep apnea and risk of cardiovascular disease and all-cause mortality: A meta-analysis of prospective cohort studies

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Abstract

Background

The association between obstructive sleep apnea (OSA) and the incidence of cardiovascular disease (CVD) has been examined in many studies. However, the findings are not entirely consistent across studies. Our goal was to evaluate the association between OSA and risk of CVD and all-cause mortality by performing a meta-analysis of prospective cohort studies.

Methods

We used generalized least squares regression models to estimate the dose–response relationship. Heterogeneity, subgroup, and sensitivity analyses and publication bias were performed.

Results

Twelve prospective cohort studies involving 25,760 participants were included in the meta-analysis. The overall combined relative risks for individuals with severe OSA compared with individuals with an AHI of < 5 were 1.79 (95% confidence interval [CI]: 1.47 to 2.18) for CVD, 1.21 (95% CI: 0.75 to 1.96) for incident fatal and non-fatal coronary heart disease, 2.15 (95% CI: 1.42 to 3.24) for incident fatal and non-fatal stroke, and 1.92 (95% CI: 1.38 to 2.69) for deaths from all-causes. A positive association with CVD was observed for moderate OSA but not for mild OSA. The results of the dose–response relationship indicated that per 10-unit increase in the apnea–hypopnea index was associated with a 17% greater risk of CVD in the general population.

Conclusions

This meta-analysis of prospective cohort studies suggests that severe OSA significantly increases CVD risk, stroke, and all-cause mortality. A positive association with CVD was observed for moderate OSA but not for mild OSA.

Introduction

Obstructive sleep apnea (OSA) is characterized by frequent episodes of total and/or partial collapse of upper airways during sleep, resulting in recurrent episodes of intermittent hypoxemia and arousal from sleep [1], [2]. This disorder affects approximately 24% of men and 9% of women [1], [3]. There is emerging research evidence for an independent association between OSA and cardiovascular disease (CVD) [4], [5], [6], [7], [8], [9], [10], [11]. However, the magnitude of the association has varied across studies and a causal link has not yet been convincingly documented. A recent meta-analysis [12] synthesized available data from nine studies, one of which [13] was based on a retrospectively selected population. In addition, the review did not consider whether data from clinic-based cohorts might affect the size or significance of the true association. Potential publication bias was also not fully explored in this report. Given that OSA is a treatable disease, a better understanding of the relationship between OSA and the risk of CVD will have important public health and clinical implications given the possibility that prevention and treatment of OSA could decrease the incidence of cardiovascular events. In addition, it has been stated that long-term continuous positive airway pressure (CPAP) improves cardiovascular risk in patients with OSA [14], [15]. However, to our knowledge, there is no study available that evaluates the impact of long-term CPAP treatment on cardiovascular risk in patients with OSA through meta-analysis.

Therefore we conducted a meta-analysis of prospective cohort studies to assess the magnitude of the association of OSA and risk of CVD and to estimate whether increased severity of OSA is associated with increased CVD risk. Also, we evaluate the impact of CPAP therapy on improvement of cardiovascular risk.

Section snippets

Search strategy

We attempted to follow the Meta-Analysis of Observational Studies in Epidemiology guidelines throughout the design, implementation, analysis, and reporting for this present meta-analysis [16]. We performed a systematic search through September 2012 for published articles using PubMed, Embase, ISI Web of Knowledge, and the Cochrane Library databases. The following search terms were used: 1) obstructive sleep apnea, sleep-disordered breathing, and CPAP therapy; 2) cardiovascular diseases,

Literature search

The initial search yielded 2517 potentially relevant citations from the electronic reference databases, of which 34 articles met the inclusion criteria and were selected for detailed assessment. Nineteen studies were further excluded because of studies on the biological pathways activated by OSA, studies that used self-reported snoring to assess OSA, or randomized controlled trials. Of the remaining 15 papers, four studies were further excluded. One additional study was included by conducting a

Discussion

Our meta-analysis of 12 prospective cohort studies showed that severe OSA is significantly and independently associated with an increased risk of CVD, stroke, and all-cause mortality. A positive association with CVD was observed for moderate OSA. In contrast, this risk is not significantly increased in patients with mild OSA. The results of the dose–response analysis in population-based prospective studies suggest that a 10-unit average increase in AHI was associated with a 17% greater risk of

Acknowledgement

XW, YPB, and GZ: developed the study concept and designed the study; ZW and YYO conducted the data extraction and validity assessment, and tabulated the data; XW: wrote the manuscript, and reviewed and edited the manuscript; and LGL and YPB: reviewed and edited the manuscript.

This work was supported by the National Science and Technology Support Program of China (2012BAI02B02).

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