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OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH MARKERS OF CEREBRAL SMALL VESSEL DISEASE IN A DOSE-DEPENDENT MANNER: A SYSTEMATIC REVIEW AND META-ANALYSIS
Abstract
Background and Aims
Cerebral small vessel disease (CSVD) manifests on neuroimaging as white matter hyperintensities (WMH), lacunes, or cerebral microbleeds (CMBs) and is a major contributor to dementia, stroke and incident death. Obstructive sleep apnea (OSA) may disrupt endothelial cell metabolism and repair, thus increasing the risk of CSVD. This systematic review/meta-analysis aims to elucidate whether OSA severity increases the likelihood of exhibiting CSVD.
Methods
This review was registered on PROSPERO and conducted in accordance with PRISMA standards. We searched Medline, Embase and Cochrane for studies reporting associations between OSA and CSVD. A random-effects model was used to meta-analyze unadjusted odds ratios (OR) derived from event rates. CSVD prevalence was compared between groups with no OSA (apnea-hypopnea index [AHI]<5), mild OSA (5≤AHI<15), moderate-severe OSA (AHI≥15) and severe OSA (AHI≥30). Study quality was assessed using the Newcastle-Ottawa Scale.
Results
Thirty-two observational studies were included: 24 reported effect sizes for WMHs, 11 for lacunes and 4 for CMBs. Eighteen studies were rated as “high-quality”. Upon pooling ORs, we found OSA severity to be significantly associated with WMHs. Compared to patients without OSA, the odds of possessing WMHs were 1.7[95%CI 0.9;3.6] in mild OSA, 3.9[2.7;5.5] in moderate-severe OSA and 4.3[1.9;9.6] in severe OSA (Figure 1). We also observed potential, albeit nonsignificant, dose responses between OSA severity and lacunes or CMBs amidst heterogeneous data.
Conclusions
This meta-analysis is the first to elucidate a potential dose-dependent relationship between OSA severity and WMH burden. Our findings invite future research to explore the role of OSA treatment in stabilizing or ameliorating CSVD progression.