Intermittent hypoxia-related alterations in vascular structure and function: a systematic review and meta-analysis of rodent data

Abstract

Obstructive Sleep Apnea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure.To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs.We searched PubMed, Embase and Web of Sciences and included 125 articles in a meta-analysis, among them 112 using wild-type rodents and 13 using Apolipoprotein E knock-out mice. We used the standardised mean difference (SMD) to compare results between studies.IH significantly increased mean arterial pressure (+13.90 mmHg (95% CI [11.88; 15.92]), systolic and diastolic blood pressure. Meta-regressions showed that mean arterial pressure change was associated with strain and year of publication. IH altered vasodilation in males but not in females, and increased endothelin-1-induced, but not phenylephrine-induced, vasoconstriction. Intima-media thickness significantly increased upon IH exposure (SMD 1.10 [0.58; 1.62], absolute values: +5.23 (2.81–7.84)). This increase was observed in mice but not in rats, and was negatively associated with age. Finally IH increased atherosclerotic plaque size in ApoE−/− mice (SMD 1.08 [0.80; 1.37]).To conclude, our meta-analysis established that IH, independently of other confounders, has a strong effect on vascular structure and physiology. Our findings support the interest of identifying and treating sleep apnea in routine cardiology practice.