Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and cerebrovascular regulation

Abstract

What is the topic of this review? This review examines the notion that obstructive sleep apnoea (OSA) and intermittent hypoxia (IH) have hormetic effects on vascular health. What advances does it highlight? Clinical (OSA patient) and experimental animal and human models report that IH is detrimental to vascular regulation. However, mild IH and, by extension, mild OSA also have physiological and clinical benefits. This review highlights clinical and experimental animal and human data linking OSA and IH to vascular disease and discusses how hormetic effects of OSA and IH relate to OSA severity, IH intensity and duration, and patient/subject age. Obstructive sleep apnoea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease, a consequence attributed in part to chronic intermittent hypoxia (IH) resulting from repetitive apnoeas during sleep. Although findings from experimental animal, and human, models have shown that IH is detrimental to vascular regulation, the severity of IH used in many of these animal studies [e.g. inspired fraction of oxygen (FI,O2) = 2-3%; oxygen desaturation index = 120 events h ] is considerably greater than that observed in the majority of patients with OSA. This may also explain disparities between animal and recently developed human models of IH, where IH severity is, by necessity, less severe (e.g. FI,O2 = 10-12%; oxygen desaturation index = 15-30 events h ). In this review, we highlight the current knowledge regarding the impact of OSA and IH on cardiovascular and cerebrovascular regulation. In addition, we critically discuss the recent notion that OSA and IH may have hormetic effects on vascular health depending on conditions such as OSA severity, IH intensity and duration, and age. In general, data support an independent causal link between OSA and vascular disease, particularly for patients with severe OSA. However, the data are equivocal for older OSA patients and patients with mild OSA, because advanced age and short-duration, low-intensity IH have been reported to provide a degree of protection against IH and ischaemic events such as myocardial infarction and stroke, respectively. Overall, additional studies are needed to investigate the beneficial/detrimental effects of mild OSA on the various vascular beds.

Vascular responses to hypoxia are not impaired in obstructive sleep apnoea patients free of overt cardiovascular disease

“…Moderate-to-severe OSA is an independent risk factor for stroke and cardiovascular disease (Beaudin et al, 2017;Somers et al, 2008).…”

“…We previously reported that patients with very severe OSA (apnoea/hypopnoea index (AHI) = 101 ± 10 events h −1 ) who were free of overt cardiovascular disease had a CBF response to hypoxia that was ∼42% lower compared to age-and BMImatched controls (Foster et al, 2007). Thereafter, Reichmuth et al (2009) (He, Kryger, Zorick, Conway, & Roth, 1988) and older age appears protective against IH-induced sympathoexcitation and oxidative stress (Beaudin et al, 2017;Quintero et al, 2016). The mean age of our OSA patients and controls was 50 years (vs. 41 and 37 years (Foster et al, 2007), and 36 and 34 years (Reichmuth et al, 2009)).…”

“…Obstructive sleep apnoea (OSA) is a chronic medical condition characterized by repetitive apnoeas and/or hypopnoeas during sleep that exposes untreated patients to chronic intermittent hypoxia (IH) and hypercapnia, surges in sympathetic nerve activity and blood pressure, increased negative intrathoracic pressure, and sleep fragmentation (Leung & Bradley, 2001). Patients with OSA are at increased risk of stroke and cardiovascular disease (Peppard, Young, Palta, & Skatrud, 2000;Redline et al, 2010); though the mechanism is likely multifactorial, the increased risk of stroke is believed to result principally from chronic IH exposure (Beaudin, Waltz, Hanly, & Poulin, 2017). The specific physiological mechanism through which IH increases stroke risk is poorly understood, but appears to include the disruption of cerebrovascular regulation.…”

Effect of age on the cardiovascular remodelling induced by chronic intermittent hypoxia as a murine model of sleep apnoea

“…Based on cross‐sectional, observational and longitudinal studies, OSA has been defined as an independent risk factor for cardiovascular and cerebrovascular diseases . Clinical and experimental studies indicate that among the cardiometabolic complications of OSA, IH is the most detrimental perturbation .…”

“…Clinical and experimental studies indicate that among the cardiometabolic complications of OSA, IH is the most detrimental perturbation . Chronic IH (CIH) during sleep induces sympathetic overactivation, oxidative stress, systemic inflammation, insulin resistance and disruption of lipid metabolism, all of which contribute to the development of early and late cardiovascular remodelling, including increased endothelial dysfunction, elevated blood pressure, increased carotid intima‐media thickness (IMT), arterial stiffness, accelerated progression of atherosclerosis and cardiac alterations …”