Obstructive sleep apnoea as a cause of nocturnal nondipping blood pressure: recent evidence regarding clinical importance and underlying mechanisms

Abstract

Obstructive sleep apnoea (OSA) is highly prevalent, with recent general population studies indicating that up to 50% of males and 23% of females have moderate or severe sleep disordered breathing (SDB) based on an apnoea-hypopnoea index (AHI) of >15 events·h -1 [1, 2]. OSA is recognised as an independent risk factor for systemic hypertension [3] and a nondipping nocturnal blood pressure profile is particularly likely in patients with OSA [4], even in the absence of significant hypertension. Furthermore, hypertension is increasingly recognised as an important predictor of prevalent OSA and appears to be more predictive than excessive day-time sleepiness in some settings [5]. However, recent evidence also indicates that only moderate-severe OSA (AHI >20 events·h -1 ) constitutes a significant independent risk for hypertension [2] and cluster analysis of sleep clinic populations indicates that particular population subtypes are especially associated with hypertension [6].These recent reports regarding the very high general prevalence of SDB and factors that influence the relationship with hypertension prompt a reassessment of the clinical relevance regarding the association between OSA and hypertension, especially nocturnal hypertension, and the underlying mechanisms that may contribute to the development of a nondipping nocturnal blood pressure profile in OSA patients. This topic is important in the context of the recent SAVE (Sleep Apnea Cardiovascular Endpoints) trial report [7] involving 2717 patients with established cardiovascular disease and moderate or severe OSA associated with minimal sleepiness who were randomised to best usual care with or without added continuous positive airway pressure (CPAP) therapy and followed for up to 7 years. CPAP therapy was not associated with any improvement in cardiac or cerebrovascular outcome, although data on secondary and other end-points in the report indicated a small but significant reduction in diastolic blood pressure. This finding is particularly relevant in the context that the average compliance with CPAP was only 3.3 h and a recent meta-analysis indicates that beneficial effects of CPAP on blood pressure in OSA patients with minimal sleepiness are largely confined to patients using CPAP for >4 h per night [8].

Childhood OSA is an independent determinant of blood pressure in adulthood: longitudinal follow-up study

“…Studies have consistently demonstrated elevated blood pressure (BP), a well-known risk factor for cardiovascular and cerebrovascular adverse outcomes, in children4 6 8 9 and adults10 with OSA. Non-dipping of nocturnal BP (reduction of nocturnal BP <10% from daytime level) has also been demonstrated in both adults and children with OSA 11–18. The phenomenon of non-dipping in nocturnal BP precedes the development of hypertension in normotensive individuals.…”

“…The phenomenon of non-dipping in nocturnal BP precedes the development of hypertension in normotensive individuals. For patients with hypertension, non-dipping is associated with increased target organ damage and worse cardiovascular prognosis 11. Therefore, prevention of BP abnormalities and non-dipping is important to reduce the risk of developing cardiovascular adverse events 19.…”

Obstructive sleep apnea syndrome and the nocturnal blood pressure profile

“…Furthermore, the up‐regulation of the renin‐angiotensin‐aldosterone and atrial natriuretic peptide systems in response to raised renin levels and intrapleural pressure swings promotes the body fluid redistribution . Crucially, over time, these autonomic and neurohumoral derangements perpetuate beyond the offending events and persist into the daytime, resulting in a disturbance of the overall circadian BP rhythm and an increase in short‐ and long‐term BPV . In this respect, there is accruing evidence that not only high absolute BP levels but even their fluctuations are closely related to the development and progression of organ damage by promoting arterial remodelling, microvascular damage, hemodynamic instability, and vascular reactivity impairment .…”

Is obstructive sleep apnoea the most important determinant of reverse dipping? Hypothesis and evidence

“…OSA may exert marked adverse effects on BP homeostasis through several hemodynamic and chemo‐mediated mechanisms, mainly triggered by the occurrence of repeated episodes of apnoea and hypoxia during sleep leading to intermittent bouts of acute BP changes during nocturnal arousals, with increases in nocturnal systolic BP up to 20‐30 mm Hg within few minutes. The mechanisms underlying the development of hypertension and paradoxical BP increase during sleep include sustained sympathetic over‐activation, endothelial dysfunction, low‐grade inflammation, and progressive increase in arterial stiffness …”