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

Abstract

From the physiopathological point of view obstructive sleep apnoea (OSA) should be regarded as the phenotype with the highest potential to disrupt the normal circadian blood pressure (BP rhythm). Despite these assumptions, it is surprising, however, to note that the data supporting a link between OSA and paradoxical increase in nighttime BP (ie, the so‐called reverse dipping pattern) are still very limited and in some ways not entirely consistent. Available evidence on the association between OSA and reverse dipping (RD pattern), contrary to what is commonly thought, is still scanty. Given the potential negative synergistic effect of these two conditions, it is essential to have studies targeting this topic available soon.

One of the distinctive features of 24‐hour ambulatory blood pressure monitoring (ABPM) is its unique ability to evaluate circadian BP changes and to classify subjects into dippers (ie, a decrease in mean systolic/diastolic nighttime BP ≥ 10% than daytime BP values) and non‐dippers (ie, a <10% BP reduction of nighttime versus daytime BP). Furthermore, within each of these two categories, the so‐called extreme dippers (ie, a nocturnal BP fall ≥ 20%) and reverse dippers (ie, a rise rather than a dip of nocturnal BP) can be identified.

Several cross‐sectional and prospective studies have shown that, compared with dippers, subjects with a non‐dipping BP pattern have a higher risk of hypertension mediated organ damage as well as a greater risk of incident cardiovascular (CV) events and all‐cause death. It has also been suggested that the increased risk of organ damage and hard outcomes is particularly pronounced in individuals with reverse dipping (RD), which represents an extreme, not so rare abnormality of the nocturnal BP profile associated with unfavorable clinical consequences.

The CV risk associated with RD pattern has been assessed by a recent meta‐analysis of five prospective studies including 6918 untreated and treated hypertensive subjects. A total of 890 CV events (13%) occurred during the follow‐up periods ranging from 41 to 120 months. In the pooled population, the risk of nonfatal and fatal CV events in RD patients was 2.5‐fold greater than in their dipper counterparts (95% CI 2.11‐2.96, P < .01) and, notably, persisted to be approximately 2.0‐fold higher as compared to non‐dippers (95% CI 1.77‐2.45, P < .001).1

As for the prevalence of RD pattern, estimates of this altered circadian BP rhythm, although of limited prevalence in general population cohorts (<5%), have been reported to be up to 10 times more prevalent in patients with secondary hypertension, type 2 diabetes, renal diseases, and obstructive sleep apnoea syndrome (OSA).

Among the aforementioned conditions associated with RD, OSA is the most frequent at the community level. Over the past 25 years, epidemiological surveys have shown a progressive, sharp increase in the prevalence of sleep‐disordered breathing. In a large population‐based study (HypnoLaus, based on polysomnography data from 2121 people), moderate‐to‐severe OSA has been diagnosed in up to 50% of men and 23% of women.2

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.3

Therefore, from the physiopathological point of view OSA should be regarded as the phenotype with the highest potential to disrupt the normal circadian BP rhythm. Despite these assumptions, it is surprising, however, to note that the data supporting a link between OSA and paradoxical increase in nighttime BP are still very limited and in some ways not entirely consistent.

We have recently performed a meta‐analysis from 14 studies published in the last two decades reporting information on the association between OSA and the non‐dipping pattern from different clinical settings including a total of 2519 normotensive, untreated, and treated hypertensive individuals without and with OSA (C. Cuspidi, M. Tadic, C. Sala, E. Gherbesi, G. Grassi, & G. Mancia, unpublished data). Among the selected studies only four provided additional findings on the prevalence of RD. In the largest of such studies encompassing more than 700 participants, the prevalence of RD in the fraction of patients with moderate‐to‐severe OSA was around 19%.4

In the other studies, the frequency of this pattern varied widely from 20% to 73%. It is worth noting that the study that reported the highest frequency, OSA was also present in 37% of dippers, 46% extreme dippers, and 49% of non‐dippers.5 Finally, the results of a couple of studies conducted in patients with 1 or more CV risk factors6 and in children with OSA7 merit to be mentioned. Both reports showed that the apnoea‐hypopnoea index, as continuous variable, was unrelated to the presence of RD pattern, after adjusting for confounders.

In conclusion available evidence on the association between OSA and RD pattern, contrary to what is commonly thought, is still scanty. Given the potential negative synergistic effect of these two conditions, it is essential to have studies targeting this topic available soon.

CONFLICT OF INTEREST

The authors report no conflicts of interest.

Cuspidi C, Gherbesi E, Tadic M. Is obstructive sleep apnoea the most important determinant of reverse dipping? Hypothesis and evidence. J Clin Hypertens. 2019;21:1594–1595. 10.1111/jch.13682