Resistant hypertension, obstructive sleep apnoea and aldosterone

Abstract

Obstructive sleep apnoea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is strongly associated with an increased risk of prevalent hypertension, whereas prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure (BP). Determining why OSA is so strongly linked to having hypertension in cross-sectional studies, but yet CPAP therapy has limited BP benefit needs further exploration. The CPAP studies do, however, indicate a wide variation in the BP effects of CPAP, with some patients manifesting a large antihypertensive benefit such that a meaningful BP effect can be anticipated in some individuals. OSA is particularly common in patients with resistant hypertension (RHTN). The reason for this high prevalence of OSA is not fully explained, but data suggest that it may be related to the high occurrence of hyperaldosteronism in patients with RHTN. In patients with RHTN, it has been shown that aldosterone levels correlate with severity of OSA and that blockade of aldosterone reduces the severity of OSA. Overall, these findings are consistent with aldosterone excess contributing to worsening of underlying OSA. We hypothesize that aldosterone excess worsens OSA by promoting accumulation of fluid within the neck, which then contributes to increased upper airway resistance.

Figure 1

Pathophysiological mechanisms involved in the aetiology of OSA-induced hypertension. RAAS, renin–angiotensin–aldosterone system.

Figure 2

AHI (ρ = 0.44, P = 0.0002) correlates with plasma aldosterone concentration (PAC) in subjects with RHTN. Reprinted with permission from Pratt-Ubunama et al.

Figure 3

Effects of 8 weeks of treatment with spironolactone on AHI; hypoxic index (HI); supine AHI; and rapid-eye-movement sleep (REM). AHI at 8 weeks (light grey bars) compared with baseline (dark grey bars) in patients with RHTN. *Different compared with baseline, P>0.05. Reprinted with permission from Gaddam et al.

Figure 4

Proposed pathophysiological mechanisms of aldosterone-induced worsening of OSA.