Influence and implications of the renin–angiotensin–aldosterone system in obstructive sleep apnea: An updated systematic review and meta‐analysis

Abstract

Obstructive sleep apnea is a chronic, sleep-related breathing disorder, which is an independent risk factor for cardiovascular disease. The renin-angiotensin-aldosterone system regulates salt and water homeostasis, blood pressure, and cardiovascular remodelling. Elevated aldosterone levels are associated with excess morbidity and mortality.We aimed to analyse the influence and implications of renin-angiotensin-aldosterone system derangement in individuals with and without obstructive sleep apnea. We pooled data from 20 relevant studies involving 2828 participants (1554 with obstructive sleep apnea, 1274 without obstructive sleep apnea). The study outcomes were the levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate. Patients with obstructive sleep apnea had higher levels of plasma renin activity (pooled wmd+ 0.25 [95% confidence interval 0.04-0.46], p = 0.0219), plasma aldosterone (pooled wmd+ 30.79 [95% confidence interval 1.05-60.53], p = 0.0424), angiotensin II (pooled wmd+ 5.19 [95% confidence interval 3.11-7.27], p < 0.001), systolic (pooled wmd+ 5.87 [95% confidence interval 1.42-10.32], p = 0.0098) and diastolic (pooled wmd+ 3.40 [95% confidence interval 0.86-5.94], p = 0.0086) blood pressure, and heart rate (pooled wmd+ 3.83 [95% confidence interval 1.57-6.01], p = 0.0009) compared with those without obstructive sleep apnea. The elevation remained significant (except for renin levels) when studies involving patients with resistant hypertension were removed. Sub-group analysis demonstrated that levels of angiotensin II were significantly higher only among the Asian population with obstructive sleep apnea compared with those without obstructive sleep apnea. Body mass index accounted for less than 10% of

Obstructive sleep apnea and vitamin D level: Has the dust settled?

“…This might be contributed by low‐grade inflammation and production of pro‐inflammatory cytokines causing endothelial dysfunction 9–11 . A recent meta‐analysis demonstrated that patients with OSA have higher level of renin‐angiotensin‐aldosterone system hormones, blood pressure, and heart rate compared with those without OSA, which may add on to the increased cardiovascular risks among this cohort 12 …”

“…[9][10][11] A recent meta-analysis demonstrated that patients with OSA have higher level of renin-angiotensinaldosterone system hormones, blood pressure, and heart rate compared with those without OSA, which may add on to the increased cardiovascular risks among this cohort. 12 Although traditionally, vitamin D is thought to play its main role in calcium homeostasis and regulation, there is now increasing evidence that low vitamin D level is associated with a multitude of cardio-metabolic complications, which has sparked new interests in these extra-skeletal associations. 13 Hypovitaminosis D is related to increased risks of cardiovascular diseases, metabolic dysfunctions, worse cardiovascular outcomes, and elevated all-cause mortality.…”

“… 9 , 10 , 11 A recent meta‐analysis demonstrated that patients with OSA have higher level of renin‐angiotensin‐aldosterone system hormones, blood pressure, and heart rate compared with those without OSA, which may add on to the increased cardiovascular risks among this cohort. 12 …”

Obesity-related kidney disease: Beyond hypertension and insulin-resistance

“…CIH also activates interstitial fibroblasts and induces renal tubular epithelial cells to undergo an epithelial-to-mesenchymal transition by upregulation of HIFs, leading to renal fibrosis ( 188 – 191 ). Nocturnal hypoxia in OSA patients over-activates the sympathetic and renin-angiotensin-aldosterone systems, associated with long-term renal impairment ( 192 – 194 ). These experimental models explain clinical studies showing that OSA contributes to CKD development and progression.…”

Sleep deprivation reduces the baroreflex sensitivity through elevated angiotensin (Ang) II subtype 1 receptor expression in the nucleus tractus solitarii

“…The endogenous Ang II exerts a tonic inhibitory modulation on BRS response via an action on AT1R but not subtype 2 receptors (AT2R) in the NTS ( Luoh and Chan, 1998 ). More interestingly, numerous studies have shown that RAS is significantly activated in sleep-deprived animals and in patients with sleep apnea ( Visniauskas et al, 2011 ; Loh et al, 2023 ). It is suggested that abnormal Ang II is also a significant pathological mediator in the brain after sleep disorders, but whether it is involved in BRS injury is unclear.…”