Meta-analysis of Effects of Obstructive Sleep Apnea on the Renin-angiotensin-aldosterone System

Background: Obstructive sleep apnea (OSA) is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system (RAAS). We meta-analyzed the effects of OSA on plasma levels of RAAS components.

Methods: Full-text studies published on MEDLINE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index ≥ 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the I (2) statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed.

Results: The meta-analysis included 13 studies, of which 10 reported results on renin (n = 470 cases and controls), 7 on angiotensin II (AngII, n = 384), and 9 on aldosterone (n = 439). AngII levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI: 2.00-4.79, P < 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension (mean differences = 1.32 ng/dL, 95% CI: 0.58-2.07, P = 0.0005). Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL (95% CI: 0.88-1.82, P < 0.00001) emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies.

Conclusions: OSA is associated with higher AngII and aldosterone levels, especially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity.