CPAP Therapy Delays Cardiovagal Reactivation and Decreases Arterial Renin-Angiotensin System Activity in Humans With Obstructive Sleep Apnea

摘要

Study Objectives:Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. The effect of OSA treatment with continuous positive airway pressure (CPAP) on the cardiovascular response to a stressor is unknown. We sought to determine the effect of CPAP therapy on heart rate variability (HRV) and arterial stiffness, at baseline, in response to, and recovery from a physiological stressor, Angiotensin II (AngII), in humans with OSA.Methods:Twenty-five incident healthy subjects (32% female; 49 2 years) with moderate-severe OSA and nocturnal hypoxia were studied in high-salt balance, a state of maximal renin-angiotensin system (RAS) suppression, before CPAP, and after 4 weeks of effective CPAP therapy (usage 4 hight) in a second identical study day. HRV was calculated by spectral power and time domain analysis. Aortic augmentation index (AIx) and carotid-femoral pulse-wave velocity (PWVcf) were measured by applanation tonometry. HRV and arterial stiffness were measured at baseline and in response to AngII challenge (3 ng/ kg/min·30 minutes, 6 ng/kg/min·30 minutes, recovery·30 minutes). The primary outcome was the association between CPAP treatment and HRV and arterial stiffness responses to, and recovery from, AngII challenge. In an exploratory analysis subjects were stratified by sex.Results:CPAP corrected OSA and nocturnal hypoxemia. CPAP treatment was associated with increased sensitivity and delayed recovery from AngII (ln HF [high frequency; recovery: 0.09 0.19 versus 0.59 0.17 ms2, P = .042; rMSSD [root mean successive differences; recovery: 0.4 2.0 versus 7.2 1.9 ms, P = .001], pNN50 [percentage of normal waves differing 50 ms compared to the preceding wave; AngII: 1.3 2.3 versus 3.0 2.4%, P = .043; recovery: 0.4 1.4 versus 6.0 1.9%, P = .001], all values pre-CPAP versus post-CPAP treatment). No differences were observed by sex. There was increased AIx sensitivity to AngII after CPAP among men (8.2 1.7 versus 11.9 2.2%, P = .046), but not women (11.4 1.5 versus 11.6 2.1%, P = .4). No change in PWVcf sensitivity was observed in either sex.Conclusions:CPAP therapy was associated with delayed cardiovagal reactivation after a stressor and down-regulation of the arterial RAS. These findings may have important implications in mitigating cardiovascular risk in both men and women with OSA.