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The Effects of Repetitive Arousals on Cardiovascular System:a Better Understanding on the Pathophysiology of Cardiovascular Diseases Secondary to OSAHS

Author: WuYanYan
Tutor: CaiBaiQiang
School: Beijing Union Medical College
Course: Clinical
Keywords: Obstructive Sleep Apnea Hypopnea Syndrome Repetitive Arousal Cardiovascular System Autonomic Nervous System Heart Rate Variability Stiffness Index Endothelial Dysfunction
CLC: R766
Type: PhD thesis
Year: 2013
Downloads: 18
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Abstract

Objectives:To investigate whether repetitive arousals will lead to overt changes in cardiovascular system in healthy subjects. To give clues to the understanding of the pathophysiology of cardiovascular diseases secondary to obstructive sleep apnea hypopnea syndrome (OSAHS) and the roles that repetitive arousals play in it.Methods:Polysomnography was conducted on two consecutive nights for twenty healthy young male subjects (age25.0±2.1, BMI22.9±1.9kg·m-2). The first night functioned as a baseline-control and was free of any intervention. On the second night, arousals were repeatedly induced by auditory stimuli applied repetitively over the whole night and the resulted arousal index (ArI) was expected to be60hr-1at the best. Sleep architecture, subjective assessment of sleep quality, blood pressure, heart rate variability (HRV) variables, arterial stiffness index and certain serum markers were compared between the two nights. Parameters of sleep architecture include total sleep time, ArI and the time spent in and the percentages of N1, N2, N3and REM sleep. St Mary’s hospital sleep questionnaire was used to evaluate the quality and continuity of sleep subjectively. Blood pressure (BP) was measured, and electrocardiography and digital volume pulse (DVP) were recorded under undisturbed conditions while subjects were awake on the following four occasions respectively, before lights-off on control night (C1), after lights-on on control night (C2), before lights-off on test night (T1), and after lights-on on test night (T2). HRV analysis was carried out applying the fast Fourier transform method and low frequency power in normalized unit (LF), high frequency power in normalized unit (HF) and LF/HF ratio (LHR) were deduced to assess the status of autonomic nervous system. Stiffness index (SI) was calculated from the contour analysis of digital volume pulse. To study the effects on BP, SI and HRV indices of the intervention, we compared the change in each of these variables over the test night (T2-T1) to the change over the control night (C2-C1). If the difference between these two changes was significant, we further compared T2to Tl and C2to Cl respectively to find out what changes occurred. CRP, IL-6, TNF-α, VEGF, NO, ET-1in serum were measured and compared between the two nights. Correlation was explored with the Spearman method.Results:The ArI on test night was actually44±9(27-55.2) hr-1. The time spent in N3 sleep on test night was significantly less than that on control night (P=0.039) and the Arl on test night was no surprisingly much higher than that on control night (P<0.001). When asked about the alertness upon awakening in the morning, subjects confessed that it was worse following the test night (P=0.019). Subjectively, they reported more arousals for the test night as compared to control night (P<0.001). The post-sleep diastolic blood pressure (DBP) was higher than the pre-sleep one for the test night (P=0.003) and the increment was remarkable when compared with the control night (P=0.026). The difference between the change in DBP over the test night and that over the control night was correlated with the difference in the percentages of N2sleep on the two nights (P=0.011). Regarding to the HRV indices, LF and LHR increased throughout the test night while HF decreased (all P<0.001). When compared with control night, all the changes over the test night were statistically significant (all P<0.001). The change in HF over the test night was correlated with the time spent in and percentage of REM sleep on the same night (P=0.003, P=0.006). The change in LHR over the test night was correlated with the same sleep indices with P value of0.008and0.027respectively. The changes in SI over the two nights were not significantly different from each other. None of the changes in any of the biomarkers between the two nights reached the significance.Conclusions:We demonstrate that exposure to repetitive arousals induced by auditory stimuli leads to elevation of sympathetic nervous system activity and reduction of parasympathetic nervous system activity, which remain evident after the arousals end for a while, indicating the cumulative effect of repetitive arousals on autonomic nervous system. Repetitive arousals also cause an increase of diastolic blood pressure in the morning which might be related to the disturbance to sleep architecture, but the underlying mechanisms has not been fully elucidated yet. Considering no obvious changes have been discovered in stiffness index or biomarkers, it is very likely that the shift in sympatho-vagal balance occurs prior to endothelial dysfunction in the development of cardiovascular disease in OSAHS patients.

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