Sympathetic Overactivity Based on Heart-Rate Variability in Patients with Obstructive Sleep Apnea and Cerebral Small-Vessel Disease

Abstract

Background and PurposeObstructive sleep apnea (OSA) is associated with cerebral white-matter changes (WMC), but the underlying mechanisms are not completely understood. Our aim was to identify the cardiovascular autonomic characteristics during sleep that are associated with cerebral WMC in OSA patients.MethodsWe recruited subjects from our sleep-center database who underwent both polysomnography and brain MRI within a 1-year period. Sixty patients who had OSA with WMC (OSA+WMC), 44 patients who had OSA without WMC (OSA−WMC), and 31 control subjects who had neither OSA nor WMC were analyzed. Linear and nonlinear indices of heart-rate variability (HRV) were analyzed in each group according to different sleep stages and also over the entire sleeping period.ResultsAmong the nonlinear HRV indices, the Poincaré ratio (SD12) during the entire sleep period was significantly increased in the OSA+WMC group, even after age adjustment. Meanwhile, detrended fluctuation analysis 1 during non-rapid-eye-movement sleep tended to be lowest in the OSA+WMC group. These indices were altered regardless of the presence of hypertension or diabetes. In the subgroup analysis of middle-aged OSA patients, approximate entropy during rapid-eye-movement sleep was significantly lower in OSA+WMC patients than in OSA−WMC patients. Overall, the nonlinear HRV indices suggest that sympathetic activity was higher in the OSA+WMC group than in the OSA−WMC and control groups.ConclusionsOur findings suggest that dysregulation of HRV, especially overactivation of sympathetic tone, could be a pathophysiologic mechanism underlying the development of WMC in OSA patients.

Autonomic function in amnestic and non-amnestic mild cognitive impairment: spectral heart rate variability analysis provides evidence for a brain–heart axis

“…No such associations were found in CN subjects .The finding that naMCI subjects had the same response to orthostatic stress as CN subjects is likely due to the fact that the exclusion criteria, inherent to a study on the cerebral substrate of HRV (see “ Methods ”), selected a low/intermediate cardiovascular risk population in which severe brain vascular burden was under-represented, thus reducing our ability to detect a significant effect. In particular, most studies demonstrating autonomic dysfunction in ischaemic brain damage have focused on subjects at high cardiovascular risk like diabetics with 64 and without 68 VAD as well as patients with obstructive sleep apnea 65 , or have not excluded individuals with cardiovascular risk factors and diseases 67 . In our naMCI group at low/intermediate cardiovascular risk, a provocative manoeuvre such as paced breathing, which challenges the parasympathetic system 80 , could have directly assessed the parasympathetic reserve and unmasked mild parasympathetic deficits.…”

“…Although there is very scant literature addressing the relationship between ischaemic brain damage and HRV, it mainly points to a parasympathetic dysfunction with sympathetic predominance. In fact, reduced parasympathetic indices and increased indices of sympathetic activation/parasympathetic withdrawal have been found among diabetics with VAD compared to only-diabetic controls 64 and in subjects with obstructive sleep apnea and white matter lesions (WML) 65 relative to those without WML . Decreased parasympathetic indices have been reported in the early stages of Binswanger's encephalopathy 66 , in MCI subjects with WML 67 and in diabetics with lacunar lesions 68 .…”

Interarm Blood Pressure Difference has Various Associations with the Presence and Burden of Cerebral Small-Vessel Diseases in Noncardioembolic Stroke Patients

“…The protocol of brain MRI used in this study was described in detail previously 2021. All brain MRI was performed using a 3-T scanner (Philips Achieva version 2.6, Best, the Netherlands).…”

“…All brain MRI was performed using a 3-T scanner (Philips Achieva version 2.6, Best, the Netherlands). Brain MRI slices were acquired parallel to the orbitomeatal line using the following parameters: TR/TE=12,000/120 ms, pixel spacing=0.449/0.449 mm, field of view (FOV)=183×230 mm, and slice thickness=5 mm for FLAIR images; TR/TE=15,000/90 ms, pixel spacing=0.240/0.240 mm, FOV=176×220 mm, and slice thickness=5 mm for T2-weighted images; and TR/TE=571/21.9 ms, pixel spacing=0.449/0.449 mm, FOV=145×250 mm, and slice thickness=5 mm for GRE images 2021…”

The Association of Autonomic Nervous System Function With Ischemic Stroke, and Treatment Strategies

“…Obstructive sleep apnea (OSA) is also a risk factor for stroke (63) and is associated with cerebral WMLs, while moderateto-severe OSA (apnea-hypopnea index ≥ 15) was positively associated with CSVD (64). Using non-linear HRV indices, over-activation of sympathetic tone was suggested to represent a pathophysiologic mechanism for development of WML in OSA patients (65). Furthermore, failed autonomic control of cerebral circulation because of hypertension was reported to predispose individuals to CSVD and cognitive impairment, in which sympathetic activation may play a major role [ Figure 2; (66)].…”