J Clin Neurol.  2018 Jul;14(3):310-319. 10.3988/jcn.2018.14.3.310.

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

• Moon J
• Choi KH
• Park JH
• Song TJ
• Choi YS
• Kim JH
• Kim HJ
• Lee HW

• KMID: 2415046
• DOI: http://doi.org/10.3988/jcn.2018.14.3.310

Abstract

BACKGROUND AND PURPOSE
Obstructive 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.
METHODS
We 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.
RESULTS
Among 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.
CONCLUSIONS
Our findings suggest that dysregulation of HRV, especially overactivation of sympathetic tone, could be a pathophysiologic mechanism underlying the development of WMC in OSA patients.

Keyword

obstructive sleep apnea; white-matter changes; heart-rate variability; nonlinear indices; sympathetic overactivation

MeSH Terms

Brain
Entropy
Humans
Hypertension
Magnetic Resonance Imaging
Polysomnography
Sleep Apnea, Obstructive*
Sleep Stages

Figure

• 

  Fig. 1 Flow chart for the selection of the study subjects. Among the patients who visited the Sleep Center of Ewha University Medical Center and underwent overnight PSG between April 2005 and May 2014, 185 patients were selected who underwent brain MRI within 1 year before or after PSG. Sixty-four of the 122 OSA patients had WMC. Thirty-three of the subjects without OSA did not have WMC. Subjects were excluded from the heart-rate variability analysis if the artifact-free and arousal-free periods of their N1, N2, or REM sleep periods were shorter than 5 min on PSG. Finally 135 subjects were included in the current study: 60 were assigned to the OSA+WMC group, 44 to the OSA−WMC, and 31 to the control group. OSA: obstructive sleep apnea, OSA+WMC: obstructive sleep apnea with white-matter changes, OSA−WMC: obstructive sleep apnea without white-matter changes, PSG: polysomnography, REM: rapid-eye-movement, WMC: white-matter changes.

• 

  Fig. 2 ApEn values during REM sleep in middle-aged OSA patients (age 45–64 years). A: ApEn values during REM sleep of each subject in the OSA−WMC group (0.94±0.23, n=18) and OSA+WMC group (0.79±0.25, n=18) (p=0.031, Mann-Whitney test). B: ROC curve analysis was performed for diagnosing OSA+WMC among middle-aged OSA patients. The area under the curve was 0.71. With a cutoff of ApEn <0.85, the sensitivity, specificity, PPV, and NPV were 55.6, 77.8, 71.4, and 63.6%, respectively. ApEn: approximate entropy, NPV: negative predictive value, OSA: obstructive sleep apnea, OSA+WMC: obstructive sleep apnea with white-matter changes, OSA−WMC: obstructive sleep apnea without white-matter changes, PPV: positive predictive value, REM: rapid-eye-movement, ROC: receiver operating characteristics.

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