Relationship of Arousals From Sleep to Sympathetic Nervous System Activity and BP in Obstructive Sleep Apnea* Jose ´ S. Loredo, MD; Michael G. Ziegler, MD; Sonia Ancoli-Israel, PhD; Jack L. Clausen, MD; and Joel E. Dimsdale, MD Study objective: Obstructive sleep apnea (OSA) patients have a high frequency of arousals. We hypothesized that arousals significantly influence tonic sympathetic nervous system function. Design: We examined the association of 11 variables measuring sympathetic activity, including plasma norepinephrine (NE), urinary NE, and BP measurements, with movement and cortical arousals. Patients: Sixty-seven subjects with various degrees of hypertension and OSA were evaluated. All patients were free from antihypertensive medications. Results: The age (range, 35 to 60 years), weight (range, 100 to 150% of ideal body weight), and diet of the subjects were similar. The movement arousal index was correlated with daytime baseline plasma NE (BNE), daytime urine NE, mean daytime diastolic BP, and systolic BP during rapid eye movement sleep (r  0.39 to 0.53; p < 0.002). Cortical arousals did not correlate with any of the variables. A multiple regression procedure was performed to examine how well movement arousals predicted those variables with significant correlations. The respiratory disturbance index (RDI) and nighttime pulse oxyhemoglobin saturation were included in the regression equation due to their close association with movement arousals. Movement arousals independently predicted BNE (t [48]  2.06; p < 0.05). No other variable independently pre- dicted any of the measurements of sympathetic activity. Conclusions: These findings suggest that movement arousals may influence daytime sympathetic tone independently of RDI and nighttime saturation. (CHEST 1999; 116:655– 659) Key words: arousals; BP; norepinephrine; obstructive sleep apnea; sympathetic nervous system Abbreviations: BNE = daytime baseline plasma norepinephrine; CAI = cortical arousal index; EMG = electromyography; MAI = movement arousal index; MDBP = mean resting diastolic BP; NE = norepinephrine; OSA = obstructive sleep apnea; RDI = respiratory disturbance index; REM = rapid eye movement; SBP = systolic BP; SNS = sympathetic nervous system; SpO 2 = pulse oxyhemoglobin saturation; TST = total sleep time T ransient increases in heart rate, BP, ventilation, and surges in sympathetic output often accom- pany arousals from sleep. These autonomic changes appear to be out of proportion to the physiologic needs of the sleeping individual. 1 Animal and human studies support the notion that arousals from sleep lead to transient activation of the sympathetic ner- vous system (SNS), 2,3 which could have cardiovascu- lar implications. 4 Increases in SNS activity is a frequently invoked hypothesis for the mechanism of the development of hypertension in patients with obstructive sleep apnea (OSA). 5–7 Hypoxia increases sympathetic nerve fir- ing, 8 especially in the presence of upper airway obstruction such as during an apneic event. 4,9 Mea- surement of plasma and urinary catecholamines also support higher sympathetic activity in sleep apnea patients. 10 –13 One of the characteristics of sleep apnea patients is their high frequency of arousals from sleep. However, it is not known if arousals contribute to the tonic activation of the SNS de- scribed in OSA. The measurement of arousals is not well standard- ized. In recent work, we found that two categories of *From the Department of Medicine (Drs. Loredo, Ziegler, and Clausen) and the Department of Psychiatry (Drs. Dimsdale and Ancoli-Israel), University of California, San Diego, San Diego, CA. Manuscript received July 14, 1998; revision accepted March 31, 1999. This work was supported in part by NIH grants HL44915, AG02711, AG08415, and RR00827. Correspondence to: Jose ´ S. Loredo, MD, UCSD Medical Center Department of Medicine, 200 West Arbor Dr, San Diego, CA 92103-8378; e-mail: jloredo@ucsd.edu CHEST / 116 / 3 / SEPTEMBER, 1999 655 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21931/ on 06/25/2017