, Rohit Arora3, 4, Nicholas L. DePace5 and Aaron I. Vinik6
(1)
Autonomic Laboratory Department of Cardiology, Drexel University College of Medicine, Philadelphia, PA, USA
(2)
ANSAR Medical Technologies, Inc., Philadelphia, PA, USA
(3)
Department of Medicine, Captain James A. Lovell Federal Health Care Center, North Chicago, IL, USA
(4)
Department of Cardiology, The Chicago Medical School, North Chicago, IL, USA
(5)
Department of Cardiology, Hahnemann Hospital Drexel University College of Medicine, Philadelphia, PA, USA
(6)
Department of Medicine, Eastern Virginia Medical School Strelitz Diabetes Research Center, Norfolk, VA, USA
From an autonomic perspective, sleep disorders fall into one of the two categories:
Parasympathetic excess (PE), which is associated with daytime sleepiness
Sympathetic excess (SE), which is associated with nighttime sleeplessness
Overview
P&S monitoring helps to detect (possibly earlier), differentiate, and document P or S involvement in sleep disorders, specifying autonomic imbalance [1–3]. Restoring and maintaining P&S imbalance minimizes effects of sleep disorders, often relieving the sleep disorder and slowing the onset of secondary disorders, such as cardiovascular disease and depression, reducing morbidity and mortality risk. Often, once the P&S balance is restored, patients tend to be more stable, enabling the physician to be more aggressive with the primary disorder, helping to maintain proper sleep function and in some cases relive the sleep dysfunction. This leads to fewer comorbidities, leading to reduced medication load and hospitalizations, improved outcomes, and reduced healthcare costs [4].
According to the American Association for Sleep Medicine website [5], of all of the parameters measured and considered, it lists P and S function at the top, but never measures P and S function directly. The reason for listing P and S function first is that (1) PE underlies daytime sleepiness and (2) SE underlies nighttime sleeplessness. Persistent fatigue or chronic fatigue syndrome and narcolepsy are associated with PE [1]. Insomnia and sleep apnea are associated with SE [2].
PE underlies daytime sleepiness and SE underlies nighttime sleeplessness. Persistent fatigue or chronic fatigue syndrome and narcolepsy are associated with PE. Insomnia and sleep apnea are associated with SE. Restoring P&S balance ameliorates sleep disorders and reduces comorbidities, reducing mortality risk, medication load, and hospitalizations, improving patient outcomes, and reducing healthcare costs [6].
P&S Monitoring in Sleep Medicine
The results of P&S monitoring reveal P&S activity that are in complete agreement with those obtained with direct invasive tools. This is the conclusion of a study published by Akselrod’s lab for which normal, standard, overnight polysomnograms from ten healthy children aged 6–17 years were studied [4]. P&S assessment was added to the study from analyses of the EKG and respiratory activity collected during the polysomnogram. The study revealed a decrease in sympathetic (LFa) activity during sleep, with minimal values during non-REM slow-wave sleep and elevated levels similar to those of wakefulness during REM. Parasympathetic (RFa) activity increased with sleep onset, reaching maximal values during slow-wave sleep, and behaved as a mirror image of the LFa. SB displayed changes similar to those in LFa. The sympathetic predominance that characterizes wakefulness decreases during non-REM sleep, is minimal in slow-wave sleep, and surges towards mean awake levels during REM sleep. SB is shifted towards parasympathetic predominance during slow-wave sleep [4].
Pereira et al. [2] investigated the cardiovascular implications of sympathetic involvement in sleep medicine. Resting SE is associated with nighttime sleeplessness. SE is also associated with tachycardia, high BP, pain, stress, and many chronic diseases [7]. SE in chronic disease, including cardiovascular disease (CVD, e.g., heart failure, cardiomyopathy, arrhythmia, hypertension, and stroke) or diseases that involve CVD (e.g., diabetes), is a known morbidity and mortality risk factor [8, 9] and is associated with most other risk factors [10, 11]. Often, SE is associated with (and may induce) very low parasympathetic activity, which leads to the need for cardiac intervention or an implanted cardiac device. In fact, SE due to chronic disease may be the mechanism for comorbidities that include nighttime sleeplessness. Therefore, the SE associated with sleep disturbances may also contribute to associated cardiovascular risks. Correcting SE to relieve the sleep disorder may also reduce morbidity and mortality risks associated with CVD [12–15].
This report presents data from a study of both parasympathetic and sympathetic involvement in sleep disorders. Specifically, this report documents the involvement of SE demonstrated by patients diagnosed with sleep disorders. Serial P&S Autonomic Assessment (see Chap. 5) was performed on 223 age- and body mass-matched patients (114 female; average age = 53.2 years) from three ambulatory clinics, 132 of which (59 %, 56 female) were found with SE with reported sleep disturbances. Patients with sleep apnea or PE were omitted and reported separately [1, 3]. Patients were prescribed 3.125–6.25 mg carvedilol. Patients contraindicated for carvedilol were omitted from the study. This study will focus on data from the initial resting baseline. The results were analyzed and presented here against 234 age-matched normals from our nationwide database. Statistical analysis was performed with SPSS v14.0.
The natural history of SE secondary to sleep disorders (not including sleep apnea) is depicted in Fig. 25.1. Note the patients’ SE from approximately age 30 onwards. Even though balance is restored in the geriatric years, the balance does not shift to the parasympathetic side as demonstrated in the normal geriatric subjects shown in the same figure. Insomnia was diagnosed in 32 patients (36 %). Hypertension was diagnosed in 64 patients (73 %). CVD was diagnosed in 57 patients (65 %). Arrhythmia was diagnosed in 17 patients (19 %). Therapy relieved symptoms of SE in 84 % of the patients over an average of 1 month. Therapy relieved sleep disturbances in 46 % of the patients within an average of 1 week. Therapy reduced hypertension in 53 % of the patients and reduced arrhythmia in 42 % of the patients. In most cases, therapy did not reduce parasympathetic activity, and in reducing sympathetic activity, the ratio (SB) was normalized; see Fig. 25.2.
Fig. 25.1
The natural history of sympathetic excess secondary to sleep disorder (not including sleep apnea). The broken curves with data points depict patients’ P&S (blue and red, respectively) responses. The solid lines depict the age-matched normals. P&S = 1.00 bpm2 is the threshold for autonomic neuropathy
Fig. 25.2
Comparing this with Fig. 25.1, the effect SE therapy on the natural history of SE secondary to sleep disorder (not including sleep apnea) is depicted. The broken curves with data points depict patients’ P&S (blue and red, respectively) responses. The solid lines depict the age-matched normals. P&S = 1.00 bpm2 is the threshold for autonomic neuropathy
SE is known to increase morbidity and mortality risk in CVD patients. SE is associated with sleep disturbances. Treating SE relieves sleep disturbances and improves quality of life. Baker et al. [3] studied the cardiovascular implications of parasympathetic involvement in sleep medicine. Resting parasympathetic excess (PE) is associated with daytime sleepiness. PE demonstrated during a sympathetic challenge is associated with sleep disturbances, including difficulty falling asleep and frequent waking [16]. PE is also associated with bradycardia, low BP, depression, and depression/anxiety syndromes [16]. Depression is a known morbidity and mortality risk factor in cardiovascular diseases (CVD), including coronary heart disease [17], heart failure [12], and coronary artery disease [13]. Therefore, the PE associated with sleep disturbances also contributes to associated cardiovascular risks. Correcting PE may reduce morbidity and mortality risks associated with CVD.
This report presents data from a study of both parasympathetic and sympathetic involvement in sleep disorders. Specifically, it documents the involvement of PE demonstrated by patients diagnosed with sleep disorders. Serial P&S assessment (see section “Autonomic assessment”) was performed on 223 patients (114 female; average age = 53.2 years) from three ambulatory clinics, 91 of which (41 %, 58 female) were found with PE with reported sleep disturbances. Patients with sleep apnea or primary sympathetic excess (SE) were omitted and reported elsewhere [1, 2]. Patients with CVD and geriatrics (patients demonstrating autonomic neuropathy) were prescribed 3.125–6.25 mg carvedilol. Carvedilol treats the CVD and seems to indirectly treat PE. Patients contraindicated for carvedilol were omitted from the study. Younger patients and patients without CVD were prescribed low-dose amitriptyline (12.5 mg QD, dinner).
Here, we focus on the 91 patients with PE. PE can be demonstrated in multiple ways, including at rest (resting PE) and during the postural change (stand) challenge (dynamic PE). Figure 25.3 depicts the resting (baseline) response plot. The blue shaded area depicts the region of PE. The grey area is normal and the diagonal broken line indicates perfect balance. The area between the diagonal broken line and the blue area indicates “a little more” parasympathetic activity (low-normal sympathovagal balance, SB). This is the area that corresponds to minimal morbidity and mortality risk as defined in the geriatric cardiology literature [14, 15]. The average patient’s resting SB response from this cohort is 0.23, with the normal range of SB being 0.4 < SB < 3.0 [18, 19].
