Consequences of Comorbid Sleep Apnea in the Metabolic Syndrome—Implications for Cardiovascular Risk

Study Objectives:

Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of OSA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome.

Design:

Prospective clinical study.

Participants:

We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18).

Measurements:

OSA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations.

Results:

MSNA (34 ± 2 vs 28 ± 1 bursts/min, P = 0.02) and mean BP (111 ± 3 vs. 99 ± 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-OSA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 ± 0.6 vs 12.2 ± 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 ± 0.6 vs 11.9 ± 1.6 msec/mm Hg, P = 0.01) in BP. MSNA was correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = −0.38, P = 0.04).

Conclusion:

Patients with MetSyn and comorbid OSA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without OSA. These adverse cardiovascular and autonomic consequences of OSA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

Citation:

Trombetta IC; Somers VK; Maki-Nunes C; Drager LF; Toschi-Dias E; Alves MJNN; Fraga RF; Rondon MUPB; Bechara MG; Lorenzi-Filho G; Negrão CE. Consequences of comorbid sleep apnea in the metabolic syndrome—implications for cardiovascular risk. SLEEP 2010;33(9):1193-1199.     

Nighttime Blood Pressure in Normotensive Subjects With Chronic Insomnia: Implications for Cardiovascular Risk

Objective:

To assess as whether insomniacs have higher nighttime blood pressure (BP) and a blunted day-to-night BP reduction, recognized markers of increased risk of cardiovascular morbidity and mortality.

Design:

Prospective case-control study.

Setting:

University hospital-based sleep research laboratory.

Participants:

Thirteen normotensive subjects with chronic primary insomnia (9 women, 42 ± 7 y) and 13 sex- and age-matched good sleepers.

Measurements and results:

Subjects underwent 2-week sleep diary and 3 sleep studies to provide subjective and objective sleep variables, and 24-h beat-to-beat BP recording to provide daytime, night-time and day-to-night BP changes ([nighttime-daytime]/daytime)*100) (BP dipping). Spectral analysis of the electroencephalogram (EEG) was also performed during sleep of night 3 to assess EEG activity in the β frequency (16-32 Hz), a measure of brain cortical activation. Nighttime SBP was higher (111 ± 15 vs 102 ± 12 mm Hg, P < 0.01) and day-to-night SBP dipping was lower (−8% ± 6% vs −15% ± 5%, P < 0.01) in insomniacs than good sleepers. Insomniacs also had higher activity in EEG β frequency (P < 0.05). Higher nighttime SBP and smaller SBP dipping were independently associated with increased EEG β activity (P < 0.05).

Conclusions:

Higher nighttime SBP and blunted day-to-night SBP dipping are present in normotensive subjects with chronic insomnia and are associated with a hyperactivity of the central nervous system during sleep. An altered BP profile in insomniacs could be one mechanism implicated in the link between insomnia and cardiovascular morbidity and mortality documented in epidemiological studies.

Citation:

Lanfranchi PA; Pennestri MH; Fradette L; Dumont M; Morin CM; Montplaisir J. Nighttime blood pressure in normotensive subjects with chronic insomnia: implications for cardiovascular risk. SLEEP 2009;32(6):760-766.     

Upper Airway Sensory Function in Children with Obstructive Sleep Apnea Syndrome

Study Objectives:

Children with the obstructive sleep apnea syndrome (OSAS) have impaired responses to hypercapnia, subatmospheric pressure, and inspiratory resistive loading during sleep. This may be due, in part, to an impairment in the afferent limb of the upper airway sensory pathway. Therefore, we hypothesized that children with OSAS had diminished upper airway sensation compared to controls.

Design:

Case-control

Setting:

Academic hospital

Participants:

Subjects with OSAS aged 6–16 years, and age- and BMI-matched controls.

Interventions:

Two-point discrimination (TPD) was measured during wakefulness with modified calipers in the anterior tongue, right interior cheek, and hard palate.

Results:

Thirteen children with OSAS and 9 controls were tested. The age (mean ± SD) for OSAS and controls was 11 ± 4 vs. 13 ± 2 years (NS); OSAS BMI Z score 2.4 ± 0.5, controls 2.2 ± 0.5 (NS); OSAS apnea hypopnea index 31 ± 48, controls 0.4 ± 0.5 events/hour (P < 0.001). Children with OSAS had impaired TPD in the anterior tongue (median [range]) = 9 [3–14] mm, controls 3 [1–7], P = 0.002) and hard palate (OSAS 6 [3–9] mm, controls 3 [1–4], P < 0.001). TPD in the cheek was similar between the groups (P = 0.12).

Conclusion:

TPD in the anterior tongue and hard palate was impaired in children with OSAS during wakefulness. We speculate that this impairment might be due to a primary sensory function abnormality or secondary to nerve damage and/or hypoxemia caused by OSAS. Further studies after treatment of OSAS are needed.

Citation:

Tapia IE; Bandla P; Traylor J; Karamessinis L; Huang J; Marcus CL. Upper airway sensory function in children with obstructive sleep apnea syndrome. SLEEP 2010;33(7):968–972.     

Airway Dilator Muscle Activity and Lung Volume During Stable Breathing in Obstructive Sleep Apnea

Study Objectives:

Many patients with obstructive sleep apnea (OSA) have spontaneous periods of stable flow limited breathing during sleep without respiratory events or arousals. In addition, OSA is often more severe during REM than NREM and more severe during stage 2 than slow wave sleep (SWS). The physiological mechanisms for these observations are unknown. Thus we aimed to determine whether the activity of two upper airway dilator muscles (genioglossus and tensor palatini) or end-expiratory lung volume (EELV) differ between (1) spontaneously occurring stable and cyclical breathing and (2) different sleep stages in OSA.

Design:

Physiologic observation.

Setting:

Sleep physiology laboratory.

Study Participants:

15 OSA patients with documented periods of spontaneous stable breathing.

Intervention:

Subjects were instrumented with intramuscular electrodes for genioglossus and tensor palatini electromyograms (EMG_GG and EMG_TP), chest and abdominal magnetometers (EELV measurement), an epiglottic pressure catheter (respiratory effort), and a mask and pneumotachograph (airflow/ventilation). Patients slept supine overnight without CPAP.

Measurements and Results:

Peak and Tonic EMG_GG were significantly lower during cyclical (85.4 ± 2.7 and 94.6 ± 4.7 % total activity) than stable breathing (109.4 ± 0.4 and 103 ± 0.8 % total activity, respectively). During respiratory events in REM, tonic EMG_GG activity was lower than during respiratory events in stage 2 (71.9 ± 5.1 and 119.6 ± 5.6 % total activity). EMG_GG did not differ between stable stage 2 and stable SWS (98.9 ± 3.2 versus 109.7 ± 4.4 % total activity), nor did EMG_TP or EELV differ in any breathing condition/sleep stage.

Conclusions:

Increased genioglossus muscle tone is associated with spontaneous periods of stable flow limited breathing in the OSA subjects studied. Reductions in genioglossus activity during REM may explain the higher severity of OSA in that stage. Increased lung volume and tensor palatini activity do not appear to be major mechanisms enabling spontaneous stable flow limited breathing periods.

Citation:

Jordan AS; White DP; Lo YL; Wellman A; Eckert DJ; Yim-Yeh S; Eikermann M; Smith SA; Stevenson KE; Malhotra A. Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea. SLEEP 2009;32(3):361–368.     

Model-Based Assessment of Cardiovascular Autonomic Control in Children with Obstructive Sleep Apnea

Study Objectives:

To quantitatively assess daytime autonomic cardiovascular control in pediatric subjects with and without obstructive sleep apnea syndrome (OSAS).

Design:

Respiration, R-R intervals, and noninvasive continuous blood pressure were monitored in awake subjects in the supine and standing postures, as well as during cold face stimulation.

Setting:

Sleep disorders laboratory in a hospital setting.

Participants:

Ten pediatric patients (age 11.4 ± 3.6 years) with moderate to severe OSAS (obstructive apnea-hypopnea index = 21.0 ± 6.6/ h) before treatment and 10 age-matched normal control subjects (age 11.5 ± 3.7 years).

Measurements and Results:

Spectral analysis of heart rate variability revealed that high-frequency power was similar and the ratio of low- to high-frequency power was lower in subjects with OSAS vs control subjects. The closed-loop minimal model allowed heart rate variability to be partitioned into a component mediated by respiratory-cardiac coupling and a baroreflex component, whereas blood pressure variability was assumed to result from the direct effects of respiration and fluctuations in cardiac output. Baroreflex gain was lower in subjects with OSAS vs control subjects. Under orthostatic stress, respiratory-cardiac coupling gain decreased in both subject groups, but baroreflex gain decreased only in controls. The model was extended to incorporate time-varying parameter changes for analysis of the data collected during cold face stimulation: cardiac output gain increased in controls but remained unchanged in OSAS.

Conclusions:

Our findings suggest that vagal modulation of the heart remains relatively normal in pediatric subjects with OSAS. However, baseline cardiovascular sympathetic activity is elevated, and reactivity to autonomic challenges is impaired.

Citation:

Chaicharn J; Lin Z; Chen ML; Ward SLD; Keens T; Khoo MCK. Model-based assessment of cardiovascular autonomic control in children with obstructive sleep apnea. SLEEP 2009;32(7):927-938.     

Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

OBJECTIVE:

Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide.

METHODS:

The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples.

RESULTS:

Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05).

CONCLUSION:

Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels.     

Upper Airway Collapsibility During REM Sleep in Children with the Obstructive Sleep Apnea Syndrome

Study Objectives:

In children, most obstructive events occur during rapid eye movement (REM) sleep. We hypothesized that children with the obstructive sleep apnea syndrome (OSAS), in contrast to age-matched control subjects, would not maintain airflow in the face of an upper airway inspiratory pressure drop during REM sleep.

Design:

During slow wave sleep (SWS) and REM sleep, we measured airflow, inspiratory time, inspiratory time/total respiratory cycle time, respiratory rate, tidal volume, and minute ventilation at a holding pressure at which flow limitation occurred and at 5 cm H₂O below the holding pressure in children with OSAS and in control subjects.

Setting:

Sleep laboratory.

Participants:

Fourteen children with OSAS and 23 normal control subjects.

Results:

In both sleep states, control subjects were able to maintain airflow, whereas subjects with OSAS preserved airflow in SWS but had a significant decrease in airflow during REM sleep (change in airflow of 18.58 ± 12.41 mL/s for control subjects vs −44.33 ± 14.09 mL/s for children with OSAS, P = 0.002). Although tidal volume decreased, patients with OSAS were able to maintain minute ventilation by increasing the respiratory rate and also had an increase in inspiratory time and inspiratory time per total respiratory cycle time

Conclusion:

Children with OSAS do not maintain airflow in the face of upper-airway inspiratory-pressure drops during REM sleep, indicating a more collapsible upper airway, compared with that of control subjects during REM sleep. However, compensatory mechanisms exist to maintain minute ventilation. Local reflexes, central control mechanisms, or both reflexes and control mechanisms need to be further explored to better understand the pathophysiology of this abnormality and the compensation mechanism.

Citation:

Huang J; Karamessinis LR; Pepe ME; Glinka SM; Samuel JM; Gallagher PR; Marcus CL. Upper airway collapsibility during REM sleep in children with the obstructive sleep apnea syndrome. SLEEP 2009;32(9):1173-1181.     

Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

OBJECTIVE:

Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy.

METHODS:

Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m²) were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h) was present in 37 patients (41%).

RESULTS:

Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47–13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43–20.12; p = 0.013].

CONCLUSION:

Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation.     

Differences in Craniofacial Structures and Obesity in Caucasian and Chinese Patients with Obstructive Sleep Apnea

Study Objectives:

To explore differences in craniofacial structures and obesity between Caucasian and Chinese patients with obstructive sleep apnea (OSA).

Design:

Inter-ethnic comparison study.

Setting:

Two sleep disorder clinics in Australia and Hong Kong.

Patients:

150 patients with OSA (74 Caucasian, 76 Chinese).

Interventions:

Anthropometry, cephalometry, and polysomnography were performed and compared. Subgroup analyses after matching for: (1) body mass index (BMI); (2) OSA severity.

Measurements and Results:

The mean age and BMI were similar between the ethnic groups. Chinese patients had more severe OSA (AHI 35.3 vs 25.2 events/h, P = 0.005). They also had more craniofacial bony restriction, including a shorter cranial base (63.6 ± 3.3 vs 77.5 ± 6.7 mm, P < 0.001), maxilla (50.7 ± 3.7 vs 58.8 ± 4.3 mm, P < 0.001) and mandible length (65.4 ± 4.2 vs 77.9 ± 9.4 mm, P < 0.001). These findings remained after correction for differences in body height. Similar results were shown in the BMI-matched analysis (n = 66). When matched for OSA severity (n = 52), Chinese patients had more craniofacial bony restriction, but Caucasian patients were more overweight (BMI 30.7 vs 28.4 kg/m², P = 0.03) and had a larger neck circumference (40.8 vs 39.1 cm, P = 0.004); however, the ratios of BMI to the mandible or maxilla size were similar.

Conclusions:

Craniofacial factors and obesity contribute differentially to OSA in Caucasian and Chinese patients. For the same degree of OSA severity, Caucasians were more overweight, whereas Chinese exhibited more craniofacial bony restriction.

Citation:

Lee RWW; Vasudavan S; Hui DS; Prvan T; Petocz P; Darendeliler MA; Cistulli PA. Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. SLEEP 2010;33(8):1075-1080.     

Endothelial Function in Normotensive Men with Obstructive Sleep Apnea Before and 6 Months After CPAP Treatment

Study Objectives:

To evaluate endothelium-dependent flow-mediated dilation (FMD) and endothelium–independent nitroglycerin (NTG)-induced dilation of the brachial artery with Doppler ultrasound in patients with obstructive sleep apnea (OSA) and impact of six months of continuous positive airway pressure (CPAP) treatment.

Design:

A prospective, controlled, observational study.

Setting:

Single-site, clinic-based.

Patients:

Twenty-nine normotensive men with OSA (apnea-hypopnea index [AHI], mean ± SD, 60.4 ± 22.1-h), and 17 men without OSA (AHI 2.5 ± 0.6-h).

Interventions:

Six months of CPAP therapy in OSA patients.

Measurements and Results:

FMD was lower in patients with OSA compared with in controls (7.19 ± 1.78 % vs 10.93 ± 2.59 %; P < 0.001) while NTG-induced vasodilation was similar in both groups (13.75 ± 1.01 % vs 14.25 ± 1.83 %; n.s.). An inverse relationship was found between FMD and AHI adjusted for age and body mass index (BMI) (β = − 0.05, P < 0.001). Following 6 months of CPAP treatment in the OSA group, FMD was increased from 7.38 ± 2.06 % to 10.45 ± 1.68; P = 0.001) in 20 patients compliant with the device whereas the corresponding values did not change in the non-user group (7.08 ± 1.50% vs 7.26 ± 1.01%). No significant changes were observed regarding the NTG–induced vasodilation after CPAP compared with the baseline values.

Conclusion:

Our results confirm the previous reports suggesting impaired endothelium-dependent FMD in OSA, and additionally document the sustained improvement in endothelial function after 6 months of CPAP treatment in complaint patients.

Citation:

Bayram NA; Ciftci B; Keles T; Durmaz T; Turhan S; Bozkurt E; Peker Y. Endothelial function in normotensive men with obstructive sleep apnea before and 6 months after CPAP treatment. SLEEP 2009;32(10):1257-1263.     

Sleep Disturbance,Daytime Sleepiness,and Neurocognitive Performance in Children with Juvenile Idiopathic Arthritis

Study Objectives:

To compare daytime sleepiness and neurobehavioral performance in children with active and inactive juvenile idiopathic arthritis (JIA), and explore relations among measures of sleep disturbance, daytime sleepiness, and neurobehavioral performance.

Design:

Cross-sectional, comparison.

Setting:

A university-based research sleep laboratory.

Participants:

Seventy (70) children 6-11 years of age with active or inactive JIA.

Measurements and Results:

Self-reported daytime sleepiness, multiple sleep latency tests (MSLTs), and computerized neurobehavioral performance test scores were obtained after 2 nights of polysomnography. Children with active disease (mean physician global rating score = 2.9 ± 1.9 SD) showed shorter mean MSLT latency (15 ± 6.0 min) than those with inactive disease (16.5 ± 5.5 min, P < 0.03). Scores on neurobehavioral performance tests showed no group differences. However, number of wake bouts predicted sustained visual attention (rapid visual processing, P < 0.05) and apnea hypopnea index (AHI) predicted reaction time (P < 0.0001), after controlling for age, IQ, medication, and disease status.

Conclusion:

Indices of sleep disturbance were associated with validated tests of neurobehavioral performance in JIA, regardless of disease activity. Additional research is needed about the extent of sleep disturbances in relation to neurocognitive performance in JIA and compared to healthy children.

Citation:

Ward TM; Archbold K; Lentz M; Ringold S; Wallace CA; Landis CA. Sleep disturbance, daytime sleepiness, and neurocognitive performance in children with juvenile idiopathic arthritis. SLEEP 2010;33(2):252-259.     

Aging Effects on Cardiac and Respiratory Dynamics in Healthy Subjects across Sleep Stages

Study Objectives:

Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk.

Design:

Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow.

Setting:

Data were collected in 7 laboratories in 5 European countries.

Participants:

180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years.

Interventions:

None.

Measurements and Results:

Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α₁ show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α₂ differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α₂ of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake).

Conclusion:

The age dependence of α₁ should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α₂) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep.

Citation:

Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955.     

Changes in Cardiac Variability after REM Sleep Deprivation in Recurrent Nightmares

Study Objectives:

To assess whether dysfunctional autonomic regulation during REM sleep as indexed by heart rate variability (HRV) is a pathophysiological factor in frequent nightmares (NMs).

Design:

Monitoring with polysomnography (PSG) and electrocardiography (ECG) for 3 consecutive nights: Night 1 (N1), adaptation night; N2, administration of partial REM sleep deprivation; N3, recovery night. Differences between NM and control (CTL) groups assessed for ECG measures drawn from wakefulness, REM sleep, and Stage 2 sleep on both N1 and N3.

Setting:

Hospital-based sleep laboratory

Participants:

Sixteen subjects with frequent NMs ( ≥ 1 NM/week; mean age = 26.1 ± 8.7 years) but no other medical or psychiatric disorders and 11 healthy comparison subjects ( < 1 NM/month; mean age = 27.1±5.6 years).

Results:

NM and CTL groups differed on 2 REM sleep measures only on N1; the NM group had longer REM latencies and REM/NREM cycle durations than did the CTL group. No differences were found on time domain and absolute frequency domain ECG measures for either N1 or N3. However, altered HRV for the NM group was suggested by significantly higher LFnu, lower HFnu, and higher LF/HF ratio than for the CTL group.

Conclusions:

Results are consistent with a higher than normal sympathetic drive among NM subjects which is unmasked by high REM sleep propensity. Results also support a growing literature linking anxiety disorders of several types (panic disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder) to altered HR variability.

Citation:

Nielsen T; Paquette T; Solomonova E; Lara-Carrasco J; Colombo R; Lanfranchi P. Changes in cardiac variability after rem sleep deprivation in recurrent nightmares. SLEEP 2010;33(1):113-122.     

Blood Pressure and Heart Rate During Continuous Experimental Sleep Fragmentation in Healthy Adults

Study Objectives:

This paper aims to determine whether experimental arousals from sleep delay the sleep related fall in cardiovascular activity in healthy adults.

Design:

We report the results of 2 studies. The first experiment manipulated arousals from sleep in young adults. The second compared the effect of frequent arousals on young and middle-aged adults. The influence of arousals were assessed in 2 ways; (1) the fall in cardiovascular activity over sleep onset and the early sleep period, and (2) the underlying sleep levels during the sleep periods in between arousals.

Setting:

Both experiments were conducted in the sleep laboratory of the Department of Psychology, The University of Melbourne, Australia.

Participants:

There were 5 male and 5 female healthy individuals in each experiment between the ages of 18–25 years (Experiment 1) and 38–55 years (Experiment 2).

Interventions:

Participants in Experiment 1 were aroused by auditory stimuli every (i) 2 min, (ii) 1 min, and (iii) 30 sec of sleep for 90 min after the first indication of sleep. In a control condition, participants slept undisturbed for one NREM sleep cycle. Experiment 2 compared the control with the 30-sec condition in the young adults and in an additional group of middle-aged adults.

Measurements and Results:

The dependent variables were blood pressure (BP) and heart rate (HR). In Experiment 1, sleep fragmentation at higher frequencies retarded the fall in BP over sleep onset but did not affect the underlying sleep levels. Experiment 2 showed that there were no age differences on the effect of arousals on changes in BP and HR during sleep.

Conclusions:

This paper supports the hypothesis that repetitive arousals from sleep independently contribute to elevations in BP at night.

Citation:

Carrington MJ; Trinder J. Blood pressure and heart rate during continuous experimental sleep fragmentation in healthy adults. SLEEP 2008;31(12):1701–1712.     

Comparison of Mandibular Advancement Splint and Tongue Stabilizing Device in Obstructive Sleep Apnea: A Randomized Controlled Trial

Study Objectives:

To compare the efficacy of a mandibular advancement splint (MAS) and a novel tongue stabilizing device (TSD) in the treatment of obstructive sleep apnea (OSA).

Design:

A randomized crossover design was used.

Patients:

Twenty-seven patients (20 male, 7 female), recruited from a tertiary hospital sleep clinic.

Measurements and Results:

The apnea-hypopnea index (AHI) was reduced with MAS (11.68 ± 8.94, P = 0.000) and TSD (13.15 ± 10.77, P = 0.002) compared with baseline (26.96 ± 17.17). The arousal index decreased for MAS (21.09 ± 9.27, P = 0.004) and TSD (21.9 ± 10.56, P = 0.001) compared with baseline (33.23 ± 16.41). Sixty-eight percent of patients achieved a complete or partial response with MAS, compared with 45% with TSD. The Epworth Sleepiness Scale (ESS) score was decreased with MAS (P = <0.001) and TSD (P = 0.002). Subjective improvements in snoring and quality of sleep were reported, with a better response for MAS than TSD. Compliance was poorer for TSD, and the side effect profiles of the 2 modalities were different. All patients were satisfied with MAS compared to TSD, and 91% of patients preferred the MAS.

Conclusion:

Objective testing showed the MAS and TSD had similar efficacy in terms of AHI reduction. Patients reported improvements with both devices; however, better compliance and a clear preference for MAS was apparent when both devices were offered. Longer term studies are needed to clarify the role of TSD.

Citation:

Deane SA; Cistulli PA; Ng AT; Zeng B; Petocz P; Darendeliler MA. Comparison of mandibular advancement splint and tongue stabilizing device in obstructive sleep apnea: a randomized controlled trial. SLEEP 2009;32(5):648-653.     

Idiopathic Hypersomnia with and without Long Sleep Time: A Controlled Series of 75 Patients

Objective:

To characterize the clinical, psychological, and sleep pattern of idiopathic hypersomnia with and without long sleep time, and provide normative values for 24-hour polysomnography.

Setting:

University Hospital

Design:

Controlled, prospective cohort

Participants:

75 consecutive patients (aged 34 ± 12 y) with idiopathic hypersomnia and 30 healthy matched controls.

Intervention:

Patients and controls underwent during 48 hours a face-to face interview, questionnaires, human leukocyte antigen genotype, a night polysomnography and multiple sleep latency test (MSLT), followed by 24-h ad libitum sleep monitoring.

Results:

Hypersomniacs had more fatigue, higher anxiety and depression scores, and more frequent hypnagogic hallucinations (24%), sleep paralysis (28%), sleep drunkenness (36%), and unrefreshing naps (46%) than controls. They were more frequently evening types. DQB1*0602 genotype was similarly found in hypersomniacs (24.2%) and controls (19.2%). Hypersomniacs had more frequent slow wave sleep after 06:00 than controls. During 24-h polysomnography, the 95% confidence interval for total sleep time was 493–558 min in controls, versus 672–718 min in hypersomniacs. There were 40 hypersomniacs with and 35 hypersomniacs without long ( > 600 min) sleep time. The hypersomniacs with long sleep time were younger (29 ± 10 vs 40 ± 13 y, P = 0.0002), slimmer (body mass index: 26 ± 5 vs 23 ± 4 kg/m²; P = 0.005), and had lower Horne-Ostberg scores and higher sleep efficiencies than those without long sleep time. MSLT latencies were normal ( > 8 min) in 71% hypersomniacs with long sleep time.

Conclusions:

Hypersomnia, especially with long sleep time, is frequently associated with evening chronotype and young age. It is inadequately diagnosed using MSLT.

Citation:

Vernet C; Arnulf I. Idiopathic Hypersomnia with and without Long Sleep Time: A Controlled Series of 75 Patients. SLEEP 2009;32(6):753-759.     

Effects of Exercise Training in Patients with Chronic Heart Failure and Sleep Apnea

Study Objectives:

To test the effects of exercise training on sleep and neurovascular control in patients with systolic heart failure with and without sleep disordered breathing.

Design:

Prospective interventional study.

Setting:

Cardiac rehabilitation and exercise physiology unit and sleep laboratory.

Patients:

Twenty-five patients with heart failure, aged 42 to 70 years, and New York Heart Association Functional Class I-III were divided into 1 of 3 groups: obstructive sleep apnea (n = 8), central sleep apnea (n = 9) and no sleep apnea (n = 7).

Interventions:

Four months of no-training (control) followed by 4 months of an exercise training program (three 60-minute, supervised, exercise sessions per week).

Measures and Results:

Sleep (polysomnography), microneurography, forearm blood flow (plethysmography), peak VO_2, and quality of life were evaluated at baseline and at the end of the control and trained periods. No significant changes occurred in the control period. Exercise training reduced muscle sympathetic nerve activity (P < 0.001) and increased forearm blood flow (P < 0.01), peak VO₂(P < 0.01), and quality of life (P < 0.01) in all groups, independent of the presence of sleep apnea. Exercise training improved the apnea-hypopnea index, minimum O₂ saturation, and amount stage 3-4 sleep (P < 0.05) in patients with obstructive sleep apnea but had no significant effects in patients with central sleep apnea.

Conclusions.

The beneficial effects of exercise training on neurovascular function, functional capacity, and quality of life in patients with systolic dysfunction and heart failure occurs independently of sleep disordered breathing. Exercise training lessens the severity of obstructive sleep apnea but does not affect central sleep apnea in patients with heart failure and sleep disordered breathing.

Citation:

Ueno LM; Drager LF; Rodrigues ACT; Rondon MUPB; Braga AMFW; Mathias W; Krieger EM; Barretto ACP; Middlekauff HR; Lorenzi-Filho G; Negrão CE. Effects of exercise training in patients with chronic heart failure and sleep apnea. SLEEP 2009;32(5):637-647.     

Associations of Moderate to Severe Asthma with Obstructive Sleep Apnea

Purpose

This study aimed to evaluate the correlation between associating factors of moderate to severe asthma with obstructive sleep apnea (OSA).

Materials and Methods

One hundred and sixty-seven patients who visited the pulmonary and sleep clinic in Severance Hospital presenting with symptoms of sleep-disordered breathing were evaluated. All subjects were screened with ApneaLink. Thirty-two subjects with a high likelihood of having OSA were assessed with full polysomnography (PSG).

Results

The mean age was 58.8±12.0 years and 58.7% of subjects were male. The mean ApneaLink apnea-hypopnea index (AHI) was 12.7±13.0/hr. The mean ApneaLink AHI for the 32 selected high risk patients of OSA was 22.3±13.2/hr, which was lower than the sleep laboratory-based PSG AHI of 39.1±20.5/hr. When OSA was defined at an ApneaLink AHI ≥5/hr, the positive correlating factors for OSA were age, male gender, and moderate to severe asthma.

Conclusion

Moderate to severe asthma showed strong correlation with OSA when defined at an ApneaLink AHI ≥5/hr.     

Effects of Modafinil on the Sleep EEG Depend on Val158Met Genotype of COMT

Study Objectives:

Modafinil may promote wakefulness by increasing cerebral dopaminergic neurotransmission, which importantly depends on activity of catechol-O-methyltransferase (COMT) in prefrontal cortex. The effects of modafinil on sleep homeostasis in humans are unknown. Employing a novel sleep-pharmacogenetic approach, we investigated the interaction of modafinil with sleep deprivation to study dopaminergic mechanisms of sleep homeostasis.

Design:

Placebo-controlled, double-blind, randomized crossover study.

Setting:

Sleep laboratory in temporal isolation unit.

Participants:

22 healthy young men (23.4 ± 0.5 years) prospectively enrolled based on genotype of the functional Val158Met polymorphism of COMT (10 Val/Val and 12 Met/Met homozygotes).

Interventions:

2 × 100 mg modafinil and placebo administered at 11 and 23 hours during 40 hours prolonged wakefulness.

Measurements and Results:

Subjective sleepiness and EEG markers of sleep homeostasis in wakefulness and sleep were equally affected by sleep deprivation in Val/Val and Met/Met allele carriers (placebo condition). Modafinil attenuated the evolution of sleepiness and EEG 5-8 Hz activity during sleep deprivation in both genotypes. In contrast to caffeine, modafinil did not reduce EEG slow wave activity (0.75-4.5 Hz) in recovery sleep, yet specifically increased 3.0-6.75 Hz and > 16.75 Hz activity in NREM sleep in the Val/Val genotype of COMT.

Conclusions:

The Val158Met polymorphism of COMT modulates the effects of modafinil on the NREM sleep EEG in recovery sleep after prolonged wakefulness. The sleep EEG changes induced by modafinil markedly differ from those of caffeine, showing that pharmacological interference with dopaminergic and adenosinergic neurotransmission during sleep deprivation differently affects sleep homeostasis.

Citation:

Bodenmann S; Landolt HP. Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT. SLEEP 2010;33(8):1027-1035.