Obstructive sleep apnea associated with cerebral hypoxemia and death

An increase in the arousal threshold may predispose critically ill patients with obstructive sleep apnea (OSA) to prolonged apneas and death during sleep. We report two cases in whom polysomnographically documented OSA resulted in EEG changes compatible with cerebral hypoxemia with subsequent respective transient encephalopathy in one instance and death in the other.     

Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke

Medeiros CAM, de Bruin VMS, Andrade GM, Coutinho WM, de Castro‐Silva C, de Bruin PFC. Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke.
Acta Neurol Scand: 2012: 126: 17–22.
© 2011 John Wiley & Sons A/S. Background and Objectives – Despite a confirmed association between obstructive sleep apnea (OSA) and stroke, the pathogenesis of OSA in stroke has not been hitherto clarified. The aim of this study was to evaluate the relationship between respiratory abnormalities and atherogenic pro‐inflammatory markers, interleukin‐1beta (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) in acute ischemic stroke patients. Methods – Nocturnal polygraphy was performed in 50 consecutive patients with acute ischemic stroke in the first week after the event. Levels of inflammatory markers (IL‐6, IL‐1β and TNF‐α) were determined from morning blood samples and comparatively analyzed between cases with and without severe OSA and with age‐matched controls. Results – All patients with acute ischemic stroke, 31 men, mean age (64.3 ± 7.7 years), had apnea‐hypopnea index (AHI) > 5 and 35 (70%) had severe OSA (AHI ≥ 30). Hypertension was more frequent in patients with severe OSA (85.7%) when compared to controls (40.0%) (P = 0.002). Stroke outcome, assessed by the Barthel index, tended to be more severe (P = 0.06) in cases with severe OSA. Patients with mild/moderate OSA and with severe OSA showed higher levels of IL‐6 when compared to controls (P = 0.01 and P = 0.000, respectively). Among cases with acute stroke and severe OSA, IL‐6 levels were correlated with lower oxyhemoglobin desaturation (r=?0.30; P = 0.001) and with the desaturation index (r = 0.15; P = 0.02). Conclusions – IL‐6, an atherogenic marker, shows a commensurate increase in stroke patients with OSA. It is correlated with oxyhemoglobin desaturation and with desaturation index and may be a surrogate measure to evaluate continuous positive airway pressure therapy.     

Obstructive sleep apnea syndrome. A review

Obstructive sleep apnea syndrome (OSAS) is a complex disorder characterized by a sleep-related collapse of the upper airway. The most likely candidate for the common pathway linking various abnormalities casually associated with OSAS (such as adenotonsillar hypertrophy, obesity, retro- or micrognathia, acromegaly, or more subtle structural anomalies) is an abnormally small upper airway lumen. Symptoms of OSAS that appear during sleep include snoring, abnormal motor activity, disturbed nocturnal sleep, a sensation of choking, heartburn, nocturia, nocturnal enuresis, and heavy sweating. Daytime waking symptoms are dominated by often profound sleepiness, which may secondarily be associated with automatic behavior, retrograde amnesia, hypnagogic hallucinations, personality changes, sexual difficulties, and headaches. Careful evaluation, both sleeping and waking, are essential to select appropriate treatment. Treatments include nasal continuous positive airway pressure, tracheostomy, weight loss, uvulopalatopharyngoplasty, mandibular advancement, and so forth.     

Obstructive sleep apnea intensifies stroke severity following middle cerebral artery occlusion

Study objectivesObstructive sleep apnea (OSA) is a sleep disorder caused by transient obstruction of the upper airway and results in intermittent hypoxia, sleep fragmentation, sympathetic nervous system activation, and arousal which can have an adverse effect on cardiovascular disease. It is theorized that OSA might intensify stroke injury. Our goal here was to develop a new model of experimental OSA and test its ability to aggravate behavioral and morphological outcomes following transient brain ischemia/reperfusion.MethodsWe used a 3D printed OSA device to expose C57BL6 mice to 3 h of OSA (obstructive apnea index of 20 events per hour) for three days. These mice were then subjected to ischemia/reperfusion using the middle cerebral artery occlusion model (MCAO) stroke and examined for overall survival, infarct size and neurological scoring.ResultsWe found that OSA transiently decreased respiration and reduced oxygen saturation with bradycardia and tachycardia typical of human responses during apneic events. Brain injury from MCAO was significantly increased by OSA as measured by infarct size and location as well as by intensification of neurological deficits; mortality following MCAO was also increased in OSA animals.ConclusionsOur findings suggest that our new model of OSA alters respiratory and cardiovascular physiological functions and is associated with enhanced ischemia/reperfusion mediated injury in our non-invasive, OSA intensified model of stroke.     

Obstructive sleep apnea and diet-controlled gestational diabetes

BackgroundObstructive sleep apnea (OSA) was shown to be associated with gestational diabetes mellitus (GDM). However, prevalence of OSA in GDM women, its relationship to metabolic control, and predictive factors have not been studied.Material and methodsEighty-two obese pregnant women with diet-controlled GDM between 24 and 34 weeks of gestation participated. The Berlin questionnaire was used to assess OSA symptoms. OSA was diagnosed using an overnight monitor. Fasting glucose and hemoglobin A1c (HbA1c) were obtained. Those with OSA underwent meal tolerance test (MTT) to assess their metabolic parameters. Classification tree analysis was used to develop a screening tool for OSA.ResultsAt a median gestational age of 29 weeks, OSA was diagnosed in 52.4% of the women, with a median apnea hypopnea index of 9.4 (interquartile range 6.4, 12.4). More severe OSA was significantly correlated with higher fasting glucose but not HbA1c. For those with OSA, sleep parameters related to oxygen desaturation significantly correlated with higher fasting insulin resistance and more severe β-cell dysfunction, as evaluated by MTT.A screening tool involving two variables, neck circumference and Berlin Questionnaire score, was developed. The sensitivity and specificity were 86% and 51%, respectively. The overall accuracy was 70%.ConclusionOSA is prevalent in obese pregnant women with diet-controlled GDM in the late second to early third trimester. OSA severity, especially the degree of oxygen desaturation, correlated with fasting glucose, insulin resistance, and β-cell function. A simple screening tool involving the Berlin Questionnaire and neck circumference can aid in predicting OSA in this patient group.     

Obstructive sleep apnea and coronary artery disease

In the recent years intensive research has revealed numerous negative consequences of obstructive sleep apnea (OSA) for the cardiovascular system. The pathophysiological interaction between OSA and coronary artery disease is complex and comprises neural, humoral, mechanical and haemodynamic components. One of the most important effects of OSA is an increase of sympathetic nerve traffic, which persists during the day and is thought to play a key role in the association of OSA and elevated systemic blood pressure. Nowadays, OSA is accepted as an independent risk factor for arterial hypertension. Several investigations support an association of OSA with ischemic ST-segment changes, ventricular arrhythmias, and sudden cardiac death. In line with this, a growing body of evidence strongly supports OSA having prognostic implications for cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) has been shown to have several beneficial effects on the cardiovascular system. Uncontrolled studies indicate that it reduces cardiovascular risk in patients with severe OSA and increased risk or manifest coronary artery disease. However, ongoing studies still have to confirm this.     

Obstructive sleep apnea and cerebral white matter change: a systematic review and meta-analysis

Obstructive sleep apnea (OSA) can cause sleep fragmentation and intermittent hypoxemia, which are linked to oxidative stress. White matter changes (WMCs) representing cerebrovascular burden and are at risk factor for oxidative ischemic injury. The current study explores the mutual relationships between OSA and WMCs. We performed a systematic review of electronic databases for clinical studies investigating OSA and WMCs. Random-effects models were used for pooled estimates calculation. A total of 22 studies were included in the meta-analysis. The results revealed a significantly higher prevalence rate of WMCs [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.52–2.80, p?<?0.001] and significantly higher severity of WMCs (Hedges’ g?=?0.23, 95% CI 0.06–0.40, p?=?0.009) in the patients with OSA than in controls. Furthermore, the results revealed a significantly higher apnea–hypopnea index (Hedges’ g?=?0.54, 95% CI 0.31–0.78, p?<?0.001) and significantly higher prevalence rate of moderate-to-severe OSA (OR 2.86, 95% CI 1.44–5.66, p?=?0.003) in the patients with WMCs than in controls, however there was no significant difference in the prevalence rate of mild OSA between the patients with WMCs and controls (OR 0.71, 95% CI 0.20–2.54, p?=?0.603). OSA was associated with a higher prevalence and more severe WMCs, and the patients with WMCs had an increased association with moderate-to-severe OSA. Future large-scale randomized controlled trials with a longitudinal design are essential to further evaluate treatment in patients with OSA.     

Obstructive sleep apnea and heart rate asymmetry microstructure during sleep

Purpose

Heart rate decelerations and accelerations have unequal input to heart rate variability (HRV) and patterns created by consecutive cardiac cycles—this phenomenon is known as heart rate asymmetry (HRA). The analysis of monotonic runs of heart rate decelerations and accelerations provides a detailed insight into the HRA microstructure and thus of HRV.

Aim

To evaluate the relation between the severity of obstructive sleep apnea (OSA) and the HRA microstructure during sleep.

Methods

Seventy-eight patients with suspected OSA underwent overnight polysomnography. The 300-min ECGs from the polysomnography were selected and analyzed. The HRA microstructure was quantified by measuring (1) the contribution of monotonic runs of decelerations or accelerations of different lengths to the number of all sinus beats, and (2) the length of the longest deceleration and acceleration runs.

Results

There were 19 patients with no/mild OSA (Apnea/Hypopnea Index (AHI) 5.1 ± 2.5/h), 18 with moderate OSA (AHI 21.8 ± 4.0/h) and 41 with severe OSA (AHI 42.8 ± 17.4/h). Patients with severe OSA had significantly reduced deceleration and acceleration runs of length 1 compared to the moderate OSA group, and compared to patients with no/mild OSA they had an increased number of longer runs (from 5 to 10 for accelerations and from 5 to 8 for decelerations; p < 0.05 for all comparisons). The longest acceleration runs were significantly longer in severe OSA group (p < 0.05) than in subjects with no/mild OSA.

Conclusions

HRA microstructure is related with OSA severity. An increased number of longer deceleration and acceleration runs is more common in severe OSA patients.     

Obstructive sleep apnea: Electromyographic and fiberoptic studies

Seventeen predominantly obstructive sleep apnea patients and four normal controls (all adult males) underwent one or both investigative protocols: (A) A fiberoptic endoscope was introduced intranasally into the pharynx and subjects were monitored continuously and filmed intermittently during wakefulness and sleep. (B) Muscles selected because of their anatomical importance in maintaining the oropharynx during the respiratory cycle were electromyographically implanted intraorally or, in tracheostomy patients, at time of surgery, and subjects were polygraphically monitored during wakefulness and sleep. In both protocols, standard electroencephalogram, chin electromyogram (EMG), electrooculogram (EOG), and respiration were monitored simultaneously. During fiberoptic studies obstructive apnea during sleep first appeared as a partial or total invagination of the posterolateral pharyngeal walls, while the laryngeal inlet remained patent. EMG recordings showed normal firing patterns in patients during unobstructed sleep. During sleep-induced obstructive apnea, however, a significant decrease or complete disappearance of EMG activity was observed in the palatoglossus, palatopharyngeus, genioglossus, superior and middle constrictors of the pharynx, and stylopharyngeus. The obstruction involves absence, during inspiration, of the activity in the pharyngeal dilators needed to counteract the loads abruptly imposed by intrathoracic negative pressure changes.     

Obstructive sleep apnea/hypopnea and systemic hypertension

Obstructive sleep apnea/hypopnea (OSAH) syndrome is a highly prevalent condition. Severe OSAH affects 2–6% of the population, although only 10% of subjects are correctly diagnosed and treated. OSAH is an important and unresolved public health care problem because of its role in the development of cardiovascular events, negative impact on quality of life, and as a cause of traffic accidents. Longitudinal and cross-sectional studies have shown a strong association between OSAH and hypertension. Moreover, a number of open-label studies, the majority of 21 controlled studies included in the present review, a systematic review, and 4 recent meta-analyses have shown a reduction of blood pressure (BP) of about 2 mm Hg with continuous positive airway pressure (CPAP). This lowering of blood pressure is significant in terms of reduction of both cardiovascular and cerebrovascular risk and death. The effect is greater in hypertensive subjects and in those with more severe OSAH. Accordingly, treatment with CPAP could be considered in patients with severe OSAH and hypertension even in the absence of symptoms. The challenge to researchers is to find markers for discriminating subjects in whom blood pressure will decrease from non-responders. This will help to refine relevant clinical indicators for CPAP treatment in clinical practice.     

Obstructive sleep apnea and depression: a review

Obstructive sleep apnea is a common sleep disorder associated with several medical conditions, increased risk of motor vehicle accidents, and overall healthcare expenditure. There is higher prevalence of depression in people with obstructive sleep apnea in both clinical and community samples. Many symptoms of depression and obstructive sleep apnea overlap causing under-diagnosis of obstructive sleep apnea in depressed patients. Sleep problems, including obstructive sleep apnea, are rarely assessed on a regular basis in patients with depressive disorders, but they may be responsible for antidepressant treatment failure. The mechanism of the relationship between obstructive sleep apnea and depression is complex and remains unclear. Though some studies suggest a mutual relationship, the relationship remains unclear. Several possible pathophysiological mechanisms could explain how obstructive sleep apnea can cause or worsen depression. Increased knowledge of the relationship between obstructive sleep apnea and depression might significantly improve diagnostic accuracy as well as treatment outcomes for both obstructive sleep apnea and depression.     

Obstructive sleep apnea and incident type 2 diabetes

ObjectivesTo determine whether severity of obstructive sleep apnea is associated with incident diabetes in middle-aged and older adults.MethodsA prospective analysis of 1453 non-diabetic participants of both the Atherosclerosis Risk in Communities Study and the Sleep Heart Health Study (mean age 63 years, 46% male) had in-home polysomnography (1996–1998) and was followed up for incident diabetes. Using the apnea–hypopnea index derived from home polysomnography, study participants were categorized as follows: <5.0 (normal), 5.0–14.9 (mild), 15.0–29.9 (moderate), and ≥30.0 events/h (severe). Incident diabetes was ascertained during annual follow-up telephone calls through 2013.ResultsDuring a median follow-up of 13 years, there were 285 incident diabetes cases among the 1453 participants. Participants with severe obstructive sleep apnea were at greater risk of incident diabetes compared to persons classified as normal after adjustment for confounders including body mass index and waist circumference (1.71 [1.08, 2.71]). The association between severe obstructive sleep apnea and incident diabetes was similar when analyses were restricted to obese individuals.ConclusionsSevere obstructive sleep apnea was associated with greater risk of incident diabetes, independent of adiposity in a community-based sample. Healthcare professionals should be cognizant of the high prevalence of OSA in the general population and the potential link to incident diabetes.     

Obstructive sleep apnea syndrome: pathogenesis of neuropsychological deficits.

Neuropsychological deficits have been documented in patients with obstructive sleep apnea syndrome (OSAS). Both nocturnal hypoxemia and impairement of daytime vigilance have been suggested as the pathogenesis of these deficits, yet it remains difficult to find good correlations between cognitive deficits and either of these physiological parameters. In the present study, 10 normal controls were compared to 10 moderately and 10 severely apneic patients, all recorded in a sleep laboratory for two consecutive nights, with a vigilance and neuropsychological assessment made during the intervening day. Relative to the controls, moderate and severe OSAS showed differences in many cognitive functions, although the severely affected showed the greater differences. Moreover, severe apneics were also worse than moderate apneics on tests that were found to be normal in the latter group. This suggests a discontinuity in the appearance of neuropsychological deficits as OSAS progresses. Further analyses revealed that reductions in general intellectual measures, as well as in executive and psychomotor tasks were all attributable to the severity of hypoxemia, while other attention and memory deficits were related to vigiance impairment. Therefore, both vigilance impairment and nocturnal hypoxemia may differentially contribute to the cognitive dysfunctions found in OSAS.     

Obstructive sleep apnea in psychiatric outpatients. A clinic-based study

Psychiatric diseases and symptoms are common among patients with obstructive sleep apnea (OSA). However, only a few studies have examined OSA in psychiatric patients. At the outpatient clinic of the Uusikaupunki Psychiatric Hospital, Finland, we used a low referral threshold to a diagnostic sleep study. An ambulatory cardiorespiratory polygraphy was performed in 114 of 221 patients. 95 patients were referred by the psychiatric clinic and 19 were examined in other clinical settings. We reviewed the medical files and retrospectively assessed the prevalence of OSA and the effect of gender, age, obesity, hypertension, type 2 diabetes, alcohol abuse, and symptoms suggesting OSA. 58 of the 221 patients (26.2%), 30 of 85 men (35.3%) and 28 of 136 women (20.6%), had OSA as determined by an apnea–hypopnea index (AHI) of 5/h or more. 20 patients (12 men and 8 women) had moderate or severe OSA (AHI ≥ 15/h). 46 patients (including 11 patients with moderate or severe OSA) were identified in the psychiatric clinic. In univariate analysis, a high body mass index, male gender, hypertension, snoring, and a history of witnessed apneas during sleep were associated with the presence of OSA. In multivariate analysis, a history of witnessed apneas did not remain significant. Age, type 2 diabetes, alcohol abuse, excessive daytime sleepiness (EDS), and fatigue did not associate with the presence of OSA. Our findings suggest that in psychiatric outpatients OSA is common but underdiagnosed. Presentation is often atypical, since many patients with OSA do not report witnessed apneas or EDS.     

Obstructive sleep apnea,shift work and cardiometabolic risk

Obstructive Sleep Apnea (OSA) is one of the most common sleep disorders, and invokes numerous negative health-related outcomes and physiopathological processes. Understanding the mechanisms by which OSA potentiates cardiometabolic risk of patients remains a current challenge. Sleep disruption is highly prevalent among shift workers and shift work (SW) is an important modulator of circadian rhythms, with health consequences intimately related to cardiometabolic health. Since the circadian timing system (CTS) interacts with the normal functioning of the ANS, CTS impact on OSA patients should be closely assessed. This review raises the question of whether SW-induced circadian misalignment potentiates the cardiometabolic risk of OSA patients, providing a novel perspective on the role of autonomic modulation as a key downstream mechanism linking cardiometabolic risk with both OSA and CTS misalignment.