Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

REM sleep episodes during the maintenance of wakefulness test in patients with sleep apnea syndrome and patients with narcolepsy

Twelve patients with sleep apnea, 12 narcoleptic patients, and 10 controls were given 20-min opportunities to remain awake while sitting comfortably. Test sessions were administered at 10:00, 12:00, 14:00, 16:00, and 18:00. Apneic and narcoleptic subjects were less capable of maintaining wakefulness than controls. Patients with sleep apnea had an average of 1.4 daytime rapid eye movement (REM) episodes with the peak incidence at 14:00. Narcoleptics also had sleep onset REM periods (mean of 2.7), whereas none of the controls had REM episodes during the daytime testing. Narcoleptic and control groups differed in the probability of REM occurring at each session. There were time-of-day differences in the probability of REM occurring between patient groups. The amount of stage REM the night preceding testing was unrelated to the occurrence of REM episodes during the day in either patient group. In addition, there were notable differences in the frequency of sleep onset REM periods when patients were sitting as opposed to being supine during nap studies. Sleep latency and frequency of REM episodes on the maintenance of wakefulness test were independent of the subject's age. The maintenance of wakefulness test proved unsatisfactory as a diagnostic procedure, but appeared useful as an adjunct procedure in the evaluation of treatment efficacy of hypersomnia.     

A negative expiratory pressure test during wakefulness for evaluating the risk of obstructive sleep apnea in patients referred for sleep studies

OBJECTIVE:

Obstructive sleep apnea is characterized by increased upper airway collapsibility during sleep. The present study investigated the use of the negative expiratory pressure test as a method to rule out obstructive sleep apnea.

METHODS:

Flow limitation was evaluated in 155 subjects. All subjects underwent a diurnal negative expiratory pressure test and a nocturnal sleep study. The severity of sleep apnea was determined based on the apnea-hypopnea index. Flow limitation was assessed by computing the exhaled volume at 0.2, 0.5, and 1.0 s (V_0.2, V_0.5, and V_1.0, respectively) during the application of a negative expiratory pressure and expressed as a percentage of the previous exhaled volume. Receiver-operating characteristic curves were constructed to identify the optimal threshold volume at 0.2, 0.5, and 1.0 s for obstructive sleep apnea detection.

RESULTS:

Mean expiratory volumes at 0.2 and 0.5 s were statistically higher (p<0.01) in healthy subjects than in all obstructive sleep apneic groups. Increasing disease severity was associated with lower expiratory volumes. The V_0.2 (%) predictive parameters for the detection of sleep apnea were sensitivity (81.1%), specificity (93.1%), PPV (98.1%), and NPV (52.9%). Sensitivity and NPV were 96.9% and 93.2%, respectively, for moderate-to-severe obstructive sleep apnea, and both were 100% for severe obstructive sleep apnea.

CONCLUSION:

Flow limitation measurement by V_0.2 (%) during wakefulness may be a very reliable method to identify obstructive sleep apnea when the test is positive and could reliably exclude moderate and severe obstructive sleep apnea when the test is negative. The negative expiratory pressure test appears to be a useful screening test for suspected obstructive sleep apnea.     

Microsleep as a marker of sleepiness in obstructive sleep apnea patients

We hypothesized that: (a) the presence of microsleep (MS) during a Maintenance Wakefulness Test (MWT) trial may represent a reliable marker of sleepiness in obstructive sleep apnea (OSA) patients; (b) the number of MSs will be higher in sleepy versus non‐sleepy patients with a borderline MWT mean sleep latency; and (c) scoring MS during MWT analysis may help physicians to recognize patients with a higher degree of sleepiness. We analysed the MWT data of 112 treatment‐naïve OSA patients: 20 with short sleep latency (SL, sleep latency <12.8 min), 43 with borderline latency (BL, sleep latency between 12.8 and 32.6 min) and 49 with normal latency (NL, sleep latency >32.6 min). Microsleep was identified in all SL, in 42 BL and in 18 NL patients, with a median latency of 5.6 min. Accordingly, patients were classified into two subgroups: group A (n = 43) with microsleep latency <5.6 min and group B (n = 69) with microsleep latency >5.6 min when present. The mean sleep latency in the MWT was 14.5 ± 7.5 min in group A and 34.6 ± 7.4 min in group B (p < 0.0001). The number of microsleep episodes during each MWT trial was higher in group A than in group B. Sleep latency survival curves demonstrated different patterns of sleep latency in these groups (log‐rank test <0.0001). This finding was confirmed in a Cox proportional hazard analysis: the presence of a mean MS latency <5.6 min is associated with an increasing risk of falling asleep during the MWT (RR, 1.93; 95 CI 1.04–3.6; p = 0.03). We conclude that the detection of microsleep may help in discriminating OSA patients with and without daytime vigilance impairment.     

Sex differences in brain oscillatory activity during sleep and wakefulness in obstructive sleep apnea

Epidemiological studies consistently show a male predominance in obstructive sleep apnea (OSA). Hormonal differences, breathing control, upper airway anatomy and fat distribution have been proposed as causes of gender differences in OSA. Clinical manifestations are accentuated in men, although white matter structural integrity is affected in women. To the best of our knowledge, no previous studies have explored gender differences in the electrical brain activity features of OSA. Polysomnography was performed on 43 patients with untreated OSA (21 women, 22 men), and power spectral density (1–50 Hz) was compared between groups across sleep and wakefulness at two levels of OSA severity. Severe versus moderate OSA showed decreased power for fast frequencies (25–29 Hz) during wakefulness. OSA men displayed decreased power of a large frequency range (sigma, beta and gamma) during sleep compared with women. Comparisons of men with severe versus moderate OSA presented significantly decreased sigma power during non‐rapid eye movement (NREM) sleep, but significantly increased delta activity during REM sleep. Meanwhile, women with severe versus moderate OSA showed no significant power differences in any condition. These findings indicated a different evolution of brain oscillations between OSA men and women with significant impairment of brain activity related to cognitive processes. Our study emphasizes the importance of understanding the differential effects of sleep disorders on men and women in order to develop more precise diagnostic criteria according to gender, including quantitative electroencephalogram (EEG) analysis tools.     

Physical examination: Mallampati score as an independent predictor of obstructive sleep apnea

STUDY OBJECTIVE: To assess the clinical usefulness of the Mallampati score in patients with obstructive sleep apnea. Mallampati scoring of the orophyarynx is a simple noninvasive method used to assess the difficulty of endotracheal intubation, but its clinical usefulness has not been validated in patients with sleep-disordered breathing. DESIGN: Prospective multivariate assessment of a predictor variable. SETTING: The UCSF Sleep Disorders Center. PATIENTS OR PARTICIPANTS: One hundred thirty-seven adult patients who were evaluated for possible obstructive sleep apnea. INTERVENTIONS: Prospective determination of the Mallampati score, assessment of other variables for multivariate analysis, and subsequent overnight polysomnography. MEASUREMENTS AND RESULTS: The Mallampati score was an independent predictor of both the presence and severity of obstructive sleep apnea. On average, for every 1-point increase in the Mallampati score, the odds of having obstructive sleep apnea (apnea-hypopnea index> or = 5) increased more than 2-fold (odds ratio [per 1-point increase] = 2.5; 95% confidence interval: 1.2-5.0; p = .01), and the apnea-hypopnea index increased by more than 5 events per hour (coefficient = 5.2; 95% confidence interval: 0.2-10; p = .04). These results were independent of more than 30 variables that reflected airway anatomy, body habitus, symptoms, and medical history. CONCLUSION: Our results indicate that Mallampati scoring is a useful part of the physical examination of patients prior to polysomnography. The independent association between Mallampati score and presence and severity of obstructive sleep apnea suggests that this scoring system will have practical value in clinical settings and prospective studies of sleep-disordered breathing.     

Association between obstructive sleep apnea severity and glucose control in patients with untreated versus treated diabetes

The purpose of this study was to determine whether the association between obstructive sleep apnea severity and glucose control differs between patients with newly diagnosed and untreated type 2 diabetes, and patients with known and treated type 2 diabetes. This multicentre cross‐sectional study included 762 patients investigated by sleep recording for suspected obstructive sleep apnea, 497 of whom were previously diagnosed and treated for type 2 diabetes (treated diabetic patients), while 265 had no medical history of diabetes but had fasting blood glucose ≥126 mg dL^?1 and/or glycated haemoglobin (HbA_1c) ≥6.5% consistent with newly diagnosed type 2 diabetes (untreated diabetic patients). Multivariate regression analyses were performed to evaluate the independent association between HbA_1c and obstructive sleep apnea severity in treated and untreated patients with diabetes. In untreated diabetic patients, HbA_1c was positively associated with apnea–hypopnea index (P = 0.0007) and 3% oxygen desaturation index (P = 0.0016) after adjustment for age, gender, body mass index, alcohol habits, metabolic dyslipidaemia, hypertension, statin use and study site. The adjusted mean value of HbA_1c increased from 6.68% in the lowest quartile of the apnea–hypopnea index (<17) to 7.20% in the highest quartile of the apnea–hypopnea index (>61; P = 0.033 for linear trend). In treated patients with diabetes, HbA_1c was associated with non‐sleep variables, including age, metabolic dyslipidaemia and insulin use, but not with obstructive sleep apnea severity. Obstructive sleep apnea may adversely affect glucose control in patients with newly diagnosed and untreated type 2 diabetes, but may have a limited impact in patients with overt type 2 diabetes receiving anti‐diabetic medications.     

Advanced emergency braking system reduces the risk of motor vehicle collisions caused by falling asleep while driving in patients with untreated obstructive sleep apnea

Obstructive sleep apnea leads to excessive daytime sleepiness and cognitive dysfunction, which are risk factors for motor vehicle collisions. We aimed to clarify if vehicles with an advanced emergency braking system could reduce motor vehicle collisions caused by falling asleep while driving among patients with untreated obstructive sleep apnea. We enrolled patients with untreated obstructive sleep apnea who underwent polysomnography. The questionnaires included the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, history of drowsy driving accidents, and use of an advanced emergency braking system. Multivariate analysis was performed, and odds ratios and 95% confidence intervals were calculated. This study included 1097 patients (mean age, 51.2 ± 12.9 years). Collisions caused by falling asleep while driving were recorded in 59 (5.4%) patients, and were more frequently observed in vehicles without an advanced emergency braking system (p = 0.045). Multivariate analysis showed that these collisions were associated with use of an advanced emergency braking system (odds ratio [95% confidence interval]: 0.39 [0.16–0.97], p = 0.04), length of driving (2.79 [1.19–6.50], p = 0.02), total sleep time (2.40 [1.62–3.55], p < 0.0001), sleep efficiency (0.94 [0.90–0.98], p = 0.003) and periodic limb movement index (1.02 [1.01–1.03], p = 0.004). The collision risk caused by falling asleep while driving in vehicles with an advanced emergency braking system was significantly lower. This study indicates that advanced emergency braking systems may be a preventive measure to reduce motor vehicle collisions among patients with untreated obstructive sleep apnea.     

Utility of home oximetry as a screening test for patients with moderate to severe symptoms of obstructive sleep apnea

OBJECTIVE: To determine the value of home oximetry as a screening test in patients with moderate to severe symptoms of obstructive sleep apnea (OSA). DESIGN: Retrospective, observational study. SETTING: The Sleep Unit of a tertiary referral, university hospital. PATIENTS: 116 patients referred for evaluation of moderate to severe symptoms of OSA in which both home oximetry and polysomnography (PSG) were performed. INTERVENTIONS: NA. RESULTS: Three numerical oximetry indices were evaluated: average of desaturations > or =4% and average of resaturations > or =3% per hour of analysis time (DI4% and RI3%, respectively); and cumulative percentages of time spent at saturations below 90% (CT90%). A qualitative assessment was also performed. Oximetry indices were compared with apnea/hypopnea index (AHI) by simple linear regression and Bland-Altman analyses. Optimal cut-off points, in terms of sensitivity and specificity, for the oximetry indices were searched using ROC analysis, at an AHI threshold of > or =10. The correlation between AHI and the desaturation indices was r = 0.50 for CT90%, r = 0.60 for DI4%, and r = 0.58 for RI3%. No bias was found between PSG and oximetry indices in Bland-Altman plots. Neither the numerical indices nor the qualitative analysis achieved an adequate (>0.8) area under the ROC curve. A CT90% <0.79 excluded OSA with 84% sensitivity. A DI4% > or =31.4 or a RI3% > or =40.5 diagnosed OSA with 97% specificity. Using these values, 38% of the patients would have been correctly classified by oximetry alone, 10% would have been incorrectly classified, and 50% could not have been classified with certainty. Eleven (15%) OSA patients would have been missed by oximetry. CONCLUSIONS: Correlation between home oximetry and PSG was not high. Oximetry was more useful to confirm than to exclude OSA in our study. Qualitative assessment was not better than numerical analysis. The greatest value of oximetry in this setting seems to be as a tool to rapidly recognize and treat more severe OSA patients in waiting list for PSG.     

Effects of short-term CPAP withdrawal on neurobehavioral performance in patients with obstructive sleep apnea

STUDY OBJECTIVE: Changes in sleep parameters and neurobehavioral functioning were systematically investigated after an acute (1 night) and short-term (7 nights) period of withdrawal from continuous positive airway pressure (CPAP) treatment and 1 subsequent night of CPAP reintroduction in patients with obstructive sleep apnea. DESIGN: Repeated-measurement within-subject design. SETTING: Sleep laboratory, university teaching hospital. PARTICIPANTS: Twenty participants receiving optimal CPAP therapy for > or = 12 months. INTERVENTIONS: CPAP withdrawal. MEASUREMENTS AND RESULTS: Polysomnograms were performed on Night 0 (with CPAP), Night 1 and Night 7 (without CPAP) and Night 8_R (with CPAP). Acute CPAP withdrawal resulted in the recurrence of sleep-disordered breathing with sleep disruption, hypoxemia, and increased subjective sleepiness. Short-term CPAP withdrawal exacerbated hypoxemia, increased subjective and objective sleepiness and poor mood ratings. Neurobehavioral functioning assessed using the Psychomotor Vigilance Task was impaired following Night 7 and associated with hypoxemia and changes in morning levels of tumor necrosis factor-alpha. However, other neurobehavioral measures were not affected. Autonomic arousals measured via respiratory-related reductions in finger blood volume by peripheral arterial tonometry decreased from Night 1 to Night 7. On Night 8_R, reintroduction of CPAP treatment eliminated most airway obstruction, maintained oxygenation, and reversed daytime sleepiness and some vigilance decrements. CONCLUSION: Despite recurrence of sleep-disordered breathing with increased sleepiness and impaired vigilance, most neurobehavioral variables were unaffected by CPAP withdrawal. The reduction in vigilance appeared to be associated with worsened hypoxemia and changed levels of tumor necrosis factor-alpha. Resumption of CPAP treatment had immediate benefits on sleep consolidation and subjective sleepiness.     

Vigilance in patients with obstructive sleep apnea and surgical patients

Aim

The Marburg vigilance test (VigiMar) is a vigilance task implemented as a four-choice reaction time task with long duration and low stimulus rate. It tests readiness for reaction under monotonous conditions characterized by sensory deprivation. This study was conducted to compare test results of subjects without sleep disorders to those of patients with untreated obstructive sleep apnea (OSA). In addition, whether patients treated for OSA by continuous positive airway pressure (CPAP) exhibited improvements in vigilance testing and whether subjects without sleep disorders have stable test results in a retest after 2 days were investigated. As test results are given for test thirds separately, these were used to determine whether there was a time-on-task effect for patients with untreated OSA and to check for internal consistency of the VigiMar test.

Patients and methods

A total of 20 patients with OSA and 20 surgical patients (knee arthroscopy) between 25 and 65 years of age were included. All patients were male. Vigilance testing was performed on the day before CPAP treatment was started or on the day before arthroscopy and 2 days later after the second CPAP night or on the first day after the surgical procedure, respectively.

Results

In the baseline vigilance test, reaction times of OSA patients were longer than those of surgical patients, especially during the last third of the test. After 2 nights CPAP, reaction times of OSA patients improved to the same level as those of surgical patients who exhibited homogenous results in baseline and postintervention testing.

Conclusion

The VigiMar test is suitable for the assessment of impaired vigilance. Its internal consistency is high, retest reliability is satisfactory, and it is sensitive for changes in vigilance after only 2 nights CPAP treatment.     

CSF hypocretin measures in patients with obstructive sleep apnea

The majority of patients with narcolepsy-cataplexy were reported to have very low cerebrospinal fluid (CSF) hypocretin-1 (orexin-A) levels. The hypocretin-1 levels of secondary excessive daytime sleepiness (EDS) disorders are not known. In this study, we found that CSF hypocretin levels in the patients with obstructive sleep apnea syndrome were within the control range. The low hypocretin levels seem to reflect only the presence of cataplexy and DR2 positive in narcoleptics but not EDS itself.     

Insomnia in untreated sleep apnea patients compared to controls

Insomnia and obstructive sleep apnea (OSA) often coexist, but the nature of their relationship is unclear. The aims of this study were to compare the prevalence of initial and middle insomnia between OSA patients and controls from the general population as well as to study the influence of insomnia on sleepiness and quality of life in OSA patients. Two groups were compared, untreated OSA patients (n = 824) and controls ≥ 40 years from the general population in Iceland (n = 762). All subjects answered the same questionnaires on health and sleep and OSA patients underwent a sleep study. Altogether, 53% of controls were males compared to 81% of OSA patients. Difficulties maintaining sleep (DMS) were more common among men and women with OSA compared to the general population (52 versus 31% and 62 versus 31%, respectively, P < 0.0001). Difficulties initiating sleep (DIS) and DIS + DMS were more common among women with OSA compared to women without OSA. OSA patients with DMS were sleepier than patients without DMS (Epworth Sleepiness Scale: 12.2 versus 10.9, P < 0.001), while both DMS and DIS were related to lower quality of life in OSA patients as measured by the Short Form 12 (physical score 39 versus 42 and mental score 36 versus 41, P < 0.001). DIS and DMS were not related to OSA severity. Insomnia is common among OSA patients and has a negative influence on quality of life and sleepiness in this patient group. It is relevant to screen for insomnia among OSA patients and treat both conditions when they co‐occur.     

Factors associated with maintenance of wakefulness test mean sleep latency in patients with mild to moderate obstructive sleep apnoea and normal subjects

This study investigated the possible factors related to the Maintenance of Wakefulness Test (MWT) mean sleep latency. A second analysis explored the characteristics of subjects who had discrepant Epworth Sleepiness Scale (ESS) and MWT scores. A total of 151 subjects (110 mild to moderate obstructive sleep apnoea (OSA) patients and 41 control subjects) were recruited for the study. The subjects completed an overnight Polysomnography (PSG), MWT, cognitive, performance and vigilance tasks and answered self-report questionnaires on mood and sleepiness. A forward stepwise multiple regression was performed on MWT mean sleep latency. The predictor variables age (r = 0.28), subjective sleep history for 1 week prior to MWT (sleep diary; r = 0.19) and number of >4% SaO2 Dips during the PSG (r = -0.21) best explained the MWT results, but only accounted for 12.8% of the variance in the test. It was found that 33% of subjects had discrepant ESS and MWT scores. A new variable was created to analyse these subjects (MWT/ESS discrepancy score; MED). A forward stepwise multiple regression analysis found that depression, performance errors and sleep disordered breathing explained 13.4% of the variance in MED scores. The MWT is a complex behavioural test whose scores do not seem to have a very robust relationship with potential predictors and co-correlates. Further comprehensive study is needed if the test is to be used in a diagnostically meaningful way.     

Comprehensive coronary plaque assessment in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non‐calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty‐one adult subjects (59 ± 9 years, 15 men) underwent a 256‐slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty‐two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea‐hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.     

Reduced mammillary body volume in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) patients show compromised emotional and cognitive functions, including anterograde memory deficits. While some memory inadequacies in OSA may result from earlier-described structural deficits in the hippocampus, mammillary body injury also could contribute, since these structures receive projections from the hippocampus via the fornix, project heavily to the anterior thalamus, and have been implicated in other conditions with memory deficiencies, such as Korsakoff's syndrome. However, volume loss in mammillary bodies has not been reported in OSA, likely a consequence of logistic difficulties in size assessment. We evaluated mammillary body volumes in 43 OSA (mean age+/-S.D., 46.9+/-9.2 years; mean apnea-hypopnea-index+/-S.D., 31.2+/-19.9 events/h) and 66 control subjects (age, 47.3+/-8.9 years). Two high-resolution T1-weighted image volumes were collected on a 3.0 T magnetic resonance scanner, averaged to improve signal-to-noise, and reoriented (without warping) into a common space. Brain sections containing both mammillary bodies were oversampled, and the bodies were manually traced and volumes calculated. OSA patients showed significantly reduced left, right, and combined mammillary body volumes compared with control subjects, after partitioning for age, gender, and head size (multivariate linear model, p<0.05). Left-side mammillary bodies showed greater volume reduction than the right side. Diminished mammillary body volume in OSA patients may be associated with memory and spatial orientation deficits found in the syndrome. The mechanisms contributing to the volume loss are unclear, but may relate to hypoxic/ischemic processes, possibly assisted by nutritional deficiencies in the syndrome.     

Advanced glycation endproducts in nondiabetic patients with obstructive sleep apnea

SUBJECT OBJECTIVE: The formation and accumulation of advanced glycation endproducts (AGEs) has been implicated in the progression of age-related diseases such as diabetes mellitus and atherosclerosis. We hypothesize that AGE concentrations may be increased in subjects with obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: One hundred nineteen nondiabetic patients with OSA and 234 age-matched healthy controls and 134 patients with type 2 diabetes were recruited for participation in the study. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit antisera raised against AGE-RNase. RESULTS: Serum AGEs were increased in OSA subjects, as compared with controls, but were less increased than the AGEs of patients with type 2 diabetes (control: 3.22 +/- 0.54 unit per mL; OSA: 3.68 +/- 0.39; diabetes mellitus: 4.11 +/- 0.99; analysis of variance p < .01). In the subjects with OSA, serum AGEs correlated with the duration of nocturnal desaturation (r = 0.21, p = .025) and plasma total 8-isoprostane concentration, a biochemical marker of oxidative stress (r = 0.22, p = .015), but not with fasting glucose level. On general linear model univariate analysis, the association between serum AGEs and 8-isoprostane was independent of age, sex, body mass index, smoking status, and glucose. CONCLUSION: Serum levels of AGEs were increased in nondiabetic subjects with OSA and were associated with the severity of OSA. Whether increased AGE formation contributes significantly to the high cardiovascular risk associated with OSA remains to be determined.     

Snoring sounds variability as a signature of obstructive sleep apnea

Snoring sounds vary significantly within and between snorers. In this study, the variation of snoring sounds and its association with obstructive sleep apnea (OSA) are quantified. Snoring sounds of 42 snorers with different degrees of obstructive sleep apnea and 15 non-OSA snorers were analyzed. The sounds were recorded by a microphone placed over the suprasternal notch of trachea, simultaneously with polysomnography (PSG) data over the entire night. We hypothesize that snoring sounds vary significantly within a subject depending on the level of obstruction, and thus the level of airflow. We also hypothesize that this variability is associated with the severity of OSA. For each individual, we extracted snoring sound segments from the respiratory recordings, and divided them into three classes: non-apneic, hypopneic, and post-apneic using their PSG information. Several features were extracted from the snoring sound segments, and compared using a nonparametric statistical test. The results show significant shift in the median of features among the snoring sound classes (p < 0.00001) of an individual. In contrast to hypopneic and post-apneic classes, the characteristics of snoring sounds did not vary significantly over time in non-apneic class. Therefore, we used the total variation norm of each subject to classify the participants as OSA and non-OSA snorers. The results showed 92.9% sensitivity, 100% specificity and 96.4% accuracy.