Measures of overnight oxygen saturation to characterize sleep apnea severity and predict postoperative respiratory depression.

BACKGROUND: Sleep apnea syndrome, characterized by recurrent cessation (apnea) or reduction (hypopnea) of breathing during sleep, is a major risk factor for postoperative respiratory depression. Challenges in sleep apnea assessment have led to the proposal of alternative metrics derived from oxyhemoglobin saturation (SpO2), such as oxygen desaturation index (ODI) and percentage of cumulative sleep time spent with SpO2 below 90% (CT90), as predictors of postoperative respiratory depression. However, their performance has been limited with area under the curve of 0.60 for ODI and 0.59 for CT90. Our objective was to propose novel features from preoperative overnight SpO2 which are correlated with sleep apnea severity and predictive of postoperative respiratory depression. METHODS: Preoperative SpO2 signals from 235 surgical patients were retrospectively analyzed to derive seven features to characterize the sleep apnea severity. The features included entropy and standard deviation of SpO2 signal; below average burden characterizing the area under the average SpO2; average, standard deviation, and entropy of desaturation burdens; and overall nocturnal desaturation burden. The association between the extracted features and sleep apnea severity was assessed using Pearson correlation analysis. Logistic regression was employed to evaluate the predictive performance of the features in identifying postoperative respiratory depression. RESULTS: Our findings indicated a similar performance of the proposed features to the conventional apnea-hypopnea index (AHI) for assessing sleep apnea severity, with average area under the curve ranging from 0.77 to 0.81. Notably, entropy and standard deviation of overnight SpO2 signal and below average burden showed comparable predictive capability to AHI but with minimal computational requirements and individuals' burden, making them promising for screening purposes. Our sex-based analysis revealed that compared to entropy and standard deviation, below average burden exhibited higher sensitivity in detecting respiratory depression in women than men. CONCLUSION: This study underscores the potential of preoperative SpO2 features as alternative metrics to AHI in predicting postoperative respiratory.

Relevance Between Reduction of SpO2 and Parasympathetic Nervous Activity During Sleep.

Sleep apnea syndrome (SAS) is associated with cardiopulmonary and dental nasopharyngeal diseases. The blood oxygen saturation (SpO2) detected using pulse oximetry is a diagnostic screening method for SAS. SAS severity is assessed using the oxygen desaturation index (ODI), which measures the number of times the SpO2 decreases by more than 3% for longer than 10 s. This study investigated the association between reduced SpO2 and parasympathetic nervous system activity (PSNA) during night sleep in young adults (n = 63; aged 20-32 years). Changes in PSNA were measured every minute for 24 h during a free-moving day using an ActiveTracer accelerometer. Pulse oximetry was performed simultaneously during sleep. All participants had significantly lower PSNA when the SpO2 decreased by 3% or more than when it did not. There were no significant differences in PSNA when an ODI cutoff of 5 events/h was used. However, participants with an ODI >5 events/h had significantly lower PSNA during normal SpO2 than those with an ODI <5 events/h, suggesting an association between SpO2 desaturation and PSNA decline during sleep. A high ODI may indicate reduced PSNA levels during sleep, affecting sleep efficiency. Treatment aimed at reducing the ODI may improve sleep quality, even in young adults.

GDF11 (Protein of Juvenility) and GDF15 (Protein of Senility) in the Plasma of Patients with Sleep Apnea Syndrome: a Pilot Study.

We performed a matched-pair analysis of the content of GDF11 and GDF15 proteins in the plasma of patients (56 middle-aged men) with obstructive sleep apnea syndrome (OSAS) and healthy volunteers (27 men with no complaints of sleep disorders). The groups were comparable in terms of age and presence of chronic diseases. No statistically significant differences in GDF11 content in the studied groups were revealed, while the content of GDF15 in the OSAS group was 1.3 times higher. These results require further research from the viewpoint of geriatric somnology and molecular biology.

Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Predictive Performance of Oximetry to Detect Sleep Apnea in Patients Taking Opioids.

BACKGROUND: Long-term use of opioids for treatment of chronic pain is associated with significant risks including worsening unrecognized or untreated sleep apnea that may increase morbidity and mortality. Overnight oximetry has been validated for predicting sleep apnea in surgical and sleep clinic patients. The objective of the study was to assess the predictive accuracy of oxygen desaturation index (ODI 4%) from home overnight oximetry when compared to apnea hypopnea index (AHI) from polysomnography for predicting sleep apnea in patients taking opioids for chronic pain. METHODS: This was a planned post hoc analysis of a prospective cohort study conducted at 5 pain clinics. Patient characteristics and daily morphine milligram equivalent (MME) dose were recorded. All consented patients underwent home overnight oximetry (PULSOX-300i, Konica Minolta Sensing, Inc, Osaka, Japan) and in-laboratory polysomnography. The predictive performance of ODI 4% from oximetry was assessed against AHI from polysomnography. RESULTS: Among 332 consented patients, 181 with polysomnography and overnight oximetry data were analyzed. The mean age and body mass index of 181 patients were 52 ± 13 years and 29 ± 6 kg/m2, respectively, with 40% men. The area under the receiver operating curve for ODI to predict moderate-to-severe sleep apnea (AHI ≥15 events/h) and severe sleep apnea (AHI ≥30 events/h) was 0.82 (95% confidence interval [CI], 0.75-0.88) and 0.87 (95% CI, 0.80-0.94). ODI ≥5 events/h had a sensitivity of 85% (95% CI, 74-92) and specificity of 57% (95% CI, 52-61) to predict moderate-to-severe sleep apnea. ODI ≥15 events/h had a sensitivity of 71% (95% CI, 55-83) and specificity of 88% (95% CI, 84-91) to predict severe sleep apnea. CONCLUSIONS: Overnight home oximetry has a high predictive performance in predicting moderate-to-severe and severe sleep apnea in patients on opioids for chronic pain. It is a useful additional tool for health care providers for the screening of sleep apnea in this high-risk group.

Association of lipoprotein levels with sleep apnea: role of autonomic dysfunction.

Objectives. Although multiple mechanisms, including autonomic dysfunction, seem to link sleep-disordered breathing (SDB) with dyslipidemia in animal studies, the data in clinical studies are limited. The aim of this study was to explore the association of lipoprotein levels with SDB measures in healthy habitual snorers. We supposed that autonomic dysfunction is the linking mechanism.Methods. We enrolled 110 previously healthy subjects with complaints of habitual snoring. To assess SDB, polysomnography was performed. Blood samples for the analysis of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) were obtained in a fasting condition after the polysomnography. Baroreflex sensitivity (BRS) was used to assess the autonomic dysfunction.Results. In stepwise multiple linear regression analysis, minimal nocturnal blood oxygen saturation (beta=-0.240, p=0.020) and neck circumference (beta=0.224, p=0.03) were the only significant contributors in model predicting TG. SDB measures were not identified as significant contributors in models predicting TC, LDL, and HDL. We failed to find any significant difference in BRS in SDB subjects when compared according to the presence or absence of hypercholesterolemia/ hypertriglyceridemia. In SDB subjects, the area under the curve in a receiver operating curve to predict hypercholesterolemia and hypertriglyceridemia by BRS was 0.468 (95% CI: 0.328-0.608) and 0.425 (95% CI: 0.304-0.546), respectively.Conclusions. Our results suggest that minimal nocturnal blood oxygen saturation is significant contributor in model predicting TG. No significant decrease in BRS was found in SDB subjects with hypercholesterolemia and hypertriglyceridemia. In SDB subjects, the role of autonomic dys-function in the development of dyslipidemia remains controversial.

Increased Platelet Aggregation in Children and Adolescents with Sleep-disordered Breathing.

Rationale: Sleep-disordered breathing (SDB) is associated with increased vascular resistance in children and adults. Persistent increased vascular resistance damages vascular endothelial cells-a marker of which is increased platelet activation.Objectives: This study compared whole-blood impedance platelet aggregation in children with clinically diagnosed SDB warranting adenotonsillectomy and healthy control subjects.Methods: Thirty children who had SDB warranting intervention clinically diagnosed by experienced pediatric otolaryngologists were recruited from adenotonsillectomy waitlists, and 20 healthy children from the community underwent overnight polysomnography to determine SDB severity (obstructive apnea-hypopnea index). Snoring frequency was collected from parents. In the morning, a fasting blood sample was taken, and whole-blood platelet aggregation was measured.Measurements and Main Results: Children with SDB exhibited increased platelet aggregation to TRAP (thrombin receptor-activating peptide) (children with SDB = 114.8 aggregation units [AU] vs. control subjects = 98.0 AU; P < 0.05) and COL antibody (96.7 vs. 82.2 AU; P < 0.05) and an increased trend in ADP antibody (82.3 vs. 69.2 AU; P < 0.07) but not aspirin dialuminate (82.1 vs. 79.5 AU; P > 0.05). No significant association was observed between either the obstructive apnea-hypopnea index and any aggregation parameter, but parental report of snoring was positively associated with TRAP aggregation (Kendall's τ-c = 0.23; P < 0.05).Conclusions: The finding of increased platelet aggregation is consistent with endothelial damage. This suggests that the profile of cardiovascular changes noted in adults with SDB may also occur in children with SDB.

Sex differences in integrated neurocardiovascular control of blood pressure following acute intermittent hypercapnic hypoxia.

Repetitive hypoxic apneas, similar to those observed in sleep apnea, result in resetting of the sympathetic baroreflex to higher blood pressures (BP). This baroreflex resetting is associated with hypertension in preclinical models of sleep apnea (intermittent hypoxia, IH); however, the majority of understanding comes from males. There are data to suggest that female rats exposed to IH do not develop high BP. Clinical data further support sex differences in the development of hypertension in sleep apnea, but mechanistic data are lacking. Here we examined sex-related differences in the effect of IH on sympathetic control of BP in humans. We hypothesized that after acute IH we would observe a rise in muscle sympathetic nerve activity (MSNA) and arterial BP in young men (n = 30) that would be absent in young women (n = 19). BP and MSNA were measured during normoxic rest before and after 30 min of IH. Baroreflex sensitivity (modified Oxford) was evaluated before and after IH. A rise in mean BP following IH was observed in men (+2.0 ± 0.7 mmHg, P = 0.03), whereas no change was observed in women (-2.7 ± 1.2 mmHg, P = 0.11). The elevation in MSNA following IH was not different between groups (4.7 ± 1.1 vs. 3.8 ± 1.2 bursts/min, P = 0.65). Sympathetic baroreflex sensitivity did not change after IH in either group (P > 0.05). Our results support sex-related differences in the effect of IH on neurovascular control of BP and show that any BP-raising effects of IH are absent in young women. These data enhance our understanding of sex-specific mechanisms that may contribute to BP changes in sleep apnea.

Patterns of adaptive servo-ventilation settings in a real-life multicenter study: pay attention to volume! : Adaptive servo-ventilation settings in real-life conditions.

BACKGROUNDS: To explain the excess cardiovascular mortality observed in the SERVE-HF study, it was hypothesized that the high-pressure ASV default settings used lead to inappropriate ventilation, cascading negative consequences (i.e. not only pro-arrythmogenic effects through metabolic/electrolyte abnormalities, but also lower cardiac output). The aims of this study are: i) to describe ASV-settings for long-term ASV-populations in real-life conditions; ii) to describe the associated minute-ventilations (MV) and therapeutic pressures for servo-controlled-flow versus servo-controlled-volume devices (ASV-F Philips®-devices versus ASV-V ResMed®-devices). METHODS: The OTRLASV-study is a cross-sectional, 5-centre study including patients who underwent ASV-treatment for at least 1 year. The eight participating clinicians were free to adjust ASV settings, which were compared among i) initial diagnosed sleep-disordered-breathing (SBD) groups (Obstructive-Sleep-Apnea (OSA), Central-Sleep-Apnea (CSA), Treatment-Emergent-Central-Sleep-Apnea (TECSA)), and ii) unsupervised groups (k-means clusters). To generate these clusters, baseline and follow-up variables were used (age, sex, body mass index (BMI), initial diagnosed Obstructive-Apnea-Index, initial diagnosed Central-Apnea-Index, Continuous-Positive-Airway-Pressure used before ASV treatment, presence of cardiopathy, and presence of a reduced left-ventricular-ejection-fraction (LVEF)). ASV-data were collected using the manufacturer's software for 6 months. RESULTS: One hundred seventy-seven patients (87.57% male) were analysed with a median (IQ25-75) initial Apnea-Hypopnea-Index of 50 (38-62)/h, an ASV-treatment duration of 2.88 (1.76-4.96) years, 61.58% treated with an ASV-V. SDB groups did not differ in ASV settings, MV or therapeutic pressures. In contrast, the five generated k-means clusters did (generally described as follows: (C1) male-TECSA-cardiopathy, (C2) male-mostly-CSA-cardiopathy, (C3) male-mostly-TECSA-no cardiopathy, (C4) female-mostly-elevated BMI-TECSA-cardiopathy, (C5) male-mostly-OSA-low-LVEF). Of note, the male-mostly-OSA-low-LVEF-cluster-5 had significantly lower fixed end-expiratory-airway-pressure (EPAP) settings versus C1 (p = 0.029) and C4 (p = 0.007). Auto-EPAP usage was higher in the male-mostly-TECSA-no cardiopathy-cluster-3 versus C1 (p = 0.006) and C2 (p < 0.001). MV differences between ASV-F (p = 0.002) and ASV-V (p < 0.001) were not homogenously distributed across clusters, suggesting specific cluster and ASV-algorithm interactions. Individual ASV-data suggest that the hyperventilation risk is not related to the cluster nor the ASV-monitoring type. CONCLUSIONS: Real-life ASV settings are associated with combinations of baseline and follow-up variables wherein cardiological variables remain clinically meaningful. At the patient level, a hyperventilation risk exists regardless of cluster or ASV-monitoring type, spotlighting a future role of MV-telemonitoring in the interest of patient-safety. TRIAL REGISTRATION: The OTRLASV study was registered on ClinicalTrials.gov (Identifier: NCT02429986 ). 1 April 2015.

Preschoolers with recurrent wheezing have a high prevalence of sleep disordered breathing.

Objective: Sleep-disordered breathing (SDB) is highly prevalent in school children with poorly-controlled asthma. However, this association has not been assessed in preschoolers with recurrent wheeze, nor in those at risk for asthma. We hypothesized that preschoolers with asthma risk (positive asthma predictive index [API]) have a higher prevalence of SDB and higher inflammatory biomarkers (blood-hsCRP and urinary-LTE4) levels than those with negative API.Method: Children 2 to 5 years of age with recurrent wheezing were classified as positive or negative API. SDB was determined by the pediatric sleep questionnaire (PSQ) and its subscale (PSQSub6). Demographic characteristics, spirometry, blood hsCRP and urinary LTE4 were assessed.Results: We enrolled 101 preschoolers: 70 completed all measurements, 55.4% were males, mean age 4.07 ± 0.87 years, 45% overweight or obese, 70% had positive API, 87.5% had rhinitis. The prevalence of SDB measured by PSQ was 40.8% and by PSQSub6 was 29.6%. However, the proportion of SDB was similar between positive and negative API groups. The hsCRP (mean ± SD) was higher in the positive than in negative API (3.58 ± 0.58 and 1.32 ± 0.36 mg/L, p = 0.69, respectively); moreover, no differences in urinary LTE4 were found between groups. No correlation of PSQ (+) or PSQSub6 (+) with hsCRP and uLTE4 was found. However, preschoolers with positive API had significantly more post-bronchodilator percentage change in FEF25-75 than negative API (24.14 ± 28.1 vs. 4.13 ± 21.8, respectively, p = 0.01).Conclusions: In preschoolers with recurrent wheezing, we should be investigating for the coexistence of SDB, using early screening methods for detecting those conditions.

Sleep-disordered breathing in adolescents with obesity: When does it start to affect cardiometabolic health?

BACKGROUND AND AIMS: Pediatric obesity and sleep-disordered breathing (SDB) are associated with cardiometabolic risk (CMR), but the degree of severity at which SDB affects cardiometabolic health is unknown. We assessed the relationship between the CMR and the apnea-hypopnea index (AHI), to identify a threshold of AHI from which an increase in the CMR is observed, in adolescents with obesity. We also compared the clinical, cardiometabolic and sleep characteristics between adolescents presenting a high (CMR+) and low CMR (CMR-), according to the threshold of AHI. METHODS AND RESULTS: 114 adolescents with obesity were recruited from three institutions specialized in obesity management. Sleep and SDB as assessed by polysomnography, anthropometric parameters, fat mass (FM), glucose and lipid profiles, and blood pressure (BP) were measured at admission. Continuous (MetScoreFM) and dichotomous (metabolic syndrome, MetS) CMR were determined. Associations between MetScoreFM and AHI adjusted for BMI, sex and age were assessed by multivariable analyses. Data of 82 adolescents were analyzed. Multivariable analyses enabled us to identify a threshold of AHI = 2 above which we observed a strong and significant association between CMR and AHI (Cohen's d effect-size = 0.57 [0.11; 1.02] p = 0.02). Adolescents with CMR+ exhibited higher MetScoreFM (p < 0.05), insulin resistance (p < 0.05), systolic BP (p < 0.001), sleep fragmentation (p < 0.01) and intermittent hypoxia than CMR- group (p < 0.0001). MetS was found in 90.9% of adolescents with CMR+, versus 69.4% in the CMR- group (p < 0.05). CONCLUSIONS: The identification of a threshold of AHI ≥ 2 corresponding to the cardiometabolic alterations highlights the need for the early management of SDB and obesity in adolescents, to prevent cardiometabolic diseases. CLINICAL TRIALS: NCT03466359, NCT02588469 and NCT01358773.

Is C-reactive protein elevated in obstructive sleep apnea? a systematic review and meta-analysis.

Purpose: This study examined whether circulating C-reactive protein (CRP) is elevated in obstructive sleep apnoea (OSA) independent of the confounding effects of comorbidities, smoking, body mass index (BMI), age and gender. Methods: A systematic review of the literature was performed using PubMed, Embase and Cochrane databases from 1 January 1997 to 1 November 2017 using the key words obstructive sleep apnoea and C-Reactive protein to identify full text English language studies that compared CRP in adult non-smoking OSA participants without comorbidities and adult healthy non-smoking control participants matched for BMI, age and gender. Data from eligible studies were subjected to meta-analysis using RevMan version 5.3. Results: Five studies (219 OSA participants, 116 controls) met the selection criteria. The total standard mean difference for circulating high sensitivity CRP was 0.61 mg/dL higher in OSA participants than in control participants (confidence interval: 0.38 to 0.84, p < 0.00001), with low between-studies heterogeneity (df = 7, p = 0.16, I2 = 33%) and minimal evidence of publication bias. Conclusions: CRP levels in non-smoking OSA participants without comorbidities were increased relative to levels in healthy matched non-smoking control participants, suggesting that pharyngeal or systemic inflammatory effects attributable to OSA may elevate CRP.

Effects of Obstructive Sleep Apnea-Hypopnea Syndrome on Serum Carcinoembryonic Antigen Levels in Patients with Type 2 Diabetes Mellitus.

BACKGROUND Type 2 diabetes mellitus (T2DM) is related to the serum carcinoembryonic antigen (CEA) level, which is used as a marker of colorectal cancer. Obstructive sleep apnea-hypopnea syndrome (OSAS) has been recently reported to have cancer-promoting effects. The aim of our study was to observe the effect of OSAS on serum levels of CEA in patients with T2DM. MATERIAL AND METHODS We enrolled 401 T2DM patients in this study. There were 244 patients with OSAS and 157 patients without OSAS. RESULTS The CEA level in T2DM patients with OSAS was higher than that in those without OSAS (p<0.05). The participants with AHI scores ≥30 had higher CEA levels than those with 5≤ AHI scores <30 (p<0.05). The AHI score and ODI score were independently associated with increased risk of high CEA level in T2DM patients (odds ratio [OR]=1.052, 95% confidence interval [CI]: 1.011~1.095) and (OR=1.214, 95% CI: 1.070~1.377). Moreover, among male T2DM patients, the AHI score and ODI score had a linear correlation with the CEA level; this association was also observed in T2DM patients who smoked, had an HbA1c level ≥7%, or had a BMI ≥28 kg/m2 (all p<0.05). CONCLUSIONS The AHI score and ODI score were positively associated with the CEA level in T2DM patients. The relationship was stronger in male T2DM patients and in those who smoked, were obese, or had poor glycemic control. The mechanism may be related to metabolic disorders, and the potential increased risk of colorectal cancer should be investigated in a prospective study.

The association of coffee consumption and oxygen desaturation index during sleep among Japanese male workers.

BACKGROUND AND OBJECTIVE: Coffee is a major caffeine-containing food source that can be used for treatment of apnea in prematurity. However, few studies have examined the association between coffee consumption and sleep-disordered breathing (SDB). We investigated whether coffee consumption is associated with the oxygen desaturation index (ODI) as a marker of SDB among middle-aged Japanese male workers. METHODS: The subjects were 1126 male local government workers aged 22-59 who participated in SDB screening in 2011-2012. Daily coffee consumption was assessed by a self-administered questionnaire. We measured 3% oxygen desaturation (3%ODI) during a night's sleep using a pulse oximeter. A general linear model was used to calculate the multivariate-adjusted means of 3%ODI per quartile of coffee consumption. We further analyzed the data after stratifying by overweight and current smoking status. RESULTS: A inverse association between coffee consumption and 3%ODI was found. The multivariate-adjusted mean of 3%ODI for the lowest and highest coffee consumption groups were 11.9 times/h and 10.6 times/h (p for trend = 0.06), respectively; 14.6 and 11.5 times/h (p for trend = 0.01) in overweight participants; and 12.7 and 11.0 times/h (p for trend = 0.06) in non-smokers. No associations were found in non-overweight and smoking workers. CONCLUSIONS: Our results suggest that higher coffee consumption was associated with lower 3% ODI as a marker of SDB in overweight and non-smoking workers.

Nocturnal Hypoxemia, But Not Sleep Apnea, Is Associated With a Poor Prognosis in Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Sleep apnea (SA) can cause repeated nocturnal arterial oxygen desaturation and result in acute increase in pulmonary arterial pressure (PAP). The presence of SA is associated with a poor prognosis in patients with chronic left-sided heart failure, but little is known for patients with pulmonary arterial hypertension (PAH). Methods and Results: We enrolled 151 patients with PAH (44±16 years old, male/female=37/114). They were all in the Nice Classification group 1 (idiopathic PAH/associated PAH=52/48%, mean PAP of 46±16 mmHg). They underwent right-heart catheterization and a sleep study with simplified polysomnography. Averaged percutaneous oxygen saturation (SpO2) during sleep was measured and an apnea-hypopnea index >5 was defined as SA. SA was noted in 58 patients (obstructive SA/central SA: 29/29). Over an average follow-up of 1,170±763 days, 32 patients died. By Kaplan-Meier analysis, there was no significant difference in deaths of patients with and without SA (χ2=2.82, P=0.093). On the other hand, the mortality in patients with lower averaged SpO2 was significantly higher than in those with higher averaged SpO2 (χ2=14.7, P<0.001) and that was the only independent variable related to death in multivariate Cox proportional hazards analysis. CONCLUSIONS: SA in patients with PAH was not associated with worse prognosis, unlike left ventricular heart failure, but nocturnal hypoxemia was related to poor prognosis.

Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy.

INTRODUCTION: Sudden unexpected death in epilepsy (SUDEP) is a major contributor to epilepsy-related mortality. It is associated with nocturnal seizures and centrally mediated postictal cardiorespiratory dysfunction (CRD), but mechanisms and contributors remain poorly understood. METHODS: We performed a prospective, cross-sectional, observational pilot study in the Columbia University Medical Center (CUMC) adult epilepsy monitoring unit (EMU) to explore relationships between periictal CRD, sleep-disordered breathing (SDB), neuroendocrine function, and clinical SUDEP risk. Thirty patients (twenty women, ten men) underwent video-electroencephalogram (EEG) with electrocardiogram (EKG) and digital pulse oximetry, inpatient or outpatient polysomnography (PSG), and comprehensive laboratory evaluation of sex steroid hormones. Sudden unexpected death in epilepsy risk was defined as Low (0-2) or High (≥3) using the revised SUDEP-7 Inventory. Sleep-disordered breathing was defined using standard criteria. Neuroendocrine dysfunction was defined as ≥1 laboratory abnormality. RESULTS: Cardiorespiratory dysfunction occurred more frequently in high-risk patients (60% vs. 27%, p = 0.018). Endocrine dysfunction was seen in 35% of patients, more in men (p = 0.018). Sleep-disordered breathing was found in 88% of fully scoreable PSGs. CONCLUSIONS: There was no significant relationship between CRD, SDB, and neuroendocrine status, though all PSGs in those with high SUDEP risk or neuroendocrine dysfunction revealed SDB. Larger studies are needed to further elucidate relationships between CRD, SDB, neuroendocrine factors, and SUDEP.

A Retrospective Study to Compare the Use of the Mean Apnea-Hypopnea Duration and the Apnea-Hypopnea Index with Blood Oxygenation and Sleep Patterns in Patients with Obstructive Sleep Apnea Diagnosed by Polysomnography.

BACKGROUND The apnea-hypopnea index (AHI) and the mean apnea-hypopnea duration (MAD) are used to measure the severity of the symptoms of obstructive sleep apnea (OSA). The aim of this study was to compare the use of the MAD with the AHI as indicators of clinical and demographic parameters, blood oxygenation, and sleep parameters in patients diagnosed with OSA by polysomnography (PSG). MATERIAL AND METHODS A retrospective study included 511 patients with OSA diagnosed by PSG and who had the AHI and the MAD measured according to the guidelines from the American Academy of Sleep Medicine (AASM). The patients were divided into two groups: patients with a short MAD and with a long MAD, according to median duration, and using the inter-quartile range (IQR), as the data were not normally distributed. Clinical and demographic parameters were recorded. Pulse oximetry was used to measure blood oxygen saturation during sleep, sleep structure was recorded, and the Epworth Sleepiness Scale (ESS) questionnaire was used to measure daytime sleepiness. RESULTS In all 511 patients with OSA, the MAD was significantly, but weakly, correlated with the AHI (r=0.17, P<0.01), but showed no significant associations with patient age (r=0.08, P=0.06), body weight (r=0.014, P=0.75), and height (r=0.06, P=0.16). Patients with a long MAD or severe OSA (n=260) had significantly worse blood oxygen levels and sleep parameters. CONCLUSIONS For patients with severe OSA, this study showed that the MAD was a useful indicator of blood oxygenation and sleep parameters.

Sleep biosignature of Type 2 diabetes: a case-control study.

AIM: To determine whether or not the sleep disturbances associated with Type 2 diabetes affect the structure of sleep. METHODS: We designed a case-control study in 76 patients with Type 2 diabetes and 76 control subjects without Type 2 diabetes, matched by age, gender, BMI and waist and neck circumferences. A subgroup of 32 patients with Type 2 diabetes was also matched with 64 control subjects without Type 2 diabetes according to apnoea-hypopnoea index score. Examination included an overnight full polysomnography. RESULTS: No differences in the percentage of time spent in either rapid eye movement or non-rapid eye movement sleep were observed between groups; however, patients with Type 2 diabetes had more microarousal events during sleep than control subjects [41.4 (total range 4.0-104.4) vs 20.7 (total range 1.3-94.5) events/h; P < 0.001]. These differences were mainly observed during the non-rapid eye movement sleep [7.4 (total range 0-107.2) vs 0.2 (total range 0-65.2) events/h; P < 0.001]. In addition, sleep variables related to oxygen saturation measures, such as the percentage of time spent with oxygen saturation ≤90%, were significantly greater during the rapid eye movement sleep in patients with Type 2 diabetes [20.3 (total range 0-99.2) vs. 10.5 (total range 0-94.0)%; P = 0.047]. This pattern was maintained in the subgroup of patients matched by apnoea-hypopnaea index. Finally, stepwise regression analyses showed that apnoea-hypopnoea index, the presence of Type 2 diabetes and fasting plasma glucose value were independently associated with the number of microarousals (R2 =0.667). CONCLUSIONS: Type 2 diabetes is associated with an altered sleep structure, with different effects according to rapid eye movement (increase in nocturnal hypoxia) or non-rapid eye movement (increase in sleep fragmentation) sleep.

Sleep-disordered breathing is associated with higher carboxymethyllysine level in elderly women but not elderly men in the cardiovascular health study.

CONTEXT: Carboxymethyl-lysine (CML) results from oxidative stress and has been linked to cardiovascular disease. OBJECTIVE: The objective of this study is to investigate the association between sleep-disordered breathing (SDB) - a source of oxidative stress - and CML. MATERIALS AND METHODS: About 1002 participants in the Cardiovascular Health Study (CHS) were studied. RESULTS: Women with SDB had significantly higher CML concentration compared with those without SDB (OR = 1.63, 95%CI = 1.03-2.58, p = 0.04). The association was not significant among men. DISCUSSION: SDB was associated with CML concentration among elderly women but not men in the Cardiovascular Health Study. CONCLUSION: Accumulation of CML may be an adverse health consequence of SDB.

Evaluation of the association between sleep apnea and polyunsaturated fatty acids profiles in patients after percutaneous coronary intervention.

The long-term outcome is poor in patients with sleep apnea and cardiovascular disease. Polyunsaturated fatty acid (PUFA) is also known as an independent predictor for adverse clinical events. However, the profile of PUFA in sleep apnea patients with coronary artery disease (CAD) is still unclear. This study aimed to clarify the association between sleep apnea and PUFA profiles in patients with CAD. Two hundred seventy-four consecutive patients undergoing percutaneous coronary intervention (PCI) were screened for sleep apnea using nocturnal oximetry. Oxygen desaturation index down to 4% (4%ODI) ≥5 was used as an indicator of sleep apnea. Baseline characteristics, including PUFA profiles, were compared between patients with and without sleep apnea. Among 243 enrolled patients, 134 (55%) had sleep apnea. The sleep apnea group included a significantly higher rate of patients with obesity, insulin-requiring diabetes, peripheral artery disease (PAD), and a higher C-reactive protein level than the non-sleep apnea group. The sleep apnea group had a significantly lower eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio than the non-sleep apnea group (0.33 vs. 0.44, respectively, p = 0.024). Additionally, EPA value and EPA/AA ratio were significantly correlated with 4%ODI (r = -0.15, p = 0.028; r = -0.16, p = 0.019, respectively). Results of logistic regression analysis indicated that the comorbidities of obesity, PAD, heart failure and EPA/AA ratio had a significant association with sleep apnea. Our results suggested that patients with sleep apnea who underwent PCI had a lower EPA/AA ratio than those without sleep apnea, and EPA value and EPA/AA ratio were significantly correlated with 4%ODI.