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Obstructive Sleep Apnea During REM Sleep and Hypertension. Results of the Wisconsin Sleep Cohort

In another study, Mokhlesi and colleagues examined the Wisconsin Sleep Cohort to quantify the independent association between prevalent hypertension (cross-sectional analysis) and incident hypertension (longitudinal analysis). The analysis included 4,385 sleep studies on 1,451 individuals as well as a subset with ambulatory blood pressure data (n = 1,085 sleep studies on 742 individuals). Given the large sample size, they were also able to perform the analyses in a subset of subjects who had no disease in non-REM sleep (i.e. non-REM AHI < 5 events per hour). In individuals with non-REM AHI less than or equal to 5, a twofold increase in REM AHI was associated with 24% higher odds of hypertension (odds ratio, 1.24; 95% confidence interval, 1.08–1.41). Longitudinal analysis revealed a significant association between REM AHI categories and the development of hypertension (P trend = 0.017). Non-REM AHI was not a significant predictor of hypertension in any of the models. The authors concluded that REM OSA is cross-sectionally and longitudinally associated with hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of REM sleep untreated.


Association of Obstructive Sleep Apnea in Rapid Eye Movement Sleep With Reduced Glycemic Control in Type 2 Diabetes: Therapeutic Implications

Obstructive sleep apnea has been associated with hypertension and type 2 diabetes (T2DM) in community-based and clinical cohorts. REM sleep usually accounts for 20–25% of total sleep time. To date, however, it remains unclear whether obstructive respiratory events during REM sleep have a different impact on cardiometabolic health compared with events during non-REM sleep. Because REM sleep predominates in the early morning hours before typical awakening, the cardiovascular and metabolic benefits of CPAP therapy may not be achieved with the typical CPAP use of 3–4 hours at the beginning of the night. In a cross-sectional analysis of 115 subjects with T2DM, Grimaldi and Mokhlesi demonstrated that only obstructive respiratory events and intermittent hypoxemia in REM sleep were associated with long-term glycemic control as assessed by HbA1c. Events in non-REM sleep were not associated with HbA1c. Their model predicted that 4 h of CPAP use would leave 60% of REM sleep untreated and would be associated with a decrease in HbA1c by approximately 0.25%. In contrast, 7 h of CPAP use would cover more than 85% of REM sleep and would be associated with a decrease in HbA1c by as much as 1%.


Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis

The authors of this study demonstrate that there are significant bacterial species that contribute to the microbiota of the mammalian gut which are regulated by circadian principles.  By altering the timing of feeding, introducing circadian distortion by simulating jet lag in mice, or by using genetic mutants animals that lack critical components of the cellular circadian clock (PER1/2 knockout), the normal cyclical presence and activity of various microbes in the gut is altered.  The consequence of this disruption as studied in this work includes significant weight gain and glucose intolerance in test mice, a finding which is interestingly ablated by the administration of oral antibiotics.   As further evidence, the authors show replication of metabolic dysfunction when microbiota from human jet lagged subjects is transplanted into the gut of germ free mice under normal conditions indicating that this dysbiosis is not only persistent after jet lag but may be regulated by intrinsic principles in the microbial pool that are unaffected by an otherwise normally functioning host environment. In summary, this article demonstrates that circadian disruption causes dysbiosis of mammalian gut microbiota causing persistent deleterious metabolic changes and may be amenable to simple therapeutic interventions.


A Matched Cohort Study of Postoperative Outcomes in Obstructive Sleep Apnea

In this matched cohort study, the authors analyzed whether patients with obstructive sleep apnea (OSA) diagnosed from polysomnography data obtained before or after surgery from a health administrative database from Manitoba, Canada, between 1987-2008, were at increased risk for postoperative complications compared with controls. Patients with a preoperative diagnosis of obstructive sleep apnea (OSA) and prescription of continuous positive airway pressure therapy were less than half as likely to experience postoperative cardiovascular complications – specifically cardiac arrest and shock. Respiratory complications were twice as likely in OSA patients, regardless of whether the OSA diagnosis was known at the time of surgery or after surgery. The OSA severity, type of surgery, age and other comorbidities were also important risk modifiers. Although this study has the limitations inherent to using health administrative data, it is the largest study that has used polysomnography to compare perioperative outcomes between undiagnosed and diagnosed OSA.


Alternative Scoring Models of STOP-Bang Questionnaire Improve Specificity To Detect Undiagnosed Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is common among surgical patients. The STOP-Bang questionnaire is a validated screening tool with a high sensitivity. However, its moderate specificity may yield fairly high false positive rate. We hypothesized that the specific combinations of predicting factors in the STOP-Bang questionnaire would improve its specificity.

The authors reported that when the STOP-Bang score was ≥ 3 (any 3 positive items), the sensitivity and specificity for identifying moderate severe OSA was 87% and 31%, respectively. The specificity for any 2 positive items from the 4 STOP questions plus BMI > 35 kg/m2, male gender, or neck circumference > 40 cm for identifying moderate-severe OSA was 85%, 77%, and 79%, respectively. Compared with STOP-Bang score ≥ 3, the predicted probability for severe OSA of the specific combinations of STOP score ≥ 2 + male and STOP score ≥ 2 + BMI increased by 36% and 42%, respectively. For severe OSA, the specific combination of STOP score ≥ 2 + BMI + male demonstrated a specificity of 97% and 86% increase in predicted probability versus any 4 positive items of STOP-Bang questionnaire.


CPAP Versus Oxygen in Obstructive Sleep Apnea

In this four-site, randomized, parallel-group clinical trial, adult patients with significant cardiac risk factors or disease were screened for obstructive sleep apnea (OSA) using the Berlin questionnaire. Following home sleep testing, patients with significant OSA (AHI 15-50events/hour) were randomized to: healthy lifestyle and sleep education (HLSE) alone (control), CPAP with HLSE (Auto-CPAP), or supplemental oxygen with HLSE (2 L/min via nasal prongs). The primary outcome was 24-hour mean arterial pressure.

Of 318 patients who underwent randomization, 281 (88%) were evaluated for ambulatory blood pressure at both baseline and follow-up. Patients randomized to both the CPAP and supplemental oxygen groups had similar reductions in nocturnal hypoxemia. The adjusted 24-hour mean arterial pressure at 12 weeks was significantly lower in the CPAP group than in either the control group (−2.4mmHg; P=0.04) or the supplemental oxygen group (−2.8mmHg; P=0.02).

Comments. In patients with cardiovascular disease or multiple cardiovascular risk factors, the treatment of OSA with Auto-CPAP with HLSE resulted in a significant reduction in blood pressure compared to supplemental oxygen with HLSE or HLSE alone. Despite similar effects on nocturnal hypoxemia, the lack of a beneficial effect of supplemental oxygen suggests that factors such as frequent arousals, hypercapnia, and variation in intrathoracic pressure may play a role in hypertension resulting from OSA. Future pragmatic studies are indicated mechanistic influences of supplemental oxygen (such as high vs. low loop gain or dose-response relationship), and prevention of long-term cardiovascular events.


Parameters From Preoperative Overnight Oximetry Predict Postoperative Adverse Events

The objective of this study is to investigate the role of preoperative overnight oximetry in predicting postoperative adverse events. Consented patients underwent a preoperative overnight monitoring of oxygen saturation with a portable oximeter. 573 patients were studied. Oxygen desaturation index (ODI), cumulative time percentage with SpO2 <90% (CT90) and mean SpO2 were identified as significant predictors for postoperative adverse events. The patients classified as high risk by ODI or CT90 or mean SpO2 had a significantly higher rate of postoperative adverse events. For ODI >28.5 vs ODI ≤28.5 events/h, the odds ratio adjusted with age, gender, body mass index and American Society of Anesthesiologists physical status was 2.2 (95% CI: 1.3–3.9). The authors conclude that patients with mean preoperative overnight SpO2 <92.7% or ODI > 28.5 events/h or CT90 >7.2% are at higher risk for postoperative adverse events. Overnight oximetry could be a useful tool to stratify patients for the risk of postoperative adverse events.


The Impact of Sleep Apnea on Postoperative Utilization of Resources and Adverse Outcomes

Sleep apnea has been associated with increase risk of postoperative complications. The authors show the impact of preoperative sleep apnea not only on an individual level, but also on a societal scale. “530,089 entries were identified for patients undergoing total hip and knee arthroplasty in a national database. In the multivariate analysis, the diagnosis of SA emerged as an independent risk factor for major postoperative complications (OR 1.47; 95% confidence interval [CI], 1.39–1.55). Pulmonary complications were 1.86 (95% CI, 1.65–2.09) times more likely and cardiac complications 1.59 (95% CI, 1.48–1.71) times more likely to occur in patients with SA. In addition, SA patients were more likely to receive ventilatory support, use more intensive care, stepdown and telemetry services, consume more economic resources, and have longer lengths of hospitalization.


Excessive Daytime Sleepiness Increases the Risk of Motor Vehicle Crash in Obstructive Sleep Apnea

A very interesting retrospective case-series observational study conducted using data from the West Australian Sleep Health Study at a tertiary hospital-based sleep clinic. It describe the incidence rate of motor vehicle crashes (MVCs) in patients with obstructive sleep apnea (OSA); and investigates MVC risk factors in OSA patients. 2673 patients were assessed for suspected sleep disordered breathing. Questionnaire data were collected including age, sex, years of driving, near-misses and MVCs, sleepiness, and consumption of alcohol and caffeinated drinks and an overnight laboratory-based polysomnography was performed.

The authors show that the crash rate was 0.06 MVC/person-year compared with the general community crash rate of 0.02 MVC/person-year. They concluded that untreated OSA was associated with an increased risk of near-misses in men and women and an increased risk of MVCs in very sleepy men. There was a strong association between excessive daytime sleepiness and increased report of near-misses. The data supports the observation that it is those patients with increased sleepiness regardless of OSA severity who are most at risk.


Nocturnal Intermittent Hypoxia is Independently Associated With Pain in Subjects Suffering From Sleep-Disordered Breathing

Obstructive sleep apnea is characterized by both sleep fragmentation and nocturnal recurrent hypoxemia. Experimental fragmentation or deprivation of sleep enhances sensitivity to pain, promotes inflammation, and advances spontaneous pain in healthy humans. The authors hypothesized that nocturnal hypoxemia would be associated with pain reports in subjects suffering from sleep-disordered breathing, independently of sleep fragmentation and inflammation. They examined the association between arterial desaturation and four different types of pain, as well as their composite measure, sequentially adjusted for: clinical characteristics, sleep fragmentation and inflammation. Decreased minimum nocturnal arterial saturation increased the odds for morning headache, headache disrupting sleep, and chest pain while in bed. A decrease in the minimum nocturnal saturation from 92 to 75% approximately doubled the odds for pain. Furthermore, the authors identified that one single-nucleotide polymorphism for the α 1 chain of collagen type XI (COL11A1-rs1676486) gene was significantly associated with headache disrupting sleep, pain disrupting sleep, and pain composite.

The authors concluded that nocturnal arterial desaturation may be associated with an increased pain in subjects with sleep-disordered breathing, independently of sleep fragmentation and inflammation.