Effects of nasal CPAP therapy on respiratory and spontaneous arousals in infants with OSA.

Obstructive sleep apnea (OSA) in infants has been shown to resolve frequently without a cortical arousal. It is unknown whether infants do not require arousal to terminate apneas or whether this is a consequence of the OSA. We studied the apnea and arousal patterns of eight infants with OSA before and after treatment with nasal continuous positive airway pressure (CPAP). These infants were age matched to eight untreated infants with OSA and eight normal infants. Polysomnographic studies were performed on each infant. We found that the majority of central and obstructive apneas were terminated without arousal in all OSA infants. After several weeks of nasal CPAP treatment, the proportion of apneas terminating with an arousal during rapid-eye-movement sleep increased in treated infants compared with untreated infants. Spontaneous arousals during rapid-eye-movement sleep were reduced in all OSA infants; however, during CPAP treatment, the spontaneous arousals increased to the normal control level. We conclude that OSA in infants possibly depresses the arousal response and treatment of these infants with nasal CPAP partially reverses this depression.     

Reduced genioglossal activity with upper airway anesthesia in awake patients with OSA.

We examined whether topical upper airway anesthesia leads to a reduction in genioglossal (GG) electromyogram (EMG) in patients with obstructive sleep apnea (OSA). Airway mechanics were also evaluated. In 13 patients with OSA, we monitored GG EMG during tidal breathing and during the application of pulses of negative airway pressure (-10 to -12 cmH(2)O). Airflow resistance and airway collapsibility were determined. All measurements were performed with and without topical anesthesia (lidocaine). Anesthesia led to a significant fall in the peak GG EMG response to negative pressure from 36.1 +/- 4.7 to 24.8 +/- 5.3% (SE) of maximum (P < 0.01). This was associated with a fall in phasic and tonic EMG during tidal breathing (phasic from 24.4 +/- 4.1 to 16.4 +/- 3.4% of maximum and tonic from 10.9 +/- 1.6 to 8.0 +/- 1.3% of maximum, P < 0.01). A significant rise in pharyngeal airflow resistance was also observed. Our results demonstrate that topical receptor mechanisms in the nasopharynx importantly influence dilator muscle activity and are likely important in driving the augmented dilator muscle activity seen in the apnea patient.     

Inspiratory-resistive loading increases the ventilatory response to arousal but does not reduce genioglossus muscle activity on the return to sleep

Arousals from sleep are thought to predispose to obstructive sleep apnea by causing hyperventilation and hypocapnia, which reduce airway dilator muscle activity on the return to sleep. However, prior studies of auditory arousals have not resulted in reduced genioglossus muscle activity [GG-electromyogram (EMG)], potentially because airway resistance prior to arousal was low, leading to a small ventilatory response to arousal and minimal hypocapnia. Thus we aimed to increase the ventilatory response to arousal by resistive loading prior to auditory arousal and determine whether reduced GG-EMG occurred on the return to sleep. Eighteen healthy young men and women were recruited. Subjects were instrumented with a nasal mask with a pneumotachograph, an epiglottic pressure catheter, and intramuscular GG-EMG electrodes. Mask CO(2) levels were monitored. Three- to 15-s arousals from sleep were induced with auditory tones after resting breathing (No-Load) or inspiratory-resistive loading (Load; average 8.4 cmH(2)O·l(-1)·s(-1)). Peak minute ventilation following arousal was greater after Load than No-Load (mean ± SE; 8.0 ± 0.6 vs. 7.4 ± 0.6 l/min, respectively). However, the nadir end tidal partial pressure of CO(2) did not differ between Load conditions (43.1 ± 0.6 and 42.8 ± 0.5 mmHg, respectively), and no period of reduced GG activity occurred following the return to sleep (GG-EMG baseline, minimum after Load and No-Load = 2.9 ± 1.2%, 3.1 ± 1.3%, and 3.0 ± 1.3% max, respectively). These findings indicate that the hyperventilation, which occurs following tone-induced arousal, is appropriate for the prevailing level of respiratory drive, because loading did not induce marked hypocapnia or lower GG muscle activity on the return to sleep. Whether similar findings occur following obstructive events in patients remains to be determined.     

Preoptic hypothalamic warming suppresses laryngeal dilator activity during sleep

Upper airway dilator activity during sleep appears to be diminished under conditions of enhanced sleep propensity, such as after sleep deprivation, leading to worsening of obstructive sleep apnea (OSA). Non-rapid eye movement (NREM) sleep propensity originates in sleep-active neurons of the preoptic area (POA) of the hypothalamus and is facilitated by activation of POA warm-sensitive neurons (WSNs). We hypothesized that activation of WSNs by local POA warming would inhibit activity of the posterior cricoarytenoid (PCA) muscle, an airway dilator, during NREM sleep. In chronically prepared unrestrained cats, the PCA exhibited inspiratory bursts in approximate synchrony with inspiratory diaphragmatic activity during waking, NREM, and REM. Integrated inspiratory PCA activity (IA), peak activity (PA), and the lead time (LT) of the onset of inspiratory activity in PCA relative to diaphragm were significantly reduced in NREM sleep and further reduced during REM sleep compared with waking. Mild bilateral local POA warming (0.5-1.2 degrees C) significantly reduced IA, PA, and LT during NREM sleep compared with a prewarming NREM baseline. In some animals, effects of POA warming on PCA activity were found during waking or REM. Because POA WSN activity is increased during spontaneous NREM sleep and regulates sleep propensity, we hypothesize that this activation contributes to reduction of airway dilator activity in patients with OSA.     

Recent advances in obstructive sleep apnea pathophysiology and treatment

Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurring collapse of the pharyngeal airway leading to restricted airflow. OSA is becoming increasingly common with at least moderate disease now evident in 17% of middle aged men and 9% of women. The list of recognized adverse health consequences associated with OSA is growing and includes daytime symptoms of sleepiness, impaired cognition and risk of motor vehicle accidents as well as associations with hypertension, cardiovascular morbidity, malignancy and all-cause mortality. In this context adequate treatment of OSA is imperative; however, there are well-recognized pitfalls in the uptake and usage of the standard treatment modality, Continuous Positive Airway Pressure (CPAP). A broad range of pathophysiological mechanisms are now recognized beyond an anatomically smaller pharyngeal airway and impaired compensatory pharyngeal muscle responsiveness. Perturbations in ventilatory control stability, low arousal threshold, sleep-related decrease in lung volume and fluid redistribution as well as upper airway surface tension have all been shown to variously contribute to sleep-disordered breathing. Many new therapies are emerging from these advances in understanding of the mechanisms of OSA. Although many may not be universally effective, the promise of phenotyping patients according to their individual pathophysiology in order to target one or more therapies may prove highly effective and allow the treatment of OSA towards a personalized medicine approach.

     

A method for measuring and modeling the physiological traits causing obstructive sleep apnea

There is not a clinically available technique for measuring the physiological traits causing obstructive sleep apnea (OSA). Therefore, it is often difficult to determine why an individual has OSA or to what extent the various traits contribute to the development of OSA. In this study, we present a noninvasive method for measuring four important physiological traits causing OSA: 1) pharyngeal anatomy/collapsibility, 2) ventilatory control system gain (loop gain), 3) the ability of the upper airway to dilate/stiffen in response to an increase in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which continuous positive airway pressure (CPAP) is dropped from an optimum to various suboptimum pressures for 3- to 5-min intervals during sleep. Each individual's set of traits is entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual. Results from 14 subjects (10 with OSA) are described. Repeatability measurements from separate nights are also presented for four subjects. The measurements and model illustrate the multifactorial nature of OSA pathogenesis and how, in some individuals, small adjustments of one or another trait (which might be achievable with non-CPAP agents) could potentially treat OSA. This technique could conceivably be used clinically to define a patient's physiology and guide therapy based on the traits.     

Effects of leptin and obesity on the upper airway function

Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that (1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that (2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob(-)/ob(-) mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (P(N)) to determine the passive expiratory critical pressure (P(CRIT)) and active responses to reductions in P(N), including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the P(N) threshold at which IFL developed, maximum inspiratory airflow (Vi(max)), and genioglossus electromyographic (EMG(GG)) activity. Elevations in body weight were associated with progressive elevations in P(CRIT) (0.1 ± 0.02 cmH(2)O/g), independent of mouse strain. P(CRIT) was also elevated in ob(-)/ob(-) compared with BL6 mice (1.6 ± 0.1 cmH(2)O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and P(N) threshold and lower VI(max). Very obese ob(-)/ob(-) mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and P(N) threshold (from -0.8 ± 1.1 to -5.6 ± 0.8 cmH(2)O) and increase in VI(max) (from 354.1 ± 25.3 to 659.0 ± 71.8 μl/s). Nevertheless, passive P(CRIT) in leptin-treated mice did not differ significantly from that seen in nontreated ob(-)/ob(-) mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.     

Genioglossus muscle activity and serotonergic modulation of hypoglossal motor output in obese Zucker rats.

Obese Zucker rats have a narrower and more collapsible upper airway compared with lean controls, similar to obstructive sleep apnea (OSA) patients. Genioglossus (GG) muscle activity is augmented in awake OSA patients to compensate for airway narrowing, but the neural control of GG activity in obese Zucker rats has not been investigated to determine whether such neuromuscular compensation also occurs. This study tests the hypotheses that GG activity is augmented in obese Zucker rats compared with lean controls and that endogenous 5-hydroxytryptamine (5-HT) contributes to GG activation. Seven obese and seven lean Zucker rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and they were implanted with GG and diaphragm wires for respiratory muscle recordings. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid and the 5-HT receptor antagonist mianserin (100 microM). Compared with lean controls, respiratory rates were increased in obese rats across sleep-wake states (P=0.048) because of reduced expiratory durations (P=0.007); diaphragm activation was similar between lean and obese animals (P=0.632). Respiratory-related, tonic, and peak GG activities were also similar between obese and lean rats (P>0.139). There was no reduction in GG activity with mianserin at the hypoglossal motor nucleus, consistent with recent observations of a minimal contribution of endogenous 5-HT to GG activity. These results suggest that despite the upper airway narrowing in obese Zucker rats, these animals have a sufficiently stable airway such that pharyngeal muscle activity is normal across sleep-wake states.     

Swallowing function and upper airway sensation in obstructive sleep apnea.

The objective of this study was to determine whether impaired upper airway (UA) mucosal sensation contributes to altered swallowing function in obstructive sleep apnea (OSA). We determined UA two-point discrimination threshold (2PDT) and vibratory sensation threshold (VST) in 15 men with untreated OSA and 9 nonapneic controls (CL). We then assessed swallowing responses to oropharyngeal fluid boluses delivered via a catheter. The threshold volume required to provoke swallowing and the mean latency to swallowing were determined, as was the phase of the respiratory cycle in which swallowing occurred [expressed as percentage of control cycle duration (%CCD)] and the extent of prolongation of the respiratory cycle after swallowing [inspiratory suppression time (IST)]. 2PDT and VST were significantly impaired in OSA patients compared with CL subjects. 2PDT was positively correlated with swallowing latency and threshold volume in CL subjects, but not in OSA patients. Threshold volume did not differ between the groups [median value = 0.1 ml (95% confidence interval = 0.1-0.2) for OSA and 0.15 ml (95% confidence interval = 0.1-0.16) for CL], whereas swallowing latency was shorter for OSA patients [3.3 (SD 0.7) vs. 3.9 (SD 0.8) s, P = 0.04]. %CCD and IST were similar for OSA patients and CL subjects. However, among OSA patients there was a significant inverse relation between VST and IST. These findings suggest that oropharyngeal sensory impairment in OSA is associated with an attenuation of inhibitory modulating inputs to reflex and central control of UA swallowing function.     

Influence of CPAP on reflex responses to tracheal irritation in anesthetized humans

We investigated the effects of lung inflation during continuous positive airway pressure breathing (CPAP) on airway defensive reflexes in 10 enflurane-anesthetized spontaneously breathing humans. The airway defensive reflexes were induced by instillation into the trachea of 0.5 ml of distilled water at two different levels of end-expiratory pressure (0 and 10 cmH2O CPAP). The tracheal irritation at an end-expiratory pressure of 0 cmH2O caused a variety of reflex responses including apnea, spasmodic panting, expiration reflex, cough reflex, an increase in heart rate, and an increase in blood pressure. Lung inflation during CPAP of 10 cmH2O did not exert any influence on these reflex responses in terms of the types, latencies, and durations of reflex responses although the intensity of the expiration reflex and cough reflex was augmented by lung inflation. Our results suggest that the pulmonary stretch receptors do not play an important role in the mechanisms of airway defensive reflexes in humans.     

Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats

Obstructive sleep apnea patients experience recurrent upper airway (UA) collapse due to decreases in the UA dilator muscle activity during sleep. In contrast, activation of UA dilators reduces pharyngeal critical pressure (Pcrit, an index of pharyngeal collapsibility), suggesting an inverse relationship between pharyngeal collapsibility and dilator activity. Since most UA muscles display phasic respiratory activity, we hypothesized that pharyngeal collapsibility is modulated by respiratory drive via neuromuscular mechanisms. Adult male Sprague-Dawley rats were anesthetized, vagotomized, and ventilated (normocapnia). In one group, integrated genioglossal activity, Pcrit, and maximal airflow (V(max)) were measured at three expiration and five inspiration time points within the breathing cycle. Pcrit was closely and inversely related to phasic genioglossal activity, with the value measured at peak inspiration being the lowest. In other groups, the variables were measured during expiration and peak inspiration, before and after each of five manipulations. Pcrit was 26% more negative (-15.0 ± 1.0 cmH(2)O, -18.9 ± 1.2 cmH(2)O; n = 23), V(max) was 7% larger (31.0 ± 1.0 ml/s, 33.2 ± 1.1 ml/s), nasal resistance was 12% bigger [0.49 ± 0.05 cmH(2)O/(ml/s), 0.59 ± 0.05 cmH(2)O/(ml/s)], and latency to induced UA closure was 14% longer (55 ± 4 ms, 63 ± 5 ms) during peak inspiration vs. expiration (all P < 0.005). The expiration-inspiration difference in Pcrit was abolished with neuromuscular blockade, hypocapnic apnea, or death but was not reduced by the superior laryngeal nerve transection or altered by tracheal displacement. Collectively, these results suggest that pharyngeal collapsibility is moment-by-moment modulated by respiratory drive and this phasic modulation requires neuromuscular mechanisms, but not the UA negative pressure reflex or tracheal displacement by phasic lung inflation.     

Continuous Positive Airway Pressure Treatment Reduces Mortality in Elderly Patients with Moderate to Severe Obstructive Severe Sleep Apnea: A Cohort Study

Obstructive sleep apnea (OSA) is much more prevalent in older people than in middle-aged or young populations, and has been associated with cardiovascular disease. Continuous positive airway pressure (CPAP) is the first-line therapy for OSA, but its long-term clinical benefit in the elderly is unclear. Here, we carried out a prospective cohort study to explore the survival rate and incidence of cardiovascular events in elderly patients with moderate to severe OSA who did or did not receive CPAP treatment. The study included 130 patients (104 male, 26 female; mean age: 77.8 ± 6.2 years) who were followed up for a mean of 5 ± 2.54 years (range, 1–8 years). Thirty-six patients received CPAP and 88 had no CPAP. The results showed that mortality in the untreated group (21.6%) was significantly higher than in the CPAP group (5.6%). Kaplan–Meier survival analysis showed that the survival rate in the CPAP group was 94.4%, which was markedly higher than the rate of 78.4% in the untreated group. The incidence of cardiovascular events was 13.9% in the CPAP group and 55.7% in the untreated group. The present study provides evidence that CPAP can reduce mortality in older patients with moderate to severe OSA, and lead to a good long-term prognosis. The study also indicates that death in older OSA patients is associated with cardiovascular disease and diabetes.     

Auditory event-related potentials in obstructive sleep apnea: effects of treatment with nasal continuous positive airway pressure

Event-related potentials (ERPs) were recorded in 47 patients with obstructive sleep apnea (OSA) syndrome prior to and after 6 weeks of treatment with continuous positive airway pressure (CPAP). Compared with a control group, the OSA patients showed ERP abnormalities: lengthened P3 latencies and decreased N2-P3 amplitudes. After 6 weeks of CPAP treatment, there was a highly significant improvement in the abnormal ERPs: the P3 and N2 latencies were shortened, but remained longer than in controls, and the N2-P3 and N1-P2 amplitudes were increased. No correlations could be established with various sleep variables. ERPs may be used as an electrophysiological marker of brain dysfunction; treatment of OSA with CPAP is probably responsible for functional brain modifications. On the other hand, possible relationships between the ERP abnormalities and the neuropsychological disorders observed in OSA remain to be established.     

Mechanisms of breathing instability in patients with obstructive sleep apnea.

The response to chemical stimuli (chemical responsiveness) and the increases in respiratory drive required for arousal (arousal threshold) and for opening the airway without arousal (effective recruitment threshold) are important determinants of ventilatory instability and, hence, severity of obstructive apnea. We measured these variables in 21 obstructive apnea patients (apnea-hypopnea index 91 +/- 24 h(-1)) while on continuous-positive-airway pressure. During sleep, pressure was intermittently reduced (dial down) to induce severe hypopneas. Dial downs were done on room air and following approximately 30 s of breathing hypercapneic and/or hypoxic mixtures, which induced a range of ventilatory stimulation before dial down. Ventilation just before dial down and flow during dial down were measured. Chemical responsiveness, estimated as the percent increase in ventilation during the 5(th) breath following administration of 6% CO(2) combined with approximately 4% desaturation, was large (187 +/- 117%). Arousal threshold, estimated as the percent increase in ventilation associated with a 50% probability of arousal, ranged from 40% to >268% and was <120% in 12/21 patients, indicating that in many patients arousal occurs with modest changes in chemical drive. Effective recruitment threshold, estimated as percent increase in pre-dial-down ventilation associated with a significant increase in dial-down flow, ranged from zero to >174% and was <110% in 12/21 patients, indicating that in many patients reflex dilatation occurs with modest increases in drive. The two thresholds were not correlated. In most OSA patients, airway patency may be maintained with only modest increases in chemical drive, but instability results because of a low arousal threshold and a brisk increase in drive following brief reduction in alveolar ventilation.     

Effect of Continuous Positive Airway Pressure on Adiponectin in Patients with Obstructive Sleep Apnea: A Meta-Analysis

Objective

Obstructive sleep apnea (OSA) has been suggested to be associated with low levels of adiponectin. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; however, previous studies assessing the effect of CPAP on adiponectin in patients with OSA yielded conflicting results. The present meta-analysis was performed to determine whether CPAP therapy could increase adiponectin levels.

Methods

Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before February 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum adiponectin was extracted for analysis. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy.

Results

Eleven studies involving 240 patients were included in this meta-analysis, including ten observational studies and one randomized controlled study. The meta-analysis showed that there was no change of adiponectin levels before and after CPAP treatment in OSA patients (SMD = 0.059, 95% confidence interval (CI) = −0.250 to 0.368, z = 0.37, p = 0.710). Subgroup analyses indicated that the results were not affected by age, baseline body mass index, severity of OSA, CPAP therapy duration, sample size and racial differences.

Conclusions

This meta-analysis suggested that CPAP therapy has no impact on adiponectin in OSA patients, without significant changes in body weight. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.     

Sensorimotor function of the upper-airway muscles and respiratory sensory processing in untreated obstructive sleep apnea

Numerous studies have demonstrated upper-airway neuromuscular abnormalities during wakefulness in snorers and obstructive sleep apnea (OSA) patients. However, the functional role of sensorimotor impairment in OSA pathogenesis/disease progression and its potential effects on protective upper-airway reflexes, measures of respiratory sensory processing, and force characteristics remain unclear. This study aimed to gain physiological insight into the potential role of sensorimotor impairment in OSA pathogenesis/disease progression by comparing sensory processing properties (respiratory-related evoked potentials; RREP), functionally important protective reflexes (genioglossus and tensor palatini) across a range of negative pressures (brief pulses and entrained iron lung ventilation), and tongue force and time to task failure characteristics between 12 untreated OSA patients and 13 controls. We hypothesized that abnormalities in these measures would be present in OSA patients. Upper-airway reflexes (e.g., genioglossus onset latency, 20 ± 1 vs. 19 ± 2 ms, P = 0.82), early RREP components (e.g., P1 latency 25 ± 2 vs. 25 ± 1 ms, P = 0.78), and the slope of epiglottic pressure vs. genioglossus activity during iron lung ventilation (-0.68 ± 1.0 vs. -0.80 ± 2.0 cmH(2)O/%max, P = 0.59) were not different between patients and controls. Maximal tongue protrusion force was greater in OSA patients vs. controls (35 ± 2 vs. 27 ± 2 N, P < 0.01), but task failure occurred more rapidly (149 ± 24 vs. 254 ± 23 s, P < 0.01). Upper-airway protective reflexes across a range of negative pressures as measured by electromyography and the early P1 component of the RREP are preserved in OSA patients during wakefulness. Consistent with an adaptive training effect, tongue protrusion force is increased, not decreased, in untreated OSA patients. However, OSA patients may be vulnerable to fatigue of upper-airway dilator muscles, which could contribute to disease progression.     

Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by noradrenergic activation. Nasal continuous positive airway pressure (CPAP) is the treatment of choice and has been shown to effectively reduce elevated norepinephrine (NE) levels. This study examined whether the reduction in NE after CPAP is due to an increase in NE clearance and/or a decrease of NE release rate. Fifty CPAP-naive OSA patients with an apnea-hypopnea index >15 were studied. NE clearance and release rates, circulating NE levels, urinary NE excretion, and blood pressure and heart rate were determined before and after 14 days of CPAP, placebo CPAP (CPAP administered at ineffective pressure), or oxygen supplementation. CPAP led to a significant increase in NE clearance (P < or = 0.01), as well as decreases in plasma NE levels (P < or = 0.018) and daytime (P < 0.001) and nighttime (P < 0.05) NE excretion. NE release rate was unchanged with treatment. Systolic (P < or = 0.013) and diastolic (P < or = 0.026) blood pressure and heart rate (P < or = 0.014) were decreased in response to CPAP but not in response to oxygen or placebo CPAP treatment. Posttreatment systolic blood pressure was best predicted by pretreatment systolic blood pressure and posttreatment NE clearance and release rate (P < 0.01). The findings indicate that one of the mechanisms through which CPAP reduces NE levels is through an increase in the clearance of NE from the circulation.     

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT)

ObjectiveThe effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D.MethodsThis randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants’ adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use).ResultsBaseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP ?13.10 [?25.49 to ?0.7] vs. sham ?7.26 [?20.2 to 5.69]; P = .519) but different in HbA1c (CPAP ?0.24 [?0.48 to ?0.003] vs sham 0.15 [?0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP ?0.26 [?0.53 to 0.002] vs sham ?0.24 [?0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012).ConclusionCPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.     

Can Continuous Positive Airway Pressure Reduce the Risk of Stroke in Obstructive Sleep Apnea Patients? A Systematic Review and Meta-Analysis

Background and Purpose

Obstructive sleep apnea (OSA) has been shown to increase the risk of stroke. Although continuous positive airway pressure (CPAP) is considered the treatment of choice for OSA, whether treating OSA with CPAP reduces the risk of stroke remains unclear. We aimed to evaluate the effects of CPAP on incidence of stroke in patients with OSA.

Materials and Methods

We conducted a systematic review and meta-analysis of all published studies that provided the number of incident strokes in OSA patients in light of their treatment status with CPAP.

Results

We identified 8 relevant studies: one randomized controlled study (RCT), 5 cohort studies, and 2 studies using administrative health data. The two overlapping cohort studies in women and the elderly and the 2 studies using administrative health data had analyzed the impact of CPAP on stroke apart from cardiac events, whereas the others had focused on the overall cardiovascular events. Based on a meta-analysis of the cohort studies, treatment with CPAP was associated with a lower incidence of stroke and cardiac events with relative risks of 0.27 [0.14–0.53], and 0.54 [0.38–0.75], respectively, although this could not be reproduced in the RCT and the studies using administrative data.

Conclusions

Treating with CPAP in patients with OSA might decrease the risk of stroke, although there is some conflicting evidence. Such effect was more pronounced in stroke than in cardiac events. Future studies analyzing stroke apart from cardiac disease would be of interest.