Effect of switching from continuous to bilevel positive airway pressure on sleep quality in patients with obstructive sleep apnea: the prospective POP IN VAuto study.

Background: Issues with tolerability and side effects can decrease continuous positive airway pressure (CPAP) device usage and the benefits of therapy. Different positive airway pressure (PAP) therapy modes providing expiratory pressure relief or using a different pressure during inspiration vs. expiration (bilevel PAP) may alleviate some of these issues. This multicenter, prospective study evaluated the effects of switching from CPAP to bilevel PAP (VAuto mode) on respiratory parameters, device usage, side effects and patient-reported outcomes in patients with obstructive sleep apnea (OSA). Methods: Eligible OSA patients had started CPAP ≥3 months previously, had good compliance (mean 6.1±2.0 h/night) and well-controlled OSA [residual apnea-hypopnea index (AHI) 4.9±3.1/h] but had pressure tolerance issues or persistent side effects/discomfort. All were switched from CPAP to bilevel PAP (AirCurve 10 VAuto; ResMed). Effectiveness (residual AHI), sleep quality, daytime sleepiness, fatigue, therapy-related side effects, and patient satisfaction/preference were assessed after 3 months and 1 year. Results: Forty patients were analyzed (68% male, age 64±11 years, body mass index 30.7±5.8 kg/m2). At 3 months and 1 year after switching to bilevel PAP, median [interquartile range] residual AHI was 4/h [2-5.3] and 3.7/h [1.8-5], respectively, and device usage was 7.0 [4.9-7.5] and 6.4 [4.4-7.3] h/night, respectively. Device switch was associated with significant reductions from baseline in expiratory PAP {from 12 [11-13] to 8 [7-9] cmH2O at 3 months (P<0.001) and 9 [8-12] cmH2O at 1 year (P=0.005)}, 95th percentile pressure {from 14 [12-14] to 10 [9-11] and 10 [8-11] cmH2O; P<0.001 and P=0.001, respectively} and leak {from 1 [0-6] to 0 [0-1] and 0 [0-2] L/min; P=0.049 and P=0.033, respectively}. The Pittsburgh Sleep Quality Index score decreased significantly from baseline to 3 and 6 months [7.2±4.0 to 5.0±3.2 (P=0.005) and 4.5±2.7 (P<0.001), respectively]. CPAP-related mouth dryness, choking sensation and aerophagia were significantly improved one year after switching to bilevel PAP. Bilevel PAP was preferred over CPAP by 90% of patients. Conclusions: Switching to bilevel PAP had several benefits in patients struggling with CPAP, facilitating therapy acceptance and ongoing device usage.

Tracheal Sound Analysis.

Tracheal sound sensors provide multiple respiratory signals that are valuable for studying upper airway characteristics. This chapter reviews the original work and ongoing research on tracheal sound analysis in relation to upper airway obstruction during sleep. Past and current research suggest that being associated with other sleep study recording sensors and advanced signal processing techniques, tracheal sound analysis can extensively contribute to the diagnosis and assessment of sleep-disordered breathing.

Positive Airway Pressure Adherence, Mortality, and Cardiovascular Events in Patients with Sleep Apnea.

Rationale: Randomized controlled trials showed no effect of positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) on cardiovascular (CV) risk. However, patient selection and low PAP adherence preclude the generalization of their data to clinical samples. Objectives: To evaluate the association between hours of PAP use, mortality, and CV morbidity in real-life conditions. Methods: Data from the Pays de la Loire Cohort were linked to health administrative data to identify incident major adverse cardiovascular events (MACEs; a composite outcome of mortality, stroke, and cardiac diseases) in patients with OSA who were prescribed PAP. Cox proportional hazards analyses were conducted to evaluate the association between MACEs and quartiles of average daily PAP use over the study period. Measurements and Main Results: After a median follow-up of 6.6 years, 961 of 5,138 patients experienced MACEs. Considering nonadherent patients (0-4 h/night) as the reference group, adjusted hazard ratios (95% confidence intervals) for MACEs were 0.87 (0.73-1.04) for the 4-6 h/night group, 0.75 (0.62-0.92) for the 6-7 h/night group, and 0.78 (0.65-0.93) for the ⩾7 h/night group (P = 0.0130). Sensitivity analyses using causal inference approaches confirmed the association of PAP use with MACEs. The association was stronger in male patients (P value for interaction = 0.0004), patients without overt CV disease at diagnosis (P < 0.0001), and those belonging to the excessively sleepy symptom subtype (P = 0.060). Conclusions: These real-life clinical data demonstrate a dose-response relationship between PAP adherence and incident MACEs in OSA. Patient support programs may help improve PAP adherence and CV outcomes in patients with OSA.

Cancer risk in patients with sleep apnoea following adherent 5-year CPAP therapy.

BACKGROUND: Increasing evidence suggests that obstructive sleep apnoea (OSA) contributes to cancer risk; however, limited data are available on the impact of continuous positive airway pressure (CPAP) therapy on cancer incidence. We aimed to determine whether adherence to CPAP therapy is associated with a reduction in all-cancer incidence compared with nonadherent patients with OSA. METHODS: The study relied on data collected by the multicentre Pays de la Loire Sleep Cohort study, linked to health administrative data, so as to identify new-onset cancer. We included patients who were prescribed CPAP for OSA, with no history of cancer before the diagnostic sleep study or during the first year of CPAP. Patients with documented CPAP use for ≥4 h per night were defined as adherent. Those who discontinued or used CPAP <4 h per night constituted the nonadherent group. A propensity score inverse probability of treatment weighting analysis was performed to assess the effect of CPAP adherence on cancer risk. RESULTS: After a median (interquartile range) follow-up of 5.4 (3.1-8.0) years, 437 (9.7%) out of 4499 patients developed cancer: 194 (10.7%) in the nonadherent group (n=1817) and 243 (9.1%) in adherent patients (n=2682). The final weighted model showed no significant impact of CPAP adherence on all-cause cancer risk (subdistribution hazard ratio 0.94, 95% CI 0.78-1.14). CONCLUSIONS: Adherence to CPAP therapy in OSA patients was not associated with a reduction in all-cancer incidence. Whether adherent CPAP therapy of OSA might reduce the risk of specific cancer sites should be further evaluated.

Effects of Repetitive Transcranial Magnetic Stimulation and Multicomponent Therapy in Patients With Fibromyalgia: A Randomized Controlled Trial.

OBJECTIVE: Fibromyalgia (FM) is a chronic painful condition partly due to alterations in pain modulation by the central nervous system. Multicomponent therapy (MT) and repetitive transcranial magnetic stimulation (rTMS) have both been reported as pain modulators in patients with FM. The aim of this study was to compare the effects of rTMS on pain with a combination of MT and rTMS versus MT alone. METHODS: Thirty-nine FM patients with visual analog scale (VAS) results for pain of ≥40 mm were randomized to active or sham rTMS (high-frequency, primary motor cortex M1) plus 12 weeks of MT (3 sessions per week combining aerobic training, pool-based exercises, and relaxation). Repetitive TMS was started 2 weeks prior to MT and maintained until the end of the program (week 14). Assessments were achieved at baseline, at week 14, and at 6 months (week 40) after completion of the program. The main criterion was pain reduction, as assessed by the weekly mean self-reported level of pain (reported daily). Secondary outcomes were cardiorespiratory fitness (graded maximal exercise test), cardiac autonomic adaptations, and FM impact (using scales for FM impact, depression, sleep efficiency, and pain catastrophizing). RESULTS: The reduction of the weekly mean of pain reported daily did not differ significantly between groups (using repeated measures of analysis of variance [ANOVA]). Two-way ANOVAs showed that pain VAS results, as well as cardiorespiratory fitness, quality of life, depression, and catastrophizing, improved significantly at week 14 and remained stable until week 40. Neither cardiac autonomic adaptations nor sleep efficiency changed significantly. CONCLUSION: Repetitive TMS did not reduce pain in patients with FM who followed the MT program.

Association Between Nocturnal Hypoxemia and Cancer Incidence in Patients Investigated for OSA: Data From a Large Multicenter French Cohort.

BACKGROUND: Previous studies have yielded inconsistent findings regarding the association between OSA and cancer in humans. RESEARCH QUESTION: Is there an association between indexes of sleep-disordered breathing severity and cancer incidence in patients investigated for suspected OSA? STUDY DESIGN AND METHODS: Data from a large multicenter cohort of cancer-free patients investigated for OSA were linked to health administrative data to identify new-onset cancer. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association of cancer incidence with OSA severity and nocturnal hypoxemia. RESULTS: After a median follow-up period of 5.8 years (interquartile range, 3.8-7.8), 718 of 8,748 patients (8.2%) had received a diagnosis of cancer. On unadjusted Kaplan-Meier survival analyses, cancer incidence was associated with increasing severity of OSA (log-rank test, P < .0005) and nocturnal hypoxemia (log-rank test, P < .0001 for both oxygen desaturation index and percent night time with oxygen saturation < 90% [T90]). After adjustment for anthropomorphic data, smoking and alcohol consumption, comorbid cardiac, metabolic, and respiratory diseases, marital status, type of sleep study, and study site, only T90 was associated with cancer incidence (adjusted hazard ratio, 1.33; 95% CI, 1.05-1.68 for T90 ≥ 13% vs < 0.01%; P = .02). On stratified analyses, the association between T90 and cancer appeared stronger in older patients with obesity and no adequate OSA therapy. Among the most frequent cancer sites, nocturnal hypoxemia was associated with lung and breast malignancies. INTERPRETATION: Nocturnal hypoxemia was associated with all-cancer incidence in patients investigated for OSA. Whether OSA therapy might reduce the risk of cancer needs further evaluation.

Sleep apnoea and endothelial dysfunction: An individual patient data meta-analysis.

We performed an individual patient data meta-analysis to investigate the association between obstructive sleep apnoea (OSA) severity and the reactive hyperaemia index (RHI) measured by peripheral arterial tonometry (PAT), a validated measurement of endothelial function, and a strong predictor of late cardiovascular (CV) events. Patients from 12 studies underwent PAT and overnight polysomnography or respiratory polygraphy for suspected OSA. Endothelial dysfunction was defined by a log-transformed RHI<0.51. Subgroup analyses were performed to investigate this relationship in specific populations. Among 730 patients without overt CV disease, 387 (53.0%) had severe OSA (apnoea-hypopnea index ≥30) and 164 (22.5%) exhibited endothelial dysfunction. After adjustment for age, gender, diastolic blood pressure, obesity, diabetes and chronic obstructive pulmonary disease, endothelial dysfunction was associated with severe OSA (odds ratio, OR [95% confidence interval]: 2.27 [1.12-4.60]; p = 0.02), and nocturnal hypoxemia defined by >20 min with oxygen saturation <90% (OR: 1.83 [1.22-2.92]; p = 0.004) or mean oxygen saturation <92% (OR: 1.52 [1.17-1.96]; p = 0.002). On subgroup analyses, the association between severe OSA and endothelial dysfunction was not significant in patients with hypertension, obesity and/or diabetes. Among adults without overt CV disease, severe OSA is independently associated with an increased risk of endothelial dysfunction that may predispose to late CV events.

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea.

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

Heat-moulded versus custom-made mandibular advancement devices for obstructive sleep apnoea: a randomised non-inferiority trial.

RATIONALE: Custom-made mandibular advancement devices (MADs) are reported as providing higher efficacy rates compared with thermoplastic heat-moulded MADs but at the price of higher costs and treatment delays. OBJECTIVE: To determine whether a thermoplastic heat-moulded titratable MAD (ONIRIS; ONIRIS SAS, Rueil Malmaison, France) is non-inferior to a custom-made acrylic titratable MAD (TALI; ONIRIS SAS, Rueil Malmaison, France) for obstructive sleep apnoea (OSA). METHODS: We conducted a multicentre, open, randomised controlled trial of patients with OSA refusing or not tolerating continuous positive airway pressure (CPAP). Participants were randomly assigned to a thermoplastic heat-moulded titratable device or a custom-made acrylic device for 2 months with stratification by centre and OSA severity. The non-inferiority primary outcome was a ≥50% reduction in apnoea-hypopnoea index (AHI) or achieving AHI <10 events/hour at 2 months. The non-inferiority margin was preset as a difference between groups of 20% for the primary outcome in the per-protocol analysis. MAIN RESULTS: Of 198 patients (mean age 51 [SD, 12] years; 138 [72.6%] men; mean body mass index 26 [SD, 2.7] kg/m2; mean AHI 26.6/hour [SD, 10.4]), 100 received TALI and 98 ONIRIS. In per-protocol analysis, the response rate was 51.7% in the TALI group versus 53.6% in the ONIRIS group (absolute difference 1.9%; 90% CI: 11% to 15%, within the non-inferiority margin). Effectiveness was the same for severity, symptoms, quality of life and blood pressure reduction. Patients in ONIRIS group reported more side effects and adherence was slightly better with TALI. CONCLUSION: In patients with OSA refusing or not tolerating CPAP, the thermoplastic heat-moulded titratable MAD was non-inferior in the short-term to the custom-made acrylic MAD. TRIAL REGISTRATION NUMBER: NCT02348970.

Effect of mandibular advancement therapy on inflammatory and metabolic biomarkers in patients with severe obstructive sleep apnoea: a randomised controlled trial.

Systemic inflammation and metabolic disorders are among the mechanisms linking obstructive sleep apnoea (OSA) and cardiovascular disease (CVD). In 109 patients with severe OSA and no overt CVD, biomarkers of inflammation (C reactive protein, interleukin-6, tumour necrosis factor-α and its receptors, adiponectin, leptin and P-selectin), glucose and lipid metabolism, and N-terminal pro-brain natriuretic peptide, were measured before and after 2 months of treatment with a mandibular advancement device (MAD) (n=55) or a sham device (n=54). MAD reduced the Apnoea-Hypopnoea Index (p<0.001) but had no effect on circulating biomarkers compared with the sham device, despite high treatment adherence (6.6 hour/night). TRIAL REGISTRATION NUMBER: NCT01426607.

Comparison of titrable thermoplastic versus custom-made mandibular advancement device for the treatment of obstructive sleep apnoea.

BACKGOUND AND OBJECTIVES: The disadvantages of custom-made mandibular advancement devices (MAD) for obstructive sleep apnoea (OSA) therapy are the cost and delay required to manufacture the device. This study aimed to evaluate the efficacy of a titrable, thermoplastic MAD compared to a custom-made MAD for OSA therapy. METHODS: In this prospective nonrandomized study, 158 patients with OSA from two French sleep centers were treated for 6 months with a titrable thermoplastic MAD (n = 86) or a custom-made MAD (n = 72). The primary outcome was the change in sleep-disordered breathing (SDB) severity. RESULTS: After adjustment for baseline values, age, body mass index and study site, no significant intergroup differences were observed between thermoplastic and custom-made MAD for the outcome of apnoea, hypopnoea and oxygen desaturation indices. No between treatment differences were observed for the outcome of subjective sleepiness, symptoms of snoring and fatigue, depressive symptoms, and quality of life. Thermoplastic MAD therapy was associated with higher side effects scores for tooth pain (p < 0.0001) and self-reported occlusal changes (p = 0.0069). Mean (SD) reported compliance was lower in the thermoplastic MAD group than in the custom-made MAD group (6.4 [0.2] vs 7.1 [0.1] h/night; p = 0.035). CONCLUSIONS: This study demonstrates the efficacy of a titrable thermoplastic MAD in reducing SDB and related symptoms in patients with mild to severe OSA. Reported compliance at 6 months was high despite more dental discomfort than with custom-made MAD.

Impact of Mandibular Advancement Therapy on Endothelial Function in Severe Obstructive Sleep Apnea.

RATIONALE: Endothelial dysfunction, a major predictor of late cardiovascular events, is linked to the severity of obstructive sleep apnea (OSA). OBJECTIVES: To determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. METHODS: In this trial, we randomized patients with severe OSA and no overt cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on an intention-to-treat basis. An embedded microsensor objectively measured treatment compliance. MEASUREMENTS AND MAIN RESULTS: A total of 150 patients (86% males; mean [SD] age, 54 [10] yr; median [interquartile range] apnea-hypopnea index, 41 [35-53]; mean [SD] Epworth sleepiness scale, 9.3 [4.2]) were randomized to effective mandibular advancement device (n = 75) or sham device (n = 75). On intention-to-treat analysis, effective mandibular advancement device therapy was not associated with improvement of endothelial function compared with the sham device. Office and ambulatory blood pressure outcomes did not differ between the two groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea-hypopnea index (P < 0.001); microarousal index (P = 0.008); and symptoms of snoring, fatigue, and sleepiness (P < 0.001). Mean (SD) objective compliance was 6.6 (1.4) h/night with the effective mandibular advancement device versus 5.6 (2.3) h/night with the sham device (P = 0.006). CONCLUSIONS: In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms but had no effect on endothelial function and blood pressure despite high treatment compliance. Clinical trial registered with www.clinicaltrials.gov (NCT 01426607).

Severe excessive daytime sleepiness induced by hydroxyurea.

Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented.

Continuous positive airway pressure treatment impact on memory processes in obstructive sleep apnea patients: a randomized sham-controlled trial.

OBJECTIVE: The aim of this study was to investigate the changes in a large panel of memory processes after six weeks of continuous positive airway pressure (CPAP) in obstructive sleep apnea (OSA) patients. This randomized controlled trial compared the influence of effective CPAP to sham CPAP over six weeks on different memory processes in OSA patients. METHODS: The study took place in a sleep laboratory and outpatient sleep clinic in a French tertiary-care university hospital. A total of 36 patients with OSA were randomized to receive either CPAP (n = 18) or sham CPAP (n = 18) for six weeks. Interventions were either effective CPAP or non-effective sham CPAP, for six weeks. All patients underwent an extensive battery of tasks evaluating three separate memory systems, before and after treatment. Verbal episodic memory was tested after forced encoding, procedural memory was tested using simplified versions of mirror drawing and reading tests, and working memory was examined with validated paradigms based on a theoretical model. RESULTS: The study subjects were 55 ± 11 years of age and 72.2% were male. The mean body mass index was 29.5 ± 4.1 kg/m2 and the apnea-hypopnea index was 37.1 ± 16.3/h. Prior to treatment, memory performances of OSA patients were altered. In an intention-to-treat analysis, memory deficits were not significantly improved after six weeks of effective CPAP compared to sham CPAP treatment. Verbal episodic, procedural, and working memory scores were comparable between both groups. CONCLUSION: Using cautious methodology in comparing effective CPAP to sham CPAP and a well-defined set of memory assessments, we did not find improvement in memory performance after six weeks of treatment.

Severe Central Sleep Apnea Associated With Chronic Baclofen Therapy: A Case Series.

Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, baclofen has been shown to decrease respiratory drive. In humans, however, use of baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic baclofen therapy for alcohol withdrawal. In one patient, baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with baclofen. Given the increasing number of patients receiving baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with baclofen usage.

Comparison of continuous positive airway pressure and bosentan effect in mildly hypertensive patients with obstructive sleep apnoea: A randomized controlled pilot study.

BACKGROUND AND OBJECTIVE: Randomized controlled trials (RCT) have shown that continuous positive airway pressure (CPAP) has only limited impact on blood pressure (BP). Alternative strategies for obstructive sleep apnoea (OSA)-associated hypertension are therefore needed. Endothelin-1 has been demonstrated a key player in the deleterious cardiovascular consequences of OSA. In OSA, CPAP treatment has never been compared with endothelin receptor antagonist medications. Thus, we assessed the respective efficacy of CPAP and bosentan in reducing 24-h diastolic BP (DBP) in patients with OSA never treated by either therapy. METHODS: In a crossover pilot study, 16 mildly hypertensive patients (office systolic BP (SBP)/DBP: 142 ± 7/85 ± 8 mm Hg) with severe OSA (55 ± 8 years; body mass index, 29.6 ± 4.2 kg/m(2) ; apnoea-hypopnoea index, 40.8 ± 20.2/h) were randomized to either CPAP (n = 7) or bosentan (125 mg/day, n = 9) first for 4 weeks. After 2-weeks of washout, the second 4-week period consisted of the alternative treatment (in crossover). The primary outcome was the 24-h mean DBP change after treatment. RESULTS: In intention-to-treat analysis, the mean difference in 24-h DBP measurements between treatments was -3.1 (-6.9/0.7) mm Hg (median, 25th/75th percentiles) (P = 0.101) with bosentan having a greater effect. CONCLUSION: In this RCT, in mildly hypertensive patients with OSA, bosentan did not modify 24-h DBP but only reduced office BP suggesting that Endothelin-1 blockade does not play a major role in treatment of OSA-related hypertension.

Impact of obstructive sleep apnea treatment by continuous positive airway pressure on cardiometabolic biomarkers: a systematic review from sham CPAP randomized controlled trials.

Reducing cardiometabolic risk may represent an important target for effective obstructive sleep apnea (OSA) treatment. The impact of continuous positive airway pressure (CPAP), the first line therapy of OSA, on metabolic or inflammatory markers is still debated. A systematic literature search using several databases was performed. We provide a systematic analysis of randomized studies comparing therapeutic versus sham CPAP intervention and also include studies using a CPAP withdrawal design. We addressed the impact of CPAP on the following cardiometabolic biomarkers: 1) plasma and urine catecholamines and their metabolites that reflect sympathetic activity; 2) insulin resistance and lipid metabolism biomarkers; 3) oxidative stress, systemic and vascular inflammation biomarkers; 4) liver enzymes highlighting the association between OSA and nonalcoholic fatty liver disease (NAFLD); 5) coagulation biomarkers. The impact of CPAP on sympathetic activity is robust across studies and occurs rapidly. In contrast to sympathetic activity, the well-designed studies included in this review failed to demonstrate that CPAP alters metabolic or inflammatory markers in OSA. CPAP did not change glucose, lipids, insulin resistance levels or the ratio of patients with metabolic syndrome. In unselected OSA patients, it is not realistic to expect a clinically relevant decrease in cardiometabolic biomarkers with CPAP therapy.