Cardio-metabolic health effects of CPAP treatment for sleep apnoea during weight loss: A randomised controlled pilot trial.

BACKGROUND AND AIMS: This study assessed whether the addition of continuous positive airway pressure (CPAP) during weight loss would enhance cardiometabolic health improvements in patients with obesity and Obstructive Sleep Apnoea (OSA). METHODS AND RESULTS: Patients with overweight or obesity, pre-diabetes and moderatesevere OSA were randomised to receive CPAP therapy with a weight loss programme (CPAP+WL) or a weight loss programme alone (WL alone). PRIMARY OUTCOME: 2-hour glucose assessed by an oral glucose tolerance test. SECONDARY OUTCOMES: 24 hr blood pressure, body composition (DEXA) and fasting blood markers. 17 patients completed 3-month follow-up assessments (8 CPAP+WL and 9 WL alone). Overall, participants in both groups lost ∼12 kg which reduced polysomnography determined OSA severity by ∼45 %. In the CPAP+WL group, CPAP use (compliance 5.29 hrs/night) did not improve any outcome above WL alone. There was no improvement in 2-hour glucose in either group. However, in the pooled (n = 17) analysis there were overall improvements in most outcomes including insulin sensitivity (.000965 units, p = .008), sleep systolic BP (- 16.2 mmHg, p = .0003), sleep diastolic BP (-9.8 mmHg, p = 0.02), wake diastolic BP (- 4.3 mmHg, p = .03) and sleepiness (Epworth Sleepiness Score -3.2, p = .0003). In addition, there were reductions in glucose area under the curve (-230 units, p = .009), total (-0.86 mmol/L, p = 0.006) and LDL cholesterol (-0.58 mmol/L, p = 0.007), triglycerides (-0.75 mmol/L, p = 0.004), fat mass (-7.6 kg, p < .0001) and abdominal fat (-310 cm3, p < .0001). CONCLUSION: Weight loss reduced OSA and improved sleepiness and cardiometabolic health. These improvements were not further enhanced by using CPAP. Results suggest weight loss should be the primary focus of treatment for patients with OSA and obesity.

Cardiac autonomic function in REM-related obstructive sleep apnoea: insights from nocturnal heart rate variability profiles.

PURPOSE: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles. METHODS: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep. RESULTS: Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001). CONCLUSION: Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk.

Characterisation of Symptom and Polysomnographic Profiles Associated with Cardiovascular Risk in a Sleep Clinic Population with Obstructive Sleep Apnoea.

Aim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without established CVD, the Framingham Risk Score (FRS) estimated 10-year absolute CVD risk, categorised as "low" (<6%), "intermediate" (6-20%), or "high" (>20%). Groups were compared on symptom and polysomnographic variables. Results: 629 patients (68% male; mean age 54.3 years, SD 11.6; mean BMI 32.3 kg/m2, SD 8.2) were included. CVD was reported in 12.2%. A further 14.3% had a low risk FRS, 38.8% had an intermediate risk FRS, and 34.7% had a high risk FRS. Groups differed with respect to age, sex and BMI. OSA severity increased with established CVD and increasing FRS. The symptom of waking too early was more prevalent in the higher FRS groups (p=0.004). CVD and FRS groups differed on multiple polysomnographic variables; however, none of these differences remained significant after adjusting for age, sex, and BMI. Conclusion: Higher CVD risk was associated with waking too early in patients with OSA. Polysomnographic variations between groups were explained by demographic differences. Further work is required to explore the influence of OSA phenotypic characteristics on susceptibility to CVD.

A comparison of two obesity-related hypoventilation disorders: Impact on sleep, quality of life and neurocognitive outcomes and the effects of positive airway pressure therapy.

Study Objectives: Symptom impact and neurocognitive function have not been previously compared between patients with obesity-associated hypoventilation disorders (obesity hypoventilation syndrome [OHS]) and hypoventilation in the setting of obesity and obstructive airways disease (OHAD). The aim of this study is to compare baseline sleep-related symptoms, health-related quality of life, and neurocognitive function between OHS and OHAD and the impact of PAP therapy on these outcomes. Methods: Epworth Sleepiness Scale (ESS), Pittsburgh Sleepiness Quality Index (PSQI), SF36, and various neurocognitive tests, in addition to anthropometric, polysomnography, lung function, and blood gas data from participants with OHS and participants with OHAD, were included in the analysis. These data were originally collected in their respective randomized clinical trials, comparing the efficacy of different PAP modes (bilevel PAP vs. CPAP) in resolving hypercapnia. Between groups (OHS vs OHAD), pre- and post-treatment (with 3 months of positive airway pressure) comparisons were made using linear mixed modeling. Results: 45 OHS participants (mean age 51 years old, 33% female, BMI 52 kg/m2, FER 0.81, PaCO2 54 mmHg, AHI 87/h) and 32 OHAD participants (mean age 61years old, 31% female, BMI 43kg/m2, FER 0.60, PaCO2 54 mmHg, AHI 59/h) were included in the analysis. Both OHS and OHAD had similar baseline ESS (14(5.6) vs. 12(5.4)), Global PSQI (10(3.2) vs. 11(4.8)), SF36 and neurocognitive test performances (other than OHAD had lower digit symbol substitution test performance). Treatment with PAP therapy resulted in similar ESS, Global PSQI, and SF36 improvements in both groups. Neurocognitive performance did not significantly improve after PAP therapy in either group. Conclusions: The symptom impact between two separate hypoventilation disorders (OHS and OHAD), in terms of sleepiness, sleep quality, quality of life, and cognitive function, were similar. OHS and OHAD had similar treatment responses in these parameters after 3 months of PAP therapy.Nocturnal ventilatory support in OHS.

Heart rate variability analysis in obstructive sleep apnea patients with daytime sleepiness.

STUDY OBJECTIVES: Recent studies suggest that sleepy patients with obstructive sleep apnea (OSA) are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with OSA using heart rate variability (HRV) analysis. We hypothesized that HRV profiles of sleepy patients would indicate higher cardiovascular risk. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESS ≥ 10) and non-sleepy OSA patients (ESS < 10). HRV parameters were averaged across available ECG signals during N2 sleep. RESULTS: A total of 421 patients were evaluated, with a mean age of 54 (14) years, body mass index of 33 (9) kg/m2, apnea-hypopnea index of 21 (28) events/h, and 66% male. The sleepy group consisted of 119 patients and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, p = 0.028), total power (TP, p = 0.031), absolute low frequency (LF, p = 0.045), and high-frequency (HF, p = 0.010) power compared to non-sleepy patients. Sleepy patients with moderate-to-severe OSA exhibited lower HRV values for: (RMSSD, p = 0.045; TP, p = 0.052), absolute LF (p = 0.051), and HF power (p = 0.025). There were no differences in other time and frequency domain HRV markers. CONCLUSIONS: This study shows a trend toward parasympathetic withdrawal in sleepy OSA patients, particularly in moderate-to-severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA.

Electroencephalographic slowing during REM sleep in older adults with subjective cognitive impairment and mild cognitive impairment.

STUDY OBJECTIVES: In older adults with Alzheimer's disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population. METHODS: Two hundred and ten older adults (mean age = 67.0, SD = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n = 75), non-amnestic MCI (naMCI, n = 85), and amnestic MCI (aMCI, n = 50). REM EEG slowing was defined as (δ + θ)/(α + σ + ß) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup. RESULTS: The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p < 0.05 and 0.06, p < 0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p < 0.05). Greater REM EEG slowing in parietal (r = -0.49) and occipital regions (r = -0.38 [O1/M2] and -0.33 [O2/M1]) were associated with poorer visuospatial performance in naMCI. CONCLUSIONS: REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories.

Obstructive sleep apnoea in obesity: A review.

Obstructive sleep apnea is a common comorbidity that occurs in individuals with obesity. It classically manifests with excessive daytime sleepiness, resulting in reduced quality of life, workplace productivity, and an increased risk of motor vehicle accidents. Weight gain plays an important role in its pathogenesis through worsening upper airway collapsibility, and current treatment options are targeted towards mechanically overcoming upper airway obstruction and weight loss. Continuous positive airway pressure therapy remains the most widely prescribed treatment for obstructive sleep apnea but poor tolerance is a common barrier to effective treatment. Sustainable weight loss is an important treatment option but can be difficult to achieve without bariatric surgery. The recent advances in incretin-based pharmacotherapies represent a promising avenue not only in achieving long-term weight loss but also in treating obstructive sleep apnoea and alleviating the burden of its symptoms and comorbidities.

Restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common sensorimotor disorder causing significant distress and is commonly seen in the primary care setting. OBJECTIVE: This article outlines the epidemiology, pathophysiology, diagnosis and management of RLS, with a focus on the primary care setting. DISCUSSION: RLS is a clinical diagnosis, although mimics exist. Brain iron deficiency, dopaminergic dysfunction and genetics underpin the poorly understood pathophysiology of this common condition. After repleting iron stores, reviewing any exacerbating medications and attending to non-pharmacological management options, there are pharmacological options that prove to be effective, although with class-specific effects that need to be considered.

Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults.

Exogenous melatonin is commonly used for sleep disorders in older adults, and its use is increasing over time. It appears to have modest efficacy in treating insomnia and circadian rhythm sleep-wake disorders. Melatonin is commonly perceived to be a safe alternative to other hypnotics and is available without prescription in some jurisdictions. New evidence suggests that endogenous melatonin has pleomorphic effects on multiple organ systems, many of which are poorly understood. This narrative review summarizes the current evidence regarding the safety of melatonin in older adults (defined by age over 65 years). Melatonin appears to have a favorable safety profile in this population, however there is a dearth of evidence regarding the safety of prolonged use. There are several factors which increase the risk of adverse effects of melatonin in older adults, and these should be taken into consideration when prescribing to this population.

One Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial.

Rationale: The combination of noradrenergic and antimuscarinic agents has recently been shown to improve upper-airway function and reduce obstructive sleep apnea (OSA) severity in short-term (⩽1 wk) proof-of-concept studies. Objectives: To determine the safety, tolerability, and potential efficacy of longer term use of different doses of the noradrenergic agent atomoxetine combined with the antimuscarinic oxybutynin (ato-oxy). Methods: Thirty-nine people with predominantly severe OSA received 80/5 mg ato-oxy, 40/5 mg ato-oxy, 40/2.5 mg ato-oxy, or placebo nightly for 30 days in a double-blind, randomized, parallel design. Participants completed three in-laboratory sleep studies (baseline, Night 1, and Night 30) to assess efficacy. Vital signs and objective measures of alertness and memory were assessed. In men, potential effects on prostate function were assessed using the International Prostate Symptom Score at baseline and Night 30. Potential adverse events were assessed during in-laboratory visits and via weekly phone calls. Results: Side effects were generally mild and consistent with known side-effect profiles of each individual drug (i.e., dose-dependent increases in dry mouth with oxybutynin). Heart rate increased by Night 30 in two active drug arms (mean ± standard deviation 8 ± 10 beats/min [P = 0.01] with 80/5 mg and 9 ± 14 beats/min [P = 0.02] with 40/2.5 mg vs. placebo). No clinically relevant changes in blood pressure, International Prostate Symptom Score, and measures of alertness and memory were observed between conditions. Apnea-hypopnea index (AHI) with 4% oxygen desaturation and hypoxic burden decreased by ∼50% with 80/5 mg ato-oxy from baseline but not versus placebo (e.g., AHI with 3% oxygen desaturation and AHI with 4% oxygen desaturation difference at Night 30 was -8.2 [95% confidence interval, -22.5 to 6.2] and -8.5 [95% confidence interval, -18.3 to 1.3] events/h, respectively). Conclusions: One month of nightly noradrenergic and antimuscarinic combination therapy was generally well tolerated, with a side-effect profile consistent with each agent alone, and was associated with an ∼50% reduction from baseline in a key OSA severity metric, the hypoxic burden with the highest dose combination. These findings highlight the potential to target noradrenergic and antimuscarinic mechanisms for OSA pharmacotherapy development. Clinical trial registered with www.anzctr.org.au (ACTRN 12619001153101).

Armodafinil to reduce the sleepiness related side-effects of sleep restriction therapy being used to treat insomnia disorder: An open label clinical trial pilot study compared with historical controls.

Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone.

Retrospective cohort study of hypersomnias of central origin from two Australian tertiary sleep disorders services.

BACKGROUND: Hypersomnias of central origin (HOCO) are diverse in origin and symptomatology and remain poorly described in an Australian population. We hypothesised that the rate of human leukocyte antigen (HLA) DQB1*0602 positivity in the Australian cohort would be comparable to international registries. AIMS: The current study aims to evaluate epidemiological and clinical characteristics of Australian patients with HOCO, including prevalence of HLA DQB1*0602 positivity, the most specific HLA marker associated with narcolepsy. METHODS: This is a retrospective study. Patients ≥ 16 years of age presenting with symptoms of hypersomnolence who attended one of two Australian sleep centres (New South Wales and Queensland) in the preceding 24 months and had undergone both HLA serology and multiple sleep latency tests (MSLTs) were included. Main outcome measures included demographics, HLA DQB1*0602 positivity, MSLT, and clinical parameters (presence of auxiliary narcolepsy symptoms, laboratory tests, relevant prescribed medications). RESULTS: Eighty-eight patients were included. HLA DQB1*0602 positivity was highest in those with type 1 narcolepsy (NT1) (95.7%) and lowest in those without a classifiable disorder (9.1%). Mean sleep latency was lowest and number of sleep-onset rapid eye movement periods (SOREMPs) highest in the NT1 group. Comorbid disorders, particularly depression and overweight/obesity, were prevalent in all cohorts. Across all diagnostic groups, dexamphetamine was the most commonly prescribed agent for excessive daytime sleepiness. CONCLUSIONS: Patients with HOCO assessed in two specialised Australian clinics demonstrate comparable clinical characteristics to other published cohorts internationally; however, available pharmacological agents in Australia do not reflect international standards of care.

Predictors of weight loss in obese patients with obstructive sleep apnea.

PURPOSE: Consistent predictors of weight loss outcomes with very low-energy diets (VLEDs) in obstructive sleep apnea (OSA) have not been identified. This study aimed to identify variables predictive of weight loss success in obese patients with OSA undertaking an intensive weight loss programme. METHODS: We analysed biological, psychological, and behavioural variables as potential predictors of weight loss in obese patients with OSA after a 2-month VLED followed by one of two 10-month weight loss maintenance diets. Actigraphy, in-lab polysomnography, urinary catecholamines, and various psychological and behavioural variables were measured at baseline, 2, and 12 months. Spearman's correlations analysed baseline variables with 2-month weight loss, and 2-month variables with 2-12 month-weight change. RESULTS: Forty-two patients completed the VLED and thirty-eight completed the maintenance diets. Actigraphy data revealed that late bedtime (rs = - 0.45, p = < 0.01) was correlated with 2-month weight loss. The change in the time that participants got out of bed (rise-time) from baseline to two months was also correlated with 2-month weight loss (rs = 0.36, p = 0.03). The Impact of Weight on Quality of Life-Lite questionnaire (IWQOL) Public Distress domain (rs = - 0.54, p = < 0.01) and total (rs = - 0.38, p = 0.02) scores were correlated with weight loss maintenance from 2 to 12 months. CONCLUSIONS: Results from this small patient sample reveal correlations between actigraphy characteristics and weight loss in obese patients with OSA. We suggest the IWQOL may also be a useful clinical tool to identify OSA patients at risk of weight regain after initial weight loss. CLINICAL TRIAL REGISTRATION: This clinical trial was prospectively registered on 18/02/2013 with the Australia and New Zealand Clinical Trials Registry (ACTRN12613000191796). PUBLIC REGISTRY TITLE: Sleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised, controlled pilot study. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363680.

A pilot randomized trial comparing CPAP vs bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease.

STUDY OBJECTIVES: Both obesity and airways disease can lead to chronic hypercapnic respiratory failure, which can be managed with positive airway pressure (PAP) therapy. The efficacy of PAP has been studied in obesity hypoventilation syndrome as well as in chronic hypercapnic chronic obstructive pulmonary disease patients, but not in patients where both obesity and airway obstruction coexist. This pilot study aims to compare the efficacy of continuous positive airway pressure vs bilevel positive airway pressure spontaneous mode in the treatment of hypoventilation disorder with obesity and obstructive airways disease. METHODS: We sequentially screened PAP-naïve patients with stable chronic hypercapnic respiratory failure (PaCO2 > 45 mm Hg), obesity (body mass index > 30 kg/m2), and obstructive airways disease. Participants were randomized to continuous positive airway pressure or bilevel positive airway pressure spontaneous mode treatment for 3 months. Participants were blinded to their PAP allocation. Change in awake PaCO2 was the primary endpoint. Secondary endpoints included change in lung function, daytime sleepiness, sleep quality, quality of life, PAP adherence, and neurocognitive function. RESULTS: A total of 32 individuals were randomized (mean ± SD: age 61 ± 11 years, body mass index 43 ± 7 kg/m2, PaCO2 54 ± 7 mm Hg, forced expiratory volume in 1 second 1.4 ± 0.6L, apnea-hypopnea index 59 ± 35 events/h). Sixteen participants in each PAP group were analyzed. Bilevel positive airway pressure yielded a greater improvement in PaCO2 compared to continuous positive airway pressure (9.4 mm Hg, 95% confidence interval, 4.3-15 mm Hg). There were no significant differences in PAP adherence, sleepiness, sleep quality, or neurocognitive function between the two therapies. CONCLUSIONS: Although both PAP modalities improved hypercapnic respiratory failure in this group of individuals, bilevel positive airway pressure spontaneous mode showed greater efficacy in reducing PaCO2. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Nocturnal ventilatory support in obesity hypoventilation syndrome; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12605000096651; Identifier: ACTRN12605000096651. CITATION: Zheng Y, Yee BJ, Wong K, Grunstein R, Piper A. A pilot randomized trial comparing CPAP vs bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease. J Clin Sleep Med. 2022;18(1):99-107.

Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity.

STUDY OBJECTIVES: The main cause of death in patients with obesity hypoventilation syndrome (OHS) is cardiac rather than respiratory failure. Here, we investigated autonomic-respiratory coupling and serum cardiac biomarkers in patients with OHS and obstructive sleep apnea (OSA) with comparable body mass index and apnea-hypopnea index. METHODS: Cardiopulmonary coupling (CPC) and cyclic variation of heart rate analysis was performed on the electrocardiogram signal from the overnight polysomnogram. Cardiac serum biomarkers were obtained in patients with OHS and OSA with a body mass index > 40 kg/m2. Samples were obtained at baseline and after 3 months of positive airway pressure (PAP) therapy in both groups. RESULTS: Patients with OHS (n = 15) and OSA (n = 36) were recruited. No group differences in CPC, cyclic variation of heart rate, and serum biomarkers were observed at baseline and after 3 months of PAP therapy. An improvement in several CPC metrics, including the sleep apnea index, unstable sleep (low-frequency coupling and elevated low-frequency coupling narrow band), and cyclic variation of heart rate were observed in both groups with PAP use. However, distinct differences in response characteristics were noted. Elevated low-frequency coupling narrow band coupling correlated with highly sensitive troponin-T (P < .05) in the combined cohort. Baseline highly sensitive troponin-T inversely correlated with awake oxygen saturation in the OHS group (P < .05). CONCLUSIONS: PAP therapy can significantly improve CPC stability in patients with obesity with OSA or OHS, with key differences. Elevated low-frequency coupling narrow band may function as a surrogate biomarker for early subclinical cardiac disease. Low awake oxygen saturation could also increase this biomarker in OHS. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Obesity Hypoventilation Syndrome and Neurocognitive Dysfunction; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367492; Identifier: ACTRN12615000122550. CITATION: Sivam S, Wang D, Wong KKH, et al. Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity. J Clin Sleep Med. 2022;18(4):1063-1071.