bluuebunny/crossref_metadata_2025 huggingface dataset:
0412 Multimethod Remote Assessment of Cognition Among Older Adults with Insomnia
Authors: Adornetti Julianna , Zhao Zhiwei , Wilckens Kristine , Wade Christine , Verceles Avelino , Chen Shuo , Buysse Daniel , Wickwire Emerson
Published: May 2023

Introduction

Cognitive complaints are common among older adults with insomnia. However, previous research is inconsistent regarding the association between insomnia and objective cognitive function. The purpose of this study was to compare subjective and objective cognitive function between older adults with insomnia and healthy sleepers. We hypothesized that relative to healthy sleepers, older adults with insomnia would display diminished subjective and objective cognitive function as measured via multiple remote assessment methods.

Methods

Participants were recruited from an academic medical center through multiple pathways. Cognitive assessments were administered via several approaches. First, subjective cognitive function was assessed via the 5-item Alert Cognition subscale of the psychometrically derived Daytime Insomnia Symptoms Scale (DISS), completed via smartphone 4x/day throughout a two-week study period (i.e., 56 administrations over 14 days). Second, objective cognitive function was assessed via telephone using the Brief Test of Adult Cognition by Telephone (BTACT), which assesses memory, reasoning, verbal fluency, and executive function. Finally, the psychomotor vigilance task [PVT], Stroop test, and a task-switching exercise were administered remotely via participant’s home desktop computer.

Results

Participants included 31 older adults who met DSM-V diagnostic criteria for insomnia disorder (67.5 [sd 6.6] years) and 33 older adults without sleep disorders (70.5 [sd 5.7] years). Large between-group differences were observed in the Alert Cognition subscale of the DISS (p-values < 0.0001); compared to healthy sleeper controls, participants with insomnia reported worsened forgetfulness, concentration, alertness, clear-headedness, and cognitive effort. No between-groups differences were observed in any domain of the BTACT or PVT. A numeric but not statistically significant between-groups difference was observed in overall response speed (e.g., Incongruent Response Time) on the Stroop test (p-values > 0.125).

Conclusion

Remote assessment of cognition is feasible among older adults with insomnia. Significant differences in subjective but not objective cognitive function, likely due to low statistical power, as cognitive deficits in insomnia tend to have small effect sizes. Overall, findings highlight the importance of multimethod assessments of cognition in older adults with insomnia and need for large sample sizes when evaluating objective cognitive function.

Support (if any)

Research was supported by an investigator-initiated research award from Merck Investigator Studies Program (PI: EMW).
0413 Neuroticism interacts with stressful experiences during deployment to predict post-deployment insomnia
Authors: So Christine , Miller Katherine , Gehrman Philip
Published: May 2023

Introduction

Negative affect traits, such as neuroticism, have been shown to be associated with greater risk for insomnia. These trait-based factors are theorized to increase stress reactivity, which can be a predisposing factor to insomnia. Military personnel represent a unique population that are subject to stressors as a nature of their occupations and may therefore be particularly vulnerable to the onset and persistence of insomnia. The present study examined prospective associations among trait-based emotional reactivity and neuroticism, exposure to stressful experiences during a combat deployment, and insomnia symptoms at 9-months post-deployment.

Methods

Data were obtained from the Army Study to Assess Risk and Resilience in Servicemembers Pre-Post Deployment Survey (PPDS). Soldiers included in these analyses (n = 1448) completed surveys prior to deployment to Afghanistan, immediately after deployment, and 9-month post-deployment. The survey included measures of insomnia symptoms, deployment-related stressors and trait-based personality measures. Logistic regression was used to examine the relationships among emotional reactivity, neuroticism and deployment stress with post-deployment insomnia.

Results

Higher trait-based neuroticism and greater exposure to deployment-related stressors were independently associated with greater risk of probable insomnia at 9-months post-deployment, but not trait-based emotional reactivity . However, there were significant interaction effects, such that among those with greater range of stressful events, neuroticism was associated with higher risk of post-deployment insomnia, while emotional reactivity was associated with lower risk.

Conclusion

A trait disposition for negative affect (i.e., neuroticism) may predispose individuals to chronic insomnia in the face of acute stressors . While neuroticism includes negative emotional reactivity, it also encompasses other characteristics (e.g., negative self-perception) that may be a stronger predictor of persistent insomnia symptoms. Service members with higher baseline neuroticism may benefit from pre-deployment skills trainings to better cope in the face of stressors and prevent/mitigate long-term problems.

Support (if any)

This study is based on public use data from Army STARRS (Inter-university Consortium for Political and Social Research, University of Michigan-http://doi.org/10.3886/ICPSR35197-v1), funded by U.S. NIMH-U01MH087981.
0421 Synchronous Virtual Cognitive Behavioral Therapy for Insomnia: Preliminary Results of Sleep Pattern Changes among Cancer Survivors
Authors: Hall Kimberly Arditte , Ma Yan , Goldstein Michael , Cunningham Tony , Park Elyse , Gorman Mark , Comander Amy , Hall Daniel
Published: May 2023

Introduction

For cancer survivors, insomnia is a frequent and distressing concern. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment, yet in-person care can be difficult for cancer survivors to access for a variety of socioeconomic, medical and logistical reasons. In a pilot randomized clinical trial, four, weekly sessions of virtually-delivered, synchronous CBT-I were feasible, acceptable, and seemingly efficacious for reducing insomnia among cancer survivors (vs. an enhanced usual care control). The aim of this secondary analysis was to characterize daily patterns in sleep diary metrics during the intervention phase.

Methods

Adults who had completed treatment for any non-metastatic cancer and had chronic insomnia (DSM-5 criteria and Insomnia Severity Index score <=15) and were randomized to receive CBT-I completed daily assessments of sleep quality (SQ), total sleep time (TST), time in bed (TIB), sleep efficiency (SE), sleep onset latency (SOL), and waking after sleep onset (WASO) for 21 days (i.e., from Session 1-4). Linear mixed models were used to compute trajectories of change for each sleep metric and -2 log likelihood, AIC, and BIC fit indices.

Results

Among 20 cancer survivors who received CBT-I (mean age 51.2 ± 17.1 years, 90% female), model fit indices indicated that across sleep metrics, linear growth models provided a better fit to the data than either quadratic or cubic growth models. Significant linear improvement was observed for SQ (B = 0.02, t = 3.60, p < 0.001), SE (B = 0.16, t = 2.01, p = 0.046), and SOL (B = -0.41, t = -2.47, p = 0.01), but not TIB, TST, or WASO (ts < 1.12, ps > 0.26).

Conclusion

Findings elucidate how sleep may be expected to change over the course CBT-I, in particular for the growing population of cancer survivors seeking virtual care for insomnia. The strengths, limitations, and potential modifications to optimize the intervention across sleep metrics will be discussed.

Support (if any)

This work was conducted with support from the American Cancer Society (Massachusetts General Hospital Institutional Research Grant, PI: Hall).
0424 Visualizing insomnia phenotypes using dimensionality reduction techniques
Authors: Bouchequet Paul , Andrillon Thomas , Solelhac Geoffroy , Rouen Alexandre , Sauvet Fabien , Léger Damien
Published: May 2023

Introduction

A large number of features can be extracted from a single hypnogram, such as stages durations, onsets, or transitions probabilities. Those numerous indicators can turn a collection of sleep records into a high dimension space. Dimensionality reduction techniques are then useful to reveal patterns in data. We used 3 dimensionality reduction techniques to visualize insomnia phenotypes from a dataset of insomnia and control sleep records: principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP).

Methods

519 sleep records have been included with the following diagnoses: 46 sleep onset insomnia, 83 sleep state misperception, 223 sleep maintenance insomnia, 117 sleep onset and maintenance insomnia and 50 controls (good sleep). We limited the feature extraction to the hypnogram as macrostructure constitute the primary source of information used for diagnosis in polysomnography. We used common macrostructure indicators such as wake after sleep onset (WASO), as well as more intricate features such as stages transitions probabilities. A first set of 54 features per hypnogram was computed. Those features were then projected in a 2 dimensional space using PCA, t-SNE and UMAP.

Results

Co-ranking matrix of the projections was computed for the 3 techniques (PCA: Kmax=103, Qlocal=0.38; tSNE: Kmax=20, Qlocal=0.44; UMAP: Kmax=160, Qlocal=0.44). UMAP was the technique that projected the hypnograms feature sets in the most meaningful way, by reflecting the individual diagnoses. Interestingly in the UMAP representation, group outliers, such as controls having nevertheless experienced nocturnal awakenings were projected next to similar insomnia subjects, which indicate a fine-grained capture of sleep quality at the individual level.

Conclusion

Dimensionality reduction and unsupervised techniques are promising methods when approaching high dimensionality spaces. A fine analysis of projected clusters could show subgroups in already known phenotypes. As literature showed robustness and applicability of those methods to larger datasets, dimensionality reduction of insomnia records could be improved by the addition of new features computed from hypnodensities generated by machine learning algorithms, or by spectral features extracted from polysomnographic signals.

Support (if any)

None
0425 A Novel Acceptance-Based Approach for PAP Adherence in Women Veterans: Improvements in Measures of Sleep Quality
Authors: Carlson Gwendolyn , Gogineni Swetha , Mitchell Michael , Josephson Karen , Zeidler Michelle , Swistun Dominika , Lee Diane , Song Yeonsu , Fung Constance , Kelly Monica , Erickson Alexander , Washington Donna , Yano Elizabeth , Alessi Cathy , Martin Jennifer
Published: May 2023

Introduction

While positive airway pressure (PAP) therapy is the most efficacious and widely used treatment for sleep disordered breathing (SDB), the initial discomfort associated with PAP use and the poor sleep experienced by patients with SDB contribute to treatment non-adherence. Women with SDB report poorer sleep quality and have lower PAP adherence rates than men. Previous interventions to improve PAP adherence have rarely targeted women. Acceptance and Commitment Therapy (ACT) utilizes patient values and mindfulness techniques to promote sustained behavior change. An ACT-based approach, in combination with behavioral sleep improvement recommendations, may improve sleep quality and reduce barriers to PAP adherence.

Methods

We analyzed data from women veterans with SDB (mean age=53.2 years [range 26-80]; n=90) who participated in a clinical trial of interventions to improve sleep quality and PAP adherence. Participants were randomly assigned to a PAP educational control intervention or an ACT-based intervention, Acceptance and the Behavioral Changes to treat Sleep Apnea (ABC-SA). We measured: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and subjective and objective (actigraphy) sleep efficiency (SE), total sleep time (TST; minutes), and number of awakenings using sleep diary and actigraphy data, respectively. Using mixed-effects models, we examined changes in sleep quality measures at post-treatment and 3-month follow-up, as compared to baseline.

Results

Women assigned to the ABC-SA intervention reported significantly greater improvements on PSQI total score (p < 0.001), ISI total score (p< 0.001), diary SE (p< 0.001), and actigraphy SE (p< 0.041), and a decrease in actigraphy TST (p< 0.013) at post-treatment compared to women assigned to the control intervention. These observed changes for the ABC-SA intervention relative to the control intervention were maintained at 3-month follow-up (p≤0.001-0.017). No group differences were observed for diary TST or number of awakenings on diary or actigraphy at post-treatment (p≥0.115) or 3-month follow-up (p≥0.248).

Conclusion

An ACT-based approach improved sleep quality in women veterans with SDB, thereby reducing a known barrier to PAP adherence. Future studies should replicate current findings in other at-risk patient groups.

Support (if any)

This research was supported by the VA HSR&D IIR 16-244. Dr. Martin was supported by VA HSR&D RCS 20-191 and NIH/NHLBI K24 HL143055
0428 Area Deprivation Index, Sleep Disordered Breathing and Incident Major Cardiovascular Events and Mortality in a Large Cohort
Authors: Orbea Cinthya Pena , Bruckman David , Schold Jesse , Foldvary-Schaefer Nancy , Thornton Daryl J , Alberts Jay L , Mehra Reena
Published: May 2023

Introduction

Epidemiological studies have shown a strong association between sleep disordered breathing (SDB) and increased incidence of cardiovascular morbidity and mortality, however, to date, the variation of SDB across the socioeconomic spectrum and how this variation is associated with major cardiovascular events (MACE) and mortality is unknown.

Methods

A retrospective cohort study was conducted using the Cleveland Clinic Sleep Laboratory Registry and included MACE-naïve adults who underwent polysomnography or home sleep apnea test. Area Deprivation Index (ADI), a biomarker of neighborhood socioeconomic disadvantage, was calculated by national rank, i.e. 25th, 50th and 75th percentiles; higher quartiles reflecting greater deprivation (ADI-Q1,2,3,4). ANOVA with pairwise testing was used to compare variables across ADI quartiles. Composite of MACE included heart failure, stroke, atrial fibrillation and myocardial Infarction or death. Cox proportional hazard regression models tested the association between ADI and SDB-measures of apnea hypopnea Index (AHI) and sleep-related hypoxia (total sleep time spent< 90%SaO2, T90) with MACE. Covariates included demographics, medications, smoking status, Elixhauser Comorbidity Score, and comorbidities. Censoring was sleep study date or last encounter in the electronic medical record. Asterisk (*) indicates statistical significance after pairwise testing. Interaction testing used competing risk (Fine & Gray method).

Results

Of 72,443 patients, those living in ADI-Q4, compared to those living in ADI-Q1, were more likely to be younger (*48.9± 3.9 vs 50.4±14.2), female (*59.9% vs 40.1%), African American (*49% vs 4.9%), with lower AHI (*13.5[5.4, 34.1]vs15.1[6.2,33.1]) and lower degree of hypoxia (T90:*2.9[0.40,19.01] vs 4.4[0.50, 25.6]). Model adjusted risk for MACE or death for those in ADI-Q4 was 79% greater than ADI-Q1 (HR=1.79,95%CI:1.51-2.12,p< 0.0001). Likewise, increased AHI severity and T90 above median were associated with 13% and 21% increased risk of MACE or death (HR=1.13,95%CI:1.07-1.19,p< 0.0001; HR=1.21,95%CI:1.51-1.27,p< 0.001) respectively. Interactions were observed between T90 and ADI with the risk of MACE (p=0.0016) or death (p=0.0051).

Conclusion

Living in areas of increasing socioeconomic deprivation confers an increased risk for MACE or death. Moreover, sleep-related hypoxia seems to modify this association. ADI appears to be useful to identify populations at risk for worse cardiovascular outcomes and to inform risk stratification for targeted interventions to decreased sleep-health disparities.

Support (if any)
0431 Different physiological characteristics of obstructive sleep apnea symptom subtypes across international sleep centers
Authors: Keenan Brendan , de Chazal Philip , Penzel Thomas , Gerardy Bethany , Magalang Ulysses , Younes Magdy , Mazzotti Diego , Pack Allan
Published: May 2023

Introduction

Obstructive Sleep Apnea (OSA) is a widespread and heterogeneous sleep disorder. Studies have identified reproducible subtypes of OSA based on patient-reported symptoms that have different cardiovascular outcomes. Prior data showed similar apnea-hypopnea index (AHI) across subtypes; however, other physiological characteristics have not been comprehensively compared among these subtypes.

Methods

1,285 participants from the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) with moderate-severe OSA (AHI≥15) were included. Differences in traditional and novel physiological traits were compared among the Disturbed Sleep (n=183 [14.2%]), Minimally Symptomatic (n=581 [45.2%]), and Excessively Sleepy (n=521 [40.5%]) subtypes using analysis of covariance (ANCOVA) adjusted for age, sex, BMI and race/ethnicity. Measures included AHI and other respiratory event indices, hypoxic burden, oxygen characteristics, sleep/wake amounts, electroencephalogram (EEG) spectral characteristics, including metrics related to the odds ratio product (ORP; a validated index of sleep depth ranging from 0.0 [deep sleep] to 2.5 [full wakefulness]), arousal intensity, and heart rate response to arousal.

Results

Compared to other subtypes, the Disturbed Sleep subtype demonstrated increased wakefulness (more wake time [p< 0.001] and wake after sleep onset [p=0.001]), higher beta frequency EEG power (14.33-20.0 Hz [p=0.025] and 20.33-35.0 Hz [p=0.004]), and less deep sleep (higher average [p=0.001] and NREM-specific [p=0.044] ORP, less time with ORP from 0.50-0.75 [p=0.004] and 0.75-1.00 [p=0.015], and more time from 2.20-2.25 [p=0.017] and 2.25-2.50 [p=0.0005]). The Excessively Sleepy subtype had more severe hypoxemia, including greater hypoxic burden (p=0.002) and lower average SpO2 (p=0.002) and minimum SpO2 (p=0.0002) compared to other subtypes.

Conclusion

Differences in physiological characteristics, including ORP-related traits, were observed among symptom subtypes. Results suggest that characteristics indicative of increased wakefulness may distinguish those with the Disturbed Sleep subtype, whereas more severe hypoxemia may characterize the Excessively Sleepy subtype. Future investigations into underlying molecular causes of symptom subtypes, particularly the Excessively Sleepy, are warranted given evidence of associations with outcomes such as cardiovascular disease.

Support (if any)

SAGIC Investigators (Ayas N, Chen NH, Cistulli P, de Chazal P, Gislason TG, Han F, Hirsch-Allen AJ, Keenan BT, Li QY, Magalang UJ, Maislin G, Mazzotti DR, McArdle N, Mindel J, Pack AI, Penzel T, Schwab RJ, Singh B, Sutherland K); NIH P01 HL094307
0433 Home sleep apnea testing in patients with a LVAD: Is it feasible?
Authors: Pusalavidyasagar Snigdhasmrithi , Airhart Sophia , Kay Jenna , Christophy Antonio , Sun Benjamin , Mudy Karol , Castleberry Anthony , Emerson Dominic , Hyden Marshall , Shaffer Andrew , Mutschler Melinda , Alexy Tamas
Published: May 2023

Introduction

Sleep related breathing disorders, including central sleep apnea (CSA), are frequent in patients with heart failure however, only limited data is known about the effect of left ventricular assist device (LVAD) placement on OSA and even less about the accuracy of home sleep apnea testing in this population (HSAT). Performing the gold standard polysomnography (PSG) is challenging in this cohort due to logistics, especially during the COVID-19 pandemic. Extending HSAT to the LVAD population would be beneficial, yet initial tests with the WatchPat® were deemed inconclusive. We decided to evaluate the validity of NOX-T3 device for HSAT compared to PSG.

Methods

This was a single center prospective, observational study that included LVAD patients who screened positive on the STOP-BANG questionnaire. A sleep study was indicated based on consultation with a sleep physician and a standard PSG was ordered. During the PSG, the NOX-T3 was also applied with the results analyzed and compared after test completion.

Results

In this preliminary analysis, 4 patients (3 male, 1 female) with a LVAD completed a PSG along with the NOX-T3. The overall severity of sleep apnea indicated by apnea hypopnea index during the PSG and the respiratory event index during the NOX-T3 were similar in this small cohort. In 2 of the 4 patients, the oximetry finding (minutes with oxygen saturations at or below 88%) were also similar during both the PSG and the NOX-T3.

Conclusion

Based on this preliminary analysis, data obtained with the NOX-T3 system were valid and compared well to the standard of care PSG in patients with a LVAD. We plan to enroll at least 10 patients in this ongoing trial, further studies will be needed to validate these results. Performing HSAT with the NOX-T3 in this unique population if PSG is not feasible would be of significant value given the morbidity of sleep apnea in this population.

Support (if any)
0435 Machine-learned combination of ventilatory, hypoxic, and arousal burdens classifies daytime sleepiness better than AHI
Authors: Wickramaratne Sajila , Kam Korey , Tolbert Thomas , Kim Yun Soung , Varga Andrew , Ayappa Indu , Rapoport David , Parekh Ankit
Published: May 2023

Introduction

The apnea-hypopnea index (AHI), the current severity metric used clinically for diagnosing obstructive sleep apnea (OSA), does not correlate well to daytime sleepiness measured via the Epworth Sleepiness Scale (ESS). Here, we assessed whether a machine-learned combination of possibly independent metrics across ventilatory/hypoxic/arousal domains would be better associated with ESS than the AHI using data from 3 large cohorts.

Methods

Polysomnography data were analyzed from The Sleep Heart Health Study (SHHS), The Multi-Ethnic Study of Atherosclerosis (MESA), and The Osteoporotic Fractures in Men (MrOS) Study. A total of N=6618 (39.9% female; age 68.7±6.6) subjects had valid data (ESS and good quality airflow/EEG/SpO2). Ventilatory burden was evaluated using a derived flow signal that utilized the sum of thoracic and abdominal effort signals for SHHS and was evaluated using the Nasal Cannula/Pressure Transducer signal for the MrOS and MESA data. Hypoxic burden was calculated as the area between the baseline and the SpO2 trace for any episode with >= 3% desaturation. Arousal burden was defined as the manually scored arousal index (number/hr.). Based on a cut-off of ESS(ESS>= 10), sleepiness was coded present or absent and was the primary outcome. Data were analyzed in two ways: using all 3 cohorts as train (70%) and test (30%), and by permutations and combinations of the 3 cohorts (70/30 split; e.g., SHHS for training, MESA and MrOS for test). Model performance metrics were the area under the receiver operating characteristic curve (AUROC) and %accuracy. For comparison, a logistic regression model using AHI3a (3% desaturation and/or EEG arousal) was fit.

Results

The logistic regression model (AHI3a) classified sleepiness with an AUROC of 0.51±0.07. The random forest model trained on 70% of all 3 cohorts achieved the highest AUROC of 0.88±0.07 (mean accuracy of 85.1± 2.13%), whereas the permutations and combinations of the 3 datasets resulted in an average AUROC of 0.63 ±0.12 (mean accuracy of 76.4±6.57%).

Conclusion

The machine-learned combination of ventilatory/hypoxic/arousal burdens classifies daytime sleepiness in OSA better than AHI3a across data from 3 large cohorts. These results suggest that OSA severity measured using machine-learned combination of ventilatory/hypoxic/arousal burdens better explains the variability in daytime sleepiness.

Support (if any)
0436 Obstructive Sleep Apnea (OSA) Patient Journey: Retrospective Analysis of Real-world Data
Authors: Wickwire Emerson , Zhang Xuan , Munson Sibyl , Benjafield Adam , Payombar Mojgan , Patil Susheel
Published: May 2023

Introduction

OSA affects about 30% of US adults and up to 90% remain undiagnosed and untreated. This study aimed to characterize the OSA patient journey by identifying the most common OSA care pathways in the U.S. We also sought to compare time from diagnosis to treatment initiation between groups.

Methods

Data was extracted from a national administrative claims database (01/01/2016–02/28/2020). Inclusion criteria included age ≥18 years and 12 months continuous enrollment before/after the first OSA diagnosis (index date). OSA was defined as ICD-10 diagnosis preceded by HSAT, in-lab PSG, and/or split-night PSG within the prior 12 months. Exclusion criteria included prior OSA diagnosis/treatment or central sleep apnea. Patient pathway, demographics (at time of OSA diagnosis), timeframes, and comorbidities were assessed. Associations between sex, region, payer, and median patient journey times were investigated using generalized linear models adjusted for baseline characteristics.

Results

A total of 86,827 OSA patients (45.1% female; median age, 50±11.8) were identified, of which 60.8% initiated PAP therapy, 1.5% received an oral appliance, and 37.6% initiated neither treatment within the year following diagnosis. For patients initiating PAP, the most common care pathways identified for patients, and their median time to treatment initiation were HSAT-only (23.4%, 35 days), PSG+titration (22.9%, 58 days), split-night titration (16.8%, 28 days), PSG-only (11.2%, 37 days), HSAT+HSAT (6.9%, 37 days), titration+titration (3.9%, 31 days) and HSAT+titration (3.5%, 75 days). Relative to patients in PSG-only, individuals in HSAT-only were more likely to initiate PAP (56.1% versus 33.6% initiation). Longer timeframes from sleep test to PAP initiation were observed for patients with commercial insurance versus Supplemental Medicare (OR: 95% CI, 1.10: 1.07–1.14) and females (1.05: 1.04–1.06). There were significant differences in patient timeframes according to region (p< 0.00001). Notable patterns of differences in journey time and PAP initiation were observed based on patient Metropolitan Statistical Area (MSA) diversity and MSA median household income levels, when combined.

Conclusion

This is the first national analysis to characterize common OSA treatment pathways. Time to treatment initiation varied widely between OSA care pathways. Patient sex, region, payer, and household income were associated with time to treatment initiation.

Support (if any)

Primasun
0437 Obstructive Sleep Apnea Symptom Subtypes and Hypoxic Burden Independently Predict Distinct Cardiovascular Outcomes
Authors: Mazzotti Diego , Magalang Ulysses , Keenan Brendan , Mindel Jesse , Younes Magdy , Penzel Thomas , Pack Allan , de Chazal Philip
Published: May 2023

Introduction

Studies on heterogeneity of obstructive sleep apnea (OSA) have identified clinically relevant symptom-based subtypes and novel OSA-specific nocturnal hypoxemia measures. Evidence suggests that moderate-severe OSA patients with the excessively sleepy subtype have increased risk of incident major adverse cardiovascular events (MACE; composite of coronary heart disease, heart failure, stroke, or cardiovascular mortality) and that OSA-specific hypoxic burden (HB) is associated with increased risk of cardiovascular disease (CVD) mortality. However, no study has comprehensively examined their combined impact. This study provides a systematic assessment of the individual and combined contribution of these factors on incident CVD risk, addressing an important gap in evidence.

Methods

Participants from the Sleep Heart Health Study with high-quality oxygen saturation, OSA severity quantified by apnea-hypopnea index (AHI), and symptom data were included. Latent class analysis on 14 symptoms was used to classify participants with moderate-severe OSA (AHI≥15) into subtypes. HB was calculated from respiratory event-related hypoxia and sleep time. Cox proportional hazards models were used to assess the relative contributions of OSA symptom subtypes and HB (natural log transformed) on risk for CVD mortality and MACE, adjusted for demographic and CVD risk factors. Analyses were performed in both CVD-free participants and all participants (adjusted for CVD at baseline).

Results

A total of 5,027 participants were analyzed, with median follow-up of 11.6 years (CVD mortality) and 11.3 years (MACE). HB was independently associated with CVD mortality in all participants (HR[95% CI] = 1.44 [1.06-1.97]; p=0.021) and CVD-free participants (1.62 [1.12-2.35]; p=0.010) controlling for symptom subtype. Conversely, symptom subtypes were independently associated with MACE incidence among CVD-free participants, controlling for HB, with the excessively sleepy participants having nearly two-fold higher risk (HR[95% CI] = 1.98 [1.26-3.10]; p=0.003) compared to those without OSA.

Conclusion

OSA symptom subtypes and HB are independently associated with distinct CVD-related endpoints. Higher HB was associated with cardiovascular mortality, controlling for symptom subtype. The excessively sleepy subtype was at higher risk of new MACE, controlling for HB. Thus, both factors are important for understanding OSA-related CVD risk.

Support (if any)

AHA (20CDA35310360), NIH (P01HL094307, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL53938, U01HL53940, U01HL53941, U01HL64360 R24 HL114473, 75N92019R002).
0440 Peripheral arterial tonometry–based measures of obstructive sleep apnea in Black, Mexican American and non-Hispanic White adults
Authors: Leng Yue , Peltz Carrie , Redline Susan , Stone Katie , O'Bryant Sid , Yaffe Kristine
Published: May 2023

Introduction

Racial/ethnic differences may exist in sleep quality and disorders, but there are limited data directly comparing objective measures of obstructive sleep apnea (OSA) among Black, Mexican American (MA) and non-Hispanic White (NHW) populations.

Methods

To date, the ongoing Health & Aging Brain among Latino Elders (HABLE)-Dormir study has enrolled 761 participants using a community-based participatory research approach. Here we describe OSA indices assessed by in-home assessments using WatchPAT, a Peripheral Arterial Tonometry (PAT)-based home sleep testing system that is validated for the diagnosis of OSA.

Results

Participants had a mean age of 65.6+/-8.2 (50-90) years, comprised of 64% women; 34% MA, 24% Black and 42% NHW adults. Over half (52.0%) of the participants had moderate or more severe OSA as defined by the respiratory event index (REI based on 3% desaturations) of >=15/hour, 73.1% with REM-OSA (REM-REI >=15/hour) and 40.6% with NREM-OSA (NREM-REI >=15/hour). The median of the average snoring volume through the night was 41 (40-61) dB. The median percentage of sleep time spent with oxygen saturation below 90% (SpO2< 90%) was 1.0%. After adjustment for age, sex, Body Mass Index, cognitive status, and history of hypertension, diabetes, stroke and heart attack, Black and MA participants were 71% and 55% more likely to have REM-OSA compared to NHW participants (p=0.04), but had similar prevalence of NREM-OSA (p=0.80) and overall OSA (p=0.32). The adjusted mean percentage of sleep time spent with over 40dB snoring volume was higher among Black (22.7%, p=0.03) and MA adults (21.2%, p=0.11) than NHW adults (18.5%). The adjusted mean prevalence of nocturnal hypoxemia (SpO2< 90% time >= 1%) was similar among Black (48.2%), MA (51.7%) and NHW (50.0%) adults; p=0.83.

Conclusion

In this middle-to-older-aged population, PAT-based measures of OSA indicate a higher prevalence in minoritized adults of REM-specific sleep apnea, a phenotype associated with increased rates of hypertension and mortality. Home-based measures that do not distinguish between REM and NREM respiratory events may underestimate sleep apnea in these groups.

Support (if any)

This research was supported by National Institutes of Health grant R01AG066137.
0448 Telemedicine Management of Obstructive Sleep Apnea Disorder: A Randomized Controlled Trial
Authors: Xu Liyue , Yi Huijie , Zhang Chi , Keenan Brendan , Pack Allan , Han Fang , Kuna Samuel
Published: May 2023

Introduction

Previous studies assessed different components of telemedicine instead of the whole telemedicine management pathway for OSA. The current study aimed to demonstrate that telemedicine management was not clinically inferior to in-person care in China based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score following three months of an auto-adjusted positive airway pressure (APAP) treatment.

Methods

Adults suspected of OSA were randomized to telemedicine (n=178) or in-person (n=178) management. Participants with AHI ≥ 15 events/hour diagnosed by a home sleep apnea test (HSAT) were treated with an APAP with a wireless modem. The participants were followed up by call at week 1 and visit at month 1 and month 3.

Results

We measured the change in FOSQ score as the primary outcome, with an a priori noninferiority delta of -1, and the mean daily hours of objectively measured APAP adherence, with an a priori noninferiority delta of -45min/day. Of the 356 subjects enrolled, 313 (87.9%) were diagnosed with OSA, and 261 (73.3%) underwent PAP setup. The mean functional outcome score following 3 months improved 1.73 points (95%CI: 1.31, 2.14) in the telemedicine group and 2.05 points (95% CI: 1.64, 2.46) in the in-person group. The lower bound of the one-sided 95% noninferiority confidence interval was -0.812. Mean daily APAP adherence at 3 months was 243.3 minutes/night (95% CI: 223.1, 263.5) in the telemedicine arm and 241.6 minutes/night (95% CI: 221.3, 261.8) in the in-person arm. The lower bound of the one-sided 95% noninferiority confidence interval was -22.2 minutes/night. Compared to in-person management, the telemedicine pathway had lower patients cost and similar health care cost.

Conclusion

Functional outcome and treatment adherence in patients managed by a comprehensive telemedicine approach is not clinically inferior to that in patients receiving in-person care.

Support (if any)

ResMed Australia funded the APAP machines. The study was supported by the National Key R&D Program of China (Z161100002616012). Liyue Xu is supported by a grant from the National Natural Science Foundation of China (NSFC 82100104).
0451 Dronabinol Plus Acetazolamide for the Treatment of Obstructive Sleep Apnoea: A Proof of Concept and Mechanistic Exploration Study
Authors: Thomson Luke , Rankin Timothy , Mehra Sumit , Naughton Matthew , Roebuck Teanau , McDermott Elizabeth , Pattichis Andreas , Smith Rafael , Germaine Jack , Walsh Rosemarie , Bleackley Mark , Edwards Bradley , Maddison Kathleen , O'Brien Terence , Walsh Jen
Published: May 2023

Introduction

Current treatments for obstructive sleep apnoea (OSA) typically target the anatomical pathophysiological endotype and are either not tolerated or effective in a significant proportion of patients. Pharmaceuticals may provide an alternative therapeutic option and may address some or all of the remaining endotypes (loop gain, muscle compensation and arousal threshold). This randomised, double-blind, placebo-controlled, cross-over study examined the effect of combination acetazolamide and dronabinol (IHL-42X) at low, medium and high doses on OSA severity and the OSA endotypes.

Methods

Participants with OSA (apnoea-hypopnoea index; AHI≥15events/hr) received 1-week of IHL-42X at each of the 3 doses and 1-week of placebo, each separated by 1-week washout. The change from baseline in AHI, oxygen desaturation index (ODI), Epworth sleepiness score (ESS), and mood (profile of mood states) on the final night of each treatment arm relative to placebo were the major endpoints. Adverse events (AEs) were monitored throughout. Exploratory analyses examined the change in OSA endotypes determined from polysomnography from baseline values.

Results

Ten of 11 participants (mean baseline AHI 40.7events/hr) completed the final night of at least one treatment arm. All doses of IHL-42X demonstrated a significant reduction in AHI from baseline when compared with placebo (low, -19.7±27.1; medium, -17.5±23.3; high, -16.4±23.8 versus placebo, -2.8±21.0events/hr; all p< 0.05). The change from baseline in ODI3% at the low, medium and high doses of IHL-42X (-15.2±24.8; -15.4±19.0 and -8.3±13.2events/hr, respectively) were not significantly different from placebo (-2.8±21.0events/hr). IHL-42X did not significantly alter ESS or mood. No serious AEs occurred. However, 31 mild-moderate possibly, probably or treatment related AEs occurred during IHL-42X dosing (4 at the low dose) and 4 occurred during placebo. Relative to baseline, loop gain decreased by 15, 21 and 20% (Cohen’s d all ≥0.59) at the low, medium and high doses, respectively, and collapsibility improved by 12.5% (d=1.06) at the low dose only.

Conclusion

One week of nightly IHL-42X at all doses was well tolerated, safe and associated with significant reductions in OSA severity. IHL-42X may act to reduce OSA severity by decreasing loop gain and upper airway collapsibility, particularly at the low dose.

Support (if any)

Incannex Healthcare Ltd supported this study.
0452 Mild-to-moderate OSA and mortality in general population: the modifying effect of age and cardiovascular/cerebrovascular morbidity
Authors: Vgontzas Alexandros , Karagkouni Efthalia , He Fan , Fernandez-Mendoza Julio , Li Yun , Karataraki Maria , Bixler Edward
Published: May 2023

Introduction

Mild-to-moderate obstructive sleep apnea (mOSA) is highly prevalent in the general population and is highly comorbid with cardiovascular and/or cerebrovascular diseases (CBVD). We examined the association between mOSA and all-cause mortality and the modifying effect of age and CBVD.

Methods

A total of 1681 adults 20-88 years old from the Penn State Adult Cohort (41.9% male, 10.5% racial/ethnic minority) were followed up for 20.1±6.2 years for all-cause mortality. The presence of mOSA was defined as an apnea/hypopnea index from 5-29.9 events/hour. CBVD was defined as a report of diagnosis or treatment for heart disease and/or stroke. Cox proportional hazards regression models were used to estimate all-cause mortality adjusted for confounders.

Results

All-cause mortality risk was significantly increased in the mOSA group in young and middle-aged adults (< 60 years) (HR=1.59, 95%CI 1.08-2.04) but not in older adults (≥60 years) (HR=1.05, 95%CI 0.80-1.39). We observed a synergistic effect between mOSA and CBVD that was stronger in those < 60 years (HR=3.82, 95%CI 2.25-6.48 in < 60 years vs 1.86 95%CI 1.14-3.04 in ≥60 years). There was an additive effect between mOSA and hypertension in < 60 but not in those ≥60 years (mOSA and hypertension HR=2.39, 95%CI 1.56-3.66 vs. 1.09 95%CI 0.75-1.57).

Conclusion

Mortality risk is increased in young and middle-aged adults with mild-to-moderate forms of OSA. The risk is even stronger in the presence of CBVD/hypertension. It appears that AHI cut-offs warranting treatment of mOSA should be adjusted based on age and prevalent clinical disorders.

Support (if any)
0455 Association of high-risk obstructive sleep apnea with endothelial dysfunction in a large population-based sample in MiHeart Study
Authors: Khosla Atulya , Aneni Ehimen , Lahan Shubham , Saxena Anshul , Ali Shozab , Feldman Theodore , Fialkow Jonathan , Nasir Khurram , Walia Harneet
Published: May 2023

Introduction

Obstructive Sleep Apnea (OSA) is associated with endothelial dysfunction and cardiovascular disease (CVD). There are limited data evaluating the association with endothelial dysfunction measured by reactive hyperemia index (RHI) in an asymptomatic population free of CVD. We hypothesized that there would be a significant association between high risk of OSA and endothelial dysfunction in the Miami Heart (MiHeart) study, a population-based cohort of relatively young individuals free of known cardiovascular disease (CVD).

Methods

Cross-sectional data from 2097 participants (mean age: 53 years, 50% female) enrolled in the MiHeart study and underwent flow-mediated dilation using the EndoPat 2000 system was analyzed for this study. OSA was determined by Berlin questionnaire (high vs. low risk); logistic regression was utilized to examine the association between high OSA risk (reference low-risk OSA) and RHI (cut off < 1.67 vs. ≥1.67) in unadjusted models, and after accounting for age, sex, race/ethnicity (model 2), and BMI, diabetes, hypertension, high cholesterol, and smoking (model 3).

Results

704 (34%) participants were categorized as high OSA risk, according to the Berlin questionnaire. These participants were more likely to be male, Hispanic and had a higher CVD risk factor burden when compared to low OSA risk. In addition, those with high OSA risk had higher prevalence of endothelial dysfunction (17.5% vs. 13.9%) than the low OSA risk (p < 0.05) group. High risk of OSA was associated with a higher risk of endothelial dysfunction in the unadjusted model (OR=1.32, 95% CI 1.03, 1.68). When adjusted for age, sex, and race/ethnicity, this association was slightly attenuated (OR 1.26, 95% CI 0.97, 1.62). Upon adjusting for CVD risk factors (model 3), the association between high-risk OSA and endothelial dysfunction was further attenuated and was not statistically significant (OR=1.18, 95% CI 0.87, 1.59). There was a strong, independent association between presence of diabetes and endothelial dysfunction (OR= 2.01, 95% CI 1.35, 2.94).

Conclusion

Younger individuals with high risk for OSA have elevated odds of endothelial dysfunction, and this relationship is likely mediated by demographics and cardiometabolic risk factors such as diabetes.

Support (if any)

The Miami Heart Study is funded by Baptist Health South Florida.
0458 Cardiovascular and sociocultural factors are associated with sleep breathing differences in a diverse Hispanic/Latino cohort
Authors: Gonzalez Kevin , Tarraf Wassim , Kosik Eena , Guarian Kenton , Voytek Bradley , González Hector , Ramos Alberto
Published: May 2023

Introduction

Obesity and or obstructive sleep apnea (OSA) can impact awake breathing patterns, such as increments in the breathing rate. However, little is known about their associations with breathing dysregulations during sleep beyond the apnea-hypopnea events. Understanding this could help elucidate treatment mechanisms or different pathways for disease. Furthermore, there is a strong connection between breathing patterns and cardiovascular disease, thus it is also critical to understand the links between cardiovascular risk factors and disease (CVD) and sleep breathing patterns.

Methods

The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective multicenter study of diverse Latinos. A total of N=16,415 participants from four major metropolitan areas and six different Hispanic/Latino backgrounds were sampled for appropriate generalization to the target population. Participants were given an ARES unirecorder device (Carlsbad, San Diego) for a single night of unsupervised at home recording (N=12,022). Raw data from cannula channel (sampled at 10Hz) was processed using the python Bycycle package. Bycycle is a cycle-by-cycle approach to analyzing time series data. Bycycle finds all peaks and throughs in cycles and allows users to extract time dependent information of cycles. We extracted breathing rate (breaths per minute), breathing variability (interquartile range of breathing rate) and time spent in inhalation phase (percent time).

Results

In multivariable models (N=10,175), age was linked to decreased breathing rate, breathing variability, and time spent in inhalation phase. Compared to females, males had higher breathing variability and spent more time in the inhalation phase. Compared to Mexicans and? Central Americans, Cubans, Dominicans, and Puerto Ricans had less time spent in inhalation phase. Dominicans and Puerto Ricans also had increased breathing rate compared to Mexicans. Smoking, body mass index, and moderate to severe OSA were associated with increased breathing rate and variability. Systolic, but not diastolic blood pressure, was associated with increased breathing rate. We found no significant associations with cardiovascular disease.

Conclusion

Factors commonly linked to OSA were associated with increased breathing rate, a compensatory mechanism for optimal oxygenation, and breathing variability. Given cessation or reduced breathing during an apnea-hypopnea event, breathing variability may add more precision to account for varying oxygen demands.

Support (if any)
0464 Deep Learning to Predict PAP Adherence in Obstructive Sleep Apnea
Authors: Rusk Samuel , Nygate Yoav , Fernandez Chris , Shi Jiaxiao M , Arguelles Jessica , Klimper Matthew T , Watson Nathaniel F , Stretch Robert , Zeidler Michelle , Sekhon Anupamjeet , Becker Kendra , Kim Joseph , Hwang Dennis
Published: May 2023

Introduction

Machine Learning (ML) algorithms to predict Positive Airway Pressure (PAP) adherence may support personalized clinical management. Models were developed to predict adherence at various time-points after PAP initiation and in moving time windows.

Methods

Deep neural network (DNN) models were trained utilizing daily PAP data (Kaiser Permanente, Southern California). The DNN was evaluated with 10-fold cross-validation on N=21,397 patients. Algorithms developed included (a) Models 1 and 2 which utilized early usage to predict adherence at 90-days and 1-year respectively, and (b) Model 3 which utilized 14 and 30-day moving windows to predict subsequent usage. Regression analyses compared ML and Naïve (i.e., future use equals previous use) predictions versus Actual adherence.

Results

Model 1 predicted “% days without usage” for first 90-days based on first 7, 14, 21, 30-days of input and at 1-year (90-day window) based on first 30, 60, 90, 180-days of input. ML was superior to Naïve in predicting adherence [R 2 for ML versus Naïve compared to Actuals for different input days— 0.495-vs-0.193; 0.660-vs-0.465; 0.748-vs-0.607; 0.828-vs-0.735 at 90-days and 0.362-vs-0.104; 0.463-vs- 0.247; 0.513-vs-0.339; 0.680-vs-0.547 at 1-year; all p< 0.05]. Model 2 predicted “hours/night” of use—ML did not outperform the Naïve prediction with similar R 2 ; however, when ML predicted < 3 hours/night, nearly all patients had “no significant usage” at 1-year (comparatively, the naïve model had no differentiating threshold to predict this outcome.) Model 3 utilized different windows of PAP usage to predict subsequent usage. ML predictive accuracy was similar using 14 or 30-days of input [R 2 for ML vs. Actuals in predicting 7, 14, and 30-day “% days used ≥4 hours” were 0.687, 0.701, 0.699 using 14- days input and 0.582, 0.702, 0.77 using 30-days input; all p< 0.05.]

Conclusion

ML algorithms based on PAP usage can predict future adherence, potentially supporting personalized treatment decisions and pre-emptive interventions when upcoming non-adherence is predicted.

Support (if any)

AASM Foundation SRA205-SR-19