Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. ...Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status. OSA prevalence is as high as 40% to 80% in patients with hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, and stroke. Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice. We recommend screening for OSA in patients with resistant/poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. In patients with New York Heart Association class II to IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable. In patients with tachy-brady syndrome or ventricular tachycardia or survivors of sudden cardiac death in whom sleep apnea is suspected after a comprehensive sleep assessment, evaluation for sleep apnea should be considered. After stroke, clinical equipoise exists with respect to screening and treatment. Patients with nocturnally occurring angina, myocardial infarction, arrhythmias, or appropriate shocks from implanted cardioverter-defibrillators may be especially likely to have comorbid sleep apnea. All patients with OSA should be considered for treatment, including behavioral modifications and weight loss as indicated. Continuous positive airway pressure should be offered to patients with severe OSA, whereas oral appliances can be considered for those with mild to moderate OSA or for continuous positive airway pressure-intolerant patients. Follow-up sleep testing should be performed to assess the effectiveness of treatment.
The gold standard for diagnosing sleep disorders is polysomnography, which generates extensive data about biophysical changes occurring during sleep. We developed the National Sleep Research Resource ...(NSRR), a comprehensive system for sharing sleep data. The NSRR embodies elements of a data commons aimed at accelerating research to address critical questions about the impact of sleep disorders on important health outcomes.
We used a metadata-guided approach, with a set of common sleep-specific terms enforcing uniform semantic interpretation of data elements across three main components: (1) annotated datasets; (2) user interfaces for accessing data; and (3) computational tools for the analysis of polysomnography recordings. We incorporated the process for managing dataset-specific data use agreements, evidence of Institutional Review Board review, and the corresponding access control in the NSRR web portal. The metadata-guided approach facilitates structural and semantic interoperability, ultimately leading to enhanced data reusability and scientific rigor.
The authors curated and deposited retrospective data from 10 large, NIH-funded sleep cohort studies, including several from the Trans-Omics for Precision Medicine (TOPMed) program, into the NSRR. The NSRR currently contains data on 26 808 subjects and 31 166 signal files in European Data Format. Launched in April 2014, over 3000 registered users have downloaded over 130 terabytes of data.
The NSRR offers a use case and an example for creating a full-fledged data commons. It provides a single point of access to analysis-ready physiological signals from polysomnography obtained from multiple sources, and a wide variety of clinical data to facilitate sleep research.
Abstract
Aims
Apnoea–hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency ...measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the ‘hypoxic burden’ would predict mortality among adults aged 40 and older.
Methods and results
The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 95% confidence interval (CI) 1.25–2.62 and 2.73 (95% CI 1.71–4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11–3.43).
Conclusion
The ‘hypoxic burden’, an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.
Traditionally, the presence and severity of obstructive sleep apnea (OSA) have been defined by the apnea-hypopnea index (AHI). Continuous positive airway pressure is generally first-line therapy ...despite low adherence, because it reliably reduces the AHI when used, and the response to other therapies is variable. However, there is growing appreciation that the underlying etiology (i.e., endotype) and clinical manifestation (i.e., phenotype) of OSA in an individual are not well described by the AHI. We define and review the important progress made in understanding and measuring physiological mechanisms (or endotypes) that help define subtypes of OSA and identify the potential use of genetics to further refine disease classification. This more detailed understanding of OSA pathogenesis should influence clinical treatment decisions as well as help inform research priorities and clinical study design. In short, treatments could be individualized on the basis of the underlying cause of OSA; patients could better understand which symptoms and outcomes will respond to OSA treatment and by how much; and researchers could select populations most likely to benefit from specific treatment approaches for OSA.
There is limited research on racial/ethnic variation in sleep disturbances. This study aimed to quantify the distributions of objectively measured sleep disordered breathing (SDB), short sleep ...duration, poor sleep quality, and self-reported sleep disturbances (e.g., insomnia) across racial/ethnic groups.
Cross-sectional study.
Six US communities.
Racially/ethnically diverse men and women aged 54-93 y in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (n = 2,230).
N/A.
Information from polysomnography-measured SDB, actigraphy-measured sleep duration and quality, and self-reported daytime sleepiness were obtained between 2010 and 2013. Overall, 15.0% of individuals had severe SDB (apnea-hypopnea index AHI ≥ 30); 30.9% short sleep duration (< 6 h); 6.5% poor sleep quality (sleep efficiency < 85%); and 13.9% had daytime sleepiness. Compared with Whites, Blacks had higher odds of sleep apnea syndrome (AHI ≥ 5 plus sleepiness) (sex-, age-, and study site-adjusted odds ratio OR = 1.78, 95% confidence interval CI: 1.20, 2.63), short sleep (OR = 4.95, 95% CI: 3.56, 6.90), poor sleep quality (OR = 1.57, 95% CI: 1.00, 2.48), and daytime sleepiness (OR = 1.89, 95% CI: 1.38, 2.60). Hispanics and Chinese had higher odds of SDB and short sleep than Whites. Among non-obese individuals, Chinese had the highest odds of SDB compared to Whites. Only 7.4% to 16.2% of individuals with an AHI ≥ 15 reported a prior diagnosis of sleep apnea.
Sleep disturbances are prevalent among middle-aged and older adults, and vary by race/ethnicity, sex, and obesity status. The high prevalence of sleep disturbances and undiagnosed sleep apnea among racial/ethnic minorities may contribute to health disparities.
Quantitative traits analyzed in Genome‐Wide Association Studies (GWAS) are often nonnormally distributed. For such traits, association tests based on standard linear regression are subject to reduced ...power and inflated type I error in finite samples. Applying the rank‐based inverse normal transformation (INT) to nonnormally distributed traits has become common practice in GWAS. However, the different variations on INT‐based association testing have not been formally defined, and guidance is lacking on when to use which approach. In this paper, we formally define and systematically compare the direct (D‐INT) and indirect (I‐INT) INT‐based association tests. We discuss their assumptions, underlying generative models, and connections. We demonstrate that the relative powers of D‐INT and I‐INT depend on the underlying data generating process. Since neither approach is uniformly most powerful, we combine them into an adaptive omnibus test (O‐INT). O‐INT is robust to model misspecification, protects the type I error, and is well powered against a wide range of nonnormally distributed traits. Extensive simulations were conducted to examine the finite sample operating characteristics of these tests. Our results demonstrate that, for nonnormally distributed traits, INT‐based tests outperform the standard untransformed association test, both in terms of power and type I error rate control. We apply the proposed methods to GWAS of spirometry traits in the UK Biobank. O‐INT has been implemented in the R package RNOmni, which is available on CRAN.
PURPOSE OF REVIEWTo provide an update on the connection between obstructive sleep apnea (OSA) and cardiovascular disease.
RECENT FINDINGSLarge prospective studies have established that OSA is ...associated with an increased incidence of hypertension and, in men, of coronary disease, stroke, and heart failure. Advances in understanding the pathophysiologic basis for these associations include identification of a role for OSA in inducing abnormalities in hepatic lipid-metabolizing enzymes, endothelial dysfunction, and upregulation of pro-inflammatory and pro-thrombotic mediators. A large body of data implicates OSA as playing a significant role in the occurrence and resistance to treatment of atrial fibrillation. Clinical trials have shown small-to-modest improvements in blood pressure associated with continuous positive airway pressure (CPAP) use, with smaller or uncontrolled studies suggesting that CPAP may improve cardiovascular outcomes or intermediate markers.
SUMMARYOSA and cardiovascular disease commonly co-aggregate. Multiple studies indicate that OSA contributes to or exacerbates cardiovascular disease, and thus may be a novel target for cardiovascular risk reduction. Although the evidence supports screening and treatment of OSA in patients at risk for cardiovascular disease, it also underscores a need for well powered clinical trials to examine the role of CPAP and other therapies in these populations.
Abstract
Study Objectives
To identify systematic biases across groups in objectively and subjectively measured sleep duration.
Methods
We investigated concordance of self-reported habitual sleep ...duration compared with actigraphy- and single-night in-home polysomnography (PSG) across white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis.
Results
Among 1910 adults, self-reported sleep duration, determined by differences between bed and wake times, was overestimated in all racial groups compared with PSG and actigraphy. Compared with whites (ρ = 0.45), correlations were significantly lower only in blacks (ρ = 0.28). Self-reporting bias for total sleep time compared with wrist actigraphy was 66 min (95% confidence interval CI: 61–71) for whites, 58 min (95% CI: 48–69) for blacks, 66 min (95% CI: 57–74) for Hispanics, and 60 min (95% CI: 49–70) for Chinese adults. Compared with PSG, self-reporting bias in whites at 73 min (95% CI: 67–79) was higher than in blacks (54 min 95% CI: 42–65) and Chinese (49 min 95% CI: 37–61) but not different from Hispanics (67 min 95% CI: 56–78). Slight agreement/concordance was observed between self-reported and actigraphy-based total sleep time (kw = 0.14 for whites, 0.10 for blacks, 0.17 for Hispanics, and 0.11 for Chinese) and PSG (kw = 0.08 for whites, 0.04 for blacks, 0.05 for Hispanics, and 0.01 for Chinese) across race/ethnicity.
Conclusions
Self-reported sleep duration overestimated objectively measured sleep across all races, and compared with PSG, overestimation is significantly greater in whites compared with blacks. Larger reporting bias reduces the ability to identify significant associations between sleep duration and health among blacks compared with whites. Sleep measurement property differences should be considered when comparing sleep indices across racial/ethnic groups.
A recent trend in increasing rates of severe maternal morbidity and mortality despite quality improvements has been noted. The goal of this study is to estimate the national prevalence of obstructive ...sleep apnea (OSA) in pregnant women and examine associations between OSA and pregnancy-related morbidities, including in-hospital maternal mortality.
A retrospective, cross-sectional analysis.
A nationally representative sample of maternal hospital discharges from 1998-2009.
The analytic sample included 55,781,965 pregnancy-related inpatient hospital discharges.
N/A.
The Nationwide Inpatient Sample (NIS) database was used to identify hospital stays for women who were pregnant or gave birth. Among these women, we determined length of hospital stay, in-hospital mortality, and used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to identify OSA and other outcome measures. Multivariable logistic regression modeling was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between OSA and each outcome. The overall rate of OSA was 3.0 per 10,000; however, the rate climbed substantially from 0.7 in 1998 to 7.3 in 2009, with an average annual increase of 24%. After controlling for obesity and other potential confounders, OSA was associated with increased odds of pregnancy-related morbidities including preeclampsia (OR, 2.5; 95% CI, 2.2-2.9), eclampsia (OR, 5.4; 95% CI, 3.3-8.9), cardiomyopathy (OR, 9.0; 95% CI, 7.5-10.9), and pulmonary embolism (OR, 4.5; 95% CI, 2.3-8.9). Women with OSA experienced a more than fivefold increased odds of in-hospital mortality (95% CI, 2.4-11.5). The adverse effects of OSA on selected outcomes were exacerbated by obesity.
Obstructive sleep apnea is associated with severe maternal morbidity, cardiovascular morbidity, and in-hospital death. Targeted interventions may improve pregnancy outcomes in this group.
IMPORTANCE: Inadequate sleep duration and quality increase the risk of obesity. Sleep timing, while less studied, is important in adolescents because increasing evening preferences (chronotypes), ...early school start times, and irregular sleep schedules may cause circadian misalignment. OBJECTIVE: To investigate associations of chronotype and social jet lag with adiposity and cardiometabolic risk in young adolescents. DESIGN, SETTING, AND PARTICIPANTS: Starting in 1999, Project Viva recruited pregnant women from eastern Massachusetts. Mother-child in-person visits occurred throughout childhood. From January 23, 2012, to October 16, 2016, 804 adolescents aged 12 to 17 years completed 5 days or more of wrist actigraphy, questionnaires, and anthropometric measurements. A cross-sectional analysis using these data was conducted from April 31, 2018, to May 1, 2019. EXPOSURES: Chronotype, measured via a continuous scale with higher scores indicating greater evening preferences, and social jet lag, measured as the continuous difference in actigraphy sleep midpoint in hours from midnight on weekends vs weekdays, with higher values representing more delayed sleep timing on weekends. MAIN OUTCOMES AND MEASURES: Adiposity, measured via anthropometry and dual-energy x-ray absorptiometry. For a subset of 479 adolescents with blood samples, cardiometabolic risk scores were computed as the mean of 5 sex- and cohort-specific z scores for waist circumference, systolic blood pressure, inversely scaled high-density lipoprotein cholesterol, and log-transformed triglycerides and homeostatic model of insulin resistance. RESULTS: Among the 804 adolescents in the study, 418 were girls and 386 were boys, with a mean (SD) age of 13.2 (0.9) years. In multivariable models adjusted for age, puberty, season, and sociodemographics, associations of chronotype and social jet lag with adiposity varied by sex. For girls, greater evening preference was associated with a 0.58-cm (95% CI, 0.12-1.03 cm; P = .04 for interaction) higher waist circumference and 0.16 kg/m2 (95% CI, 0.01-0.31 kg/m2; P = .03 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry; each hour of social jet lag was associated with a 1.19-cm (95% CI, 0.04-2.35 cm; P = .21 for interaction) higher waist circumference and 0.45 kg/m2 (95% CI, 0.09-0.82 kg/m2; P = .01 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry. Associations of social jet lag and evening chronotypes persisted for many measures of adiposity after adjustment for sleep duration and other lifestyle behaviors. By contrast, no associations were observed in boys. There were no associations with the cardiometabolic risk score for either sex, although statistical power was low for this outcome. CONCLUSIONS AND RELEVANCE: Evening chronotypes and social jet lag were associated with greater adiposity in adolescent girls but not adolescent boys. Interventions aimed at improving sleep schedules may be useful for obesity prevention, especially in girls.
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