Novel Sleep Phenotypic Profiles Associated With Incident Atrial Fibrillation in a Large Clinical Cohort.

BACKGROUND: While sleep disorders are implicated in atrial fibrillation (AF), the interplay of physiologic alterations and symptoms remains unclear. Sleep-based phenotypes can account for this complexity and translate to actionable approaches to identify at-risk patients and therapeutic interventions. OBJECTIVES: This study hypothesized discrete phenotypes of symptoms and polysomnography (PSG)-based data differ in relation to incident AF. METHODS: Data from the STARLIT (sleep Signals, Testing, And Reports LInked to patient Traits) registry on Cleveland Clinic patients (≥18 years of age) who underwent PSG from November 27, 2004, to December 30,2015, were retrospectively examined. Phenotypes were identified using latent class analysis of symptoms and PSG-based measures of sleep-disordered breathing and sleep architecture. Phenotypes were included as the primary predictor in a multivariable-adjusted Cox proportional hazard models for incident AF. RESULTS: In our cohort (N = 43,433, age 51.8 ± 14.5 years, 51.9% male, 74.9% White), 7.3% (n = 3,166) had baseline AF. Over a 7.6- ± 3.4-year follow-up period, 8.9% (n = 3,595) developed incident AF. Five phenotypes were identified. The hypoxia subtype (n = 3,245) had 48% increased incident AF (HR: 1.48; 95% CI: 1.34-1.64), the apneas + arousals subtype (n = 4,592) had 22% increased incident AF (HR: 1.22; 95% CI: 1.10-1.35), and the short sleep + nonrapid eye movement subtype (n = 6,126) had 11% increased incident AF (HR: 1.11; 95% CI: 1.01-1.22) compared with long sleep + rapid eye movement (n = 26,809), the reference group. The hypopneas subtype (n = 2,661) did not differ from reference (HR: 0.89; 95% CI: 0.77-1.03). CONCLUSIONS: Consistent with prior evidence supporting hypoxia as an AF driver and cardiac risk of the sleepy phenotype, this constellation of symptoms and physiologic alterations illustrates vulnerability for AF development, providing potential value in enhancing our understanding of integrated sleep-specific symptoms and physiologic risk of atrial arrhythmogenesis.

Intensive support does not improve positive-airway pressure use in spinal cord injury/disease: a randomized clinical trial.

STUDY OBJECTIVE: Treatment of sleep-disordered breathing (SDB) with positive airway pressure (PAP) therapy has unique clinical challenges in individuals living with spinal cord injuries and diseases (spinal cord injury [SCI]/D). Interventions focused on increasing PAP use have not been studied in this population. We aimed to evaluate the benefits of a program to increase PAP use among Veterans with SCI/D and SDB. METHODS: Randomized controlled trial comparing a behavioral Intervention (n = 32) and educational control (n = 31), both including one face-to-face and five telephone sessions over 3 months. The intervention included education about SDB and PAP, goal setting, troubleshooting, and motivational enhancement. The control arm included non-directive sleep education only. RESULTS: Primary outcomes were objective PAP use (nights ≥4 hours used within 90 days) and sleep quality (Pittsburgh Sleep Quality Index [PSQI] at 3 months). These did not differ between intervention and control (main outcome timepoint; mean difference 3.5 [-9.0, 15.9] nights/week for PAP use; p = .578; -1.1 [-2.8, 0.6] points for PSQI; p = .219). Secondary outcomes included fatigue, depression, function, and quality of life. Only fatigue improved significantly more in the intervention versus the control group (p = .025). Across groups, more PAP use was associated with larger improvements in sleep quality, insomnia, sleepiness, fatigue, and depression at some time points. CONCLUSIONS: PAP use in Veterans with SCI/D and SDB is low, and a 3-month supportive/behavioral program did not show significant benefit compared to education alone. Overall, more PAP use was associated with improved symptoms suggesting more intensive support, such as in-home assistance, may be required to increase PAP use in these patients. CLINICAL TRIALS INFORMATION: Title: "Treatment of Sleep Disordered Breathing in Patients with SCI." Registration number: NCT02830074. Website: https://clinicaltrials.gov/study/NCT02830074?cond=Sleep%20Apnea&term=badr&rank=5.

Improving Referral Patterns for Bronchoscopic Lung Volume Reduction: A Quality Improvement Initiative.

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment option for patients with severe emphysema and hyperinflation refractory to optimal medical care. This therapy is effective in improving functional status and quality of life, underscoring the importance of identifying potential procedure candidates. To our knowledge, scalable strategies to improve the referral of advanced lung disease patients are lacking. This quality improvement project aimed to increase identification and referral for BLVR in a large Veterans Affairs academic medical center. We show implementing case identification within a pulmonary function testing report, in conjunction with provider education, increased referral rates for BLVR. Because of the ubiquity of lung function testing, other advanced lung disease programs may consider adopting this strategy to improve patients' access to timely clinical evaluation and therapy.

Sleep-disordered Breathing and Inpatient Outcomes in Nonsurgical Patients: Analysis of the Nationwide Inpatient Cohort.

Rationale: Sleep-disordered breathing (SDB) is associated with increased complications and length of stay (LOS) after surgery. SDB-related adverse consequences for nonsurgical admissions are not well defined. Objectives: Evaluate associations between SDB and subtypes and LOS, cost, and mortality in nonsurgical patients. Methods: This retrospective cohort analysis used adult nonsurgical admissions from the 2017 National Inpatient Sample of the Healthcare Costs and Utilization Project. SDB associations with LOS (primary outcome), costs, and mortality were evaluated via logistic regression. Covariates included age, sex, Elixhauser Comorbidity Index, socioeconomic status, hospital type, and insurance type. Results: The cohort included 6,046,544 hospitalizations. Compared with those without SDB, patients with SDB were older (63.6 ± 13.5 vs. 57.4 ± 20.7 yr), higher proportion male (55.8% vs. 40.9%), and more likely to be White (75.7% vs. 66.5%). SDB was associated with increased odds of increased LOS and hospitalization costs (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.16-1.17 and OR, 1.67; 95% CI, 1.66-1.67 in adjusted analyses, respectively) but lower mortality (OR, 0.79; 95% CI, 0.77-0.81). The results for obstructive sleep apnea (OSA) echoed those for SDB. Obesity hypoventilation syndrome had substantially increased LOS (OR, 3.05; 95% CI, 2.98-3.13), mortality (1.76; 95% CI, 1.66-1.86), and costs (OR, 2.67; 95% CI, 2.60-2.73) even after adjustment. Conclusions: Obesity hypoventilation syndrome is associated with higher LOS, mortality, and costs during hospitalization, whereas OSA, despite higher LOS and costs, is associated with decreased mortality. Investigation is warranted on whether paradoxically higher costs but lower mortality in OSA may be indicative of less vigilance in hospitalized patients with undiagnosed SDB.

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

Racial Differences in Positive Airway Pressure Adherence in the Treatment of Sleep Apnea.

Although data are limited, studies suggest on average lower positive airway pressure use in Black, indigenous, and people of color (BIPOC) compared with Whites in most but not all studies. Most of these observational studies are certainly limited by confounding by socioeconomic status and other unmeasured factors that likely contribute to differences. The etiology of these observed disparities is likely multifactorial, due in part to financial limitations, differences in sleep opportunity, poor sleep quality due to environmental disruptions, and so forth. These disparities in sleep health are likely related to chronic inequities, including experiences of racism, neighborhood features, structural, and contextual factors. Dedicated studies focusing on understanding adherence in BIPOC are lacking. Further research is needed to understand determinants of PAP use in BIPOC subjects and identify feasible interventions to improve sleep health and reduce sleep apnea treatment disparities.

Sleep apnea screening instrument evaluation and novel model development and validation in the paroxysmal atrial fibrillation population.

Standard sleep apnea (SA) screening instruments perform suboptimally in the atrial fibrillation (AF) population. We evaluated and optimized common OSA screening tools in the AF population. Participants of the Sleep Apnea and Atrial Fibrillation Biomarkers and Electrophysiologic Atrial Triggers (SAFEBEAT, NCT02576587) age (±5 years)-, sex-, body mass index (BMI ± 5 kg/m2)-matched case control study (n = 150 each group) completed concurrent questionnaires and overnight polysomnography. Models based on STOP, STOP-BANG, Berlin, NoSAS and Epworth Sleepiness Scale and also models with STOP-BANG predictors with resting heart rate or left atrial volume were constructed. "Best subset" analysis was used to select a predictor subset for evaluation. We assessed test performance for two outcome thresholds: apnea-hypopnea index (AHI) ≥ 5 and AHI ≥ 15. Paroxysmal AF participants were: 61.3 ± 12.1 years, BMI = 31.2 ± 6.6 kg/m2 with median AHI = 11.8(IQR: 3.8, 24.5); 65 (43.3%) with AHI ≥ 15. Only STOP and STOP-BANG did not perform worse in AF relative to controls. For AHI ≥ 15, STOP-BANG (AUC 0.71, 95%CI:0.55-0.85) did not perform as well as NABS - a composite of neck circumference, age, and BMI as continuous variables and snoring (AUC 0.88, 95%CI:0.76-0.96). Optimal model for AHI ≥ 15 was NABS (sensitivity = 45%, specificity = 97%). For AHI ≥ 5, NABS was also the best performing (AUC 0.82, 95%CI:0.68-0.92, sensitivity = 78%, specificity = 67%). We identify a novel, short-item SA screening instrument for use in paroxysmal AF, i.e. NABS, with improved discriminative ability compared to commonly-used instruments. Further validation studies are needed to assess utility in other AF subtypes. Trial registration: clinicaltrials.gov NCT02576587.

Predictors of Intraprocedural Respiratory Bronchoscopy Complications.

PURPOSE: Sleep apnea can increase adverse outcomes during ambulatory surgery but not during gastrointestinal endoscopy. We hypothesize that STOP-BANG is associated with intraprocedural bronchoscopy respiratory complications. METHODS: Consecutive patients undergoing bronchoscopy under moderate sedation were prospectively administered the STOP-BANG questionnaire. Participants were assessed for intraprocedural complications including hypoxemia (oxygen saturation≤85%), bradypnea (respiratory rate<8), premature procedure cessation as well as the use of nonrebreather mask, bag-mask ventilation, jaw lift/chin tilt, nasal/oral airway, and naloxone administration. Associations were assessed via logistic regression. Least absolute shrinkage and selection operator was used for multivariable model variable selection. RESULTS: The 223 participants-mean age 61.1±15.5 years, body mass index 25.4kg/m (interquartile range: 22.4 to 30.7), 50.7% female, and 45.3% inpatient-had a high rate of respiratory complications (37.7%). There were no associations between STOP-BANG score and respiratory complications [odds ratio (OR)=1.07, 95% confidence interval (CI): 0.92-1.25]. Asthma was protective in univariable models (OR=0.26, 95% CI: 0.04-0.98), whereas endobronchial ultrasound (OR=2.34, 95% CI: 1.35-4.10) and the number of procedure types (OR=1.24, 95% CI: 1.01-1.51) was associated with increased complications. The following factors were associated with respiratory complications in both multivariable and univariate analyses: increasing age (OR=1.28/decade, 95% CI: 1.03-1.61), baseline oxygen use per each liters per minute (OR=1.57, 95% CI: 1.21-2.09), and bronchoscopy duration (OR=1.20/10 min, 95% CI: 1.08-1.33). CONCLUSION: Bronchoscopy respiratory complications are common. STOP-BANG was not associated with increased immediate bronchoscopy complication risk. Increasing age, oxygen use, and bronchoscopy duration were associated with respiratory complications; increased vigilance in these circumstances may prevent complications.

Sex-Specific Differential Responses of Circulating Biomarkers in Obstructive Sleep Apnea Treatment. A Post Hoc Analysis of a Randomized Controlled Trial.

Rationale: Knowledge of sex-specific changes of cardiovascular biomarkers in response to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) is limited.Objectives: We hypothesized a differential sex-specific cardiovascular biomarker response with CPAP therapy for OSA.Methods: Participants with moderate-severe OSA (apnea-hypopnea index, 15 events/h) were randomized to CPAP versus sham and completed polysomnography and collection of biomarkers of inflammation (myeloperoxidase, fibrinogen, paraoxonase, interleukin [IL]-6, IL-6 soluble receptor, aryl esterase, oxidized low-density lipoprotein, lipoprotein A, plasminogen activator inhibitor 1, and F2-isoprostane urine/creatinine ratio) and vascular measures at baseline and 8 weeks of therapy with either CPAP (n = 72) or sham treatment (n = 70). Post hoc secondary analyses of sex-study arm interaction relative to change in inflammatory biomarkers were evaluated via linear regression with adjustment for baseline biomarker value, age, race, body mass, index, waist circumference, and CPAP adherence. Interactions were further evaluated via sex-stratified analyses.Results: The study sample comprised a total of 149 participants aged 50.8 ± 11.7 years; 55% were male, and 55% were white. Participants had a median apnea-hypopnea index of 26.3 events per hour (interquartile range, 13-37). There were substantial interactions between study arm and sex for myeloperoxidase, paraoxonase, and fibrinogen (P = 0.03, P = 0.03, and P = 0.08, respectively). No significant interactions were found for the vascular measures. Estimates were similar but with decreased power in sex-stratified analyses, with decreased biomarkers in women and increased biomarkers in men.Conclusions: Differential sex-specific responses to CPAP therapy for OSA were observed for circulating inflammatory biomarkers, which persisted after adjustment for confounders. These findings set the stage for validation studies and, if confirmed, biochemical pathway elucidation to inform sex-specific personalized treatment approaches.Clinical trial registered with www.clinicaltrials.gov (NCT00607893).

Individual periodic limb movements with arousal are temporally associated with nonsustained ventricular tachycardia: a case-crossover analysis.

STUDY OBJECTIVES: Both periodic limb movements during sleep (PLMS) and arousals are associated with sympathetic nervous system activation and may be arrhythmogenic. We hypothesize a temporal relationship exists between individual PLMS, particularly with arousal, and nonsustained ventricular tachycardia (NSVT) events. METHODS: A bidirectional time-stratified case-crossover design was used to assess temporal associations between PLMS and NSVT during sleep in 49 Osteoporotic Fractures in Men Sleep Study participants with NSVT in a community-based cohort (n = 2,911). Sleep time was divided into approximate 30-min segments. For each NSVT (n = 141), we selected a preceding 30-s hazard period and three randomly chosen 30-s control periods from sleep within the same segment and evaluated for PLMS, respiratory events, minimum saturation, and arousals. Odds ratios and 95% confidence intervals-OR (95% CI)-were determined by conditional logistic regression; covariates included EEG arousals, minimum saturation, and respiratory events in the same hazard/control period. RESULTS: Participants with NSVT were 79.5 ± 6.2 years with a PLMS index of 32.1 (IQR: 10.1, 61.4) and apnea-hypopnea index of 17.1 (IQR: 9.4, 26.1). PLMS without arousal were not significantly associated with NSVT (OR = 0.80, 95% CI: 0.41-1.59). PLMS with arousal were associated with NSVT in unadjusted analyses (OR = 2.50, 95% CI: 1.11-5.65) and after adjustment (OR = 2.31, 95% CI: 1.02-5.25). Arousals associated with PLMS were associated with NSVT in unadjusted (OR = 2.84, 95% CI: 1.23-6.56) and adjusted analyses (OR = 2.61, 95% CI: 1.13-6.05). CONCLUSIONS: PLMS with (but not without) arousals are temporally associated with a greater than twofold higher odds of subsequent NSVT episodes. PLMS-related arousals may be physiologically important ventricular arrhythmia triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00070681.

CPAP Adherence Predictors in a Randomized Trial of Moderate-to-Severe OSA Enriched With Women and Minorities.

BACKGROUND: Suboptimal CPAP adherence in OSA clinical trials involving predominantly white men limits interpretability and generalizability. We examined predictors of CPAP adherence in a clinical trial enriched with minorities. METHODS: The Sleep Apnea Stress Study-a randomized, double-blind, sham-controlled trial of patients with moderate-to-severe OSA-included participants with complete 8-week adherence data (n = 138). Overnight 14-channel polysomnography, anthropometry, socioeconomic status, mood questionnaires, and week 1 CPAP adherence were analyzed via adjusted linear models relative to CPAP adherence (average minutes per night usage). RESULTS: Overall, age was 51 ± 12 years, 55% of the patients were male, 55% were white, BMI was 36.7 ± 7.7 kg/m2, and median apnea-hypopnea index was 20 (interquartile range, 13-37). In univariate analyses adherence increased with randomization to active CPAP (81 min; 95% CI, 30-132), increasing age (35 min/decade; 95% CI, 13-57), white race (78 min, 95% CI, 26-129), and per hour of week 1 adherence (41 min, 95% CI, 32-51). Active CPAP (48 min, 95% CI, 6-91), increasing age (27 min/decade, 95% CI, 10-44), and higher 1-week adherence (36 min/h, 95% CI, 27-46) were significantly associated with improved adherence in multivariable analyses. Subgroup analyses showed stronger associations of adherence with treatment arm in whites and increasing age in minorities. Increasing age and white race were more strongly associated with adherence in women. CONCLUSIONS: In this trial with near-even sex distribution and high ethnic minority representation, we identified CPAP assignment, increasing age, and early adherence to be associated with improved adherence in addition to sex-specific and race-specific adherence differences. These results can inform targeted clinical trial adherence optimization strategies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00607893; URL: www.clinicaltrials.gov.

A 15-Year-Old Boy with Mysterious Variability in Apnea-Hypopnea Index.

CASE PRESENTATION: A 15-year-old boy presented as a direct referral for polysomnography for evaluation of snoring, unrefreshing sleep, and daytime sleepiness despite a self-reported average of 8 hours of sleep a night. The mother reported he snored intermittently, although there were no witnessed apneic episodes or fragmented sleep. He denied morning headaches. He reported that his sleep was generally unrefreshing and he would experience significant daytime sleepiness, especially after school or when doing his homework. However, his Epworth Sleepiness Scale score was only 3 of 24. He denied any symptoms consistent with a movement disorder, parasomnia, cataplexy, hypnogogic/hypnopompic hallucinations, sleep paralysis, circadian rhythm disorders, or insomnia. He reported a family history of sleep apnea in his grandfather.

OSA and Cardiac Arrhythmogenesis: Mechanistic Insights.

A surge of data has reproducibly identified strong associations of OSA with cardiac arrhythmias. As an extension of epidemiologic and clinic-based findings, experimental investigations have made strides in advancing our understanding of the putative OSA and cardiac arrhythmogenesis mechanistic underpinnings. Although most studies have focused on the links between OSA and atrial fibrillation (AF), relationships with ventricular arrhythmias have also been characterized. Key findings implicate OSA-related autonomic nervous system fluctuations typified by enhanced parasympathetic activation during respiratory events and sympathetic surges subsequent to respiratory events, which contribute to augmented arrhythmic propensity. Other more immediate pathophysiologic influences of OSA-enhancing arrhythmogenesis include intermittent hypoxia, intrathoracic pressure swings leading to atrial stretch, and hypercapnia. Intermediate pathways by which OSA may trigger arrhythmia include increased systemic inflammation, oxidative stress, enhanced prothrombotic state, and vascular dysfunction. Long-term OSA-associated sequelae such as hypertension, atrial enlargement and fibrosis, ventricular hypertrophy, and coronary artery disease also predispose to cardiac arrhythmia. These factors can lead to a reduction in atrial effective refractory period, triggered and abnormal automaticity, and promote slowed and heterogeneous conduction; all of these mechanisms increase the persistence of reentrant arrhythmias and prolong the QT interval. Cardiac electrical and structural remodeling observed in OSA animal models can progress the arrhythmogenic substrate to further enhance arrhythmia generation. Future investigations clarifying the contribution of specific OSA-related mechanistic pathways to arrhythmia generation may allow targeted preventative therapies to mitigate OSA-induced arrhythmogenicity. Furthermore, interventional studies are needed to clarify the impact of OSA pathophysiology reversal on cardiac arrhythmogenesis and related adverse outcomes.

Longitudinal relationships of periodic limb movements during sleep and incident atrial fibrillation.

OBJECTIVES: This study aimed to examine relationship between periodic limb movements during sleep (PLMS) and incident atrial fibrillation/flutter (AF). METHODS: Prospective multicenter cohort (n = 2273: adjudicated AF group; n = 843: self-reported AF group) of community-dwelling men without prevalent AF were followed for an average of 8.3 years (adjudicated) and 6.5 years (self-reported). PLMS index (PLMI, <5 (ref), ≥5 to <30, ≥30) and PLM arousal index (PLMAI, <1 (ref), ≥1 to <5, ≥5) were measured by polysomnography. Incident adjudicated and self-reported AF were analyzed by Cox proportional hazards and logistic regression, respectively, and adjusted for age, clinic, race, body mass index (BMI), alcohol use, cholesterol level, cardiac medications, pacemaker, apnea-hypopnea index, renal function, and cardiac risk. The interaction of age and PLMS was examined. RESULTS: In this primarily Caucasian (89.8%) cohort of older men (mean age 76.1 ± 5.5 years) with BMI of 27.2 ± 3.7, there were 261 cases (11.5%) of adjudicated and 85 cases (10.1%) of self-reported incident AF. In the overall cohort, PLMI and PLMAI were not associated with adjudicated or self-reported AF. There was some evidence of an interaction of age and PLMI (p = 0.08, adjudicated AF) and PLMAI (p ≤ 0.06, both outcomes). Among men aged ≥76 years, the highest PLMI tertile was at increased risk of adjudicated AF (≥30 vs. <5; hazard ratio (HR) = 1.63, 1.01-2.63) and the middle PLMAI tertile predicted increased risk of both outcomes (1 to <5 vs. <1; adjudicated, HR = 1.65, 1.05-2.58; self-reported HR = 5.76, 1.76-18.84). No such associations were found in men aged <76 years. CONCLUSIONS: Although PLMS do not predict AF incidence in the overall cohort, the findings suggest PLMS increases incident AF risk in the older subgroup.

Central Sleep-disordered Breathing Predicts Incident Atrial Fibrillation in Older Men.

RATIONALE: Although research supports a sleep-disordered breathing and atrial fibrillation association, prospective data examining sleep-disordered breathing predicting incident atrial fibrillation are lacking. OBJECTIVES: To investigate sleep-disordered breathing indices as predictors of incident atrial fibrillation. METHODS: A cohort (n = 843) of ambulatory older men without prevalent atrial fibrillation was assessed for baseline sleep indices: apnea-hypopnea index, central sleep apnea (central apnea index, ≥5 vs. <5), central sleep apnea or Cheyne-Stokes respiration, obstructive apnea-hypopnea index, and percentage of sleep time with less than 90% oxygen saturation. Incident clinically symptomatic adjudicated or self-reported atrial fibrillation outcome was ascertained (mean follow-up, 6.5 ± 0.7 yr). We used logistic regression models adjusted for age, race, body mass index, cardiopulmonary disease, alcohol use, pacemaker, cholesterol, cardiac medications, and alternate apnea type for obstructive and central apnea. Age interaction terms and median age-stratified analyses were performed. MEASUREMENTS AND MAIN RESULTS: Central sleep apnea (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.18-5.66) and Cheyne-Stokes respiration with central sleep apnea (OR, 2.27; 95% CI, 1.13-4.56), but not obstructive apnea or hypoxemia, predicted incident atrial fibrillation. Central apnea, Cheyne-Stokes respiration, and sleep-disordered breathing-age interaction terms were significant (P < 0.05). Unlike the case with younger participants, among participants aged 76 years or older (albeit with small atrial fibrillation counts), atrial fibrillation was related to central apnea (OR, 9.97; 95% CI, 2.72-36.50), Cheyne-Stokes respiration with central apnea (OR, 6.31; 95% CI, 1.94-20.51), and apnea-hypopnea index (OR, 1.22; 95% CI, 1.08-1.39 [per 5-unit increase]). CONCLUSIONS: In older men, central apnea and Cheyne-Stokes respiration predicted increased atrial fibrillation risk, with findings being strongest in older participants in whom overall sleep-disordered breathing also increased atrial fibrillation risk.

Obstructive sleep apnea: role of intermittent hypoxia and inflammation.

Obstructive sleep apnea results in intermittent hypoxia via repetitive upper airway obstruction leading to partial or complete upper airway closure, apneas and hypopneas, respectively. Intermittent hypoxia leads to sympathetic nervous system activation and oxidative stress with a resultant systemic inflammatory cascade. The putative mechanism by which obstructive sleep apnea has been linked to numerous pathologic conditions including stoke, cardiovascular disease, hypertension, and metabolic derangements is through these systemic effects. Treatment of obstructive sleep apnea appears to reduce systemic markers of inflammation and ameliorates the adverse sequelae of this disease.