Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Sleep Patterns and Obesity: Hispanic Community Health Study/Study of Latinos Sueño Ancillar Study.

BACKGROUND: The relationship of poor sleep patterns to the increased risk of obesity has been reported, but the results are variable. This study evaluated the association between objectively measured sleep patterns and obesity in a representative adult population of Hispanic/Latino subjects living in the United States. METHODS: This cross-sectional study was an analysis of a multicenter, community-based cohort of 2,156 participants aged 18 to 64 years from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Recruitment was conducted in San Diego, California; Chicago, Illinois; Bronx, New York; and Miami, Florida. Models were controlled for age, sex, ethnic background, site, income, education, and apnea-hypopnea index. Seven days of wrist actigraphy data were collected. Obesity was defined as BMI ≥ 30 kg/m2, and abdominal obesity was defined as waist circumference ≥ 88 cm in women and ≥ 102 cm in men. Napping was defined as more than one 15-min nap per week. RESULTS: An inverse linear relationship was found between sleep duration and prevalence of obesity (P linear trend ≤ 0.01). A reduction of 1 h sleep increased obesity prevalence by 4.1% (95% CI, 1.6-6.6; P = .002) and abdominal obesity prevalence by 3.6% (95% CI, 1.1-6.1; P = .007). Daytime napping increased obesity prevalence by 10.4% (95% CI, 3.5-17.3; P = .004) and abdominal obesity prevalence by 7.1% (95% CI, 1.0-13.2; P = .02). CONCLUSIONS: In a population of young to older adult Hispanic/Latino subjects, we found an inverse linear association between sleep duration and the prevalence of obesity. Daytime napping was strongly associated with greater adiposity. Interventional and longitudinal studies are needed to better understand how abnormal sleep patterns contribute to the obesity epidemic.

Sleep Timing, Stability, and BP in the Sueño Ancillary Study of the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Timing and stability of the sleep-wake cycle are potential modifiable risk factors for cardiometabolic disease. The aim of this study was to evaluate the relationship between objective measures of sleep-wake timing and stability with cardiometabolic disease risk. METHODS: In this multicenter, cross-sectional, population-based study, actigraphy data were obtained from the 2,156 adults, aged 18 to 64 years, recruited from the Sueño ancillary study of the Hispanic Community Health Study/Study of Latinos (2010-2013). These data were correlated with measures of cardiometabolic disease risk, including systolic and diastolic BPs, homeostatic assessment of insulin resistance, glycosylated hemoglobin, BMI, and hypertension and diabetes status. RESULTS: Each 10% decrease in interdaily stability was associated with a 3.0% absolute increase in the prevalence of hypertension (95% CI, 0.6-5.3; P < .05), an increase in systolic BP by 0.78 mm Hg (95% CI, 0.12-1.45; P < .05) and an increase in diastolic BP by 0.80 mm Hg (95% CI, 0.28-1.32; P < .05). In addition, delaying the midpoint of sleep by 1 h was associated with an increase in systolic BP by 0.73 mm Hg (95% CI, 0.30-1.16; P < .01) and diastolic BP by 0.53 mm Hg (95% CI, 0.17-0.90; P < .01). These associations were not significant after adjusting for shift work status. No association was found between interdaily stability or sleep timing and diabetes, BMI, or insulin resistance. CONCLUSIONS: These results suggest that beyond sleep duration, the timing and regularity of sleep-wake schedules are related to hypertension prevalence and BP.

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans.

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2 < 90%] and a secondary trait (respiratory event duration) in a Hispanic/Latino American population study of 11 575 individuals with significant variation in ancestral background. Linear mixed models were performed using previously inferred African, European and Amerindian local genetic ancestry markers. Global African ancestry was associated with a lower AHI, higher SaO2 and shorter event duration. Admixture mapping analysis of the primary OSA traits identified local African ancestry at the chromosomal region 2q37 as genome-wide significantly associated with AHI (P < 5.7 × 10-5), and European and Amerindian ancestries at 18q21 suggestively associated with both AHI and percentage time SaO2 < 90% (P < 10-3). Follow-up joint ancestry-SNP association analyses identified novel variants in ferrochelatase (FECH), significantly associated with AHI and percentage time SaO2 < 90% after adjusting for multiple tests (P < 8 × 10-6). These signals contributed to the admixture mapping associations and were replicated in independent cohorts. In this first admixture mapping study of OSA, novel associations with variants in the iron/heme metabolism pathway suggest a role for iron in influencing respiratory traits underlying OSA.

Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

Sleep Patterns and Hypertension Using Actigraphy in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: The aim of this study was to evaluate the association between actigraphy-based measures of sleep and prevalent hypertension in a sample of US Latinos. METHODS: We analyzed data from 2,148 participants of the Sueño Sleep Ancillary Study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), who underwent 1 week of wrist actigraphy to characterize sleep duration, sleep efficiency, sleep fragmentation index, and daytime naps. Insomnia was defined as an Insomnia Severity Index ≥ 15. Hypertension was defined based on self-reported physician diagnosis. Survey linear regression was used to evaluate the association of sleep measures with hypertension prevalence. Sensitivity analyses excluded participants with an apnea-hypopnea index (AHI) ≥ 15 events/h. RESULTS: The mean age was 46.3 ± 11.6 years, and 65% of the sample consisted of women. The mean sleep duration was 6.7 ± 1.1 hours. Thirty-two percent of the sample had hypertension. After adjusting for age, sex, ethnic background, site, and AHI, each 10% reduction in sleep efficiency was associated with a 7.5% (95% CI, -12.9 to -2.2; P = .0061) greater hypertension prevalence, each 10% increase in sleep fragmentation index was associated with a 5.2% (95% CI, 1.4-8.9; P = .0071) greater hypertension prevalence, and frequent napping was associated with a 11.6% greater hypertension prevalence (95% CI, 5.5-17.7; P = .0002). In contrast, actigraphy-defined sleep duration (P = .20) and insomnia (P = .17) were not associated with hypertension. These findings persisted after excluding participants with an AHI ≥ 15 events/h. CONCLUSIONS: Independent of sleep-disordered breathing, we observed associations between reduced sleep continuity and daytime napping, but not short sleep duration, and prevalent hypertension.

Actigraphic Sleep Patterns of U.S. Hispanics: The Hispanic Community Health Study/Study of Latinos.

Study objective: To assess the extent to which objective sleep patterns vary among U.S. Hispanics/Latinos. Methods: We assessed objective sleep patterns in 2087 participants of the Hispanic Community Health Study/Study of Latinos from 6 Hispanic/Latino subgroups aged 18-64 years who underwent 7 days of wrist actigraphy. Results: The age- and sex-standardized mean (SE) sleep duration was 6.82 (0.05), 6.72 (0.07), 6.61 (0.07), 6.59 (0.06), 6.57 (0.10), and 6.44 (0.09) hr among individuals of Mexican, Cuban, Dominican, Central American, Puerto Rican, and South American heritage, respectively. Sleep maintenance efficiency ranged from 89.2 (0.2)% in Mexicans to 86.5 (0.4)% in Puerto Ricans, while the sleep fragmentation index ranged from 19.7 (0.3)% in Mexicans to 24.2 (0.7)% in Puerto Ricans. In multivariable models adjusted for age, sex, season, socioeconomic status, lifestyle habits, and comorbidities, these differences persisted. Conclusions: There are important differences in actigraphically measured sleep across U.S. Hispanic/Latino heritages. Individuals of Mexican heritage have longer and more consolidated sleep, while those of Puerto Rican heritage have shorter and more fragmented sleep. These differences may have clinically important effects on health outcomes.

Association Between Sleep Timing, Obesity, Diabetes: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Cohort Study.

Study Objectives: Recent studies implicate inadequate sleep duration and quality in metabolic disease. Fewer studies have examined the timing of sleep, which may be important because of its potential impact on circadian rhythms of metabolic function. We examined the association between sleep timing and metabolic risk among Hispanic/Latino adults. Methods: Cross-sectional data from community-based study of 13429 participants aged 18-74 years. People taking diabetic medications were excluded. Sleep timing was determined from self-reported bedtimes and wake times. Chronotype was defined as the midpoint of sleep on weekends adjusted for sleep duration on weekdays. Other measurements included body mass index (BMI), fasting glucose levels, estimated insulin resistance (HOMA-IR), glucose levels 2 hours post oral glucose ingestion, and hemoglobin A1c. Survey linear regression models tested associations between sleep timing and metabolic measures. Analyses were stratified by diabetes status and age-group when significant interactions were observed. Results: Among participants with diabetes, fasting glucose levels were positively associated with bedtime (approximately +3%/hour later, p < .01) and midpoint of sleep (approximately +2%/hour later, p < .05). In participants with and without diabetes combined, HOMA-IR was positively associated with midpoint of sleep (+1.5%/hr later, p < .05), and chronotype (+1.2%/hour later, p < .05). Associations differed by age-group. Among those < 36 years, later sleep timing was associated with lower BMI, lower fasting glucose, and lower HbA1c, but the opposite association was observed among older participants. Conclusions: Later sleep timing was associated with higher estimated insulin resistance across all groups. Some associations between sleep timing and metabolic measures may be age-dependent.

Obstructive Sleep Apnea and Cognition in Parkinson's disease.

OBJECTIVE: Obstructive sleep apnea (OSA) is very common in Parkinson's disease (PD). OSA is known to affect patients' cognition. The present study assessed whether PD patients with OSA (PD + OSA) score lower on cognitive measures than those without OSA (PD - OSA). In addition, this study evaluated whether treating the OSA with continuous positive airway pressure (CPAP) in PD + OSA patients results in an improved cognitive functioning. METHODS: Eighty-six patients with PD underwent an overnight polysomnography screen for OSA and were administered the Mini-Mental Status Exam (MMSE) and the Montreal Cognitive Assessment (MoCA). This resulted in 38 patients with PD + OSA who were randomly assigned to receive either therapeutic CPAP for 6 weeks (n = 19) or placebo CPAP for three weeks followed by therapeutic CPAP for three weeks (n = 19). Intervention participants completed a neurocognitive battery at baseline and 3- and 6-week time-points. RESULTS: Patients with PD + OSA scored significantly lower than PD - OSA on the MMSE and MoCA after controlling for age, education, and PD severity. OSA was a significant predictor of cognition (MMSE p <0.01; MoCA p = 0.028).There were no significant changes between groups in cognition when comparing three weeks of therapeutic CPAP with 3 weeks of placebo CPAP. Comparisons between pre-treatment and 3-week post-therapeutic CPAP for the entire sample also revealed no significant changes on overall neuropsychological (NP) scores. CONCLUSIONS: Findings suggest that PD patients with OSA show worse cognitive functioning on cognitive screening measures than those without OSA. However, OSA treatment after three or six weeks of CPAP may not result in overall cognitive improvement in patients with PD.

Comparison of Self-Reported Sleep Duration With Actigraphy: Results From the Hispanic Community Health Study/Study of Latinos Sueño Ancillary Study.

Most studies of sleep and health outcomes rely on self-reported sleep duration, although correlation with objective measures is poor. In this study, we defined sociodemographic and sleep characteristics associated with misreporting and assessed whether accounting for these factors better explains variation in objective sleep duration among 2,086 participants in the Hispanic Community Health Study/Study of Latinos who completed more than 5 nights of wrist actigraphy and reported habitual bed/wake times from 2010 to 2013. Using linear regression, we examined self-report as a predictor of actigraphy-assessed sleep duration. Mean amount of time spent asleep was 7.85 (standard deviation, 1.12) hours by self-report and 6.74 (standard deviation, 1.02) hours by actigraphy; correlation between them was 0.43. For each additional hour of self-reported sleep, actigraphy time spent asleep increased by 20 minutes (95% confidence interval: 19, 22). Correlations between self-reported and actigraphy-assessed time spent asleep were lower with male sex, younger age, sleep efficiency <85%, and night-to-night variability in sleep duration ≥1.5 hours. Adding sociodemographic and sleep factors to self-reports increased the proportion of variance explained in actigraphy-assessed sleep slightly (18%-32%). In this large validation study including Hispanics/Latinos, we demonstrated a moderate correlation between self-reported and actigraphy-assessed time spent asleep. The performance of self-reports varied by demographic and sleep measures but not by Hispanic subgroup.

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.

RATIONALE: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability. OBJECTIVES: To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts. METHODS: Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration. MEASUREMENTS AND MAIN RESULTS: Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10-8 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10-8 for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10-7). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility. CONCLUSIONS: These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.

Sex-Specific Prediction Models for Sleep Apnea From the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: We developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects. METHODS: Cross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea-hypopnea index ≥ 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex × covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered. RESULTS: A total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea index ≥ 15 events per hour) was 6.1% in female subjects and 13.5% in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie, age, BMI, self-reported snoring). The sex-interaction model (C statistic, 0.836) contained sex, age, age × sex, BMI, BMI × sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SA risk calculator: one in English (https://www.montefiore.org/sleepapneariskcalc.html) and another in Spanish (http://www.montefiore.org/sleepapneariskcalc-es.html). CONCLUSIONS: We created an internally validated, highly discriminating, well-calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects.

Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos.

RATIONALE: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. OBJECTIVES: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. METHODS: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. MEASUREMENTS AND MAIN RESULTS: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. CONCLUSIONS: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

High Prevalence of Obstructive Sleep Apnea in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease.

RATIONALE: When obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in the so-called "overlap" syndrome, a high risk for mortality and morbidity has been reported. There is controversy about the prevalence of OSA in people affected by COPD. OBJECTIVES: The purpose of this study was to investigate objective meaures of sleep-disordered breathing in patients with moderate to severe COPD to test the hypothesis that COPD is associated with an increased prevalence of OSA. METHODS: Fifty-four patients (54% men) with moderate to severe COPD were enrolled prospectively (mean ± SD, FEV1 = 42.8 ± 19.8% predicted, and FEV1/FVC = 42.3 ± 13.1). Twenty patients (37%) were on supplemental oxygen at baseline. Exercise tolerance; questionnaires related to symptoms, sleep, and quality of life; and home polysomnography were obtained. MEASUREMENTS AND MAIN RESULTS: Forty-four patients had full polysomnography suitable for analysis. OSA (apnea-hypopnea index > 5/h) was present in 29 subjects (65.9%). Sleep efficiency was poor in 45% of subjects. CONCLUSIONS: OSA is highly prevalent in patients with moderate to severe COPD referred to pulmonary rehabilitation. Sleep quality is also poor among this selected group. These patients have greater-than-expected sleep-disordered breathing, which could be an important contributory factor to morbidity and mortality. Pulmonary rehabilitation programs should consider including a sleep assessment in patients with moderate to severe COPD and interventions when indicated to help reduce the impact of OSA in COPD.

Reproducibility of a Standardized Actigraphy Scoring Algorithm for Sleep in a US Hispanic/Latino Population.

STUDY OBJECTIVES: While actigraphy is considered objective, the process of setting rest intervals to calculate sleep variables is subjective. We sought to evaluate the reproducibility of actigraphy-derived measures of sleep using a standardized algorithm for setting rest intervals. DESIGN: Observational study. SETTING: Community-based. PARTICIPANTS: A random sample of 50 adults aged 18-64 years free of severe sleep apnea participating in the Sueño sleep ancillary study to the Hispanic Community Health Study/Study of Latinos. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants underwent 7 days of continuous wrist actigraphy and completed daily sleep diaries. Studies were scored twice by each of two scorers. Rest intervals were set using a standardized hierarchical approach based on event marker, diary, light, and activity data. Sleep/wake status was then determined for each 30-sec epoch using a validated algorithm, and this was used to generate 11 variables: mean nightly sleep duration, nap duration, 24-h sleep duration, sleep latency, sleep maintenance efficiency, sleep fragmentation index, sleep onset time, sleep offset time, sleep midpoint time, standard deviation of sleep duration, and standard deviation of sleep midpoint. Intra-scorer intraclass correlation coefficients (ICCs) were high, ranging from 0.911 to 0.995 across all 11 variables. Similarly, inter-scorer ICCs were high, also ranging from 0.911 to 0.995, and mean inter-scorer differences were small. Bland-Altman plots did not reveal any systematic disagreement in scoring. CONCLUSIONS: With use of a standardized algorithm to set rest intervals, scoring of actigraphy for the purpose of generating a wide array of sleep variables is highly reproducible.

Periodontitis and Sleep Disordered Breathing in the Hispanic Community Health Study/Study of Latinos.

STUDY OBJECTIVES: To investigate the association between sleep disordered breathing (SDB) and severe chronic periodontitis. DESIGN: Cross-sectional data analysis from the Hispanic Community Health Study/Study of Latinos. SETTING: Community-based setting with probability sampling from four urban US communities. PARTICIPANTS: 12,469 adults aged 18-74 y. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Severe chronic periodontitis was defined using the Centers for Disease Control and Prevention/American Academy of Periodontology case classification based on full-mouth periodontal assessments performed by calibrated dentists. SDB was evaluated in standardized home sleep tests, and defined as the number of apnea plus hypopnea events associated with ≥ 3% desaturation, per hour of estimated sleep. SDB was quantified using categories of the apnea-hypopnea index (AHI): 0.0 events (nonapneic); 0.1-4.9 (subclinical); 5.0-14.9 (mild); and ≥ 15 (moderate/severe). Covariates were demographic characteristics and established periodontitis risk factors. C-reactive protein was a potential explanatory variable. Using survey estimation, multivariable binary logistic regression estimated odds ratios (OR) and 95% confidence limits (CL). Following adjustment for confounding, the SDB and periodontitis relationship remained statistically significant, but was attenuated in strength and no longer dose-response. Compared with the nonapneic referent, adjusted odds of severe periodontitis were 40% higher with subclinical SDB (OR = 1.4, 95% CL: 1.0, 1.9), 60% higher with mild SDB (OR = 1.6, 95% CL: 1.1, 2.2) and 50% higher with moderate/severe SDB (OR = 1.5, 95% CL: 1.0, 2.3) demonstrating an independent association between SDB and severe periodontitis. CONCLUSIONS: This study identifies a novel association between mild sleep disordered breathing and periodontitis that was most pronounced in young adults.

Obstructive sleep apnea and neurocognitive function in a Hispanic/Latino population.

OBJECTIVE: We evaluated the association between obstructive sleep apnea (OSA) and neurocognitive function among community-dwelling Hispanic/Latino individuals in the United States. METHODS: Cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos middle-aged and older adults, aged 45 to 74 years, with neurocognitive test scores at baseline measurements from 2008 to 2011. Neurocognitive scores were measured using the Word Fluency (WF) Test, the Brief-Spanish English Verbal Learning Test (SEVLT), and the Digit Symbol Substitution (DSS) Test. OSA was defined by the apnea-hypopnea index (AHI). Multivariable linear regression models were fit to evaluate relations between OSA and neurocognitive scores. RESULTS: The analysis consisted of 8,059 participants, mean age of 56 years, 55% women, and 41% with less than high school education. The mean AHI was 9.0 (range 0-142; normal AHI <5/h). There was an association between the AHI and all 4 neurocognitive test scores: Brief-SEVLT-sum (ß = -0.022) and -recall (ß = -0.010), WF (ß = -0.023), and DSS (ß = -0.050) at p < 0.01 that was fully attenuated by age. In the fully adjusted regression model, female sex was a moderating factor between the AHI and WF (ß = -0.027, p < 0.10), SVELT-sum (ß = -0.37), SVELT-recall (ß = -0.010), and DSS (ß = -0.061) at p < 0.01. CONCLUSION: OSA was associated with worse neurocognitive function in a representative sample of Hispanic/Latino women in the United States.

Parkinson's disease and REM sleep behavior disorder result in increased non-motor symptoms.

OBJECTIVE: Rapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinson's disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD. METHODS: A total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD. RESULTS: Among the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p=0.01). The RBD group reported more NMS of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and overall NMS (p=0.002). CONCLUSION: In PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation.

Continuous positive airway pressure improves sleep and daytime sleepiness in patients with Parkinson disease and sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA), common in Parkinson disease (PD), contributes to sleep disturbances and daytime sleepiness. We assessed the effect of continuous positive airway pressure (CPAP) on OSA, sleep, and daytime sleepiness in patients with PD. DESIGN: This was a randomized placebo-controlled, crossover design. Patients with PD and OSA were randomized into 6 w of therapeutic treatment or 3 w of placebo followed by 3 w of therapeutic treatment. Patients were evaluated by polysomnography (PSG) and multiple sleep latency test (MSLT) pretreatment (baseline), after 3 w, and after 6 w of CPAP treatment. Analyses included mixed models, paired analysis, and within-group analyses comparing 3 w to 6 w of treatment. SETTING: Sleep laboratory. PARTICIPANTS: Thirty-eight patients with PD (mean age = 67.2 ± 9.2 y; 12 females). INTERVENTION: Continuous positive airway pressure. MEASUREMENTS: PSG OUTCOME MEASURES: sleep efficiency, %sleep stages (N1, N2, N3, R), arousal index, apnea-hypopnea index (AHI), and % time oxygen saturation < 90% (%time SaO2 < 90%). MSLT outcome measures: mean sleep-onset latency (MSL). RESULTS: There were significant group-by-time interactions for AHI (P < 0.001), % time SaO2 < 90% (P = 0.02), %N2 (P = 0.015) and %N3 (P = 0.014). Subjects receiving therapeutic CPAP showed significant decrease in AHI, %time SaO2 < 90%, %N2, and significant increase in %N3 indicating effectiveness of CPAP in the treatment of OSA, improvement in nighttime oxygenation, and in deepening sleep. The paired sample analyses revealed that 3 w of therapeutic treatment resulted in significant decreases in arousal index (t = 3.4, P = 0.002). All improvements after 3 w were maintained at 6 w. Finally, 3 w of therapeutic CPAP also resulted in overall decreases in daytime sleepiness (P = 0.011). CONCLUSIONS: Therapeutic continuous positive airway pressure versus placebo was effective in reducing apnea events, improving oxygen saturation, and deepening sleep in patients with Parkinson disease and obstructive sleep apnea. Additionally, arousal index was reduced and effects were maintained at 6 weeks. Finally, 3 weeks of continuous positive airway pressure treatment resulted in reduced daytime sleepiness measured by multiple sleep latency test. These results emphasize the importance of identifying and treating obstructive sleep apnea in patients with Parkinson disease.

Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep.

Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.