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.

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.

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.

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.

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.

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.

Characterizing Fatigue: The Effects of Ethnicity and Acculturation.

It is unknown if fatigue measures like the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF; Stein, Jacobsen, Blanchard, & Thors, 2004) appropriately describe fatigue in Hispanics or if acculturation plays a role in fatigue. This study compared fatigue in community samples of Hispanics and Anglos. The MFSI-SF and pertinent questionnaires were administered to adults in San Diego County via telephone survey. Some differences in fatigue were observed in initial comparisons between Hispanics and Anglos, including when acculturation was considered. When age and education were controlled, Hispanics reported less general fatigue than Anglos, regardless of acculturation status, p = < .01. Exploratory factor analyses indicate that the MFSI-SF general-fatigue subscale was problematic for Hispanics. Implications, limitations, and future directions are discussed.

The obesity-hypoventilation syndrome and respiratory failure in the acute trauma patient.

BACKGROUND: The Emergency Department experience, for many patients, involves procedures and therapies that can compromise ventilation. In the acute trauma patient, these include spinal immobilization, supine positioning, and the administration of sedative and analgesic medications. Patients with the obesity-hypoventilation syndrome have a syndrome distinct from mere obesity, and are more sensitive to these insults. OBJECTIVE: To describe a case of respiratory failure in a patient with the obesity-hypoventilation syndrome resulting from injuries and therapies that in any other patient would not be expected to cause respiratory failure. CASE REPORT: A 59-year-old woman suffered a mechanical fall, fractured her T6 vertebral body and right proximal humerus, and, after spinal immobilization and the administration of routine doses of opioid analgesics, suffered significant hypoxemia and respiratory acidosis. Reversal agents were ineffective, but non-invasive mechanical ventilation restored adequate respiration. CONCLUSION: Although obesity-hypoventilation syndrome occurs in only a minority of morbidly obese patients, it is important because the consequences of respiratory failure can be severe if not recognized and anticipated. Such patients will not be able to adequately increase ventilation in response to mounting hypercapnia. The condition is easily addressed through non-invasive ventilation.

A Model for Studying Neuropsychological Effects of Sleep Intervention: The Effect of 3-week Continuous Positive Airway Pressure Treatment.

PURPOSE: Patients with obstructive sleep apnea (OSA) commonly have cognitive complaints. There are few randomized studies that have examined neuropsychological effects of continuous positive airway pressure (CPAP) treatment in patients with OSA. In this double-blind trial, we examined if a 3-week CPAP treatment compared with placebo CPAP treatment has specific therapeutic effects on cognitive impairments in patients with OSA and if there are specific domains of cognitive impairments sensitive to 3-week CPAP treatment. SUBJECTS AND METHODS: Thirty-eight newly diagnosed patients with untreated OSA underwent neuropsychological testing before and after 3-weeks CPAP or Placebo CPAP treatment. The two treatment groups (therapeutic CPAP, and placebo-CPAP) were compared using repeated measures analysis of variance (ANOVA). RESULTS AND CONCLUSION: Impairments in neuropsychological functioning ranged from 2.6% to 47.1% before treatment. In response to 3 weeks of treatment, there was no significant time by treatment interaction for a global deficit score of neuropsychological functioning. Only the Stroop Color (number correct) test showed significant improvement specific to CPAP treatment. The study demonstrates the importance of further randomized placebo controlled studies in this area.

Sleep health in U.S. Hispanic population.

The importance of sleep on health has only been recently recognized, and the general public and the medical community are not yet fully knowledgeable about this issue. The great majority of sleep research has been performed in whites of European descent and to a lesser extent in African Americans, making generalization of the findings to other ethnic and racial groups difficult. Very little sleep research has been done in U.S. Hispanics. However, based on the available literature and the high prevalence of risk factors in Hispanics, such as obesity, diabetes, living in the inner city, and use of alcohol, the prevalence of such important sleep disorders such as obstructive sleep apnea and sleep habits such as poor sleep hygiene are suspected to be high. There is also some evidence that acculturation to the U.S. life style may lead to worse sleep habits in Hispanics, including fewer hours of sleep. Two current large NIH sponsored studies of sleep in U.S. Hispanics promise to significantly add to the literature on various sleep disorders such as sleep disordered breathing, insomnia, restless legs syndrome, periodic limb movement disorder, and sleep habits such as short sleep duration and sleep hygiene.

Day/Night rhythm of hemostatic factors in obstructive sleep apnea.

STUDY OBJECTIVES: To investigate the hypothesis that day/night patterns of prothrombotic activity differ between patients with obstructive sleep apnea (OSA) and individuals with no OSA. DESIGN: Prothrombotic markers' day/night rhythms recorded over one 24-h period. SETTING: General clinical research center. PATIENTS: 38 untreated OSA patients as verified by polysomnography (apnea-hypopnea index > or = 10/h sleep) and 22 non-OSA controls. MEASUREMENTS AND RESULTS: Blood samples were collected every 2 h to measure plasma levels of fibrinolysis-inhibiting plasminogen activator inhibitor (PAI)-1 and the primary fibrin degradation product D-dimer. Day/night variation in hemostasis factors was examined using a cosinor analysis. Mesor (mean) PAI-1 over the 24-h period was higher (P = 0.015), and mesor of D-dimer was lower (P = 0.001) in patients with OSA than in the non-OSA controls. These group differences stayed significant when controlling for age and gender. After further adjustment for body mass index, mean arterial pressure, and smoking, the relationship between OSA and PAI-1 became non-significant, but the relationship between OSA and D-dimer continued to be significant (P = 0.006). In the fully adjusted analysis, the amplitude (peak) for D-dimer was lower in OSA patients than in non-OSA controls (P = 0.048). The acrophase (time of the peak) for PAI-1 and D-dimer did not significantly differ between groups. CONCLUSIONS: The relatively higher average level of PAI-1 and lower average level of D-dimer across the 24-h in OSA patients might reflect decreased fibrinolytic capacity and fibrin degradation, respectively. The findings provide some evidence for a prothrombotic state in OSA, but were only partially independent of metabolic variables.

Arousal frequency is associated with increased fatigue in obstructive sleep apnea.

OBJECTIVE: Fatigue is an important and often underemphasized symptom in patients with obstructive sleep apnea (OSA). Sleep fragmentation, i.e., arousals and disruptions in sleep architecture, is common in patients with OSA and may potentially contribute to their fatigue. We hypothesized that arousal frequency and changes in sleep architecture contribute to the fatigue experienced by patients with OSA. DESIGN: Seventy-three patients with diagnosed but untreated OSA (AHI > or = 15) were enrolled in this study. A baseline polysomnogram was obtained, and fatigue was measured with the Multidimensional Fatigue Symptom Inventory-short form (MFSI-sf). We evaluated the association between fatigue and arousals and various polysomongraphic variables, including sleep stages and sleep efficiency. RESULTS: Significant correlations between MFSI-sf subscale scores and various arousal indices were noted. Emotional fatigue scores were associated with total arousal index (r = 0.416, p = .021), respiratory movement arousal index (r = 0.346, p = .025), and spontaneous movement arousal index (r = 0.378, p = .025). Physical fatigue scores were associated with total arousal index (r = 0.360, p = .033) and respiratory movement arousal index (r = 0.304, p = .040). Percent of stage 1 sleep and REM sleep were also associated with physical and emotional fatigue scores. Hierarchal linear regression analysis demonstrated that emotional fatigue scores were independently associated with spontaneous movement arousals after controlling for age, body mass index, depression, and sleep apnea severity. CONCLUSIONS: These findings suggest that arousals may contribute to the fatigue seen in patients with OSA.

The roles of TNF-alpha and the soluble TNF receptor I on sleep architecture in OSA.

OBJECTIVE: Patients with obstructive sleep apnea (OSA) have been described to have increased levels of inflammatory cytokines (particularly TNF-alpha) and have severely disturbed sleep architecture. Serum inflammatory markers, even in normal individuals, have been associated with abnormal sleep architecture. Not much is known about the role the TNF receptor plays in the inflammation of OSA nor if it is associated with changes in sleep architecture or arousals during the night. We hypothesized that the TNF receptor might play an important role in the inflammation as well as sleep architecture changes in patients with OSA. DESIGN: Thirty-six patients with diagnosed (AHI > 15) but untreated OSA were enrolled in this study. Baseline polysomnograms as well as TNF-alpha and soluble TNF receptor I (sTNF-RI) serum levels were obtained on all patients. We evaluated the association between serum levels of TNF-alpha and sTNF-RI with various polysomongraphic characteristics, including sleep stages and EEG arousals. RESULTS: sTNF-RI levels were significantly correlated with snore arousals (r value 0.449, p value 0.009), spontaneous movement arousals (r value 0.378, p value 0.025), and periodic limb movement arousals (r value 0.460, p value 0.008). No statistically significant correlations were observed with TNF-alpha to any polysomnographic variables. To control for statistical significance with multiple comparisons, a MANOVA was performed with TNF-alpha and sTNF-RI as dependent variables and sleep architecture measures and arousals as independent variables. The model for sTNF-RI was statistically significant (F value 2.604, p value 0.03), whereas the model for TNF-alpha was not, suggesting sleep quality significantly affects sTNF-RI. Hierarchal linear regression analysis demonstrated that sTNF-RI was independently associated with spontaneous movement arousal index scores after controlling for age, body mass index, and sleep apnea severity. CONCLUSIONS: These findings suggest that sTNF-RI is associated with arousals during sleep, but not with other measures in patients with OSA.

Relationship between inflammation and cognitive function in obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction. MATERIALS AND METHODS: Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1). RESULTS: sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02). CONCLUSIONS: sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.

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.

Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T<90]). DESIGN: Retrospective case series. PATIENTS AND SETTING: 109 adult patients with OSA at a university hospital general clinical research center. MEASUREMENTS AND RESULTS: Markers of hypoxia (lowest oxygen saturation level and %T<90), correlated significantly with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (Pearson's r = -0.31 to -0.38, P <0.003), while apnea hypopnea index, body mass index, blood pressure, fasting glucose, triglyceride, and cholesterol levels did not. Hierarchical linear regression was then done to determine the best predictors of aminotransferase levels. Markers of metabolic syndrome were entered as one block and markers of sleep apnea as another. Regression analyses explained 16.3% of the variance in AST and 18.9% of the variance in ALT, with %T<90 playing the largest role. CONCLUSIONS: In patients with obstructive sleep apnea, serum aminotransferase levels are better predicted by markers of oxygen desaturation than by factors traditionally associated with the metabolic syndrome.

Obstructive sleep apnea in older adults.

The "typical" presentation of obstructive sleep apnea (OSA) is chronic loud snoring and excessive daytime sleepiness in middle-aged obese men. OSA can result in increased risk for cardiovascular morbidity and mortality. The diagnostic features of OSA in older adults are similar to those in younger adults; however, the older adult may be less likely to seek medical attention or have the sleep disorder recognized because symptoms of snoring, sleepiness, fatigue, nocturia, unintentional napping, and cognitive dysfunction may be ascribed to the aging process itself or to other disorders. This article reviews the basic terminology and pathophysiology of sleep-disordered breathing, discusses why OSA may be even more prevalent in older adults than in the middle-aged group, and reviews similarities and differences between the two groups in the manifestations, consequences, and treatments of OSA.

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.