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We studied healthy infant feeding practices among 308 mother-infant pairs, including exclusive breastmilk, satiety cues, complementary food introduction, sugary beverage intake, and bottle use in bed. We examined associations of individual and cumulative infant feeding practices through 12 months of age with body mass index (BMI) z -score at 2 years. Exclusive breastmilk and avoidance of bottle use in bed were associated with lower BMI z -score (β -0.29 units; 95% CI, -0.56, -0.02 units and β -0.32 units; 95% CI, -0.57, -0.07, respectively), when accounting for maternal pre-pregnancy BMI, household income, infant sex, race, and ethnicity. Adherence to 4--5 practices, compared to ≤ 2 practices, was associated with lower BMI z -score (β -0.84 units; 95% CI, -1.35, -0.34 units). Adherence to healthy infant feeding practices may reduce risk of excessive adiposity in early childhood. Targeting multiple infant feeding practices may be a more effective way to prevent childhood adiposity.

We introduce the concept of cardiac neuroautonomic renewability and a method for its quantification. This concept refers to the involuntary nervous system’s capacity to improve cardiac control in response to restorative interventions, such as sleep. We used the change in heart rate fragmentation (ΔHRF), before sleep onset compared with after sleep termination, to quantify the restorative effects of sleep. We hypothesized that the ability to improve cardiac neuroautonomic functionality would diminish with age and be associated with lower risk of major adverse cardiovascular events (MACE). We analyzed the ECG channel of polysomnographic recordings from an ancillary investigation of the Multi-Ethnic Study of Atherosclerosis (MESA). In a cohort of 659 participants (mean ± SD age, 69.7 ± 8.8; 42% male), HRF was significantly ( P < 0.001) lower after sleep (before: 74 ± 12%, after: 67 ± 13%). Furthermore, the magnitude of the decrease significantly ( P < 0.001) diminished with cross-sectional age. In addition, a larger reduction in HRF following sleep (i.e., higher ΔHRF) was associated with lower risk of MACE, independent of traditional cardiovascular risk factors and current measures of sleep quality. Specifically, over a mean follow-up period of 6.4 ± 1.6 yr, in which 60 participants had their first MACE, a one-SD (12%) increase in ΔHRF was associated with a 36% (95% CI: 12%–53%) decrease in the risk of MACE. The results demonstrate the restorative impact of sleep on heart rate control. As such they support the concept of cardiac neuroautonomic renewability and the utility of ΔHRF for its quantification.

Rationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2)oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).

Chronic exposure to stress is associated with metabolic syndrome (MetS), but the mechanism is unclear. We investigated the associations between chronic burden, sleep, and MetS in the Coronary Artery Risk Development in Young Adults Study.Chronic burden was self-reported (2000-2001) according to experiences with stressors for longer than 6 months. Wrist actigraphy-measured sleep duration and sleep efficiency were collected for 6 days; sleep duration, sleep quality, and daytime sleepiness were self-reported (2003-2004). MetS was measured during the clinic visit, from 2005 to 2006. Multivariable logistic and Cox proportional hazard models were fit to determine the associations of interest. Mediation by sleep was assessed using the product of coefficients approach.Among participants ( n = 606), the average (standard deviation) age was 40 (3.6) years, 58% were female, and 43% were Black. The prevalences of chronic burden, short sleep (≤6 hours), and MetS were 35%, 43% and 20.5%, respectively. High versus low chronic burden was associated with shorter self-reported sleep duration and higher daytime sleepiness. Chronic burden was associated with 1.85 higher odds (95% confidence interval = 1.11-3.09) of MetS. Sleep characteristics were not associated with MetS. There was no evidence that sleep mediated the chronic burden-MetS relation.Burden of chronic stress may be an emerging novel risk factor for both poor sleep and MetS.

Study objectivesThe clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial.MethodsParticipants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10).ResultsIn 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73).ConclusionsAlthough subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP); URL: https://clinicaltrials.gov/ct2/show/NCT00642486; Identifier: NCT00642486.CitationPascoe M, Bena J, Andrews ND, etal. Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study. J Clin Sleep Med. 2022;18(4):1027-1034.

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, −5.7%; adjusted 95% CI, −8.8% to −2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a treatment target for many patients with obstructive sleep apnea (OSA). We aimed to understand the prevalence, risk factors, and quality of life associated with EDS in a nonclinical, “real world” sample of patients with OSA. METHODS: Cross-sectional survey of patients with OSA participating in an online peer support community, assessing demographics, comorbidities, treatment, and quality of life. Differences in those with and without EDS (Epworth Sleepiness Scale > and ≤ 10) were assessed. RESULTS: The sample (n = 422) was 54.2% male, 65.9% were ≥ 55 years, and 43.3% reported sleeping ≤ 6 hours/night. EDS was identified among 31.0% of respondents and 51.7% reported sleepiness as a precipitating factor for seeking initial OSA treatment. EDS was more prevalent in individuals reporting asthma, insomnia symptoms, positive airway pressure (PAP) use less than 6 hours/night on ≥ 5 nights/week, or sleep duration < 6 hours/night. After adjusting for demographics and comorbidities, patients with EDS reported poorer mental and physical health and well-being, lower disease-specific functional status, more activity and work impairment, and more driving impairment (P values < .05). In the subsample (n = 265) with high PAP adherence, 26.0% reported EDS, and similar associations between EDS and outcomes were observed. CONCLUSIONS: These “real world” data suggest that patients seeking online OSA support experience a high prevalence of EDS, which was associated with poorer quality of life and worse functional status. Associations persisted among respondents with high self-reported PAP-therapy adherence, potentially driving these individuals to seek online support for sleepiness-related symptoms. CITATION: Wanberg LJ, Rottapel RE, Reid ML, et al. Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort. J Clin Sleep Med. 2021;17(12):2363–2372.

STUDY OBJECTIVES: Short sleep duration (SD) is associated with cardiovascular disease. We investigated the relationship between objective SD and subclinical atherosclerosis employing hybrid positron emission tomography/magnetic resonance imaging with (18)F-FDG tracer in the MESA cohort. METHODS: We utilized data from Multi-Ethnic Study of Atherosclerosis-SLEEP and Multi-Ethnic Study of Atherosclerosis-PET ancillary studies. SD and sleep fragmentation index (SFI) were assessed using 7-day actigraphy. The primary and secondary outcomes were carotid inflammation, defined using target-to-background ratios, and measures of carotid wall remodeling (carotid wall thickness), summarized by SD category. Multivariable linear regression was performed to assess the association between SD and SFI with the primary/secondary outcomes, adjusting for several covariates including apnea-hypopnea index, and cardiovascular disease risk. RESULTS: Our analytical sample (n = 58) was 62% female (mean age 68 ± 8.4 years). Average SD was 5.1 ± 0.9 hours in the short SD group (≤ 6 h/night, 31%), and 7.1 ± 0.8 hours in the normal SD group (69%). Prevalence of pathologic vascular inflammation (maximal target-to-background ratio > 1.6) was higher in the short SD group (89% vs 53%, P = .01). Those with short SD had a higher maximal target-to-background ratio (1.77 vs 1.71), although this was not statistically significant (P = .39). Carotid wall thickness was positively associated with SFI even after adjusting for covariates (Beta [standard error] = 0.073 ± [0.032], P = .03). CONCLUSIONS: Prevalence of pathologic vascular inflammation was higher among those who slept ≤ 6 hours, and vascular inflammation was higher among those with a SD of ≤ 6 hours. Interestingly, SFI was positively associated with carotid wall thickness even after adjustment for covariates. Our results are hypothesis generating but suggest that both habitual SD and SFI should be investigated in future studies as potential risk factors for subclinical atherosclerosis. CITATION: Kundel V, Reid M, Fayad Z, et al. Sleep duration and vascular inflammation using hybrid positron emission tomography/magnetic resonance imaging: results from the Multi-Ethnic Study of Atherosclerosis. J Clin Sleep Med. 2021;17(10):2009–2018.

Objective In this study, we examine associations between objectively measured weekend night vs. school night sleep patterns, weight status, and weight-related behaviors among adolescents. Design Cross-sectional study. Setting Five Minnesota high schools that started early (7:30 or 7:45 AM) in Spring 2016. Participants Ninth grade students, ages 14.5-16 years (n = 284). Measurements Students completed surveys, had body measurements taken, and wore sleep (wrist) actigraphs for 1 week (n = 284). We examined weekend night-school night differences in sleep duration and sleep timing. We then assessed whether these factors were related to weight status and weight-related behaviors (eating behaviors, food consumption, physical activity, beverage consumption) using generalized linear mixed models. Results On average, students slept 1.5 hours (95% confidence interval 1.3-1.7) more and had a sleep midpoint 1.9 hours (1.8-2.1) later on weekend nights compared to school nights. Female students had larger increases in sleep duration on weekend nights than males but similar timing differences. Sleep duration differences were uncorrelated with sleep timing differences (r = 0.01). Neither duration nor timing differences were associated with overweight, obesity, or any of the eating behaviors we examined. However, sleeping longer on weekend nights than on school nights was associated with lower probability of being active 6-7 days per week (p = .02). Conclusions Adolescents have substantial sleep duration and sleep timing differences on weekend nights vs. school nights. While these differences may not be associated with weight status or weight-related behaviors, they reflect the reality that most adolescents have schedules that restrict their sleep.

Background Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. Methods The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation Results We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10−8) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways. Conclusions We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.

Background Although sufficient and healthy sleep is inversely associated with cardiovascular disease (CVD) and its risk factors, the American Heart Association's Life's Simple 7 (LS7), as a measure of cardiovascular health (CVH), did not include sleep. We evaluated an expanded measure of CVH that includes sleep as an eighth metric in relation to CVD risk. Methods and Results The analytic sample consisted of MESA (Multi‐Ethnic Study of Atherosclerosis) Sleep Study participants who had complete data on sleep characteristics from overnight polysomnography, 7‐day wrist actigraphy, validated questionnaires, and the outcome. We computed the LS7 score and 4 iterations of a new CVH score: score 1 included sleep duration, score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea), scores 3 and 4 included sleep characteristics associated with CVD in MESA (score 3: sleep duration and efficiency, daytime sleepiness, and obstructive sleep apnea; score 4: score 3+sleep regularity). Multivariable‐adjusted logistic and Cox proportional hazards models evaluated associations of the LS7 and CVH scores 1 to 4 with CVD prevalence and incidence. Among 1920 participants (mean age: 69±9 years; 54% female), there were 95 prevalent CVD events and 93 incident cases (mean follow‐up, 4.4 years). Those in the highest versus lowest tertile of the LS7 score and CVH scores 1 to 4 had up to 80% lower odds of prevalent CVD. The LS7 score was not significantly associated with CVD incidence (hazard ratio, 0.62 [95% CI, 0.37–1.04]). Those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratio, 0.57 [95% CI, 0.33–0.97]; and hazard ratio, 0.53 [95% CI, 0.32–0.89]), respectively. Conclusions CVH scores that include sleep health predicted CVD risk in older US adults. The incorporation of sleep as a CVH metric, akin to other health behaviors, may enhance CVD primordial and primary prevention efforts. Findings warrant confirmation in larger cohorts over longer follow‐up.

Publisher's version (útgefin grein)., Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles., This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338. Study-specific acknowledgements can be found in the Supplementary Notes 2 and 4. The data on coronary artery disease have been contributed by the Myocardial Infarction Genetics and CARDIoGRAM investigators, and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG.

Aims To quantify the arousal burden (AB) across large cohort studies and determine its association with long-term cardiovascular (CV) and overall mortality in men and women. Methods and results We measured the AB on overnight polysomnograms of 2782 men in the Osteoporotic Fractures in Men Study (MrOS) Sleep study, 424 women in the Study of Osteoporotic Fractures (SOF) and 2221 men and 2574 women in the Sleep Heart Health Study (SHHS). During 11.2 ± 2.1 years of follow-up in MrOS, 665 men died, including 236 CV deaths. During 6.4 ± 1.6 years of follow-up in SOF, 105 women died, including 47 CV deaths. During 10.7 ± 3.1 years of follow-up in SHHS, 987 participants died, including 344 CV deaths. In women, multivariable Cox proportional hazard analysis adjusted for common confounders demonstrated that AB is associated with all-cause mortality [SOF: hazard ratio (HR) 1.58 (1.01–2.42), P = 0.038; SHHS-women: HR 1.21 (1.06–1.42), P = 0.012] and CV mortality [SOF: HR 2.17 (1.04–4.50), P = 0.037; SHHS-women: HR 1.60 (1.12–2.28), P = 0.009]. In men, the association between AB and all-cause mortality [MrOS: HR 1.11 (0.94–1.32), P = 0.261; SHHS-men: HR 1.31 (1.06–1.62), P = 0.011] and CV mortality [MrOS: HR 1.35 (1.02–1.79), P = 0.034; SHHS-men: HR 1.24 (0.86–1.79), P = 0.271] was less clear. Conclusions Nocturnal AB is associated with long-term CV and all-cause mortality in women and to a lesser extent in men.

IntroductionWe aimed to determine whether obesity or metabolic syndrome (MetS) modify associations between sleep-disordered breathing (SDB), self-reported sleep duration (SD), and phenotypes of combined SDB/SD with 7-year neurocognitive decline (ND) in a community based-cohort of U.S. Hispanic/Latinos (N=5500) in different age and sex groups.MethodsThe exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (

Rationale: Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea–hypopnea index (AHI). Respiratory event duration is a he...

BackgroundSleep-disordered breathing (SDB) in pregnancy is associated with adverse maternal outcomes. The relationship between SDB and infant birthweight is unclear. This study's primary aim is to determine if objectively measured SDB in pregnancy is associated with infant birthweight.MethodsWe measured SDB objectively in early (6-15 weeks' gestation) and mid (22-31 weeks' gestation) pregnancy in a large cohort of nulliparous women. SDB was defined as an Apnea-Hypopnea Index ≥5 and in secondary analyses we also examined measures of nocturnal hypoxemia. We used a modified Poisson regression approach to estimate relative risks (RR) of large-for-gestational-age (LGA: >90th percentile for gestational age) and small-for-gestational-age (SGA

Background/objectives Neck circumference, an index of upper airway fat, has been suggested to be an important measure of body-fat distribution with unique associations with health outcomes such as obstructive sleep apnea and metabolic disease. This study aims to study the genetic bases of neck circumference. Methods We conducted a multi-ethnic genome-wide association study of neck circumference, adjusted and unadjusted for BMI, in up to 15,090 European Ancestry (EA) and African American (AA) individuals. Because sexually dimorphic associations have been observed for anthropometric traits, we conducted both sex-combined and sex-specific analysis. Results We identified rs227724 near the Noggin (NOG) gene as a possible quantitative locus for neck circumference in men (N = 8831, P = 1.74 × 10−9) but not in women (P = 0.08). The association was replicated in men (N = 1554, P = 0.045) in an independent dataset. This locus was previously reported to be associated with human height and with self-reported snoring. We also identified rs13087058 on chromosome 3 as a suggestive locus in sex-combined analysis (N = 15090, P = 2.94 × 10−7; replication P =0.049). This locus was also associated with electrocardiogram-assessed PR interval and is a cis-expression quantitative locus for the PDZ Domain-containing ring finger 2 (PDZRN3) gene. Both NOG and PDZRN3 interact with members of transforming growth factor-beta superfamily signaling proteins. Conclusions Our study suggests that neck circumference may have unique genetic basis independent of BMI.

Heart rate fragmentation (HRF), a marker of abnormal sinoatrial dynamics, was shown to be associated with incident cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA). Here, we test the hypothesis that HRF is also associated with incident atrial fibrillation (AF) in the MESA cohort of participants who underwent in-home polysomnography (PSG) and in two high-risk subgroups: those ≥70 yr taking antihypertensive medication and those with serum concentrations of NH(2)-terminal prohormone B-type natriuretic peptide (NT-proBNP) >125 pg/ml (top quartile). Heart rate time series (n = 1,858) derived from the ECG channel of the PSG were analyzed using newly developed HRF metrics, traditional heart rate variability (HRV) indices and two widely used nonlinear measures. Eighty-three participants developed AF over a mean follow-up period of 3.83 ± 0.87 yr. A one-standard deviation increase in HRF was associated with a 31% (95% CI: 3–66%) increase in risk of incident AF, in Cox models adjusted for age, height, NT-proBNP, and frequent premature supraventricular complexes. Furthermore, HRF added value to the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF models. Traditional HRV and nonlinear indices were not significantly associated with incident AF. In the two high-risk subgroups defined above, HRF was also significantly associated with incident AF in unadjusted and adjusted models. These findings support the translational utility of HRF metrics for short-term (∼4-yr) prediction of AF. In addition, they support broadening the concept of atrial remodeling to include electrodynamical remodeling, a term used to refer to pathophysiological alterations in sinus interbeat interval dynamics. NEW & NOTEWORTHY This study is the first demonstration that heart rate fragmentation (HRF), a marker of anomalous sinoatrial dynamics, is an independent predictor of atrial fibrillation (AF). Traditional measures of heart rate variability and two widely used nonlinear measures were not associated with incident AF in the Multi-Ethnic Study of Atherosclerosis. Fragmentation measures added value to the strongest contemporary predictors of AF, including ECG-derived parameters, coronary calcification score, serum concentrations of NH(2)-terminal prohormone B-type natriuretic peptide, and supraventricular ectopy. The computational algorithms for quantification of HRF could be readily incorporated into wearable ECG monitoring devices.

ObjectiveTo test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI.MethodsWe studied 492 participants (age 58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume, and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE ε4 carrier status, stroke risk factors, sleeping pill use, body mass index, and depression.ResultsLess slow-wave sleep was associated with lower cortical brain volume (absolute duration, β [standard error] = 0.20 [0.08], p = 0.015; percentage, 0.16 [0.08], p = 0.044), lower subcortical brain volume (percentage, 0.03 [0.02], p = 0.034), and higher white matter hyperintensities volume (absolute duration, −0.12 [0.05], p = 0.010; percentage, −0.10 [0.04], p = 0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts.ConclusionLoss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

Objective:During the perinatal period, modifiable behaviours contributing to excess weight gain, including sugar-sweetened beverage (SSB) intake, are understudied. We examined the extent to which perinatal SSB intake affects postpartum weight retention (PPWR).Design:We measured SSB intake frequency in the third trimester and 1-month postpartum using the NHANES Dietary Screener Questionnaire. We assessed the association between SSB intake and PPWR (difference between 6-month postpartum and pregravid weight) using multivariable regression adjusted for socio-demographic and anthropometric variables.Setting:Greater Boston area.Participants:Three hundred forty-eight mother–infant pairs in the Rise and SHINE prospective birth cohort.Results:Mean age was 32·7 (sd 5·0) years; the sample was 47 % white, 32 % Hispanic, 14 % Asian and 7 % Black. Women reported mean daily SSB intake frequencies of 0·9 (sd 1·2) and 0·7 (sd 1·0) times/d in the third trimester and 1-month postpartum, respectively. At 6-month postpartum, average weight retention was 3·4 (sd 5·7) kg; 108 (sd 31 %) women had substantial PPWR, defined as a ≥ 5 kg increase between pregravid and 6-month postpartum weight. Each 1-time/d increment in SSB intake frequency during the third trimester (β = 0·46 kg (95 % CI, 0·07, 0·86)) and 1-month postpartum (β = 0·52 kg (95 % CI 0·03, 1·00)) was associated with higher weight retention at 6 months. Increased SSB intake frequency in the third trimester (OR: 1·37; 95 % CI 1·10, 1·75) and 1-month postpartum (OR: 1·17; 95 % CI 0·92, 1·52) resulted in higher odds of substantial PPWR.Conclusions:SSB consumption during the perinatal period is associated with higher weight retention at 6-month postpartum. Avoiding SSB may reduce the risk of excess weight retention.

Study Objectives We evaluated if self-reported sleepiness was associated with neuroimaging markers of brain aging and ischemic damage in a large community-based sample. Methods Participants from the Framingham Heart Study Offspring cohort (n = 468, 62.5 ± 8.7 years old, 49.6%M) free of dementia, stroke, and neurological diseases, completed sleep questionnaires and polysomnography followed by magnetic resonance imaging (MRI), 3 years later on average. We used linear and logistic regression models to evaluate the associations between Epworth Sleepiness Scale (ESS) scores and total brain, cortical and subcortical gray matter, and white matter hyperintensities volumes, and the presence of covert brain infarcts. Results Higher sleepiness scores were associated with larger total brain volume, greater cortical gray matter volume, and a lower prevalence of covert brain infarcts, even when adjusting for a large array of potential confounders, including demographics, sleep profiles and disorders, organic health diseases, and proxies for daytime cognitive and physical activities. Interactions indicated that more sleepiness was associated with larger cortical gray matter volume in men only and in APOE ε4 noncarriers, whereas a trend for smaller cortical gray matter volume was observed in carriers. In longitudinal analyses, those with stable excessive daytime sleepiness over time had greater total brain and cortical gray matter volumes, whereas baseline sleepiness scores were not associated with subsequent atrophy or cognitive decline. Conclusion Our findings suggest that sleepiness is not necessarily a marker of poor brain health when not explained by diseases or sleep debt and sleep disorders. Rather, sleepiness could be a marker of preserved sleep-regulatory processes and brain health in some cases.

Introduction Sleep, sedentary behavior, and physical activity are each independently associated with cardiovascular health (CVH). It is unknown how substituting time in sedentary behavior with sleep or physical activity affects overall CVH. Methods Data for this analysis were taken from the Multi-Ethnic Study on Atherosclerosis Sleep Ancillary Study. Eligible participants (N = 1718) wore Actiwatch accelerometers for 24 h and had at least 3 d of valid accelerometry. The American Heart Association's Life's Simple 7 was used to represent the CVH score after excluding the physical activity component, with higher scores indicating more favorable CVH. Isotemporal substitution modeling was conducted to examine the effect of substituting 30 min of sedentary time for an equivalent amount of sleep, light-intensity physical activity (LIPA), or moderate to vigorous physical activity (MVPA). Results Substituting 30 min of sedentary time to sleep, LIPA, and MVPA was associated with a significantly higher CVH score [β (95% confidence interval) = 0.077 (0.056), 0.039 (0.033), and 0.485 (0.127), respectively]. Substituting 30 min of sedentary time to sleep was associated with lower body mass index (BMI). Substituting 30 min of sedentary time to LIPA was associated with higher diastolic blood pressure and total cholesterol, and lower BMI. Substituting 30 min of sedentary time to MVPA was associated with lower systolic and diastolic blood pressure, and lower BMI. Conclusions Sleep, LIPA, and MVPA are all associated with more favorable overall CVH and several key risk factors for cardiovascular disease. These findings underscore the importance of lifestyle modifications in improving CVH.

The associations between objective measures of sleep duration and bone outcomes in older men are unknown. No consistent, significant association was identified between sleep duration and bone mineral density (BMD) in the current analysis. However, future research should determine if vitamin D status modifies this relationship. Prior studies, predominantly in women, reported that long and short self-reported sleep duration are associated with lower BMD. Associations between actigraphy-determined sleep duration and BMD or bone turnover markers (BTMs) in older men are unknown. Men in The Osteoporotic Fractures in Men (MrOS) Study with wrist actigraphy and concurrent BMD assessment but without comorbidities affecting bone health were included. Sleep duration was considered as a continuous (N = 1926) and dichotomized variable where men were classified as getting the recommended (7–8 h/night; N = 478) or short (< 6 h/night; N = 577) sleep. The cross-sectional association between BMD, BTMs, and sleep duration was examined using a t test or linear regression, where appropriate, in unadjusted and adjusted models. There were no clinically or statistically significant differences in BMD at the L-spine, total hip, or femoral neck between men getting the recommended vs. short sleep duration, using actigraphy or self-reported sleep duration (all p ≥ 0.07). When sleep duration was considered as a continuous variable, femoral neck BMD was higher in men with longer self-reported sleep duration (β = 0.006 ±0.003, p = 0.02), but this was not significant after further adjustment. In men with low 25OHD (< 20 ng/mL), longer actigraphy-determined sleep duration was associated with higher total hip BMD (β = 0.016 ± 0.008; p = 0.04). Sleep duration and BTMs were not associated. Sleep duration was not associated with hip or L-spine BMD or BTMs in older men. Future research should determine if vitamin D status or other factors modify this relationship.

Background Sleep is an important aspect of child development and health. Disparities in childhood sleep have been observed as early as infancy, but little is known about the factors contributing to them. Purpose The objective of this study was to examine whether intrinsic, contextual, and parenting factors contribute to differences in sleep duration between Hispanic/Latinx and non-Hispanic white infants at 6 months of age. Methods We analyzed data of 119 Hispanic/Latinx and 146 non-Hispanic white infants in Rise & SHINE, a prospective birth cohort study of mother–infant dyads. Mothers reported their infant’s sleep patterns using the Brief Infant Sleep Questionnaire at 6 months. Mothers also completed surveys measuring intrinsic (sex, gestational length, and birth weight), contextual (cultural, environmental, and familial), and parenting (behaviors and practices) factors. We used multivariable linear and logistic regression analyses to examine the contributing effects of these clusters of variables on the association between racial/ethnic background and infant sleep duration. Results Hispanic/Latinx infants slept 38 min less than white infants at 6 months (β: −0.63 [95% confidence interval: −1.07, −0.19]) and were nearly three times more likely to not meet the minimum sleep recommendation. The differences persisted after adjustment for intrinsic factors but were attenuated after additional adjustment for contextual and parenting factors, especially having a foreign-born mother and later bedtime. Conclusions The results of this study demonstrate that differences in sleep duration among Hispanic/Latinx infants compared to their white counterparts are present as early as 6 months of age and that context and parenting matter.

Background Heart failure (HF) is a leading cause of morbidity and mortality and although it is linked to sleep apnea, which physiological stressors most strongly associate with incident disease is unclear. We tested whether sleep apnea-specific hypoxic burden (SASHB) predicts incident HF in two independent cohort studies. Research Question In comparison with apnea-hypopnea index (AHI), how does sleep apnea-specific hypoxic burden predict incident HF? Study Design and Methods The samples were derived from two cohort studies: The Sleep Heart Health Study (SHHS), which included 4,881 middle-aged and older adults (54.4% women), age 63.6 ± 11.1 years; and the Outcomes of Sleep Disorders in Older Men (MrOS), which included 2,653 men, age 76.2 ± 5.4 years. We computed SASHB as the sleep apnea-specific area under the desaturation curve from pre-event baseline. We used Cox models for incident HF to estimate the adjusted hazard ratios (HRs) for natural log-transformed SASHB and AHI adjusting for multiple confounders. Results The SASHB predicted incident HF in men in both cohorts, whereas AHI did not. Men in SHHS and MrOS had adjusted HRs (per 1SD increase in SASHB) of 1.18 (95% CI, 1.02-1.37) and 1.22 (95% CI, 1.02-1.45), respectively. Associations with SASHB were observed in men with both low and high AHI levels. Associations were not significant in women. Interpretation In men, the hypoxic burden of sleep apnea was associated with incident HF after accounting for demographic factors, smoking, and co-morbidities. The findings Suggest that quantification of an easily measured index of sleep apnea-related hypoxias may be useful for identifying individuals at risk for heart disease, while also suggesting targets for intervention.

BACKGROUND Obstructive sleep apnea (OSA), nocturnal hypertension, and nondipping systolic blood pressure (BP) are each highly prevalent among African Americans. However, few data are available on the association between OSA and nighttime BP in this population. METHODS We examined the association of OSA with nighttime BP among African Americans who completed 24-hour ambulatory BP monitoring (ABPM) at Exam 1 (2000–2004) of the Jackson Heart Study (JHS) and subsequently participated in the JHS Sleep Study (2012–2016). Type 3 home sleep apnea testing was used to assess OSA measures, including respiratory event index (REI4%) and percent sleep time RESULTS Among 206 participants who completed ABPM and participated in the Jackson Heart Sleep Study, 50.5% had nocturnal hypertension and 26.2% had moderate to severe OSA (REI4% ≥15 events/hour). After multivariable adjustment, each SD (13.3 events/hour) increase in REI4% was associated with 1.75 mm Hg higher nighttime DBP (95% confidence interval (CI): 0.38, 3.11) and a prevalence ratio of 1.11 (95% CI: 1.00, 1.24) for nocturnal hypertension. Each SD (10.4%) increase in nocturnal hypoxemia was associated with a 1.91 mm Hg higher nighttime SBP (95% CI: 0.15, 3.66). CONCLUSIONS Severity of OSA and nocturnal hypoxemia were associated with high nighttime BP in African American participants in the JHS.

Objective Self-reported "sleep quality" often is assessed in epidemiologic studies. However, the bases for variation in sleep quality is not fully understood. We quantified the extent to which subjective sleep quality was related to sleep disorders and sleep characteristics among 795 African American adults. Method Between 2012 and 2016, participants underwent home sleep apnea testing and 1-week actigraphy (estimating sleep duration, efficiency, fragmentation, latency). Sleep quality, insomnia and restless legs syndrome symptoms, sleepiness, and physician diagnosis of sleep disorders were self-reported. We fit linear regression models to determine the extent to which subjective and objective sleep measures as well as depressive symptoms and anxiety were related to subjective sleep quality. Results After adjustment for covariates, worse sleep quality scores were associated with insomnia and restless legs syndrome symptoms, sleep apnea, physician diagnosis of a sleep disorder, and actigraphy-based fragmented sleep, lower sleep efficiency, and shorter sleep duration. Insomnia symptoms explained the most variance in subjective sleep quality, 21%. Other sleep measures each explained 3% to 7% and psychosocial factors explained 8% to 9% of the variance in subjective sleep quality after adjustment for confounders. Conclusions The weak associations of sleep quality with sleep disorders and objectively measured sleep disturbances are consistent with concepts of "sleep health" as a multidimensional construct. Sleep quality is a patient-centered outcome that provides unique information over objective measurements of sleep disturbances.

OBJECTIVE To identify sleep duration trajectories from early to middle adulthood and their associations with incident type 2 diabetes. RESEARCH DESIGN AND METHODS Using a group-based modeling approach, we identified sleep duration trajectories based on sleep duration in ages 20–25, 26–35, 36–45, and 46+ years, which were retrospectively assessed in 2009 among 60,068 women from the Nurses’ Health Study II (median age 54.9 years) who were free of diabetes, cardiovascular disease, and cancer. We investigated the prospective associations between sleep duration trajectories and diabetes risk (2009–2017) using multivariable Cox proportional hazards models. RESULTS We documented 1,797 incident diabetes cases over a median follow-up of 7.8 years (442,437 person-years). Six sleep duration trajectories were identified: persistent 5-, 6-, 7-, or 8-h sleep duration and increased or decreased sleep duration. After multivariable adjustment for diabetes risk factors, compared with the persistent 7-h sleep duration group, the hazard ratio was 1.43 (95% CI 1.10, 1.84) for the 5-h group, 1.17 (1.04, 1.33) for the 6-h group, 0.96 (0.84, 1.10) for the 8-h group, 1.33 (1.09, 1.61) for the increased sleep duration group, and 1.32 (1.10, 1.59) for the decreased sleep duration group. Additional adjustment for time-updated comorbidities and BMI attenuated these associations, although a significantly higher risk remained in the decreased sleep duration group (1.24 [1.03, 1.50]). CONCLUSIONS Persistent short sleep duration or changes in sleep duration from early to middle adulthood were associated with higher risk of type 2 diabetes in later life. These associations were weaker after obesity and metabolic comorbidities were accounted for.

Background Inflammation is implicated as one of many factors related to the development of chronic disease; thus, identifying its modifiable risk factors offers potential intervention targets to reduce risk. Purpose To investigate whether depression and anxiety symptoms may indirectly affect high-sensitivity C-reactive protein (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) through sleep duration and adiposity (i.e., percentage body fat and waist circumference). Methods Multiple regression analyses were performed on Hispanic Community Health Study/Study of Latinos Youth (ages 8–16 years) cross-sectional baseline data, which were weighted to adjust for sampling design. Data were collected at a clinical assessment, including fasting blood samples, self-report surveys, and objectively measured anthropometrics. Results Adjusting for sociodemographic covariates, depression symptoms were associated with log hs-CRP (β = .011, p = .047) but not PAI-1 (p = .285). Percentage body fat and waist circumference were positively related to depression symptoms (p = .026 and p = .028, respectively) and log hs-CRP (p < .001 for both). When including adiposity in the hs-CRP model, the associations of depression symptoms with hs-CRP were attenuated and became nonsignificant. Monte Carlo confidence intervals (CIs) showed that the indirect effects from depression symptoms to CRP through percentage body fat (95% CI: .0006, .0119) and waist circumference (95% CI: .0004, .0109) were statistically significant. Conclusions Results indicate that the association between psychological distress and inflammation may occur indirectly through adiposity in Hispanic/Latino children. If findings are replicated in causal designs, reducing depression symptoms and adiposity among Hispanic/Latino children may be avenues for primary prevention of inflammation in later years.

IntroductionTo determine if sleep-disordered breathing (SDB), daytime sleepiness, insomnia, and sleep duration predict seven-year neurocognitive decline in US Hispanics/Latinos (N = 5247).MethodsThe exposures were baseline SDB, daytime sleepiness, insomnia, and sleep duration. The outcomes were change in episodic learning and memory (B-SEVLT-Sum and SEVLT-Recall), language (word fluency [WF]), processing speed (Digit Symbol Substitution), and a cognitive impairment screener (Six-item Screener [SIS]).ResultsMean age was 63 ± 8 years, with 55% of the population being female with 7.0% Central American, 24.5% Cuban, 9.3% Dominican, 35.9% Mexican, 14.4% Puerto Rican, and 5.1% South American background. Long sleep (>9 hours), but not short sleep (

Background Genetic and lifestyle factors have considerable effects on obesity and related diseases, yet their effects in a clinical cohort are unknown. This study in a patient biobank examined associations of a BMI polygenic risk score (PRS), and its interactions with lifestyle risk factors, with clinically measured BMI and clinical phenotypes. Methods The Mass General Brigham (MGB) Biobank is a hospital-based cohort with electronic health record, genetic, and lifestyle data. A PRS for obesity was generated using 97 genetic variants for BMI. An obesity lifestyle risk index using survey responses to obesogenic lifestyle risk factors (alcohol, education, exercise, sleep, smoking, and shift work) was used to dichotomize the cohort into high and low obesogenic index based on the population median. Height and weight were measured at a clinical visit. Multivariable linear cross-sectional associations of the PRS with BMI and interactions with the obesity lifestyle risk index were conducted. In phenome-wide association analyses (PheWAS), similar logistic models were conducted for 675 disease outcomes derived from billing codes. Results Thirty-three thousand five hundred eleven patients were analyzed (53.1% female; age 60.0 years; BMI 28.3 kg/m2), of which 17,040 completed the lifestyle survey (57.5% female; age: 60.2; BMI: 28.1 (6.2) kg/m2). Each standard deviation increment in the PRS was associated with 0.83 kg/m2 unit increase in BMI (95% confidence interval (CI) =0.76, 0.90). There was an interaction between the obesity PRS and obesity lifestyle risk index on BMI. The difference in BMI between those with a high and low obesogenic index was 3.18 kg/m2 in patients in the highest decile of PRS, whereas that difference was only 1.55 kg/m2 in patients in the lowest decile of PRS. In PheWAS, the obesity PRS was associated with 40 diseases spanning endocrine/metabolic, circulatory, and 8 other disease groups. No interactions were evident between the PRS and the index on disease outcomes. Conclusions In this hospital-based clinical biobank, obesity risk conferred by common genetic variants was associated with elevated BMI and this risk was attenuated by a healthier patient lifestyle. Continued consideration of the role of lifestyle in the context of genetic predisposition in healthcare settings is necessary to quantify the extent to which modifiable lifestyle risk factors may moderate genetic predisposition and inform clinical action to achieve personalized medicine.

BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma. METHODS: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician’s diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes. RESULTS: A genome-wide significant association was identified between baseline FEV(1)/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10(−8) in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10(−6)). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV(1) (P = 3.3 × 10(−3)), postbronchodilator (PB) FEV(1) (7.3 × 10(−3)), and PB FEV(1)/FVC ratio (P = 2.7 × 10(−3)). The identified baseline FEV(1)/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR. CONCLUSIONS: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

BACKGROUND: Results of previous studies examining associations between cigarette smoking and sleep-disordered breathing (SDB) are inconsistent. We therefore investigated this association in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). METHODS: A total of 13,863 US Hispanic/Latino subjects, 18 to 76 years old, provided smoking histories and underwent home SDB testing. Logistic regression analyses were conducted to assess the independent association of smoking and SDB with covariate adjustment. Sex- and age-stratified analyses were performed. RESULTS: The weighted prevalence of moderate to severe SDB was 9.7% (95% CI, 9.0-10.5). No independent and statistically significant association was observed between ever smoking (defined as minimum lifetime cigarette use of 100) and moderate to severe SDB (defined as an apnea-hypopnea index ≥ 15 events per hour) (OR, 1.02; 95% CI, 0.85-1.22; P = .85). Sex and age were effect modifiers of the aforementioned association. Stratification according to age and sex revealed that younger (aged 35-54 years) female smokers had 83% higher odds of SDB compared with younger female never smokers (OR, 1.83; 95% CI, 1.19-2.81; P = .01). A significant dose-response relation was noted between smoking intensity and SDB in younger female smokers (P < .01). Lastly, use of ≥ 10 cigarettes per day was associated with a nearly threefold increase in SDB odds in younger female ever smokers. These associations were not observed in younger male subjects. CONCLUSIONS: In the HCHS/SOL, no independent and statistically significant association was found between smoking and SDB. Sex and age stratification revealed a novel statistically significant association between smoking and SDB in younger (35-54 years old) female smokers. Our findings highlight the importance of investigating sex- and age-specific associations of SDB risk factors.

Background Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being. Objective The primary aim of this study was to determine whether a standard 8-session web-based mindfulness-based cognitive therapy (MBCT) program, compared with a brief 3-session mindfulness intervention, improved overall participant well-being. In addition, we sought to explore whether the treatment effects differed based on the baseline characteristics of the participants (ie, moderators). Methods Participants were recruited from 17 patient-powered research networks, web-based communities of stakeholders interested in a common research area. Participants were randomized to either a standard 8-session MBCT or a brief 3-session mindfulness training intervention accessed on the web. The participants were followed for 12 weeks. The primary outcome of the study was well-being, as measured by the World Health Organization—Five Well-Being Index. We hypothesized that MBCT would be superior to a brief mindfulness training. Results We randomized 4411 participants, 3873 (87.80%) of whom were White and 3547 (80.41%) of female sex assigned at birth. The mean baseline World Health Organization—Five Well-Being Index score was 50.3 (SD 20.7). The average self-reported well-being in each group increased over the intervention period (baseline to 8 weeks; model-based slope for the MBCT group: 0.78, 95% CI 0.63-0.93, and brief mindfulness group: 0.76, 95% CI 0.60-0.91) as well as the full study period (ie, intervention plus follow-up; baseline to 20 weeks; model-based slope for MBCT group: 0.41, 95% CI 0.34-0.48; and brief mindfulness group: 0.33, 95% CI 0.26-0.40). Changes in self-reported well-being were not significantly different between MBCT and brief mindfulness during the intervention period (model-based difference in slopes: −0.02, 95% CI −0.24 to 0.19; P=.80) or during the intervention period plus 12-week follow-up (−0.08, 95% CI −0.18 to 0.02; P=.10). During the intervention period, younger participants (P=.05) and participants who completed a higher percentage of intervention sessions (P=.005) experienced greater improvements in well-being across both interventions, with effects that were stronger for participants in the MBCT condition. Attrition was high (ie, 2142/4411, 48.56%), which is an important limitation of this study. Conclusions Standard MBCT improved well-being but was not superior to a brief mindfulness intervention. This finding suggests that shorter mindfulness programs could yield important benefits across the general population of individuals with various medical conditions. Younger people and participants who completed more intervention sessions reported greater improvements in well-being, an effect that was more pronounced for participants in the MBCT condition. This finding suggests that standard MBCT may be a better choice for younger people as well as treatment-adherent individuals. Trial Registration ClinicalTrials.gov NCT03844321; https://clinicaltrials.gov/ct2/show/NCT03844321

Study Objectives Recent work on US Whites from clinical samples used obstructive sleep apnea (OSA) symptoms to generate phenotypes for individuals with moderate-severe OSA which suggested 3 to 5 symptom classes. However, it is unknown whether similar classes generalize to diverse Hispanics/Latino adults. Therefore, we sought to fill this gap by empirically deriving sleep phenotypes among a large sample of diverse Hispanics/Latinos. Methods We used data from The Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008–2011), a prospective cohort study designed using a multisite multistage probability sample of adults 18–74 years old. The subpopulation of interest included participants with moderate-severe OSA symptoms (≥15 respiratory event index (REI) events per hour; n = 1,605). We performed latent class analysis for complex survey data using 15 common OSA symptoms (e.g. Epworth Sleepiness Scale) and 4 comorbidities to identify phenotype classes. Results Average age was 52.4 ± 13.9 years and 34.0% were female. Mean REI was 33.8 ± 22.5 events per hour. Fit statistics and clinical significance suggested that a three-class solution provided the best fit to the data. The three phenotypes were: (1) Minimally Symptomatic (47.7%), (2) Excessive sleepiness (37.1%), and (3) Disturbed Sleep (15.2%). Sensitivity models were consistent with the main proposed solution. Conclusions Derived sleep phenotypes among diverse Hispanic/Latinos were consistent with recent findings from the Sleep Apnea Global Interdisciplinary Consortium, but we found notable differences in class prevalence relative to Whites. Further research is needed to link derived sleep phenotypes to health comorbidities in diverse populations.

Study Objectives Suboptimal sleep is associated with obesity and its sequelae in children and adults. However, few studies have examined the association between sleep and physical growth in infants who experience rapid changes in sleep/wake patterns. We examined the longitudinal association of changes in objectively assessed sleep/wake patterns with changes in growth between ages 1 and 6 months. Methods We studied 298 full-term infants in the longitudinal Rise & SHINE cohort study. Changes from 1 and 6 months in nighttime sleep duration, wake after sleep onset (WASO), and number of waking bouts ≥5 min were assessed using ankle actigraphy. Overweight was defined as age- and sex-specific weight for length ≥95th percentile. Generalized estimating equation analyses adjusted for infants′ and mothers′ characteristics. Results The mean (SD) birth weight was 3.4 (0.4) kg; 48.7% were boys. In multivariable adjusted models, each 1-h increase in nighttime sleep duration between months 1 and 6 was associated with a 26% decrease in the odds of overweight from 1 to 6 months (odds ratio [OR] = 0.74; 95% confidence interval [CI, 0.56, 0.98]). Each 1-unit decrease in number of waking bouts was associated with a 16% decrease in the odds of overweight (OR = 0.84; 95% CI [0.72, 0.98]). Changes in WASO were not associated with the odds of overweight. Conclusions Greater increases in nighttime sleep duration and more consolidation of nighttime sleep were associated with lower odds of overweight from 1 to 6 months. Adverse sleep patterns as early as infancy may contribute to excess adiposity.

Study Objectives African-Americans have a high burden of poor sleep, yet, psychosocial determinants (e.g. discrimination) are understudied. We investigated longitudinal associations between everyday discrimination and sleep quality and duration among African-Americans (N = 3404) in the Jackson Heart Study. Methods At Exam 1 (2000–2004) and Exam 3 (2008–2013), participants completed the Everyday Discrimination Scale, rated their sleep quality (1 = poor to 5 = excellent), and self-reported hours of sleep. A subset of participants (N = 762) underwent 7-day actigraphy to objectively measure sleep duration and sleep quality (Sleep Exam 2012–2016). Changes in discrimination were defined as low stable (reference), increasing, decreasing, and high stable. Within-person changes in sleep from Exam 1 to Exam 3 were regressed on change in discrimination from Exam 1 to Exam 3 while adjusting for age, sex, education, income, employment, physical activity, smoking, body mass index, social support, and stress. Results At Exam 1, the mean age was 54.1 (12.0) years; 64% were female, mean sleep quality was 3.0 (1.1) and 54% were short sleepers. The distribution of the discrimination change trajectories were 54.1% low stable, 13.5% increasing, 14.6% decreasing, and 17.7% were high stable. Participants who were in the increasing (vs. low stable) discrimination group had greater decrease in sleep quality. There was no association between change in discrimination and change in sleep duration. Among Sleep Exam participants, higher discrimination was cross-sectionally associated with shorter self-reported sleep duration, independent of stress. Conclusion Discrimination is a unique stressor for African-Americans; thus, future research should identify interventions to reduce the burden of discrimination on sleep quality.

Background Multiple aspects of sleep and Sleep Disordered Breathing (SDB) have been linked to hypertension. However, the standard measure of SDB, the Apnoea Hypopnea Index (AHI), has not identified patients likely to experience large improvements in blood pressure with SDB treatment. Methods To use machine learning to select sleep and pulmonary measures associated with hypertension development when considered jointly, we applied feature screening followed by Elastic Net penalized regression in association with incident hypertension using a wide array of polysomnography measures, and lung function, derived for the Sleep Heart Health Study (SHHS). Findings At baseline, n=860 SHHS individuals with complete data were age 61 years, on average. Of these, 291 developed hypertension ~5 years later. A combination of pulmonary function and 18 sleep phenotypes predicted incident hypertension (OR=1.43, 95% confidence interval [1.14, 1.80] per 1 standard deviation (SD) of the phenotype), while the apnoea-hypopnea index (AHI) had low evidence of association with incident hypertension (OR =1.13, 95% confidence interval [0.97, 1.33] per 1 SD). In a generalization analysis in 923 individuals from the Multi-Ethnic Study of Atherosclerosis, aged 65 on average with 615 individuals with hypertension, the new phenotype was cross-sectionally associated with hypertension (OR=1.26, 95% CI [1.10, 1.45]). Interpretation A unique combination of sleep and pulmonary function measures better predicts hypertension compared to the AHI. The composite measure included indices capturing apnoea and hypopnea event durations, with shorter event lengths associated with increased risk of hypertension. Funding This research was supported by National Heart, Lung, and Blood Institute (NHLBI) contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and by National Center for Advancing Translational Sciences grants UL1-TR- 000040, UL1-TR-001079, and UL1-TR-001420. The MESA Sleep ancillary study was supported by NHLBI grant HL-56984. Pulmonary phenotyping in MESA was funded by NHLBI grants R01-HL077612 and R01-HL093081. This work was supported by NHLBI grant R35HL135818 to Susan Redline.

Study Objectives To quantify the gender-specific associations between insomnia symptoms and subclinical atherosclerosis, measured by coronary artery calcium (CAC) scores, which has strong predictive value for incident cardiovascular disease. Methods We analyzed data from 1,429 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants completed standardized questionnaires and underwent polysomnography (PSG) and 7-day actigraphy. Insomnia symptoms were defined as: self-reported trouble falling, staying or returning to sleep, early-morning awakenings, or hypnotic use, for ≥5 nights/week. MESA assessed CAC using computed tomography. We employed multivariable linear regression to model the probability of CAC >0 overall and to model the linear continuous effect among those with nonzero CAC. Results Our sample was a mean age of 68.1 ± 9.1 years, 53.9% female, and 36.2% white, 28.0% black, 24.2% Hispanic, and 11.5% Chinese-American. Insomnia symptoms were present in 49.7% of men and 47.2% of women. In multivariable-adjusted analyses, insomnia symptoms was associated with an 18% higher prevalence of CAC (PR 1.18, 95% CI 1.04, 1.33) among females, but no association was observed among males (PR 1.00, 95% CI 0.91, 1.08). There was no evidence that the association between insomnia symptoms and prevalence of CAC >0 differed by objective sleep duration status (by single-night PSG or multi-night actigraphy) in females or males. Conclusions We found that among women, insomnia symptoms were associated with an 18% higher prevalence of CAC compared to no insomnia. Insomnia symptoms were not associated with CAC prevalence in men. Additionally, there was no evidence that the association between insomnia symptoms and CAC score >0 differed by objective short sleep duration status.

Study Objectives Disrupted daily rhythms are associated with mild cognitive impairment (MCI) and dementia. The specific nature of how rhythms and cognition are related, however, is unknown. We hypothesized characteristics from a nonparametric estimate of circadian rest-activity rhythm patterns would be associated to the development of MCI or dementia. Methods Wrist actigraphy from 1232 cognitively healthy, community-dwelling women (mean age 82.6 years) from the Study of Osteoporotic Fractures was used to estimate rest-activity patterns, including intradaily variability (IV), interdaily stability (IS), most active 10-hour period (M10), least active 5-hour period (L5), and relative amplitude (RA). Logistic regression examined associations of these predictors with 5-year incidence of MCI or dementia. Models were adjusted for potential confounders. Results Women with earlier sleep/wake times had higher risk of dementia, but not MCI, (early vs. average L5 midpoint: OR, 1.66; 95% CI, 1.08–2.55) as did women with smaller day/night activity differentials (low vs. high RA: OR, 1.96; 95% CI, 1.14–3.35). IV, IS, and M10 were not associated with MCI or dementia. Conclusion The timing and difference in day/night amplitude, but not variability of activity, may be useful as predictors of dementia.

Traditionally, the presence and severity of obstructive sleep apnea (OSA) have been defined by the apnea–hypopnea index (AHI). Continuous positive airway pressure is generally first-line therapy despite low adherence, because it reliably reduces the AHI when used, and the response to other therapies is variable. However, there is growing appreciation that the underlying etiology (i.e., endotype) and clinical manifestation (i.e., phenotype) of OSA in an individual are not well described by the AHI. We define and review the important progress made in understanding and measuring physiological mechanisms (or endotypes) that help define subtypes of OSA and identify the potential use of genetics to further refine disease classification. This more detailed understanding of OSA pathogenesis should influence clinical treatment decisions as well as help inform research priorities and clinical study design. In short, treatments could be individualized on the basis of the underlying cause of OSA; patients could better understand which symptoms and outcomes will respond to OSA treatment and by how much; and researchers could select populations most likely to benefit from specific treatment approaches for OSA.

BackgroundMechanisms underlying blood pressure (BP) changes in obstructive sleep apnoea (OSA) are incompletely understood. We assessed the associations between BP and selected polysomnography (PSG) traits: sleep depth, airflow limitation measurements and OSA-specific hypoxic burden.MethodsThis cross-sectional analysis included 2055 participants from the Multi-Ethnic Study of Atherosclerosis who underwent PSG and BP measurements in 2010–2013. Sleep depth was assessed using the ‘OR product’, a continuous measure of arousability. Airflow limitation was assessed by duty cycle (Ti/Tt) and % of breaths with flow limitation, and hypoxia by ‘hypoxic burden’. Primary outcomes were medication-adjusted systolic BP (SBP) and diastolic BP (DBP). We used generalised linear models adjusted for age, sex, race/ethnicity, smoking, education, body mass index, alcohol use, periodic limb movements and alternative physiological disturbances.ResultsThe sample had a mean age of 68.4 years and apnoea–hypopnoea index of 14.8 events/hour. Sleep depth was not significantly associated with BP. Every 1 SD increment in log-transformed non-rapid eye movement duty cycle was associated with 0.9% decrease in SBP (95% CI: 0.1% to 1.6%), even after adjusting for sleep depth and hypoxic burden. Every 1 SD increment in log-transformed hypoxic burden was associated with a 1.1% increase in SBP (95% CI: 0.1% to 2.1%) and 1.9% increase in DBP (95% CI: 1.0% to 2.8%) among those not using hypertension medications.ConclusionsHigher duty cycle was associated with lower SBP overall and hypoxic burden with higher SBP and DBP among non-BP medication users. These findings suggest changes in both respiratory effort and oxygenation during sleep influence BP.

PURPOSE: Evidence suggests that snoring is associated with increased risk for cardiovascular disease (CVD) events such as myocardial infarction and stroke. Limited data exists pertaining to this association among African Americans. We therefore examined the association between self-reported habitual snoring and incident CVD in the Jackson Heart Study (JHS), a population-based cohort study of African Americans. METHODS: Self-reported data on snoring and risk factors for CVD were collected at baseline (2000-2004). Participants were followed prospectively for the development of incident CVD. Habitual snoring was defined as present if the participants reported it as “often” or “almost always” or absent if reported as “sometimes”, “never”, or “seldom”. A CVD event included stroke, myocardial infarction, coronary revascularization procedure or fatal CHD event. Cox proportional hazards models assessed the independent association between self-reported habitual snoring and incident CVD event adjusting for multiple covariates including age, sex, hypertension, body mass index, diabetes, hypercholesterolemia, smoking status. RESULTS: The snorer group consisted of 787 participants (mean age 52.1 years) and the non-snorer group consisted of 3708 participants (mean age 54.9 years). Frequency of incident CVD events in the snorer group was not significantly different from the non-snorer group. The fully adjusted hazard ratio for a CVD event in the snorer group was 1.01 (95% confidence interval [0.69, 1.47], p-value of 0.96). CONCLUSION: In conclusion, self-reported habitual snoring was not associated with incident CVD amongst this large African American cohort. Future studies providing objective data on snoring and sleep apnea may provide more information on the snoring-CVD association among African Americans.

PURPOSE: Sleep apnea is associated with increased risk of cardiovascular disease. Elevated plasma galectin-3 levels, a biomarker associated with myocardial fibrosis, are also associated with adverse cardiovascular events, including heart failure. Our objective was to determine the relationship between severity of sleep apnea and plasma levels of galectin-3 and to determine whether this relationship was modified by sex. METHODS: We performed a cross-sectional study of 471 Mexican-Americans from Starr County, TX who underwent an overnight, in-home sleep evaluation and plasma measurement of galectin-3. Severity of sleep apnea was based on apnea hypopnea index (AHI). Multivariable linear regression modeling was used to determine the association between categories of sleep apnea and galectin-3. We also tested for interactions by sex. RESULTS: The mean age was 53 years and 74% of the cohort were female. The prevalence of moderate to severe sleep apnea (AHI>15 apnea-hypopnea events per hour) was 36.7%. Moderate to severe sleep apnea was associated with increased levels of galectin-3 in the entire population, but we identified a statistically significant interaction between galectin-3 levels and category of sleep apnea by sex (p-for interaction=0.02). Plasma galectin levels were significantly higher in women with moderate or severe sleep apnea than women with no/mild sleep apnea (multivariable adjusted p< 0.001), but not in men (p=0.5). CONCLUSIONS: Sleep apnea is associated elevated galectin-3 levels in women but not men. Our findings highlight a possible sex-specific relationship between sleep apnea and galectin-3, a biomarker of potential myocardial fibrosis that has been associated with increased cardiovascular risk.

INTRODUCTION: We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer’s disease risk. METHODS: We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia-free Framingham Heart Study participants (62.65 ± 8.7 years, 50.9% male). Additionally, we explored insomnia symptoms combined with self-reported short habitual sleep duration and effect modification by apolipoprotein E (APOE) ε4 allele status. RESULTS: More severe insomnia symptoms were associated with lower performance on global cognition, and immediate and delayed Logical Memory recall, especially when insomnia symptoms were combined with short sleep duration. The association between insomnia symptoms and poorer memory recall was more pronounced in APOE ε4 allele carriers. DISCUSSION: Insomnia symptom severity was associated with worse subsequent global cognitive and memory performance, which was especially apparent in APOE ε4 allele carriers, suggesting that poor sleep might be particularly detrimental when the brain is already vulnerable to neurodegeneration.

Study Objectives We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches. Methods Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in the United Kingdom/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for sociodemographics. Average and SD of 11 sleep measures over 7 days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures. Results In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency, and wake after sleep onset were not associated with global T-scores according to rank regression (p = 0.51, p = 0.09, p = 0.16, respectively). In contrast, global T-scores were associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency, and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males). Conclusions Using multivariable analytical approaches, measures of sleep continuity, timing, and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in the assessment of health and functioning.

Because of their roles as potential risk factors, we evaluated whether obstructive sleep apnea (OSA) severity interacts with interleukin-6 (IL-6) in predicting incident dementia of the Alzheimer’s type (DAT). In 269 dementia-free participants, IL-6 and the apnea-hypopnea index (AHI) were measured at baseline and incident DAT was surveilled for up to 22.8 years. Cox models revealed a significant interaction: In the lowest IL-6 quartile only, a higher AHI was associated with an elevated risk of DAT. The association between OSA severity and incident DAT might be especially apparent in the absence of inflammation or absence of potential benefits from IL-6.