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1.
J Clin Sleep Med ; 15(7): 973-978, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31383234

RESUMO

STUDY OBJECTIVES: Low physical activity (PA) is associated with poor health outcomes in chronic obstructive pulmonary disease (COPD). Overlap syndrome (OVS), the co-occurrence of COPD and obstructive sleep apnea (OSA), is highly prevalent. Little is known about PA in OVS, and its relationship with markers of systemic inflammation. METHODS: We studied 256 persons with stable COPD, 61 (24%) of whom had OVS, who were well characterized in two previous PA studies. PA was directly assessed with the Omron HJ-720ITC pedometer. C-reactive protein (CRP) and interleukin-6 (IL-6) were assayed from peripheral blood. Linear regression models, adjusting for age and forced expiratory volume in 1 second (FEV1) % predicted, assessed daily step counts and CRP and IL-6 levels in OVS, compared to COPD alone. Linear regression models, adjusting for age, FEV1 % predicted, and coronary artery disease, assessed the relationships between PA and CRP and IL-6 in those with OVS versus those with COPD alone. RESULTS: Compared to COPD alone, persons with OVS walked 672 fewer steps per day (95% CI -1,317 to -28, P = .041). Those with OVS had significantly higher levels of CRP and IL-6 compared to COPD alone. In OVS, each 1,000 fewer steps walked was associated with a 0.875 ng/mL (95% CI 0.767 to 0.997) increase in IL-6, independent of lung function. CONCLUSIONS: Persons with OVS have significantly lower levels of PA and higher levels of inflammatory biomarkers, compared to COPD alone. Lower PA is significantly associated with higher IL-6 levels in OVS.

2.
Med Care ; 57(8): 601-607, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31295189

RESUMO

OBJECTIVE: To develop and validate a measure that estimates individual level poverty in Medicare administrative data that can be used in studies of Medicare claims. DATA SOURCES: A 2008 to 2013 Medicare Current Beneficiary Survey linked to 2008 to 2013 Medicare fee-for-service beneficiary summary file and census data. STUDY DESIGN AND METHODS: We used the Medicare Current Beneficiary Survey to define individual level poverty status and linked to Medicare administrative data (N=38,053). We partitioned data into a measure derivation dataset and a validation dataset. In the derivation data, we used a logistic model to regress poverty status on measures of dual eligible status, part D low-income subsidy, and demographic and administrative data, and modeled with and without linked census and nursing home data. Each beneficiary receives a predicted poverty score from the model. Performance was evaluated in derivation and validation data and compared with other measures used in the literature. We present a measure for income-only poverty as well as one for income and asset poverty. PRINCIPAL FINDINGS: A score (predicted probability of income poverty) >0.5 yielded 58% sensitivity, 94% specificity, and 84% positive predictive value in the derivation data; our score yielded very similar results in the validation data. The model's c-statistic was 0.84. Our poverty score performed better than Medicaid enrollment, high zip code poverty, and zip code median income. The income and asset version performed similarly well. CONCLUSIONS: A poverty score can be calculated using Medicare administrative data for use as a continuous or binary measure. This measure can improve researchers' ability to identify poverty in Medicare administrative data.

3.
PLoS Genet ; 15(4): e1007739, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30990817

RESUMO

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.


Assuntos
Hexoquinase/genética , Subunidade alfa de Receptor de Interleucina-18/genética , Oxiemoglobinas/metabolismo , Sono/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular Neuronais/genética , Biologia Computacional , Proteínas da Matriz Extracelular/genética , Feminino , Redes Reguladoras de Genes , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Hipóxia/sangue , Hipóxia/genética , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas do Tecido Nervoso/genética , Oxigênio/sangue , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Serina Endopeptidases/genética , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/genética , Adulto Jovem
4.
Med Care ; 57(6): 444-452, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31008898

RESUMO

OBJECTIVE: To examine changes in more and less discretionary condition-specific postacute care use (skilled nursing, inpatient rehabilitation, home health) associated with Medicare accountable care organization (ACO) implementation. DATA SOURCES: 2009-2014 Medicare fee-for-service claims. STUDY DESIGN: Difference-in-difference methodology comparing postacute outcomes after hospitalization for hip fracture and stroke (where rehabilitation is fundamental to the episode of care) to pneumonia, (where it is more discretionary) for beneficiaries attributed to ACO and non-ACO providers. PRINCIPAL FINDINGS: Across all 3 cohorts, in the baseline period ACO patients were more likely to receive Medicare-paid postacute care and had higher episode spending. In hip fracture patients where rehabilitation is standard of care, ACO implementation was associated with 6%-8% increases in probability of admission to a skilled nursing facility or inpatient rehabilitation (compared with home without care), and a slight reduction in readmissions. In a clinical condition where rehabilitation is more discretionary, pneumonia, ACO implementation was not associated with changes in postacute location, but episodic spending decreased 2%-3%. Spending decreases were concentrated in the least complex patients. Across all cohorts, the length of stay in skilled nursing facilities decreased with ACO implementation. CONCLUSIONS: ACOs decreased spending on postacute care by decreasing use of discretionary services. ACO implementation was associated with reduced length of stay in skilled nursing facilities, while hip fracture patients used institutional postacute settings at higher rates. Among pneumonia patients, we observed decreases in spending, readmission days, and mortality associated with ACO implementation.

5.
Nat Commun ; 10(1): 1100, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30846698

RESUMO

Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10-8; 43 loci at p < 6 × 10-9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10-4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.


Assuntos
Loci Gênicos , Sono/genética , Acelerometria , Adulto , Idoso , Grupo com Ancestrais do Continente Europeu , Feminino , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Autorrelato , Sono/fisiologia , Reino Unido
6.
Am J Respir Crit Care Med ; 200(4): 493-506, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30764637

RESUMO

Rationale: Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular consequences.Objectives: To characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study.Methods: Data from 1,207 patients with OSA (apnea-hypopnea index ≥ 15 events/h) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease and its components (coronary heart disease, heart failure, and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality.Measurements and Main Results: Four symptom subtypes were identified (disturbed sleep [12.2%], minimally symptomatic [32.6%], excessively sleepy [16.7%], and moderately sleepy [38.5%]), similar to prior studies. In adjusted models, although no significant associations with prevalent cardiovascular disease were found, the excessively sleepy subtype was associated with more than threefold increased risk of prevalent heart failure compared with each of the other subtypes. Symptom subtype was also associated with incident cardiovascular disease (P < 0.001), coronary heart disease (P = 0.015), and heart failure (P = 0.018), with the excessively sleepy again demonstrating increased risk (hazard ratios, 1.7-2.4) compared with other subtypes. When compared with individuals without OSA (apnea-hypopnea index < 5), significantly increased risk for prevalent and incident cardiovascular events was observed mostly for patients in the excessively sleepy subtype.Conclusions: OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.

7.
Psychiatry Res ; 273: 247-251, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30658209

RESUMO

The relationship between three markers of chronic hypoxia (altitude, smoking and chronic obstructive pulmonary disease (COPD)) and suicide risk has not been well-studied. We conducted a population-based cohort study evaluating the association between chronic hypoxia and suicide risk. Patients entered the cohort in their first year with a documented healthcare encounter and remained in the cohort until their death or the end of the study period. Generalized estimating equation (GEE) methodology was used to assess the association between suicide and three risk markers of chronic hypoxia. Findings were summarized using odds ratio (OR) and 95% confidence intervals (CI). Among the 9,620,944 patients in the cohort, there were 22,403 suicide deaths. There was a statistically significant progression of suicide risk as altitude rose in increments of 1000 m (OR: 1.22). There was a strong association between the number of hypoxic conditions and the odds of suicide. Patients with three markers of chronic hypoxia was nearly four times more likely to die by suicide than patients with no markers (OR: 3.96). Chronic hypoxia is a risk factor for suicide and having multiple indicators of hypoxia confers a greater risk for suicide, indicating a dose-response relationship.

8.
J Am Coll Cardiol ; 73(2): 145-147, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30654885
9.
Hum Mol Genet ; 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30403821

RESUMO

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 oxyhemoglobin saturation 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.

11.
Health Aff (Millwood) ; 37(6): 975-979, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29863917

RESUMO

From 2013 to 2017 the Centers for Medicare and Medicaid Services redacted Medicare claims that included diagnosis or procedure codes related to substance abuse. The redaction policy was in effect as the Affordable Care Act and the opioid epidemic changed the health care landscape. The policy substantially altered prevalence estimates of common chronic conditions that co-occur with substance abuse.

12.
Sleep ; 41(6)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29522193

RESUMO

Study Objectives: To quantify the association between insomnia or poor sleep with objective short sleep duration and incident cardiovascular disease (CVD) and mortality in the general population. Methods: We conducted a time-to-event analysis of Sleep Heart Health Study data. Questionnaires and at-home polysomnography (PSG) were performed between 1994 and 1998. Participants were followed for a median of 11.4 years (Q1-Q3, 8.8-12.4 years) until death or last contact. The primary exposure was insomnia or poor sleep with short sleep defined as follows: difficulty falling asleep, difficulty returning to sleep, early morning awakenings, or sleeping pill use, 16-30 nights per month; and total sleep of <6 hr on PSG. We used proportional hazard models to estimate the association between insomnia or poor sleep with short sleep and CVD, as well as all-cause mortality. Results: Among 4994 participants (mean age: 64.0 ± 11.1 years), 14.1 per cent reported insomnia or poor sleep, of which 50.3 per cent slept <6 hr. Among 4437 CVD-free participants at baseline, we observed 818 incident CVD events. After propensity adjustment, there was a 29 per cent higher risk of incident CVD in the insomnia or poor sleep with short sleep group compared with the reference group (HR: 1.29, 95% CI: 1.00, 1.66), but neither the insomnia or poor sleep only nor short sleep only groups were associated with higher incident CVD. Insomnia or poor sleep with objective short sleep was not associated with all-cause mortality (HR: 1.07, 95% CI: 0.86, 1.33). Conclusions: Insomnia or poor sleep with PSG-short sleep was associated with higher risk of incident CVD. Future studies should evaluate the impact of interventions to improve insomnia with PSG-short sleep on CVD.

14.
BMC Med ; 16(1): 44, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29554902

RESUMO

BACKGROUND: Insufficient sleep duration and obstructive sleep apnea, two common causes of sleep deficiency in adults, can result in excessive sleepiness, a well-recognized cause of motor vehicle crashes, although their contribution to crash risk in the general population remains uncertain. The objective of this study was to evaluate the relation of sleep apnea, sleep duration, and excessive sleepiness to crash risk in a community-dwelling population. METHODS: This was a prospective observational cohort study nested within the Sleep Heart Health Study, a community-based study of the health consequences of sleep apnea. The participants were 1745 men and 1456 women aged 40-89 years. Sleep apnea was measured by home polysomnography and questionnaires were used to assess usual sleep duration and daytime sleepiness. A follow-up questionnaire 2 years after baseline ascertained driving habits and motor vehicle crash history. Logistic regression analysis was used to examine the relation of sleep apnea and sleep duration at baseline to the occurrence of motor vehicle crashes during the year preceding the follow-up visit, adjusting for relevant covariates. The population-attributable fraction of motor vehicle crashes was estimated from the sample proportion of motor vehicle crashes and the adjusted odds ratios for motor vehicle crash within each exposure category. RESULTS: Among 3201 evaluable participants, 222 (6.9%) reported at least one motor vehicle crash during the prior year. A higher apnea-hypopnea index (p < 0.01), fewer hours of sleep (p = 0.04), and self-reported excessive sleepiness (p < 0.01) were each significantly associated with crash risk. Severe sleep apnea was associated with a 123% increased crash risk, compared to no sleep apnea. Sleeping 6 hours per night was associated with a 33% increased crash risk, compared to sleeping 7 or 8 hours per night. These associations were present even in those who did not report excessive sleepiness. The population-attributable fraction of motor vehicle crashes was 10% due to sleep apnea and 9% due to sleep duration less than 7 hours. CONCLUSIONS: Sleep deficiency due to either sleep apnea or insufficient sleep duration is strongly associated with motor vehicle crashes in the general population, independent of self-reported excessive sleepiness.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Privação do Sono/epidemiologia , Acidentes de Trânsito/psicologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
15.
Ann Am Thorac Soc ; 15(2): 117-126, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29388810

RESUMO

The purpose of this workshop was to identify knowledge gaps in the perioperative management of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). A single-day meeting was held at the American Thoracic Society Conference in May, 2016, with representation from many specialties, including anesthesiology, perioperative medicine, sleep, and respiratory medicine. Further research is urgently needed as we look to improve health outcomes for these patients and reduce health care costs. There is currently insufficient evidence to guide screening and optimization of OSA and OHS in the perioperative setting to achieve these objectives. Patients who are at greatest risk of respiratory or cardiac complications related to OSA and OHS are not well defined, and the effectiveness of monitoring and other interventions remains to be determined. Centers involved in sleep research need to develop collaborative networks to allow multicenter studies to address the knowledge gaps identified below.

16.
Am J Respir Crit Care Med ; 197(5): 653-660, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29112823

RESUMO

RATIONALE: Obstructive sleep apnea (OSA) during REM sleep is a common disorder. Data on whether OSA that occurs predominantly during REM sleep is associated with health outcomes are limited. OBJECTIVES: The present study examined the association between OSA during REM sleep and a composite cardiovascular endpoint in a community sample with and without prevalent cardiovascular disease. METHODS: Full-montage home polysomnography was conducted as part of the Sleep Heart Health Study. The study cohort was followed for an average of 9.5 years, during which time cardiovascular events were assessed. Only participants with a non-REM apnea-hypopnea index (AHI) of less than 5 events/h were included. A composite cardiovascular endpoint was determined as the occurrence of nonfatal or fatal events, including myocardial infarction, coronary artery revascularization, congestive heart failure, and stroke. Proportional hazards regression was used to derive the adjusted hazards ratios for the composite cardiovascular endpoint. MEASUREMENTS AND MAIN RESULTS: The sample consisted of 3,265 subjects with a non-REM AHI of less than 5.0 events/h. Using a REM AHI of less than 5.0 events/h as the reference group (n = 1,758), the adjusted hazards ratios for the composite cardiovascular endpoint in those with severe REM OSA (≥30 events/h; n = 180) was 1.35 (95% confidence interval, 0.98-1.85). Stratified analyses demonstrated that the association was most notable in those with prevalent cardiovascular disease and severe OSA during REM sleep with an adjusted hazards ratio of 2.56 (95% confidence interval, 1.46-4.47). CONCLUSIONS: Severe OSA that occurs primarily during REM sleep is associated with higher incidence of a composite cardiovascular endpoint, but in only those with prevalent cardiovascular disease.

17.
Sleep ; 41(1)2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087522

RESUMO

We sought to quantify the association between slow-wave (stage N3) sleep and hypertension in a large cohort of middle-aged men and women. Data from 1850 participants free of baseline hypertension from the Sleep Heart Health Study were analyzed. The primary exposure was percentage of N3 sleep on baseline in-home polysomnography and the primary outcome was incident hypertension, defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90 mm Hg, and/or use of any blood pressure lowering medications at follow-up. Multivariable logistic regression models were adjusted for study site, age, sex, race, waist circumference, tobacco use, alcohol use, apnea-hypopnea index, nocturnal oxygen desaturation, sleep duration, sleep efficiency, and arousal index. Mean age was 59.4 ± 10.1 years and 55.5% were female. The mean baseline systolic and diastolic blood pressure was 118.8 and 70.6 mm Hg, respectively. Approximately 30% of the sample developed hypertension during a mean follow-up of 5.3 years. In the multi-adjusted model, participants in quartiles 1 (<9.8%) and 2 (9.8%-17.7%) of N3 sleep had significantly greater odds of incident hypertension compared with those in quartile 3 (17.7%-25.2%) (OR 1.69, 95% CI 1.21-2.36, p = .002 and OR 1.45, 95% CI 1.04-2.00, p = .03, respectively). No significant effect modification by sex on the N3-hypertension association was observed. In conclusion, compared with intermediate levels of N3 sleep (overlapping the "normal" adult range), lower levels of percent N3 sleep are associated with increased odds of incident hypertension in both men and women, independent of potential confounders, including indices of sleep apnea and sleep fragmentation.

18.
Eur Respir J ; 50(5)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29191951

RESUMO

We evaluated factors associated with subjective and objective sleepiness at baseline and after 6 months of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA).We analysed data from the Apnoea Positive Pressure Long-term Efficacy Study (APPLES), a prospective 6-month multicentre randomised controlled trial with 1105 subjects with OSA, 558 of who were randomised to active CPAP. Epworth sleepiness scale (ESS) scores and the mean sleep latency (MSL) on the maintenance of wakefulness test at baseline and after 6 months of CPAP therapy were recorded.Excessive sleepiness (ESS score >10) was present in 543 (49.1%) participants. Younger age, presence of depression and higher apnoea-hypopnoea index were all associated with higher ESS scores and lower MSL. Randomisation to the CPAP group was associated with lower odds of sleepiness at 6 months. The prevalence of sleepiness was significantly lower in those using CPAP >4 h·night-1versus using CPAP ≤4 h·night-1 Among those with good CPAP adherence, those with ESS >10 at baseline had significantly higher odds (OR 8.2, p<0.001) of persistent subjective sleepiness.Lower average nightly CPAP use and presence of sleepiness at baseline were independently associated with excessive subjective and objective sleepiness after 6 months of CPAP therapy.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Distúrbios do Sono por Sonolência Excessiva/prevenção & controle , Apneia Obstrutiva do Sono/terapia , Vigília/fisiologia , Adulto , Depressão , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo
19.
Front Genet ; 8: 151, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29093733

RESUMO

Obstructive sleep apnea (OSA) is a common sleep breathing disorder associated with an increased risk of cardiovascular and cerebrovascular diseases and mortality. Although OSA is fairly heritable (~40%), there have been only few studies looking into the genetics of OSA. In the present study, we aimed to identify genetic variants associated with symptoms of sleep apnea by performing a whole-exome sequence meta-analysis of symptoms of sleep apnea in 1,475 individuals of European descent. We identified 17 rare genetic variants with at least suggestive evidence of significance. Replication in an independent dataset confirmed the association of a rare genetic variant (rs2229918; minor allele frequency = 0.3%) with symptoms of sleep apnea (p-valuemeta = 6.98 × 10-9, ßmeta = 0.99). Rs2229918 overlaps with the 3' untranslated regions of ERCC1 and CD3EAP genes on chromosome 19q13. Both genes are expressed in tissues in the neck area, such as the tongue, muscles, cartilage and the trachea. Further, CD3EAP is localized in the nucleus and mitochondria and involved in the tumor necrosis factor-alpha/nuclear factor kappa B signaling pathway. Our results and biological functions of CD3EAP/ERCC1 genes suggest that the 19q13 locus is interesting for further OSA research.

20.
Neurology ; 89(12): 1244-1250, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28835407

RESUMO

OBJECTIVE: Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS). METHODS: Our sample comprised a subset of 321 FHS Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998 and who were aged over 60 years at the time of sleep assessment (mean age 67 ± 5 years, 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for a maximum of 19 years for incident dementia (mean follow-up 12 ± 5 years). RESULTS: We observed 32 cases of incident dementia; 24 were consistent with Alzheimer disease dementia. After adjustments for age and sex, lower REM sleep percentage and longer REM sleep latency were both associated with a higher risk of incident dementia. Each percentage reduction in REM sleep was associated with approximately a 9% increase in the risk of incident dementia (hazard ratio 0.91; 95% confidence interval 0.86, 0.97). The magnitude of association between REM sleep percentage and dementia was similar following adjustments for multiple covariates including vascular risk factors, depressive symptoms, and medication use, following exclusions for persons with mild cognitive impairment at baseline and following exclusions for early converters to dementia. Stages of non-REM sleep were not associated with dementia risk. CONCLUSIONS: Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia.


Assuntos
Demência/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , Sono REM/fisiologia , Idoso , Demência/etiologia , Feminino , Seguimentos , Humanos , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Polissonografia , Risco , Transtornos do Sono-Vigília/complicações
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