Investigation of the Relationships Between Sleep Behaviors and Risk of Health Lifespan Termination: A Prospective Cohort Study Based on 323,373 UK-Biobank Participants

Abstract Objectives: To examine the associations between insomnia, napping, daytime sleepiness, and getting up from bed with the risk of health lifespan termination using a prospective cohort design based on the UK-Biobank (UKB) database. Methods: Our study population consisted of 323,373 UKB participants enrolled in the UKB study from 2006 to 2010 and followed up to 2016. The outcome variable was health lifespan that was characterized by eight events strongly associated with ageing. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for risk of terminated health lifespan were computed in Cox proportional hazards models. Furthermore, we collapsed each of the four sleep behavior factors into binary categories (high vs. low-risk groups) to explore the Population Attributable Risk percentages (PAR%).Results: Participants in the high-risk subgroups of the four sleep behaviors had a significantly higher risk of terminated health lifespan; that is, 'usually insomnia' (HR=1.05, 95% CI: 1.03-1.07; P<0.001), 'usually napping' (HR=1.22, 95% CI: 1.18-1.26; P<0.01), 'excessive daytime sleepiness' (HR=1.25, 95% CI: 1.19-1.32; P<0.001), and 'difficult getting up from bed' (HR=1.08, 95% CI: 1.05-1.10; P<0.001). The corresponding PAR% indicated that about 7% of the terminated health lifespan events in this cohort would have been eliminated if all people were in the low-risk sleep groups.Conclusion: We observed that frequent insomnia, napping, daytime sleepiness, and 'difficult getting up from bed' are associated with increased risk of terminated health lifespan. Therefore adherence to healthy sleep behavior is significant for healthy lifespan.

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Associations Between Sleep Quality and Health Span: A Prospective Cohort Study Based on 328,850 UK Biobank Participants

Frontiers in Genetics ◽

10.3389/fgene.2021.663449 ◽

2021 ◽

Vol 12 ◽

Author(s):

Muhammed Lamin Sambou ◽

Xiaoyu Zhao ◽

Tongtong Hong ◽

Jingyi Fan ◽

Til Bahadur Basnet ◽

...

Keyword(s):

Cohort Study ◽

Sleep Quality ◽

Prospective Cohort ◽

Population Attributable Risk ◽

Chronic Obstructive ◽

Poor Sleep ◽

Uk Biobank ◽

Health Span ◽

Sleep Behavior ◽

Reduced Risk

ObjectiveTo examine the associations between sleep quality and health span using a prospective cohort design based on the UK Biobank (UKB).Materials and MethodsThis longitudinal cohort study enrolled 328,850 participants aged between 37 and 73 years from UKB to examine the associations between sleep quality and risk of terminated health span. End of health span was defined by eight events strongly associated with longevity (cancer, death, congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, and diabetes), and a sleep score was generated according to five sleep behavioral factors (sleep duration, chronotype, sleeplessness, daytime sleepiness, and snoring) to characterize sleep quality. The hazard ratio (HR) and 95% confidence intervals (CIs) were calculated by multivariate-adjusted Cox proportional hazards model. Moreover, we calculated population attributable risk percentage (PAR%) to reflect the public health significance of healthy sleep quality.ResultsCompared with poor sleep quality, participants with healthy sleep quality had a 15% (HR: 0.85, 95% CI: 0.81–0.88) reduced risk of terminated health span, and those of less-healthy sleep quality had a 12% (HR: 0.88, 95% CI: 0.85–0.92) reduced risk. Linear trend results indicated that the risk of terminated health span decreased by 4% for every additional sleep score. Nearly 15% health span termination events in this cohort would have been prevented if a healthy sleep behavior pattern was adhered to (PAR%: 15.30, 95% CI: 12.58–17.93).ConclusionHealthy sleep quality was associated with a reduced risk of premature end of health span, suggesting healthy sleep behavior may extend health span. However, further studies are suggested for confirmation of causality and potential mechanism.

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Understanding sleep-wake behavior in late chronotype adolescents: The role of circadian phase, sleep timing, and evening vigilance

10.31234/osf.io/npkeu ◽

2021 ◽

Author(s):

Christin Lang ◽

Cele Richardson ◽

Gorica Micic ◽

Michael Gradisar

Keyword(s):

Sleep Quality ◽

Mood Disorders ◽

Sleep Duration ◽

Daytime Sleepiness ◽

Sleep Diary ◽

General Tendency ◽

Sleep Behavior ◽

Increased Risk ◽

Phase Angles

Background. Growing evidence supports a link between late chronotype and increased risk for affective disorders. Yet, the tendency toward a late chronotype and the onset of mood disorders often emerge during adolescence. Few studies have examined the relationship among school-aged adolescence. Therefore, the present study aimed to investigate the specific role of sleep and circadian related measures in late chronotype adolescents and their impact on mood. Furthermore, we explored to what extend severeness is explained by bedtime behavior, evening vigilance, and circadian phase.Methods. Nineteen male adolescents (M = 16.4 yrs ± 1.0 yrs), who were part of a larger study, were included in the analyses. Chronotype was assessed with the Munich Chronotype questionnaire, circadian timing via salivary dim light melatonin onset (DLMO), and habitual sleep behavior with a 7-day sleep diary. Further questionnaires evaluated daytime sleepiness, sleep quality, and mood. Evening vigilance (Go/NoGo) and sleepiness (Karolinska Sleepiness Scale) were used as a proxy for sleep propensity. Results. The average sleep duration on school nights was 7.78 hours (±1.65), and 9.00 hours (±1.42) on weekend nights. Mean DLMO was observed at 23.13 h (± 1.65), with a weekend phase angle of entrainment for DLMObedtime of 2.48 hours. Regression fittings revealed a general tendency of shorter phase angles with delayed DLMOs. In contrast, further analysis with chronotype subgroups revealed that this was only true for light and moderate late types, whereas extreme late types presented with wide phase angles. While no differences in daytime sleepiness and sleep duration were found between subgroups, sleep quality and mood decreased with increasing lateness. Extreme late chronotypes experienced higher evening sleepiness, whereas slight late types presented with higher evening vigilance. Chronotype but not DLMO predicted bedtime on school- and particularly weekend-nights. Conclusions. Our findings highlight that with increasing lateness, the risk for impaired sleep quality and mood disorders increases. Given that DLMO was not predictive of bedtime, our data indicate that factors contributing to a late chronotype are versatile and complex, particularly for extreme late types.

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Transthyretin-stabilizing mutation T119M is not associated with protection against vascular disease or death in the UK Biobank

10.1101/771626 ◽

2019 ◽

Author(s):

Margaret M. Parker ◽

Simina Ticau ◽

James Butler ◽

David Erbe ◽

Madeline Merkel ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cerebrovascular Disease ◽

Vascular Disease ◽

Prospective Cohort ◽

Proportional Hazards ◽

Disease Diagnosis ◽

Cox Proportional Hazards ◽

Uk Biobank ◽

The Uk ◽

Large Prospective Cohort

AbstractBackgroundDestabilized transthyretin (TTR) can result in the progressive, fatal disease transthyretin-mediated (ATTR) amyloidosis. A stabilizing TTR mutation, T119M, is the basis for a therapeutic strategy to reduce destabilized TTR. Recently, T119M was associated with extended lifespan and lower risk of cerebrovascular disease in a Danish cohort. We aimed to determine whether this finding could be replicated in the UK Biobank.MethodsTTR T119M carriers were identified in the UK Biobank, a large prospective cohort of ∼500,000 individuals. Association between T119M genotype and inpatient diagnosis of vascular disease, cardiovascular disease, cerebrovascular disease, and mortality was analyzed.ResultsFrequency of T119M within the white UK Biobank population (n=337,148) was 0.4%. Logistic regression comparing T119M carriers to non-carriers found no association between T119M and vascular disease (odds ratio [OR]=1.08; p=.27), cardiovascular disease (OR=1.08; p=.31), cerebrovascular disease (OR=1.1; p=.42), or death (OR=1.2; p=.06). Cox proportional hazards regression showed similar results (hazard ratio>1, p>.05). Age at death and vascular disease diagnosis were similar between T119M carriers and non-carriers (p=.12 and p=.38, respectively).ConclusionsThere was no association between the TTR T119M genotype and risk of vascular disease or death in a large prospective cohort study, indicating that TTR tetramer stabilization through T119M is not protective in this setting.

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Associations with covid-19 hospitalisation amongst 406,793 adults: the UK Biobank prospective cohort study

10.1101/2020.05.06.20092957 ◽

2020 ◽

Cited By ~ 8

Author(s):

Anthony P Khawaja ◽

Alasdair N Warwick ◽

Pirro G Hysi ◽

Alan Kastner ◽

Andrew Dick ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Antihypertensive Medication ◽

Severe Disease ◽

Chronic Obstructive ◽

Uk Biobank ◽

Antihypertensive Medications ◽

Asian Ethnicity ◽

Increased Risk

ABSTRACTOBJECTIVESTo identify the sociodemographic, lifestyle, comorbidity and antihypertensive medication associations with the development of hospitalisation with covid-19 in an English population.DESIGNProspective cohort studySETTINGThe population-based UK Biobank study was linked to English covid-19 test results.PARTICIPANTSIndividuals resident in England and alive in 2020.MAIN OUTCOME MEASURESCases (n=605) were defined by a positive covid-19 test result conducted between 16th March and 16th April 2020, during a restricted testing policy for hospitalised individuals with severe disease.RESULTSA total of 406,793 participants were included. Mean age on 1st January 2020 was 68 years (range 48 to 85 years). 55% were women. In multivariable models, major independent risk factors for hospitalisation with covid-19 were male sex (odds ratio 1.52; 95% confidence interval 1.28 to 1.81; P<0.001), South Asian ethnicity (2.02; 1.28 to 3.17; P=0.002) or black ethnicity (3.09; 2.18 to 4.38; P<0.001) compared to white ethnicity, greater residential deprivation (1.92 for most deprived quartile compared to least deprived quartile; 1.50 to 2.47; P<0.001), higher BMI (2.04 for BMI >35 compared to <25 Kg/m2; 1.50 to 2.77; P<0.001), former smoking (1.39 compared to never smoked; 1.16 to 1.66; P<0.001), and comorbidities hypertension (1.28; 1.06 to 1.53; P=0.009) and chronic obstructive pulmonary disease (1.81; 1.34 to 2.44; P<0.001). Increased risk was observed with increasing number of antihypertensive medications used rather than any individual class.CONCLUSIONUnderstanding why these factors confer increased risk of severe covid-19 in the population may help elucidate the underlying mechanisms as well as inform strategy and policy to prevent this disease and its consequences. We found no evidence of increased risk with specific classes of antihypertensive medication.

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Visual impairment and risk of dementia in two population-based prospective cohorts: UK Biobank and EPIC-Norfolk

The Journals of Gerontology Series A ◽

10.1093/gerona/glab325 ◽

2021 ◽

Author(s):

Thomas J Littlejohns ◽

Shabina Hayat ◽

Robert Luben ◽

Carol Brayne ◽

Megan Conroy ◽

...

Keyword(s):

Visual Impairment ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Uk Biobank ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Promising Target ◽

Increased Risk

Abstract Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there are a lack of large studies with objective measures of vison and with more than ten years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and EPIC-Norfolk. In both cohorts, visual acuity was measured using a “logarithm of the minimum angle of resolution” (LogMAR) chart and categorised as no (≤0.30 LogMAR), mild (>0.3 - ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62,206 UK Biobank and 7,337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk. respectively, 1,113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% Confidence Interval [CI] 0.92-1.72) and 2.16 (95% CI 1.37-3.40), in UK Biobank, and 1.05 (95% CI 0.72-1.53) and 1.93 (95% CI 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but were not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention, however the possibility of reverse causation cannot be excluded.

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Role of quantitative gene expression using RT-PCR in the prediction of recurrence risk in resected T1 clear cell renal cell carcinoma (ccRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.338 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 338-338

Author(s):

S. Campbell ◽

D. Knezevic ◽

T. Maddala ◽

W. F. Novotny ◽

M. Zhou ◽

...

Keyword(s):

Gene Expression ◽

Cleveland Clinic ◽

Recurrence Risk ◽

Cox Proportional Hazards ◽

Low Risk ◽

Rt Pcr ◽

Cell Renal Cell Carcinoma ◽

Data Set ◽

Qpcr Analysis ◽

Increased Risk

338 Background: Current pathology and clinical methods do not accurately estimate risk of recurrence in all patients with pT1 ccRCC. Quantitative RT-PCR (qPCR) analysis was performed on resected ccRCC tumors to identify genes associated with recurrence that significantly augment current prognostic tools. Methods: A retrospective observational cohort consisting of 931 patients (434 T1a, 201 T1b, 296 T2/3) with ccRCC was evaluated. All patients underwent nephrectomy between 1985 and 2003 at Cleveland Clinic and had paraffin-embedded tumor blocks. Patients with inherited ccRCC or inadequate follow-up (< 6 months or no recurrence data) were excluded. qPCR analysis of 732 genes was performed on all patients. Cox Proportional Hazards regression models were used to evaluate the association between gene expression and recurrence-free interval (RFI). Results: 448 genes were significantly (unadj. p < 0.05) associated with RFI, from which 72 genes were carried forward for further study (Rini, ASCO 2010, #4501). Angiogenesis is the strongest among the pathways represented, from which 3 genes (AQP1, NOS3, PPAP2B) were selected for this analysis. Incorporating these 3 genes, a subset of higher risk patients among those classified as low risk by Leibovich criteria was identified. By Leibovich criteria, 85% of the patients in the cohort with pT1 tumors (< 7.0 cm) were identified as low risk - 7% recurrence at 5 years (95% CI: 5%, 9%). Incorporating these 3 genes, 9% of these patients were found to be at increased risk for recurrence - 19% at 5 years (95% CI: 7%, 21%). For the subset of T1a patients (< 4.0 cm), 98.6% were low risk according to the Leibovich criteria - 7% recurrence at 5 years (95% CI: 4%, 10%). Incorporating the 3 genes, 11% of these patients were found to be at increased risk - 20% at 5 years (95% CI: 7%, 31%). Conclusions: Addition of 3 angiogenesis-related genes to the Leibovich criteria in patients with pT1 tumors refines stratification of patient risk in a subset of patients. More precise estimation of recurrence risk will help to tailor surveillance and refine inclusion into clinical trials. These genes will be incorporated into an algorithm that requires validation in an external data set. [Table: see text]

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Baseline vitamin D status, sleep patterns, and the risk of incident type 2 diabetes in data from the UK Biobank study

10.2337/figshare.12746681 ◽

2020 ◽

Author(s):

Mengying Wang ◽

Tao Zhou ◽

Xiang Li ◽

Hao Ma ◽

Zhaoxia Liang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Daytime Sleepiness ◽

Lower Risk ◽

Uk Biobank ◽

Sleep Patterns ◽

Serum 25Ohd ◽

Sleep Behaviors ◽

The Uk

Background: Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D), but the results are inconsistent. Emerging evidence suggests that vitamin D metabolism is linked to sleep behaviors. We investigated the prospective association between serum 25-hydroxyvitamin D (25OHD) and the risk of incident T2D, and whether such association was modified by sleep behaviors. Research design and methods: The study included 350 211 individuals free of diabetes in the UK Biobank. Serum 25OHD (nmol/L) concentrations were measured. Five sleep behaviors including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness were included to generate overall sleep patterns, defined by healthy sleep scores. We also calculated genetic risk scores of sleep patterns. Results: During a median follow-up of 8.1 years, we documented 6940 incident T2D cases. We found that serum 25OHD were significantly associated with a lower risk of incident T2D, and the multivariate adjusted hazard ratio (HR; 95% confidence interval [CI]) for per 10 nmol/L increase was 0.88 (0.87-0.90). We found a significant interaction between 25OHD and overall sleep patterns on the risk of incident T2D (P for interaction=0.002). The inverse association between high 25OHD and T2D was more prominent among participants with healthier sleep patterns. Among the individual sleep behaviors, daytime sleepiness showed the strongest interaction with 25OHD (P for interaction=0.0006). The reduced HR of T2D associated with high 25OHD appeared to be more evident among participants with no frequent daytime sleepiness compared with those with excessive daytime sleepiness. The genetic variations of the sleep patterns did not modify the relation between 25OHD and T2D. Conclusions: Our study indicates that higher serum 25OHD concentrations are associated with a lower risk of incident T2D; and such relations are modified by overall sleep patterns, with daytime sleepiness being the major contributor.

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Baseline vitamin D status, sleep patterns, and the risk of incident type 2 diabetes in data from the UK Biobank study

10.2337/figshare.12746681.v1 ◽

2020 ◽

Author(s):

Mengying Wang ◽

Tao Zhou ◽

Xiang Li ◽

Hao Ma ◽

Zhaoxia Liang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Daytime Sleepiness ◽

Lower Risk ◽

Uk Biobank ◽

Sleep Patterns ◽

Serum 25Ohd ◽

Sleep Behaviors ◽

The Uk

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Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study

SLEEP ◽

10.1093/sleep/zsac003 ◽

2022 ◽

Author(s):

Zheran Liu ◽

Yaxin Luo ◽

Yonglin Su ◽

Zhigong Wei ◽

Ruidan Li ◽

...

Keyword(s):

Cohort Study ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Mendelian Randomization ◽

Causal Link ◽

Uk Biobank ◽

Inverse Variance ◽

Increased Risk ◽

Weighted Median ◽

The Uk

Abstract Study Objectives Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. Methods Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Beta values and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. Results In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR=1.24, 95% CI=1.02-1.5; daytime napping [sometimes vs. never]: RR=1.12, 95% CI=1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR= 1.04, 95% CI=1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. Conclusions Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.

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External validation of two predictive scores of chemotherapy toxicities among older patients with solid cancer, from ELCAPA prospective cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.12050 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 12050-12050

Author(s):

Maxime Frelaut ◽

Philippe Caillet ◽

Stephane Culine ◽

Elena Paillaud ◽

Christophe Tournigand ◽

...

Keyword(s):

High Risk ◽

Prospective Cohort ◽

Older Patients ◽

Risk Groups ◽

Low Risk ◽

Solid Cancer ◽

Cancer Type ◽

Severe Toxicity ◽

Increased Risk ◽

Grade 3

12050 Background: Severe chemotherapy toxicities are frequent among older patients, and may have a major impact on mortality, comorbidities, and quality of life. Two scores were developed to predict severe toxicities: Chemotherapy Risk Assessment Scale for High-age patients (CRASH) score, and Cancer and Aging Research Group Study (CARG) score. The main objective of the present study was to evaluate the predictive value of both scores on an external cohort. Secondary objective was to identify individual predictive factors of severe chemotherapy toxicities. Methods: The Elderly Cancer Patients (ELCAPA) survey consists in a prospective cohort including patients aged 70 years or older referred for a geriatric assessment (GA) before anticancer treatment, such as chemotherapy for solid cancer. CARG and CRASH score were retrospectively collected. Main endpoint was grade 3/4/5 toxicities for CARG-score, hematologic grade 4/5 and non-hematologic grade 3/4/5 toxicities for CRASH-score. Calibration and discrimination (Area Under ROC Curve, AUC) were evaluated. Results: From July 2010 to March 2017, 248 patients were included. Among them, 150 (61%) experienced severe toxicity as defined in CARG study, and 126 (51%) as defined in CRASH study. There was no increased risk of toxicity in intermediate and high risk groups of CARG-score compared to low risk group (OR = 0.3, IC95% [0.1 – 1.4], p= 0.1; and OR = 0.4, IC95%[0.1 – 1.7], p= 0.2 respectively, AUC-ROC = 0.55). Similarly, there was no more risk of severe toxicities in intermediate low, intermediate high, and high risk groups compared to low risk groups of CRASH combined score (respectively OR = 1, IC95% [0.3 – 3.6], p= 0.99; OR = 1, IC95% [0.3 – 3.4], p= 0.9; OR = 1.5, IC95% [0.3 – 8.1], p= 0.67; AUC-ROC = 0.52). A multivariate predictive model including cancer type, performance status (PS 0 vs. PS 1-2), number of severe comorbidities (Cumulative Illness Rating Scale for Geriatrics, CIRS-G, ≥1 grade 3 or 4 comorbidity), body mass index (BMI > 25 kg/m² protective vs. normal BMI), and Chemotox score (1 vs. 0) had an AUC of 0.78. Conclusions: Neither CARG nor CRASH score was predictive of severe chemotherapy toxicities in the ELCAPA cohort. There is a need to identify new predictors of chemotherapy toxicity in older patients with solid cancers.

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