Publications by authors named "Mika Kivimaki"

1,089 Publications

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Return to work after lumbar disc herniation surgery: an occupational cohort study.

Acta Orthop 2021 Jul 16:1-6. Epub 2021 Jul 16.

Department of Orthopedics and Traumatology, Turku University Hospital and University of Turku, Turku, Finland.

Background and purpose - Lumbar disc herniation is a common surgically treated condition in the working-age population. We assessed health-related risk factors for return to work (RTW) after excision of lumbar disc herniation. Previous studies on the subject have had partly contradictory findings.Patients and methods - RTW of 389 (n = 111 male, n = 278 female; mean age 46 years, SD 8.9) employees who underwent excision of lumbar disc herniation was assessed based on the Finnish Public Sector Study (FPS). Baseline information on occupation, preceding health, and health-risk behaviors was derived from linkage to national health registers and FPS surveys before the operation. The likelihood of RTW was analyzed using Cox proportional hazard univariable and multivariable modelling.Results - 95% of the patients had returned to work at 12 months after surgery, after on average 78 days of sickness absence. Faster RTW in the univariable Cox model was associated with a small number of sick leave days (< 30 days) before operation (HR 1.3, 95% CI 1.1-1.6); high occupational position (HR 1.6, CI 1.2-2.1); and age under 40 years (HR 1.5, CI 1.1-1.9). RTW was not associated with sex or the health-related risk factors obesity, physical inactivity, smoking, heavy alcohol consumption, poor self-rated health, psychological distress, comorbid conditions, or purchases of pain or antidepressant medications in either the univariable or multivariable model.Interpretation - Almost all employees returned to work after excision of lumbar disc herniation. Older age, manual job, and prolonged sick leave before the excision of lumbar disc herniation were risk factors for delayed return to work after the surgery.
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http://dx.doi.org/10.1080/17453674.2021.1951010DOI Listing
July 2021

Comparison of the predictive accuracy of multiple definitions of cognitive impairment for incident dementia: a 20-year follow-up of the Whitehall II cohort study.

Lancet Healthy Longev 2021 Jul;2(7):e407-e416

Université de Paris, Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases, Paris, France.

Background: Studies generally use cognitive assessment done at one timepoint to define cognitive impairment in order to examine conversion to dementia. Our objective was to examine the predictive accuracy and conversion rate of seven alternate definitions of cognitive impairment for dementia.

Methods: In this prospective study, we included participants from the Whitehall II cohort study who were assessed for cognitive impairment in 2007-09 and were followed up for clinically diagnosed dementia. Algorithms based on poor cognitive performance (defined using age-specific and sex-specific thresholds, and subsequently thresholds by education or occupation levels) and objective cognitive decline (using data from cognitive assessments in 1997-99, 2002-04, and 2007-09) were used to generate seven alternate definitions of cognitive impairment. We compared predictive accuracy using Royston's , the Akaike information criterion (AIC), sensitivity, specificity, and Harrell's C-statistic.

Findings: 5687 participants, with a mean age of 65·7 years (SD 5·9) in 2007-09, were included and followed up for a median of 10·5 years (IQR 10·1-10·9). Over follow-up, 270 (4·7%) participants were clinically diagnosed with dementia. Cognitive impairment defined using both cognitive performance and decline had higher hazard ratios (from 5·08 [95% CI 3·82-6·76] to 5·48 [4·13-7·26]) for dementia than did definitions based on cognitive performance alone (from 3·25 [2·52-4·17] to 3·39 [2·64-4·36]) and cognitive decline alone (3·01 [2·37-3·82]). However, all definitions had poor predictive performance (C-statistic ranged from 0·591 [0·565-0·616] to 0·631 [0·601-0·660]), primarily due to low sensitivity (21·6-48·4%). A predictive model containing age, sex, and education without measures of cognitive impairment had better predictive performance (C-statistic 0·783 [0·758-0·809], sensitivity 74·2%, specificity 72·2%) than all seven definitions of cognitive impairment (all p<0·0001).

Interpretation: These findings suggest that cognitive impairment in early old age might not be useful for dementia prediction, even when it is defined using longitudinal data on cognitive decline and thresholds of poor cognitive performance additionally defined by education or occupation.

Funding: National Institutes of Health, UK Medical Research Council.
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http://dx.doi.org/10.1016/S2666-7568(21)00117-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245324PMC
July 2021

Association between change in cardiovascular risk scores and future cardiovascular disease: analyses of data from the Whitehall II longitudinal, prospective cohort study.

Lancet Digit Health 2021 Jul;3(7):e434-e444

Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland; Department of Epidemiology and Public Health, University College London, London, UK.

Background: Evaluation of cardiovascular disease risk in primary care, which is recommended every 5 years in middle-aged and older adults (typical age range 40-75 years), is based on risk scores, such as the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) and American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) algorithms. This evaluation currently uses only the most recent risk factor assessment. We aimed to examine whether 5-year changes in SCORE and ASCVD risk scores are associated with future cardiovascular disease risk.

Methods: We analysed data from the Whitehall II longitudinal, prospective cohort study for individuals with no history of stroke, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, definite angina, heart failure, or peripheral artery disease. Participants underwent clinical examinations in 5-year intervals between Aug 7, 1991, and Dec 6, 2016, and were followed up for incident cardiovascular disease until Oct 2, 2019. Levels of, and 5-year changes in, cardiovascular disease risk were assessed using the SCORE and ASCVD risk scores and were analysed as predictors of cardiovascular disease. Harrell's C index, continuous net reclassification improvement, the Akaike information criterion, and calibration analysis were used to assess whether incorporating change in risk scores into a model including only a single risk score assessment improved the predictive performance. We assessed the levels of, and 5-year changes in, SCORE and ASCVD risk scores as predictors of cardiovascular disease and disease-free life-years using Cox proportional hazards and flexible parametric survival models.

Findings: 7574 participants (5233 [69·1%] men, 2341 [30·9%] women) aged 40-75 years were included in analyses of risk score change between April 24, 1997, and Oct 2, 2019. During a mean follow-up of 18·7 years (SD 5·5), 1441 (19·0%; 1042 [72·3%] men and 399 [27·7%] women) participants developed cardiovascular disease. Adding 5-year change in risk score to a model that included only a single risk score assessment improved model performance according to Harrell's C index (from 0·685 to 0·690, change 0·004 [95% CI 0·000 to 0·008] for SCORE; from 0·699 to 0·700, change 0·001 [0·000 to 0·003] for ASCVD), the Akaike information criterion (from 17 255 to 17 200, change -57 [95% CI -97 to -13] for SCORE; from 14 739 to 14 729, change -10 [-28 to 7] for ASCVD), and the continuous net reclassification index (0·353 [95% CI 0·234 to 0·447] for SCORE; 0·232 [0·030 to 0·344] for ASCVD). Both favourable and unfavourable changes in SCORE and ASCVD were associated with cardiovascular disease risk and disease-free life-years. The associations were seen in both sexes and all age groups up to the age of 75 years. At the age of 45 years, each 2-unit improvement in risk scores was associated with an additional 1·3 life-years (95% CI 0·4 to 2·2) free of cardiovascular disease for SCORE and an additional 0·9 life-years (95% CI 0·5 to 1·3) for ASCVD. At age 65 years, this same improvement was associated with an additional 0·4 life-years (95% CI 0·0 to 0·7) free of cardiovascular disease for SCORE and 0·3 life-years (95% CI 0·1 to 0·5) for ASCVD. These models were developed into an interactive calculator, which enables estimation of the number of cardiovascular disease-free life-years for an individual as a function of two risk score measurements.

Interpretation: Changes in the SCORE and ASCVD risk scores over time inform cardiovascular disease risk prediction beyond a single risk score assessment. Repeat data might allow more accurate cardiovascular risk stratification and strengthen the evidence base for decisions on preventive interventions.

Funding: UK Medical Research Council, British Heart Foundation, Wellcome Trust, and US National Institute on Aging.
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http://dx.doi.org/10.1016/S2589-7500(21)00079-0DOI Listing
July 2021

Hospital-treated infectious diseases and the risk of dementia: a large, multicohort, observational study with a replication cohort.

Lancet Infect Dis 2021 Jun 21. Epub 2021 Jun 21.

Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland; Finnish Institute of Occupational Health, Helsinki, Finland; Department of Epidemiology and Public Health, University College London, London, UK.

Background: Infections have been hypothesised to increase the risk of dementia. Existing studies have included a narrow range of infectious diseases, relied on short follow-up periods, and provided little evidence for whether the increased risk is limited to specific dementia subtypes or attributable to specific microbes rather than infection burden. We aimed to compare the risk of Alzheimer's disease and other dementias across a wide range of hospital-treated bacterial and viral infections in two large cohorts with long follow-up periods.

Methods: In this large, multicohort, observational study, the analysis was based on a primary cohort consisting of pooled individual-level data from three prospective cohort studies in Finland (the Finnish Public Sector study, the Health and Social Support study, and the Still Working study) and an independent replication cohort from the UK Biobank. Community-dwelling adults (≥18 years) with no dementia at study entry were included. Follow-up was until Dec 31, 2012, in the Health and Social Support study, Dec 31, 2016, in the public sector study and the Still Working study, and Feb 7, 2018, in the replication cohort. Through record linkage to national hospital inpatient registers, we ascertained exposure to 925 infectious diseases (using the International Classification of Diseases 10th Revision codes) before dementia onset, and identified incident dementia from hospital records, medication reimbursement entitlements, and death certificates. Hazard ratios (HRs) for the associations of each infectious disease or disease group (index infection) with incident dementia were assessed by use of Cox proportional hazards models. We then repeated the analysis after excluding incident dementia cases that occurred during the first 10 years after initial hospitalisation due to the index infection.

Findings: From March 1, 1986, to Jan 1, 2005, 260 490 people were included in the primary cohort, and from Dec 19, 2006, to Oct 1, 2010, 485 708 people were included in the replication cohort. In the primary cohort analysis based on 3 947 046 person-years at risk (median follow-up 15·4 years [IQR 9·8-21·0]), 77 108 participants had at least one hospital-treated infection before dementia onset and 2768 developed dementia. Hospitalisation for any infectious disease was associated with increased dementia risk in the primary cohort (adjusted HR [aHR] 1·48 [95% CI 1·37-1·60]) and replication cohort (2·60 [2·38-2·83]). The association remained when analyses were restricted to new dementia cases that occurred more than 10 years after infection (aHR 1·22 [95% CI 1·09-1·36] in the primary cohort, the replication cohort had insufficient follow-up data for this analysis), and when comorbidities and other dementia risk factors were considered. There was evidence of a dose-response association between the number of episodes of hospital-treated infections and dementia risk in both cohorts (p=0·0007). Although the greatest dementia risk was seen for central nervous system (CNS) infections versus no infection (aHR 3·01 [95% CI 2·07-4·37]), excess risk was also evident for extra-CNS infections (1·47 [1·36-1·59]). Although we found little difference in the infection-dementia association by type of infection, associations were stronger for vascular dementia than for Alzheimer's disease (aHR 2·09 [95% CI 1·59-2·75] versus aHR 1·20 [1·08-1·33] in the primary cohort and aHR 3·28 [2·65-4·04] versus aHR 1·80 [1·53-2·13] in the replication cohort).

Interpretation: Severe infections requiring hospital treatment are associated with long-term increased risk of dementia, including vascular dementia and Alzheimer's disease. This association is not limited to CNS infections, suggesting that systemic effects are sufficient to affect the brain. The absence of infection specificity combined with evidence of dose-response relationships between infectious disease burden and dementia risk support the hypothesis that increased dementia risk is driven by general inflammation rather than specific microbes.

Funding: UK Medical Research Council, US National Institute on Aging, Wellcome Trust, NordForsk, Academy of Finland, and Helsinki Institute of Life Science.
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http://dx.doi.org/10.1016/S1473-3099(21)00144-4DOI Listing
June 2021

Alternative duty work as workplace-initiated procedure to reduce sickness absence.

BMC Public Health 2021 06 16;21(1):1154. Epub 2021 Jun 16.

Finnish Institute of Occupational Health, Helsinki, Finland.

Purpose: Alternative duty work is a procedure that enables an employee with a short-term disability to perform modified duties as an alternative to sickness absence. We examined whether the implementation of an alternative duty policy was associated with reduced sickness absence in the Finnish public sector.

Methods: Two city administrations (A and D) that implemented an alternative duty work policy to their employees (n = 5341 and n = 7538) served as our intervention cities, and two city administrations (B and C) that did not implement the policy represented the reference cities (n = 6976 and n = 6720). The outcomes were the number of annual days, all episodes, and short-term (< 10 days) episodes during the 2 years before versus the 2 years after the intervention year. We applied repeated measures negative binomial regression analyses, using the generalized estimating equations method and the difference-in-difference analysis to compare the intervention and control cities (adjusted for sex, age, type of job contract, occupational class).

Results: During the five-year study period, the number of sickness absence days and episodes increased in both the intervention and control cities. Covariate-adjusted analysis of relative risk showed that the overall increase in post- versus pre-intervention sickness absence days was smaller in intervention City A, RR = 1.14 (95% CI = 1.09-1.21) than in control cities B and C, RR = 1.19 (95% CI =1.14-1.24), group × time interaction p < 0.02. In intervention City D, we found a corresponding result regarding all sickness absence episodes and short-term sickness absence episodes but not days.

Conclusions: This follow-up suggests that implementing an alternative duty work policy may marginally decrease employees' sickness absences.
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http://dx.doi.org/10.1186/s12889-021-11181-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207644PMC
June 2021

Association of rotating shift work schedules and the use of prescribed sleep medication: A prospective cohort study.

J Sleep Res 2021 Jun 14:e13349. Epub 2021 Jun 14.

Department of Public Health, University of Turku, Turku, Finland.

We examined whether working rotating shifts, with or without night work, is associated with the purchase of prescribed sleep medication, and whether the association is dependent on age. Data were obtained from a longitudinal cohort study of Finnish public sector employees who responded to questions on work schedule and background characteristics in 2000, 2004 and 2008. The data were linked to national register data on redeemed prescriptions of hypnotic and sedative medications, with up to 11 years of follow-up. Age stratified Cox proportional hazard regression models were computed to examine incident use of medication comparing two groups of rotating shift workers (those working shifts that included night shifts and those whose schedules did not include night shifts) with day workers who worked in a similar range of occupations. Shift work with night shifts was associated with increased use of sleep medication in all age groups, after adjustments for sex, occupational status, marital status, alcohol consumption, smoking and physical activity levels (hazard ratio [HR], [95% confidence interval, CI] 1.14 [1.01-1.28] for age group ≤39 years; 1.33 [1.19-1.48] for age group 40-49 years; 1.28 [1.13-1.44] for age group ≥50 years). Shift work without nights was associated with medication use in the two older age groups (HR [95% CI] 1.14 [1.01-1.29] and 1.17 [1.05-1.31] for age groups 40-49 years and >50 years, respectively). These findings suggest that circadian disruption and older age puts rotating shift workers, and especially those who work nights, at increased risk of developing clinically significant levels of sleep problems.
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http://dx.doi.org/10.1111/jsr.13349DOI Listing
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Modifications to residential neighbourhood characteristics and risk of 79 common health conditions: a prospective cohort study.

Lancet Public Health 2021 Jun;6(6):e396-e407

Department of Public Health, University of Turku, Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.

Background: Observational studies have identified a link between unfavourable neighbourhood characteristics and increased risk of morbidity, but it is unclear whether changes in neighbourhoods affect future disease risk. We used a data-driven approach to assess the impact of neighbourhood modification on 79 health outcomes.

Methods: In this prospective cohort study, we used pooled, individual-level data from two Finnish cohort studies: the Health and Social Support study and the Finnish Public Sector study. Neighbourhood characteristics (mean educational level, median income, and employment rate of residents, and neighbourhood green space) and individual lifestyle factors of community-dwelling individuals were assessed at baseline (at different waves starting between 1998 and 2013). We repeated assessment of neighbourhood characteristics and lifestyle factors approximately 5 years from each baseline assessment, after which follow-up began for health conditions diagnosed according to the WHO International Classification of Diseases for 79 common health conditions using linkage to electronic health records. We used Cox proportional hazard regression models to compute adjusted hazard ratios (HRs) of incident disease associated with neighbourhood characteristics and changes in neighbourhood characteristics over time and logistic regression analysis to compute adjusted odds of association between changes in neighbourhood characteristics and individual lifestyle factors.

Findings: 114 786 individuals (87 012 [75·8%] women; mean age 44·4 years [SD 11·1]) had complete data and were included in this cohort study. During 1·17 million person-years at risk, we recorded 164 368 new-onset health conditions and 3438 deaths. Favourable changes in neighbourhood characteristics were associated with reduced risk of all-cause mortality and incidence of 19 specific health conditions. Unfavourable changes were correspondingly associated with increased risk of mortality and 27 specific health conditions. Among participants who did not move residence during the observation period, relative to individuals who continually lived in disadvantaged neighbourhoods, those who experienced favourable modifications in neighbourhood characteristics had a lower risk of future diabetes (HR 0·84, 95% CI 0·75-0·93), stroke (0·49, 0·29-0·83), skin disease (0·72, 0·53-0·97), and osteoarthritis (0·87, 0·77-0·99). Living in a neighbourhood with improving characteristics was also associated with improvements in individual-level health-related lifestyle factors. Among participants who lived in advantaged residential environments at baseline, unfavourable changes in neighbourhood characteristics were associated with an increased risk of diabetes, stroke, skin disease, and osteoarthritis compared with individuals who lived in advantaged neighbourhoods throughout the study period.

Interpretation: Favourable modifications to residential neighbourhoods showed robust, longitudinal associations with a range of improvements in health outcomes, including improved health behaviours and reduced risk of cardiometabolic, infectious, and orthopaedic conditions.

Funding: UK Medical Research Council, US National Institute on Aging, NordForsk, and Academy of Finland.
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http://dx.doi.org/10.1016/S2468-2667(21)00066-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172714PMC
June 2021

Integrating large-scale neuroimaging research datasets: Harmonisation of white matter hyperintensity measurements across Whitehall and UK Biobank datasets.

Neuroimage 2021 08 20;237:118189. Epub 2021 May 20.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford, UK. Electronic address:

Large scale neuroimaging datasets present the possibility of providing normative distributions for a wide variety of neuroimaging markers, which would vastly improve the clinical utility of these measures. However, a major challenge is our current poor ability to integrate measures across different large-scale datasets, due to inconsistencies in imaging and non-imaging measures across the different protocols and populations. Here we explore the harmonisation of white matter hyperintensity (WMH) measures across two major studies of healthy elderly populations, the Whitehall II imaging sub-study and the UK Biobank. We identify pre-processing strategies that maximise the consistency across datasets and utilise multivariate regression to characterise study sample differences contributing to differences in WMH variations across studies. We also present a parser to harmonise WMH-relevant non-imaging variables across the two datasets. We show that we can provide highly calibrated WMH measures from these datasets with: (1) the inclusion of a number of specific standardised processing steps; and (2) appropriate modelling of sample differences through the alignment of demographic, cognitive and physiological variables. These results open up a wide range of applications for the study of WMHs and other neuroimaging markers across extensive databases of clinical data.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118189DOI Listing
August 2021

Trajectories of work ability from mid-life to pensionable age and their association with retirement timing.

J Epidemiol Community Health 2021 May 12. Epub 2021 May 12.

Department of Public Health, University of Turku and Turku University Hospital, Turku, Finland.

Background: This study aimed to identify the trajectories of work ability over 16 years preceding the individual pensionable age and to examine the association with retirement timing.

Methods: The study population consisted of 2612 public sector employees from the Finnish Retirement and Aging study and the Finnish Public Sector study. Participants were grouped into 'no-extension' (retired at the individual pensionable date or worked no longer than 6 months after that date) and 'extension' (worked more than 6 months after individual pensionable age). Trajectories of self-reported work ability score (0-10) in maximum of eight measurement points over 16 years preceding retirement were examined using the group-based latent trajectory analysis. Log-binomial regression was used to analyse the association between trajectory groups and extended employment.

Results: Four stable ('Stable excellent', 7%; 'Stable high', 62%; 'Stable medium', 24%; 'Low', 4%) and one decreasing ('Declining', 3%) work ability trajectories were identified. After taking into account gender, age, occupational status, marital status and self-rated health, 'Stable excellent' trajectory was associated with a higher likelihood of extended employment compared with the 'Low' (risk ratio (RR) 2.38, 95% CI 1.21 to 4.68) and to the 'Declining' (RR 2.82, 95% CI 1.32 to 6.01) trajectories. There was no difference in retirement timing between 'Declining', 'Low' and 'Stable medium' trajectories.

Conclusion: Work ability remained relatively stable among majority of the participants over 16 years of follow-up. Stable excellent work ability from mid-life to late career was associated with higher likelihood of extending employment beyond individual pensionable age than those with low or declining work ability.
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http://dx.doi.org/10.1136/jech-2021-216433DOI Listing
May 2021

Patterns of working hour characteristics and risk of sickness absence among shift-working hospital employees: a data-mining cohort study.

Scand J Work Environ Health 2021 Jul 31;47(5):395-403. Epub 2021 Mar 31.

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Objectives: Data mining can complement traditional hypothesis-based approaches in characterizing unhealthy work exposures. We used it to derive a hypothesis-free characterization of working hour patterns in shift work and their associations with sickness absence (SA).

Methods: In this prospective cohort study, complete payroll-based work hours and SA dates were extracted from a shift-scheduling register from 2008 to 2019 on 6029 employees from a hospital district in Southwestern Finland. We applied permutation distribution clustering to time series of successive shift lengths, between-shift rest periods, and shift starting times to identify clusters of similar working hour patterns over time. We examined associations of clusters spanning on average 23 months with SA during the following 23 months.

Results: We identified eight distinct working hour patterns in shift work: (i) regular morning (M)/evening (E) work, weekends off; (ii) irregular M work; (iii) irregular M/E/night (N) work; (iv) regular M work, weekends off; (v) irregular, interrupted M/E/N work; (vi) variable M work, weekends off; (vii) quickly rotating M/E work, non-standard weeks; and (viii) slowly rotating M/E work, non-standard weeks. The associations of these eight working-hour clusters with risk of future SA varied. The cluster of irregular, interrupted M/E/N work was the strongest predictor of increased SA (days per year) with an incidence rate ratio of 1.77 (95% confidence interval 1.74-1.80) compared to regular M/E work, weekends off.

Conclusions: This data-mining suggests that hypothesis-free approaches can contribute to scientific understanding of healthy working hour characteristics and complement traditional hypothesis-driven approaches.
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http://dx.doi.org/10.5271/sjweh.3957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259704PMC
July 2021

Psychiatric disorders as risk factors for type 2 diabetes: An umbrella review of systematic reviews with and without meta-analyses.

Diabetes Res Clin Pract 2021 Jun 7;176:108855. Epub 2021 May 7.

Department of Psychology, University of Southern Denmark, Odense, Denmark; STENO Diabetes Centre Odense, Odense University Hospital, Odense, Denmark; School of Psychology, Deakin University, Geelong, Australia. Electronic address:

Having a psychiatric disorder may increase the risk of developing type 2 diabetes[T2D] and this umbrella review aims to determine whether people with a psychiatric disorder have an increased risk of developing T2D and to investigate potential underlying mechanisms. A literature search was performed to identify systematic reviews of longitudinal studies investigating different psychiatric disorders as risk factors for incident T2D in humans (≥18 years). A total of 8612 abstracts were identified, 180 full-text articles were read, and 25 systematic reviews were included. Six categories of psychiatric disorders were identified. Except for eating disorders, all psychiatric disorders were associated with increased risk of incident T2D ranging from RR = 1.18 [95% CI 1.12-1.24] to RR = 1.60 [95% CI 1.37-1.88] for depression; from RR = 1.27 [95% CI 1.19-1.35] to OR = 1.50 [95% CI 1.08-2.10] for use of antidepressant medication; from OR = 1.93 [1.37-2.73] to OR = 1.94 [1.34-2.80] for use of antipsychotic medication; from RR = 1.55 [95% CI 1.21-1.99] to RR = 1.74 [95% CI 1.30-2.34] for insomnia, and finally showed OR = 1.47 [95% CI 1.23-1.75] for anxiety disorders. Plausible underlying mechanisms were discussed, but in most reviews corrections for mechanisms did not explain the association. Notable, only 16% of the systematic reviews had a high methodological quality.
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http://dx.doi.org/10.1016/j.diabres.2021.108855DOI Listing
June 2021

Adverse Childhood Experiences and the Risk of Coronary Heart Disease in Adulthood: Examining Potential Psychological, Biological, and Behavioral Mediators in the Whitehall II Cohort Study.

J Am Heart Assoc 2021 May 3;10(10):e019013. Epub 2021 May 3.

Department of Psychiatry McGill University Montreal Canada.

Background This study investigated potential psycho-bio-behavioral mediators of the association between adverse childhood experiences (ACEs) and the risk of coronary heart disease (CHD) in adulthood. Methods and Results Participants were 5610 British civil servants (mean age, 55.5; 28% women) from the Whitehall II cohort study without CHD at baseline in 1997 to 1999 (wave 5) when retrospective data on the number of ACEs were collected via questionnaire (range, 0-8). Potential mediators assessed at wave 5 included depression and anxiety symptoms, health behaviors (smoking, alcohol dependence, sleep, and physical activity), and cardiometabolic dysregulations. New diagnoses of CHD (myocardial infarction, definite angina, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty) were assessed from wave 6 (2001) to wave 11 (2012-2013). Logistic regressions examined associations between ACEs, potential mediators, and CHD during the follow-up period. Natural indirect effects were examined using mediation analysis. A total of 566 (10.1%) participants developed CHD during the follow-up period. ACEs were associated with an increased likelihood of CHD (odds ratio per ACE, 1.09; 95% CI, 1.00-1.19). Controlling for age and sex, mediation analyses revealed an indirect effect of depression symptoms (natural indirect effects, 1.05; 95% CI, 1.03-1.07), anxiety symptoms (natural indirect effects, 1.12; 95% CI, 1.10-1.15), and a greater number of cardiometabolic dysregulations (natural indirect effects, 1.02; 95% CI, 1.01-1.03) in the association between ACEs and incident CHD. Behavioral factors were not statistically significant mediators. Conclusions Depression symptoms, anxiety symptoms, and cardiometabolic dysregulations partially mediated the association between ACEs and CHD. Regular screening and treatment of symptoms of psychological disorders and cardiometabolic dysregulations may help mitigate the long-term health burden of ACEs.
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http://dx.doi.org/10.1161/JAHA.120.019013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200717PMC
May 2021

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

Nutrients 2021 Apr 7;13(4). Epub 2021 Apr 7.

Postgraduate Program in Epidemiology Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil.

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction ( = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, = 61%) for total fish, 1.04 (1.01-1.07, = 46%) for fatty fish, and 1.02 (1.00-1.04, = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
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http://dx.doi.org/10.3390/nu13041223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068031PMC
April 2021

Association Between Age at Diabetes Onset and Subsequent Risk of Dementia.

JAMA 2021 04;325(16):1640-1649

Epidemiology of Ageing and Neurodegenerative Diseases, Université de Paris, Inserm U1153, Paris, France.

Importance: Trends in type 2 diabetes show an increase in prevalence along with younger age of onset. While vascular complications of early-onset type 2 diabetes are known, the associations with dementia remains unclear.

Objective: To determine whether younger age at diabetes onset is more strongly associated with incidence of dementia.

Design, Setting, And Participants: Population-based study in the UK, the Whitehall II prospective cohort study, established in 1985-1988, with clinical examinations in 1991-1993, 1997-1999, 2002-2004, 2007-2009, 2012-2013, and 2015-2016, and linkage to electronic health records until March 2019. The date of final follow-up was March 31, 2019.

Exposures: Type 2 diabetes, defined as a fasting blood glucose level greater than or equal to 126 mg/dL at clinical examination, physician-diagnosed type 2 diabetes, use of diabetes medication, or hospital record of diabetes between 1985 and 2019.

Main Outcomes And Measures: Incident dementia ascertained through linkage to electronic health records.

Results: Among 10 095 participants (67.3% men; aged 35-55 years in 1985-1988), a total of 1710 cases of diabetes and 639 cases of dementia were recorded over a median follow-up of 31.7 years. Dementia rates per 1000 person-years were 8.9 in participants without diabetes at age 70 years, and rates were 10.0 per 1000 person-years for participants with diabetes onset up to 5 years earlier, 13.0 for 6 to 10 years earlier, and 18.3 for more than 10 years earlier. In multivariable-adjusted analyses, compared with participants without diabetes at age 70, the hazard ratio (HR) of dementia in participants with diabetes onset more than 10 years earlier was 2.12 (95% CI, 1.50-3.00), 1.49 (95% CI, 0.95-2.32) for diabetes onset 6 to 10 years earlier, and 1.11 (95% CI, 0.70-1.76) for diabetes onset 5 years earlier or less; linear trend test (P < .001) indicated a graded association between age at onset of type 2 diabetes and dementia. At age 70, every 5-year younger age at onset of type 2 diabetes was significantly associated with an HR of dementia of 1.24 (95% CI, 1.06-1.46) in analyses adjusted for sociodemographic factors, health behaviors, and health-related measures.

Conclusions And Relevance: In this longitudinal cohort study with a median follow-up of 31.7 years, younger age at onset of diabetes was significantly associated with higher risk of subsequent dementia.
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http://dx.doi.org/10.1001/jama.2021.4001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080220PMC
April 2021

Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

J Urol 2021 Apr 27:101097JU0000000000001822. Epub 2021 Apr 27.

Institute for Reproductive and Developmental Biology, Imperial College London, UK.

Purpose: Genome-wide association studies have not identified replicable genetic risk loci for stress or urgency urinary incontinence.

Materials And Methods: We carried out a discovery stage, case control, genome-wide association study in 3 independent discovery cohorts of European women (8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in 6 additional studies of European ancestry (4,069). We collected bladder biopsies from women with incontinence to further investigate bladder expression of implicated genes and pathways (50) and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models in METAL (http://www.sph.umich.edu/csg/abecasis/metal/), and whole transcriptome analyses using Affymetrix® arrays with replication with TaqMan® polymerase chain reaction.

Results: In the discovery stage, we identified 16 single nucleotide polymorphisms genotyped or imputed at 5 loci that reached genome-wide significance (p <5×10). In replication, rs138724718 on chromosome 2 near the macrophage receptor with collagenous structure () gene (replication p=0.003) was associated with stress incontinence. In addition, rs34998271 on chromosome 6 near the endothelin 1 () gene (replication p=0.0008) was associated with urgency incontinence. In combined meta-analyses of discovery and replication cohorts, associations with genome-wide significance for these 2 single nucleotide polymorphisms were confirmed. Transcriptomics analyses showed differential expression of 7 of 19 genes in the endothelin pathway between stress and urgency incontinence (p <0.0001).

Conclusions: We uncovered 2 new risk loci near the genes endothelin 1 (), associated with urgency incontinence, and macrophage receptor with collagenous structure (), associated with stress incontinence. These loci are biologically plausible given their roles in smooth muscle contraction and innate host defense, respectively.
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http://dx.doi.org/10.1097/JU.0000000000001822DOI Listing
April 2021

Association of sleep duration in middle and old age with incidence of dementia.

Nat Commun 2021 04 20;12(1):2289. Epub 2021 Apr 20.

Université de Paris, Inserm U1153, Epidemiology of Ageing and Neurodegenerative diseases, Paris, France.

Sleep dysregulation is a feature of dementia but it remains unclear whether sleep duration prior to old age is associated with dementia incidence. Using data from 7959 participants of the Whitehall II study, we examined the association between sleep duration and incidence of dementia (521 diagnosed cases) using a 25-year follow-up. Here we report higher dementia risk associated with a sleep duration of six hours or less at age 50 and 60, compared with a normal (7 h) sleep duration, although this was imprecisely estimated for sleep duration at age 70 (hazard ratios (HR) 1.22 (95% confidence interval 1.01-1.48), 1.37 (1.10-1.72), and 1.24 (0.98-1.57), respectively). Persistent short sleep duration at age 50, 60, and 70 compared to persistent normal sleep duration was also associated with a 30% increased dementia risk independently of sociodemographic, behavioural, cardiometabolic, and mental health factors. These findings suggest that short sleep duration in midlife is associated with an increased risk of late-onset dementia.
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http://dx.doi.org/10.1038/s41467-021-22354-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058039PMC
April 2021

Study Protocol: The Heart and Brain Study.

Front Physiol 2021 31;12:643725. Epub 2021 Mar 31.

Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.

Background: It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart-brain association remain unclear. Recent evidence suggests that impairments in vascular phenotypes and cerebrovascular reactivity (CVR) may play an important role in cognitive decline. The combines state-of-the-art vascular ultrasound, cerebrovascular magnetic resonance imaging (MRI) and cognitive testing in participants of the long-running Whitehall II Imaging cohort to examine these processes together. This paper describes the study protocol, data pre-processing and overarching objectives.

Methods And Design: The 775 participants of the Whitehall II Imaging cohort, aged 65 years or older in 2019, have received clinical and vascular risk assessments at 5-year-intervals since 1985, as well as a 3T brain MRI scan and neuropsychological tests between 2012 and 2016 (Whitehall II Wave MRI-1). Approximately 25% of this cohort are selected for the , which involves a single testing session at the University of Oxford (Wave MRI-2). Between 2019 and 2023, participants will undergo ultrasound scans of the ascending aorta and common carotid arteries, measures of central and peripheral blood pressure, and 3T MRI scans to measure CVR in response to 5% carbon dioxide in air, vessel-selective cerebral blood flow (CBF), and cerebrovascular lesions. The structural and diffusion MRI scans and neuropsychological battery conducted at Wave MRI-1 will also be repeated. Using this extensive life-course data, the will examine how 30-year trajectories of vascular risk throughout midlife (40-70 years) affect vascular phenotypes, cerebrovascular health, longitudinal brain atrophy and cognitive decline at older ages.

Discussion: The study will generate one of the most comprehensive datasets to examine the longitudinal determinants of the heart-brain association. It will evaluate novel physiological processes in order to describe the optimal window for managing vascular risk in order to delay cognitive decline. Ultimately, the will inform strategies to identify at-risk individuals for targeted interventions to prevent or delay dementia.
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http://dx.doi.org/10.3389/fphys.2021.643725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046163PMC
March 2021

'Return to Work' Coordinator Model and Work Participation of Employees: A Natural Intervention Study in Finland.

J Occup Rehabil 2021 Apr 7. Epub 2021 Apr 7.

Finnish Institute of Occupational Health, Topeliuksenkatu 40, 00250, Helsinki, Finland.

Purpose Employers increasingly use 'return to work' (RTW) coordinators to support work ability and extend working careers, particularly among employees with reduced work ability. We examined whether applying this model was associated with changes in employee sickness absence and disability retirements. Methods We used data from the Finnish Public Sector study from 2009 until 2015. Employees where the model was introduced in 2012 constituted the cases (n = 4120, one municipality) and employees where the model was not in use during the follow-up, represented the controls (n = 5600, two municipalities). We analysed risk of disability retirement in 2013-2015 and risk of sickness absence after (2013-2015) vs. before (2009-2011) intervention by case-control status. Results The incidence of disability retirement after the intervention was lower in cases compared to controls both in the total population (hazard ratio HR = 0.49, 95% CI 0.30-0.79) and in the subgroup of participants with reduced work ability (HR = 0.34, 95% CI 0.12-0.99). The risk of sickness absence increased from pre-intervention to post-intervention period both among cases and controls although the relative increase was greater among cases (RR = 1.26, 95% CI 1.14-1.40) than controls (RR = 1.03, 95% CI 0.97-1.08). In the group of employees with reduced work ability, no difference in sickness absence trends between cases and controls was observed. Conclusions These findings suggest that RTW-coordinator model may increase employee sickness absence, but decrease the risk of disability retirement, i.e., permanent exclusion from the labour market.
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http://dx.doi.org/10.1007/s10926-021-09970-xDOI Listing
April 2021

Serum transthyretin and risk of cognitive decline and dementia: 22-year longitudinal study.

Neurol Sci 2021 Mar 26. Epub 2021 Mar 26.

Department of Epidemiology and Public Health, Institute of Epidemiology and Health Care, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK.

Serum transthyretin (TTR) may be an early biomarker for Alzheimer's disease and related disorders (ADRD). We investigated associations of TTR measured at baseline with cognitive decline and incident ADRD and whether TTR trajectories differ between ADRD cases and non-cases, over 22 years before diagnosis. A total of 6024 adults aged 45-69 in 1997-1999 were followed up until 2019. TTR was assessed three times, and 297 cases of dementia were recorded. Higher TTR was associated with higher cognitive function at baseline; however, TTR was unrelated to subsequent change in cognitive function. TTR at baseline did not predict ADRD risk (hazard ratio per SD TTR (4.8 mg/dL) = 0.97; 95% confidence interval: 0.94-1.00). Among those later diagnosed with ADRD, there was a marginally steeper downward TTR trajectory than those free of ADRD over follow-up (P=0.050). Our findings suggest TTR is not neuroprotective. The relative decline in TTR level in the preclinical stage of ADRD is likely to be a consequence of disease processes.
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http://dx.doi.org/10.1007/s10072-021-05191-5DOI Listing
March 2021

Increased mortality risk associated with statins in the CORONADO study.

Diabetes Metab 2021 05 17;47(3):101250. Epub 2021 Mar 17.

University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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http://dx.doi.org/10.1016/j.diabet.2021.101250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968747PMC
May 2021

White matter hyperintensities classified according to intensity and spatial location reveal specific associations with cognitive performance.

Neuroimage Clin 2021 7;30:102616. Epub 2021 Mar 7.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford, UK.

White matter hyperintensities (WMHs) on T-weighted images are radiological signs of cerebral small vessel disease. As their total volume is variably associated with cognition, a new approach that integrates multiple radiological criteria is warranted. Location may matter, as periventricular WMHs have been shown to be associated with cognitive impairments. WMHs that appear as hypointense in T-weighted images (Tw) may also indicate the most severe component of WMHs. We developed an automatic method that sub-classifies WMHs into four categories (periventricular/deep and Tw-hypointense/nonTw-hypointense) using MRI data from 684 community-dwelling older adults from the Whitehall II study. To test if location and intensity information can impact cognition, we derived two general linear models using either overall or subdivided volumes. Results showed that periventricular Tw-hypointense WMHs were significantly associated with poorer performance in the trail making A (p = 0.011), digit symbol (p = 0.028) and digit coding (p = 0.009) tests. We found no association between total WMH volume and cognition. These findings suggest that sub-classifying WMHs according to both location and intensity in Tw reveals specific associations with cognitive performance.
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http://dx.doi.org/10.1016/j.nicl.2021.102616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995650PMC
March 2021

Does life satisfaction reduce risk of incident hypertension and stroke? Evidence from the Whitehall II cohort.

J Psychosom Res 2021 05 4;144:110414. Epub 2021 Mar 4.

Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Lee Kum Sheung Center for Health and Happiness, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Background: Previous studies showed life satisfaction is related to reduced risk of coronary heart disease and diabetes, but its association with other cardiometabolic endpoints including hypertension and stroke remains unexplored. This study examined life satisfaction's prospective association with incident hypertension and stroke in middle-aged adults.

Methods: At baseline (1985-1988), 6225 healthy British civil servants aged 35-55 from the Whitehall II cohort completed the validated Satisfaction with Life Scale and provided information regarding sociodemographics, a range of health-related factors, and psychological distress. Incident hypertension was ascertained according to clinic-derived measures of systolic or diastolic blood pressure of ≥140/90 mmHg, respectively, or self-reports of either physician-diagnosed hypertension or hypertensive medication use. Incident stroke and transient ischemic attack (TIA) were ascertained by self-reported physician diagnosis. Follow-up assessments occurred every 2-5 years through 2017. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) of hypertension and stroke/TIA risk separately.

Results: Over a 31-year follow-up, 2703 cases of hypertension and 370 cases of stroke/TIA occurred. Life satisfaction was not related to risk of developing hypertension but was associated with 12% decreased risk of stroke/TIA after controlling for sociodemographics, health status, and health behaviors (HR = 0.88; 95%CI = 0.79-0.98). However, the association was attenuated after adjustment for psychological distress.

Conclusions: No robust associations were found between life satisfaction and incident hypertension and stroke/TIA, respectively, after accounting for well-established risk factors and psychological distress. More research is needed to understand why associations of life satisfaction with cardiometabolic health seem to vary across endpoints.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110414DOI Listing
May 2021

Phenotypic frailty and multimorbidity are independent 18-year mortality risk indicators in older men : The Helsinki Businessmen Study (HBS).

Eur Geriatr Med 2021 Mar 4. Epub 2021 Mar 4.

University of Helsinki, Helsinki, Finland.

Purpose: Multimorbidity, prefrailty, and frailty are frequent in ageing populations, but their independent relationships to long-term prognosis in home-dwelling older people are not well recognised.

Methods: In the Helsinki Businessmen Study (HBS) men with high socioeconomic status (born 1919-1934, n = 3490) have been followed-up from midlife. In 2000, multimorbidity (≥ 2 conditions), phenotypic prefrailty and frailty were determined in 1365 home-dwelling men with median age of 73 years). Disability was assessed as a possible confounder. 18-year mortality follow-up was established from registers and Cox regression used for analyses.

Results: Of the men, 433 (31.7%) were nonfrail and without multimorbidity at baseline (reference group), 500 (36.6%) and 82 (6.0%) men had prefrailty or frailty, respectively, without multimorbidity, 84 (6.2%) men had multimorbidity only, and 201 (14.7%) and 65 (4.8%) men had prefrailty or frailty together with multimorbidity. Only 30 (2.2%) and 86 (6.3%) showed signs of ADL or mobility disability. In the fully adjusted analyses (including ADL disability, mental and cognitive status) of 18-year mortality, frailty without multimorbidity (hazard ratio 1.62, 95% confidence interval 1.13-2.31) was associated with similar mortality risk than multimorbidity without frailty (1.55, 1.17-2.06). The presence of both frailty and multimorbidity indicated a strong mortality risk (2.93, 2.10-4.07).

Conclusion: Although multimorbidity is generally considered a substantial health problem, our long-term observational study emphasises that phenotypic frailty alone, independently of disability, may be associated with a similar risk, and a combination of multimorbidity and frailty is an especially strong predictor of mortality.
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http://dx.doi.org/10.1007/s41999-021-00472-wDOI Listing
March 2021

Association of shift work with mood disorders and sleep problems according to chronotype: a 17-year cohort study.

Chronobiol Int 2021 Apr 15;38(4):518-525. Epub 2021 Feb 15.

Finnish Institute of Occupational Health, Helsinki, Finland.

Both evening chronotype and shift work are associated with depressive symptoms. This study examined whether the association between shift work and mood disorders and sleep problems varies by chronotype. The study population included 10637 participants from the Finnish Hospital Personnel Cohort Study. Work schedule was assessed using repeated questionnaires between 2000 and 2017. Chronotype, assessed using a single item from the Diurnal Type Scale, was categorized into definite morning, somewhat morning, somewhat evening, and definite evening types. The presence of mood disorders was identified by the 12-item General Health Questionnaire. Sleep problems were assessed by self-reported frequency of difficulty falling asleep and maintaining asleep. Longitudinal fixed effects models were used to examine the associations between shift work and the presence of mood disorders and sleep problems, stratified by chronotype. We found that fixed night work was associated with mood disorders among somewhat evening (adjusted odds ratio [OR] 1.91, 95% CI 1.09-3.34) and definite evening-type workers (adjusted OR 2.05, 95% CI 1.06-3.98). Shift work with night shifts was associated with mood disorders among definite evening-type workers (adjusted OR 1.75, 95% CI 1.18-2.60). Similarly, fixed night work was associated with difficulty maintaining sleep only among evening-type workers. In conclusion, evening chronotype increase the vulnerability to mood disorders and sleep disturbances related to night work.
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http://dx.doi.org/10.1080/07420528.2021.1885431DOI Listing
April 2021

Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.

Sci Rep 2021 Feb 4;11(1):3100. Epub 2021 Feb 4.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.
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http://dx.doi.org/10.1038/s41598-021-82714-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862626PMC
February 2021

Heart Rate and Heart Rate Variability Changes Are Not Related to Future Cardiovascular Disease and Death in People With and Without Dysglycemia: A Downfall of Risk Markers? The Whitehall II Cohort Study.

Diabetes Care 2021 Apr 1;44(4):1012-1019. Epub 2021 Feb 1.

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Objective: Higher resting heart rate (rHR) and lower heart rate variability (HRV) are associated with increased risk of cardiovascular disease (CVD) and all-cause mortality in people with and without diabetes. It is unknown whether temporal changes in rHR and HRV may contribute to this risk. We investigated associations between 5-year changes in rHR and HRV and risk of future CVD and death, taking into account participants' baseline glycemic state.

Research Design And Methods: In this prospective, population-based cohort study we investigated 4,611 CVD-free civil servants (mean [SD] age, 60 [5.9] years; 70% men). We measured rHR and/or six indices of HRV. Associations of 5-year change in 5-min rHR and HRV with fatal and nonfatal CVD and all-cause mortality or the composite of the two were assessed, with adjustments made for relevant confounders. Effect modification by glycemic state was tested.

Results: At baseline, 63% of participants were normoglycemic, 29% had prediabetes, and 8% had diabetes. During a median (interquartile range) follow-up of 11.9 (11.4; 12.3) years, 298 participants (6.5%) experienced a CVD event and 279 (6.1%) died of non-CVD-related causes. We found no association between 5-year changes in rHR and HRV and future events. Only baseline rHR was associated with all-cause mortality. A 10 bpm-higher baseline HR level was associated with an 11.4% higher rate of all-cause mortality (95% CI 1.0-22.9%; = 0.032). Glycemic state did not modify associations.

Conclusions: Changes in rHR and HRV and possibly also baseline values of these measures are not associated with future CVD or death in people with or without dysglycemia.
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http://dx.doi.org/10.2337/dc20-2490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985416PMC
April 2021