| 1. |
- Kivimäki, M., et al.
(författare)
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Job strain as a risk factor for coronary heart disease : A collaborative meta-analysis of individual participant data
- 2012
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 380:9852, s. 1491-1497
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Tidskriftsartikel (refereegranskat)abstract
- Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1•49 million person-years at risk (mean follow-up 7•5 years [SD 1•7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1•23 (95% CI 1•10-1•37). This effect estimate was higher in published (1•43, 1•15-1•77) than unpublished (1•16, 1•02-1•32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1•31, 1•15-1•48) and 5 years (1•30, 1•13-1•50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3•4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.
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| 2. |
- Dumurgier, J., et al.
(författare)
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A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:7, s. E669-E678
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging. Methods Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF beta-amyloid (A beta) peptide biomarkers. These A beta cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. Results A total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. Discussion The proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
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| 3. |
- Saddiki, H., et al.
(författare)
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Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study
- 2020
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Background The epsilon 4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association betweenAPOEgenotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of beta-amyloid peptide (A, beta-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated withAPOEgenotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least oneAPOE epsilon 4 allele. Compared with non-epsilon 4 carriers, heterozygous epsilon 4 carriers had a 4.6 (95% confidence interval 4.1-5.2;p< 0.001) and epsilon 4/epsilon 4 homozygotes a 25.4 (20.4-31.2;p< 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (pfor interaction < 0.001). The PAF associated with carrying at least one epsilon 4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect ofAPOE epsilon 2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE epsilon 4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect ofAPOE epsilon 4 at the population level. Author summaryWhy was this study done? The epsilon 4 allele of apolipoprotein E () gene () and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The recent development of diagnostic criteria based on biomarkers that reflect brain beta-amyloid and tau lesions (beta-amyloid deposition, pathologic tau, neurodegeneration [A/T/N] classification]) increases homogeneity in diagnosed cases. The strength of association of AD with risk factors can be better determined using biomarker-based AD compared with AD diagnosis based only on clinical criteria because the latter are known to lack specificity as a result of difficulties in ruling out other causes of dementia. What did the researchers do and find? We compared the overall and age-specific association between and AD using a case-control study that included 1,593 AD cases from memory clinics with positive cerebrospinal fluid biomarkers and 11,723 dementia-free controls drawn from two longitudinal cohort studies. The use of a large number of cases and controls allows assessment of whether the association between and AD is dependent on age. Compared with controls, patients with AD were more likely to carry one (odds ratio [OR] = 4.6) or two (OR = 25.3). This association was significantly modified by age, with the strongest association seen between 65 and 70 years of age and weaker associations at the two tails of the age distribution. What do these findings mean? Incorporating biomarkers for diagnosis of AD identified an association with that is apparently greater than has been previously reported using clinical diagnosis of the disease. The impact of on the risk of AD was strongest between the 65 and 70 years of age, earlier than the mean age at diagnosis in this study, which was 72.8 years.
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| 4. |
- Heikkila, K., et al.
(författare)
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Job strain and the risk of severe asthma exacerbations : a meta-analysis of individual-participant data from 100 000 European men and women
- 2014
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 69:6, s. 775-783
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. MethodsWe analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. ResultsDuring a median follow-up of 10years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). ConclusionsOur findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.
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| 5. |
- Lindbohm, J. V., et al.
(författare)
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Plasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:4, s. 612-24
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Plasma proteins affect biological processes and are common drug targets but their role in the development of Alzheimer's disease and related dementias remains unclear. We examined associations between 4953 plasma proteins and cognitive decline and risk of dementia in two cohort studies with 20-year follow-ups. Methods In the Whitehall II prospective cohort study proteins were measured using SOMAscan technology. Cognitive performance was tested five times over 20 years. Linkage to electronic health records identified incident dementia. The results were replicated in the Atherosclerosis Risk in Communities (ARIC) study. Results Fifteen non-amyloid/non-tau-related proteins were associated with cognitive decline and dementia, were consistently identified in both cohorts, and were not explained by known dementia risk factors. Levels of six of the proteins are modifiable by currently approved medications for other conditions. Discussion This study identified several plasma proteins in dementia-free people that are associated with long-term risk of cognitive decline and dementia.
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| 6. |
- Theorell, Töres, et al.
(författare)
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Job strain in relation to body mass index : pooled analysis of 160 000 adults from 13 cohort studies
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 272:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies. J Intern Med 2012; 272: 6573. Background. Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. Objectives. To examine the association between job strain and body mass index (BMI) in a large adult population. Methods. We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). Results. A total of 86 429 participants were of normal weight (BMI 18.524.9 kg m-2), 2149 were underweight (BMI < 18.5 kg m-2), 56 572 overweight (BMI 25.029.9 kg m-2) and 13 523 class I (BMI 3034.9 kg m-2) and 3073 classes II/III (BMI = 35 kg m-2) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.001.25], obese class I (odds ratio 1.07, 95% CI 1.021.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.011.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. Conclusions. In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a U-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a population level.
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| 7. |
- Ferrie, J E, et al.
(författare)
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Diagnosis-specific sickness absence and all-cause mortality in the GAZEL study.
- 2009
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Ingår i: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 63:1, s. 50-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aims to examine diagnosis-specific sickness absence as a risk marker for all-cause mortality. METHODS: Prospective occupational cohort (the GAZEL study). Medically certified sickness absence spells >7 days for 15 diagnostic categories, 1990-1992, were examined in relation to all-cause mortality, January 1993-February 2007. The reference group for each diagnostic category was participants with no spell >7 days for that diagnosis. The participants were French public utility workers (5271 women and 13 964 men) aged 37-51 years in 1990, forming the GAZEL study. Over the follow-up period, there were 144 deaths in women and 758 in men. RESULTS: 7875 employees (41.0%) had at least one spell of sickness absence >7 days over the 3-year period. The commonest diagnoses were mental disorders, musculoskeletal diseases, respiratory diseases and external causes in both sexes; genitourinary diseases in women, and digestive and circulatory diseases in men. Of these common diagnoses, mental disorders in women, hazard ratio (95% confidence intervals) 1.24 (1.1 to 1.4), and mental disorders 1.35 (1.3 to 1.5), digestive diseases 1.29 (1.1 to 1.6) and circulatory diseases 1.35 (1.2 to 1.6) in men were associated with mortality after adjustment for age, employment grade and sickness absence in all other diagnostic categories. CONCLUSIONS: Employees with medically certified absence spells of 1 week or more over a 3-year period had a 60% excess risk of early death. In women and men this excess risk was associated with some of the commonest diagnoses of sickness absence, in particular mental disorders. Sickness absence for mental disorders may be a useful early indicator of groups at increased risk of fatal disease.
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| 8. |
- Heikkilä, K., et al.
(författare)
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Job strain and health-related lifestyle : Findings from an individual-participant meta-analysis of 118 000 working adults
- 2013
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Ingår i: American Journal of Public Health. - 0090-0036 .- 1541-0048. ; 103:11, s. 2090-2097
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We examined the associations of job strain, an indicator of work-related stress, with overall unhealthy and healthy lifestyles. Methods. We conducted a meta-analysis of individual-level data from 11 European studies (cross-sectional data: n = 118 701; longitudinal data: n = 43 971). We analyzed job strain as a set of binary (job strain vs no job strain) and categorical (high job strain, active job, passive job, and low job strain) variables. Factors used to define healthy and unhealthy lifestyles were body mass index, smoking, alcohol intake, and leisure-time physical activity. Results. Individuals with job strain were more likely than those with no job strain to have 4 unhealthy lifestyle factors (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.12, 1.39) and less likely to have 4 healthy lifestyle factors (OR = 0.89; 95% CI = 0.80, 0.99). The odds of adopting a healthy lifestyle during study follow-up were lower among individuals with high job strain than among those with low job strain (OR = 0.88; 95% CI = 0.81, 0.96). Conclusions. Work-related stress is associated with unhealthy lifestyles and the absence of stress is associated with healthy lifestyles, but longitudinal analyses suggest no straightforward cause-effect relationship between workrelated stress and lifestyle. Copyright © 2013 by the American Public Health Association®.
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| 9. |
- Kivimäki, M, et al.
(författare)
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Sickness absence as a prognostic marker for common chronic conditions : analysis of mortality in the GAZEL study.
- 2008
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Ingår i: Occup Environ Med. - : BMJ. - 1470-7926 .- 1351-0711. ; 65:12, s. 820-6
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Tidskriftsartikel (refereegranskat)abstract
- Sickness absence as a prognostic marker for common chronic conditions: analysis of mortality in the GAZEL study.Kivimäki M, Head J, Ferrie JE, Singh-Manoux A, Westerlund H, Vahtera J, Leclerc A, Melchior M, Chevalier A, Alexanderson K, Zins M, Goldberg M.Department of Epidemiology and Public Health, University College London, London, UK. m.kivimaki@ucl.ac.ukOBJECTIVES: To determine whether sickness absence is a prognostic marker in terms of mortality among people with common chronic conditions. METHODS: Prospective occupational cohort study of 13,077 men and 4871 women aged 37-51 from the National Gas and Electricity Company, France. Records of physician-certified sickness absences over a 3-year period were obtained from employers' registers. Chronic conditions were assessed in annual surveys over the same period. The main outcome measure was all-cause mortality (803 deaths, mean follow-up after assessment of sickness absence: 13.9 years). RESULTS: In Cox proportional hazard models adjusted for age, sex, socioeconomic position and co-morbidity, >28 annual sickness-absence days versus no absence days was associated with an excess mortality risk among those with cancer (hazard ratio 5.4, 95% CI 2.2 to 13.1), depression (1.7, 1.1 to 2.8), chronic bronchitis or asthma (2.7, 1.6 to 4.6) and hypertension (1.6, 1.0 to 2.6). The corresponding hazard ratios for more than five long (>14 days) sickness-absence episodes per 10 person-years versus no such episodes were 5.4 (2.2 to 13.1), 1.8 (1.3 to 2.7), 2.0 (1.3 to 3.2) and 1.8 (1.2 to 2.7), respectively. Areas under receiver operating characteristics curves for these absence measures varied between 0.56 and 0.73, indicating the potential of these measures to distinguish groups at high risk of mortality. The findings were consistent across sex, age and socioeconomic groups and in those with and without co-morbid conditions. CONCLUSION: Data on sickness absence may provide useful prognostic information for common chronic conditions at the population level.
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| 10. |
- Madsen, I. E. H., et al.
(författare)
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Job strain as a risk factor for clinical depression : systematic review and meta-analysis with additional individual participant data
- 2017
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 47:8, s. 1342-1356
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Forskningsöversikt (refereegranskat)abstract
- Background. Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. Method. We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. Results. We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). Conclusions. Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
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