European Heart Journal , 38(34): 2621-2628 Kivimäki, M...

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Citation for the original published paper (version of record)

Kivimaumlki M Nyberg S T Batty G D Kawachi I Jokela M et al (2017)Long working hours as a risk factor for atrial fibrillation a multi-cohort studyEuropean Heart Journal 38(34) 2621-2628httpsdoiorg101093eurheartjehx324

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NB When citing this work cite the original published paper

Permanent link to this versionhttpurnkbseresolveurn=urnnbnseumudiva-139787

Long working hours as a risk factor for atrial

fibrillation a multi-cohort study

Mika Kivimeuroaki123 Solja T Nyberg2 G David Batty14 Ichiro Kawachi5

Markus Jokela6 Lars Alfredsson78 Jakob B Bjorner9 Marianne Borritz10

Hermann Burr11 Nico Dragano12 Eleonor I Fransson1314 Katriina Heikkileuroa1516

Anders Knutsson17 Markku Koskenvuo2 Meena Kumari18 Ida EH Madsen9

Martin L Nielsen19 Maria Nordin1420 Tuula Oksanen3 Jan H Pejtersen21

Jaana Pentti2 Reiner Rugulies922 Paula Salo323 Martin J Shipley1

Sakari Suominen2425 Tores Theorell14 Jussi Vahtera2526 Peter Westerholm27

Hugo Westerlund14 Andrew Steptoe1 Archana Singh-Manoux28 Mark Hamer29

Jane E Ferrie30 Marianna Virtanen3 and Adam G Tabak131 for the IPD-Work

consortium

1Department of Epidemiology and Public Health University College London WC1E 6BT London UK 2Clinicum Faculty of Medicine University of Helsinki Tukholmankatu 8 B00290 Helsinki Finland 3Finnish Institute of Occupational Health Topeliuksenkatu 41 B 00250 Helsinki Finland 4Centre for Cognitive Ageing and Cognitive EpidemiologyUniversity of Edinburgh 7 George Square EH8 9JZ Edinburgh UK 5Department of Social amp Behavioral Sciences Harvard TH Chan School of Public Health 677 HuntingtonAvenue Kresge Building 7th Floor Boston Massachusetts 02115 USA 6Department of Psychology and Logopedics Faculty of Medicine University of Helsinki Haartmaninkatu3 00014 Helsinki Finland 7Centre for Occupational and Environmental Medicine Stockholm County Council Solnaveuroagen 4 113 65 Stockholm Sweden 8Institute ofEnvironmental Medicine Nobels veuroag 13 Karolinska Institutet 171 77 Stockholm Sweden 9National Research Centre for the Working Environment Lersoslash Parkalle 105 2100Copenhagen oslash Denmark 10Bispebjerg University Hospital Copenhagen Department of Occupational and Environmental Medicine Bispebjerg Bakke 23_20F DK-2400Copenhagen NV Denmark 11Federal Institute for Occupational Safety and Health (BAuA) Noldnerstraszlige 4042 10317 Berlin Germany 12Institute of Medical SociologyMedical Faculty University of Dusseldorf Universiteuroatsstraszlige 1 D-40225 Dusseldorf Germany 13School of Health and Welfare Jonkoping University Barnarpsgatan 39 551 11Jonkoping Sweden 14Stress Research Institute Stockholm University Frescati Hagveuroag 16 A 114 19 Stockholm Sweden 15Department of Health Services Research and PolicyLondon School of Hygiene and Tropical Medicine UK 15-17 Tavistock Place WC1H 9SH London UK 16Clinical Effectiveness Unit The Royal College of Surgeons 35-43Lincolnrsquos Inn Fields WC2A 3PE London UK 17Department of Health Sciences Mid Sweden University Holmgatan 10 851 70 Sundsvall Sweden 18Institute for Social andEconomic Research University of Essex Wivenhoe Park Colchester CO4 3SQ Essex UK 19AS3 Employment AS3 Companies Hasselager Centervej 35 DK-8260 VIBY JDenmark 20Department of Psychology Umea University SE-901 87 Umea Sweden 21Danish National Centre for Social Research Herluf Trolles Gade 11 1052 Copenhagen KDenmark 22Department of Public Health and Department of Psychology University of Copenhagen Noslashrregade 10 PO Box 2177 1017 Copenhagen K Denmark23Department of Psychology University of Turku Assistentinkatu 7 20014 Turku Finland 24University of Skovde Hogskoleveuroagen 28 541 45 Skovde Sweden 25Department ofPublic Health University of Turku Joukahaisenkatu 3-5 A 20520 Turku Finland 26Turku University Hospital Kiinamyllynkatu 4-8 20521 Turku Finland 27Department of MedicalSciences Uppsala University Akademiska sjukhuset 75185 Uppsala Sweden 28Inserm U1018 Centre for Research in Epidemiology and Population Health Hopital Paul-Brousse16 avenue Paul Vaillant-Couturier Batiment 1516 94807 Villejuif Cedex France 29School of Sport Exercise and Health Sciences National Centre Sport amp Exercise MedicineLoughborough University Epinal Way Loughborough LE11 3TU UK 30School of Social and Community Medicine University of Bristol Oakfield House Oakfield Grove BristolBS8 2BN UK and 311st Department of Medicine Semmelweis University Faculty of Medicine Budapest euroUlloi ut 26 1085 Budapest Hungary

Received 3 January 2017 revised 5 April 2017 editorial decision 29 May 2017 accepted 26 June 2017 online publish-ahead-of-print 13 July 2017

See page 2629 for the editorial comment on this article (doi 101093eurheartjehx385)

Aims Studies suggest that people who work long hours are at increased risk of stroke but the association of long work-ing hours with atrial fibrillation the most common cardiac arrhythmia and a risk factor for stroke is unknown Weexamined the risk of atrial fibrillation in individuals working long hours (gt_55 per week) and those working standard35ndash40 hweek

Methodsand results

In this prospective multi-cohort study from the Individual-Participant-Data Meta-analysis in Working Populations(IPD-Work) Consortium the study population was 85 494 working men and women (mean age 434 years) with norecorded atrial fibrillation Working hours were assessed at study baseline (1991ndash2004) Mean follow-up for incident

Corresponding author Tel thorn44 207 679 8260 Fax +44 207 419 6732 Email mkivimakiuclacuk

VC The Author 2017 Published by Oxford University Press on behalf of the European Society of Cardiology

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (httpcreativecommonsorglicensesby40) which permitsunrestricted reuse distribution and reproduction in any medium provided the original work is properly cited

European Heart Journal (2017) 38 2621ndash2628 CLINICAL RESEARCHdoi101093eurheartjehx324 Atrial fibrillation

Downloaded from httpsacademicoupcomeurheartjarticle-abstract383426213958185Long-working-hours-as-a-risk-factor-for-atrialby Umea university library Medical library useron 03 October 2017

atrial fibrillation was 10 years and cases were defined using data on electrocardiograms hospital records drug reim-bursement registers and death certificates We identified 1061 new cases of atrial fibrillation (10-year cumulativeincidence 124 per 1000) After adjustment for age sex and socioeconomic status individuals working long hours hada 14-fold increased risk of atrial fibrillation compared with those working standard hours (hazard ratio = 142 95CI = 113ndash180 P = 0003) There was no significant heterogeneity between the cohort-specific effect estimates(I2 = 0 P = 066) and the finding remained after excluding participants with coronary heart disease or stroke at base-line or during the follow-up (N = 2006 hazard ratio = 136 95 CI = 105ndash176 P = 00180) Adjustment for potentialconfounding factors such as obesity risky alcohol use and high blood pressure had little impact on this association

Conclusion Individuals who worked long hours were more likely to develop atrial fibrillation than those working standard hours

Keywords Atrial fibrillation bull Life stress bull Risk factors bull Cohort study

Background

Atrial fibrillation is the most common cardiac arrhythmia and contrib-utes to the development of several adverse health outcomes such asstroke heart failure and multi-infarct dementia1ndash3 Cardiovascularand respiratory disease hypertension and left ventricular hypertro-phy are risk factors for atrial fibrillation245 Additionally findings fromobservational studies have been used to suggest that maintaining alifestyle that reduces the risk of cardiovascular diseasemdashavoidance ofobesity smoking and heavy alcohol consumptionmdashmay also have apositive impact on rates of atrial fibrillation6ndash8

Although the 2016 European Guidelines for cardiovascular diseaseprevention acknowledges psychosocial stress at work as a potentialrisk factor for cardiovascular disease9 citing evidence that show longworking hours to be associated with increased stroke risk10 little isknown about the role of long working hours as a potential risk factorof atrial fibrillation In principle stress and long working hours mayenhance functional re-entry repetitive pulmonary vein and atrialfiring1112 and autonomic nervous system abnormalities13 inducingarrhythmia vulnerability14 Thus some studies have found that stressand lsquoexhaustionrsquo predict symptomatic atrial fibrillation1516 Howeverthis evidence is uncertain because it is based on small study samplesAccordingly we conducted a large-scale study on long workinghours and incident atrial fibrillation in the general populationusing data from cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work)Consortium101718

Methods

ParticipantsIn ten cohort studies of the IPD-Work Consortium data on workinghours and atrial fibrillation were available although in two studies (theIntervention Project on Absence and Well-being and the Work Lipidsand Fibrinogen study Norrland) the low number of participants with longworking hours (n = 6 and 55 respectively) and atrial fibrillation during thefollow-up (n = 0 among participants working long hours in both studies)precluded inclusion of these studies in the analysis The remaining eightstudies were included in the analyses the Copenhagen PsychosocialQuestionnaire Study (COPSOQ) I and COPSOQ-II the Danish WorkEnvironment Cohort Study (DWECS) the Finnish Public Sector Study

(FPS) the Health and Social Support study (HeSSup) the PUMA studythe Whitehall II study and the Work Lipids and Fibrinogen study(WOLF) Stockholm (see Supplementary material online Appendix S1)Most of these were multi-purpose studies designed to examine healtheffects across a range of risk factors including those related to workplaceThe analytic sample comprised 85 494 participants (29 579 men and55 915 women) from the UK Denmark Sweden and Finland who werefree of atrial fibrillation at baseline (1991ndash2004) All studies wereapproved by the relevant local or national ethics committee and all partic-ipants gave informed consent to participate

Assessment of working hours andcovariates at baselineWorking hours were assessed at baseline which was between 1991 and2004 depending on the cohort study As in previous studies we classifiedworking hours into categories of lsquoless than 35hrsquo lsquo35ndash40 hrsquo lsquo41ndash48 hrsquo lsquo49ndash54 hrsquo and lsquogt_55 hweekrsquo101718 The first category includes part-time work-ers and the second category is the reference group of full-time workerswith standard working hours The category of 41ndash48 hweek includesthose working more than standard hours but still in accordance with theEuropean Union Working Time Directive (200388EC) which guaranteesemployees the right to limit weekly working time at 48 h on average Theremaining two categories include working times beyond this thresholdwith the top category of 55 or more hours per week being the most com-monly used definition for long working hours in medical research1017ndash20

Pre-defined harmonized covariates included potential confounderssuch as age sex and socioeconomic status (SES high intermediate lowunknown) and potential mediators such as smoking (current ex neversmoker) body mass index (BMI calculated as weight (in kilograms)height(in meters) squared and categorized according to the WHO classifica-tion lt185 185ndash249 250ndash299 300ndash349 gt_35 kgm2) physical activity(sedentary moderately active highly active) and alcohol consumption(non-use moderate women 1ndash14 drinksweek men 1ndash21 drinksweekintermediate women 15ndash20 drinksweek men 22ndash27 drinksweek riskywomen 21 or more drinksweek men 28 or more drinksweek)

As ascertainment of atrial fibrillation in the Whitehall II study was byelectrocardiogram (ECG) the gold standard method and the studyincluded the widest range of atrial fibrillation risk factors of all IPD-Workstudies a further set of analyses were undertaken in those data onlyAdditional non-cardiovascular and cardiovascular risk factors at baselinedeemed to act as potential confounders or mediators of the long workinghours-atrial fibrillation relationship included521 Prevalent infectionhigh sys-temic inflammation defined using serum C-reactive protein (high-sensitivityimmunonephelometric assay in a BN ProSpec nephelometer

2622 M Kivimeuroaki et al


values gt10 mgL) self-reported respiratory illness and doctor-diagnosedheart trouble (including valve disease and congestive heart failure) left ven-tricular hypertrophy (Minnesota codes 3-1 3-3 3-4) diabetes mellitus(defined as fasting glucose gt70 mmolL or a 2-h post load glucosegt111 mmolL during a 75 g oral glucose tolerance test or self-reporteddoctor-diagnosed diabetes) depressive and anxiety symptoms usingthe General Health Questionnaire caseness22 systolic blood pressure (theaverage of two readings taken in the sitting position after 5 min of rest withthe Hawksley random-0 sphygmomanometer) use of antihypertensivemedication total and high-density-lipoprotein (HDL) cholesterol concen-trations (measured by automated enzymatic colorimetric methods)

To examine whether cardiovascular disease preceded or followedatrial fibrillation we assessed coronary heart disease and stroke events atbaseline and follow-up Coronary heart disease was denoted by diagnos-tic codes I21ndashI22 in ICD-10 410 in ICD-9 (in hospitalization data) orusing the MONICA criteria (Whitehall II study clinical examination)23

Coronary death included diagnostic codes I20ndashI25 in ICD-10 410ndash414 inICD-9 Stroke included diagnostic codes I60 I61 I63 I64 in ICD-10 and430 431 433 434 436 in ICD-9

Outcome ascertainmentIn WOLF HeSSup PUMA FPS DWECS COPSOQ-I and COPSOQ-IIcases of atrial fibrillation at baseline and follow-up were identified usingelectronic patient records of hospitalizations and deaths [InternationalStatistical Classification of Diseases and Related Health Problems (ICD)diagnostic codes I48 (ICD-10) 4273 (ICD-9) or 4274 (ICD-8)] In FPSand HeSSup atrial fibrillation cases were additionally identified from thenationwide drug reimbursement register for the treatment of this condi-tion In that register entitlement to reimbursement is based on a detailedmedical examination and predefined criteria for the diagnosis In theWhitehall II study atrial fibrillation was assessed using resting ECGs(Minnesota code 83x) at baseline in 1991 and at follow-up examinationsin 1997 2003 and 2008 In each study participants with any indication ofpre-existing atrial fibrillation in electronic health records or ECG at base-line were excluded (n = 250)

Statistical analysisWe analysed anonymized or pseudonymized individual-level data fromeach cohort We studied the associations between long working hoursand baseline covariates using logistic regression for dichotomous covari-ates (obesity physical inactivity current smoking risky alcohol use infec-tionhigh systemic inflammation respiratory disease heart trouble leftventricular hypertrophy diabetes depressive and anxiety symptoms anti-hypertensive medication) and analysis of variance for continuous covari-ates (systolic blood pressure total and HDL cholesterol) with adjustmentfor age (continuous variable) sex and SES (categorical variables) To exam-ine the extent to which incident atrial fibrillation was due to pre-existingcardiovascular disease we computed the proportion of incident atrialfibrillation cases who had a record of cardiovascular disease (coronaryheart disease or stroke) before atrial fibrillation was first recorded

After confirming that the proportional hazards assumptions were notviolated we used Cox proportional hazards models to generate hazardratios and 95 confidence intervals (CI) for long working hours (55 h ormore per week) compared with standard (35ndash40) working hours (refer-ence) in predicting incident atrial fibrillation in participants free of thisarrhythmia at baseline In the basic statistical model effect estimates wereadjusted for age (continuous variable) sex and SES (categorical variable)at baseline Adjustment for SES is important because long working hourswere more common in participants with high SES (69 worked longhours) relative to those in low SES group (46) To examine whetherthe association between long working hours and atrial fibrillation was

mediated by poor lifestyle factors adjustments were made for smoking(never ex- current smoker) alcohol consumption (non-use moderaterisky) BMI (categorical) and physical activity (inactive moderately activehighly active) at baseline In analyses carried out in the Whitehall II studyadditional adjustments were made for doctor-diagnosed heart abnormal-ities infectionhigh systemic inflammation respiratory disease heartproblems left ventricular hypertrophy diabetes mellitus depressive andanxiety symptoms use of antihypertensive medication (all dichotomousvariables) systolic blood pressure and total and HDL-cholesterol (contin-uous variables) all measured at baseline

Meta-analysis based on random-effects modelling was used tocombine results from each cohort We examined heterogeneity of thecohort-specific estimates using the I2 statistic (a higher value indicatinga greater degree of heterogeneity) In sensitivity analyses we examinedthe association separately in men and women by age group (lt50 vsgt50 years at baseline) and by socioeconomic status (high intermedi-ate low) We also stratified the analysis by the method of case ascer-tainment to examine whether the association between long workinghours and atrial fibrillation was attenuated when the ascertainmentwas based on electronic health records from registers of hospitaladmissions deaths and drug reimbursement as compared with ECGassessment

The statistical software SAS (version 94) was used to analyse study-specific data and Stata (MP version 131) was used to compute the meta-analyses

Results

Of the 85 494 participants 35 were men and the mean age was434 years (range 17ndash70) at baseline (Table 1) During the meanfollow-up of 100 years 1061 participants were diagnosed with atrialfibrillation (10-year cumulative incidence 124 per 1000) In 714 ofcases atrial fibrillation was diagnosed before the age of 65 (see

Table 1 Baseline characteristics of participants byatrial fibrillation status at follow-up

All

N 5 85 494

Incident

cases N 5 1061

Non-cases

N 5 84 433

Age years

Mean 434 516 433

Range (17ndash70) (21ndash69) (17ndash70)

Sex N ()

Men 29 579 (345) 678 (639) 28 901 (342)

Women 55 915 (655) 383 (361) 55 532 (658)

Socioeconomic status N ()

High 22 555 (264) 336 (317) 22 219 (263)

Intermediate 41 570 (486) 432 (407) 41 138 (487)

Low 19 625 (230) 279 (263) 19 346 (229)

Unknown 1744 (20) 14 (13) 1730 (20)

Country N ()

UK 6649 (78) 224 (211) 6425 (76)

Denmark 12 563 (147) 161 (152) 12 402 (147)

Sweden 5551 (65) 131 (123) 5420 (64)

Finland 60 731 (710) 545 (514) 60 186 (713)

All participants were free of atrial fibrillation at study baseline

Long working hours as a risk factor for atrial fibrillation 2623


Supplementary material online Appendix S2) This is as expectedgiven the young mean age and length of follow-up Of the incidentatrial fibrillation cases 867 had no cardiovascular disease duringthe study period whereas 102 of incident cases of atrial fibrillationhad pre-existing cardiovascular disease when atrial fibrillation wasfirst recorded (see Supplementary material online Appendix S3)

A total of 4484 (52) participants worked gt_55 hweek and53 468 (625) worked standard 35ndash40 hours at baseline Longworking hours were associated with a slightly poorer lifestyle profileat baseline characterized by a higher prevalence of obesity leisure-time physical inactivity smoking and risky alcohol use (Table 2Supplementary material online Appendix S4) Analysis of further base-line covariates in the Whitehall II study show that participants work-ing long hours were more likely to have depressive and anxietysymptoms and less likely to have left ventricular hypertrophy thanthose working standard hours

In age sex and SES-adjusted analyses participants working longhours were at increased risk of incident atrial fibrillation the hazardratio compared with those working standard hours is 142 (95CI 113ndash180 P = 00031) (Figure 1) There was little heterogeneity inthe cohort-specific estimates I2 = 0 P = 066 Additional adjustmentfor lifestyle factors marginally attenuated the association between longvs standard working hours and incident atrial fibrillation (141 95CI 110ndash180 P = 00059 I2 = 0 P = 062) (see Supplementary mate-rial online Appendix S5) The association between long working hoursand atrial fibrillation remained after adjustment for pre-existing coro-nary heart disease at the time of atrial fibrillation diagnosis (141 95CI 112ndash178 P = 00039) and excluding participants with

cardiovascular disease at baseline (N = 549 hazard ratio 141 95 CI111ndash179 P = 00054) or cardiovascular disease at baseline or follow-up (N = 2006 hazard ratio = 136 95 CI = 105ndash176 P = 00180)

As the Whitehall II study had available data on several other poten-tial risk factors for atrial fibrillation further adjustments were per-formed using data from this cohort The hazard ratio for long vsstandard working hours as a predictor of incident atrial fibrillationwas 141 (95 CI 093ndash214 P = 01045 N = 6649 224 incident casesof atrial fibrillation) after adjustment for age sex and SES this is closeto that observed in the total population (Figure 1) Additional adjust-ment for lifestyle factors infectionhigh systemic inflammation respi-ratory disease doctor-diagnosed heart trouble (including valvedisease and congestive heart failure) left ventricular hypertrophy dia-betes mellitus depressive and anxiety symptoms systolic blood pres-sure antihypertensive medication total and HDL-cholesterol hadlittle effect on this estimate (142 95 CI 091ndash223 P = 012N = 5867 195 incident cases of atrial fibrillation)

Figure 2 shows the shape of the association between all the catego-ries of working hours and incident atrial fibrillation There was adose-response gradient with hazard ratios of 102 117 and 142 for41ndash48 49ndash54 and gt_55 working hours per week compared withstandard 35ndash40 working hours per week

Sensitivity analysisIn meta-analysis stratified by method of ascertainment of atrial fibrilla-tion (Figure 1) the age- sex- and SES-adjusted hazard ratio for longworking hours compared with standard working hours was 14195 CI 093ndash214 P = 0105 for the one study using

Table 2 Differences in lifestyle biological and psychological factors between individuals working long (55 hweek)and standard (35ndash40 hweek) working hours

Working hours category

Baseline characteristic Long Standard

IPD-Work cohortsa Prevalence () Odds ratiob (95 CI) P-value

Obese 118 105 134 (117 to 154) lt00001

Physically inactive 217 191 118 (107 to 130) 00007

Smoking 249 223 115 (102 to 131) 0026

Risky alcohol use 84 57 118 (104 to 133) 00084

Whitehall IIc

Infectionhigh inflammation 21 22 126 (066 to 242) 048

Respiratory disease 79 65 130 (091 to 184) 015

Heart trouble (incl valve disease) 74 79 088 (062 to 124) 045

Left ventricular hypertrophy 86 99 070 (050 to 096) 0028

Diabetes mellitus 14 26 074 (035 to 157) 043

Depressive and anxiety symptoms 272 200 157 (127 to 195) lt00001

Antihypertensive medication 33 63 066 (040 to 108) 010

Unadjusted mean Mean differencea (95 CI) P-value

Systolic blood pressure (mmHg) 1193 1199 -11 (-23 to 01) 0071

Total cholesterol (mmolL) 64 64 00 (-01 to 01) 049

HDL-cholesterol (mmolL) 14 14 -001 (-004 to 002) 057

a4486 participants with long working hours and 53 502 participants with standard working hoursbOdds ratios and mean differences for long compared with standard hours with risk factor as the outcome Adjustment for age sex and socioeconomic statusc584 participants with long working hours and 3016 participants with standard working hours



electrocardiogram 132 95 CI 093ndash188 P = 0124 for the twostudies using records from hospital admissions death and drug reim-bursements and 165 95 CI 103ndash266 P = 0038 for the five stud-ies using records from hospital admissions and deaths only Instratified analyses the association between long working hours andatrial fibrillation did not differ between men and women (P = 0267)participants younger than 50 and those 50 years or older at baseline(P = 0704) or by socioeconomic group (P = 0186)

Discussion

It was found in this multi-cohort study of 85 494 men and womenthat those working 55 h or more a week had an approximately 40higher risk of atrial fibrillation compared with those working a stand-ard 35ndash40-h week Nine out of ten incident atrial fibrillation casesoccurred among those free of pre-existing or concurrent cardiovas-cular disease suggesting that the observed excess risk of atrial fibrilla-tion is likely to reflect the effect of long working hours rather thanthe effect of pre-existing or concurrent cardiovascular diseaseMultivariable adjusted analyses showed that the association was notattributable to socioeconomic circumstances lifestyles or commonrisk factors for atrial fibrillation In combination these findings suggestthat long working hours is a risk factor for atrial fibrillation

We are not aware of other studies on long working hours andatrial fibrillation although our investigation is in agreement withsmall-scale studies linking other work-related stressors such as job

strain to this condition2425 The mechanisms underlying the associa-tion between long working hours and atrial fibrillation are not knownA recent systematic review of observational evidence from over 20million men and women found that obesity smoking hypertensionand high systemic inflammation were associated with an increasedrisk of atrial fibrillation whereas evidence on cholesterol and physicalactivity was inconsistent21 Other studies have also suggested thathigh alcohol consumption and obesity-related conditions such assleep apnea may have a role in the aetiology of atrial fibrillation2627

In the present study the prevalence of obesity smoking physicalinactivity and high alcohol consumption was higher in individualsworking long hours than in the standard working hours group butthe difference was small (lt3 percentage points) Similarly thereappeared to be no difference in systemic inflammation systolic bloodpressure or cholesterol As such classic risk factors for atrial fibrilla-tion are unlikely to mediate the association between long workinghours and atrial fibrillation In contrast there has been the suggestionof a link between extensive overtime working and autonomic nerv-ous system abnormalities13 a risk factor for atrial fibrillation142829

As such stress-related mechanisms that may trigger arrhythmia suchas autonomic dysfunction might be a more promising focus for futurestudies on long working hours and atrial fibrillation than mediation viaclassic cardiovascular disease risk factors

In absolute terms the increased risk of atrial fibrillation among indi-viduals with long working hours is relatively modest The number ofcases varied between 13 and 449 in the included studies none of thestudy-specific associations between long working hours and atrial

Figure 1 Random-effects meta-analysis of the association of long vs standard working hours with incident atrial fibrillation adjusted for age sexand socioeconomic status HR hazard ratio



fibrillation reached statistical significance at conventional levels Incontrast the association was highly significant in our pooled sampleincluding a total of 1061 incident atrial fibrillation cases The methodof atrial fibrillation ascertainment was not uniform across studiesmdashinonly one study were participants repeatedly assessed using an elec-trocardiogram the gold standard method while in two other studiescases were identified via records from hospital admissions death cer-tificates or drug reimbursements and in five studies only recordsfrom hospital admissions and deaths were available The occurrenceof atrial fibrillation is likely to be underestimated in the seven recordlinkage studies as they may miss undiagnosed and mildly symptomaticcases While the study using an electrocardiogram is stronger meth-odologically atrial fibrillation can be episodic and these ldquoparoxysmalrdquocases are difficult to identify even with an electrocardiogramImportantly however the relative risk of atrial fibrillation among indi-viduals with long working hours was similar across the studies irre-spective of the method of ascertainment 14 in the study with ECGascertainment 13 in studies using hospital prescription and deathrecords and 14 in those with hospital and death records only Thissuggests that misclassification was random in terms of participantsrsquoworking hours and has therefore not caused a significant bias

While novel and large in scale our study has several limitationsFirst as described heterogeneous assessment of atrial fibrillation is adrawback Second working hours and lifestyle factors were onlyassessed at study induction As working hours vary over time ourfindings may under- or overestimate the true effect due to imprecisemeasurement of long-term exposure Similarly a lack of repeat meas-urement of lifestyle factors prevented us from examining potentialbehavioural mediators in the association between long workinghours and atrial fibrillation Third the overall study population(N = 85 494) included more women (65) than men (35) This wasbecause the largest cohortmdashthe Finnish Public Sector study(N = 44 505)mdashis 81 female reflecting the sex distribution of publicsector workers in Finland at the time of study enrolment That therewas no significant sex difference in the association between working

hours and atrial fibrillation suggests our sex-adjusted analyses of menand women combined provide an accurate estimation of the associa-tion Fourth it is noteworthy that despite differences between thestudies in terms of year of recruitment (range from 1991 to 2004)

Figure 2 Association of categories of weekly working hours with incident atrial fibrillation Estimates are adjusted for age sex and socioeconomicstatus

Summarizing Figure Association between working hoursand risk of atrial fibrillation (AF) in 85 494 men and women free ofAF at baseline During the mean follow-up of 100 years 1061 devel-oped AF The figure shows that persons who worked 55 hours ormore per week had a 14-fold increased risk of AF compared tothose working standard 35ndash40 weekly hours (A) This estimate didnot vary according to the method of AF ascertainment (B)



study population location methodology and settings there was nosignificant heterogeneity in study-specific estimates of the associationbetween long working hours and risk of atrial fibrillation This sup-ports the robustness of the main finding

Conclusion

Our findings raise the hypothesis that long working hours may affectthe risk of atrial fibrillation (Summarizing Figure) We showed thatemployees working long hours were 40 more likely to develop thiscardiac arrhythmia than those working standard hours As this associ-ation appeared to be independent of known risk factors for atrialfibrillation further research is needed to determine mechanismsunderlying the link between long working hours and atrial fibrillationFurthermore the participants of this study were from the UKDenmark Sweden and Finland Although there is no reason toassume that the association would be dependent on geographicalregion the generalizability of our findings to other countries remainsto be confirmed

Supplementary material

Supplementary material is available at European Heart Journal online

Authorsrsquo contributions

MK along with AT developed the hypothesis SN and IM per-formed statistical analyses MK wrote the first draft all authors con-tributed to study concept and design analysis and interpretation ofdata and drafting or critical revision of the manuscript for importantintellectual content or in addition data acquisition

FundingIPD-Work consortium was supported by NordForsk a Nordic ResearchProgramme on Health and Welfare the EU New OSH ERA researchprogramme the Finnish Work Environment Fund Finland the SwedishResearch Council for Working Life and Social Research Sweden DanishNational Research Centre for the Working Environment DenmarkNordForsk and the UK Medical Research Council (K013351 to MK)

Conflict of interest none declared

References1 Falk RH Atrial fibrillation N Engl J Med 20013441067ndash10782 Schnabel RB Sullivan LM Levy D Pencina MJ Massaro JM Drsquoagostino RB Sr

Newton-Cheh C Yamamoto JF Magnani JW Tadros TM Kannel WB Wang TJEllinor PT Wolf PA Vasan RS Benjamin EJ Development of a risk score foratrial fibrillation (Framingham Heart Study) a community-based cohort studyLancet 2009373739ndash745

3 Rahman F Kwan GF Benjamin EJ Global epidemiology of atrial fibrillation NatRev Cardiol 201411639ndash654

4 Huxley RR Lopez FL Folsom AR Agarwal SK Loehr LR Soliman EZ MaclehoseR Konety S Alonso A Absolute and attributable risks of atrial fibrillation in rela-tion to optimal and borderline risk factors the Atherosclerosis Risk inCommunities (ARIC) study Circulation 20111231501ndash1508

5 Lip GY Tse HF Lane DA Atrial fibrillation Lancet 2012379648ndash6616 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B Castella M

Diener HC Heidbuchel H Hendriks J Hindricks G Manolis AS Oldgren JPopescu BA Schotten U Van Putte B Vardas P Agewall S Camm J BaronEsquivias G Budts W Carerj S Casselman F Coca A De Caterina R Deftereos

S Dobrev D Ferro JM Filippatos G Fitzsimons D Gorenek B Guenoun MHohnloser SH Kolh P Lip GY Manolis A McMurray J Ponikowski P RosenhekR Ruschitzka F Savelieva I Sharma S Suwalski P Tamargo JL Taylor CJ VanGelder IC Voors AA Windecker S Zamorano JL Zeppenfeld K 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS The Task Force for the management of atrial fibrillation of theEuropean Society of Cardiology (ESC) Developed with the special contributionof the European Heart Rhythm Association (EHRA) of the ESCEndorsed by theEuropean Stroke Organisation (ESO) Eur Heart J 2016372893ndash2962

7 January CT Wann LS Alpert JS Calkins H Cigarroa JE Cleveland JC Jr Conti JBEllinor PT Ezekowitz MD Field ME Murray KT Sacco RL Stevenson WGTchou PJ Tracy CM Yancy CW ACCAHA Task Force Members 2014 AHAACCHRS guideline for the management of patients with atrial fibrillation execu-tive summary a report of the American College of CardiologyAmerican HeartAssociation Task Force on practice guidelines and the Heart Rhythm SocietyCirculation 20141302071ndash2104

8 Jones C Pollit V Fitzmaurice D Cowan C Guideline Development Group Themanagement of atrial fibrillation summary of updated NICE guidance BMJ2014348g3655

9 Piepoli MF Hoes AW Agewall S Albus C Brotons C Catapano AL CooneyMT Corra U Cosyns B Deaton C Graham I Hall MS Hobbs FD Loslashchen MLLollgen H Marques-Vidal P Perk J Prescott E Redon J Richter DJ Sattar NSmulders Y Tiberi M van der Worp HB van Dis I Verschuren WM AuthorsTask Force Members 2016 European Guidelines on cardiovascular disease pre-vention in clinical practice The Sixth Joint Task Force of the European Society ofCardiology and Other Societies on Cardiovascular Disease Prevention in ClinicalPractice Eur Heart J 2016372315ndash2381

10 Kivimaki M Jokela M Nyberg ST Singh-Manoux A Fransson EI Alfredsson LBjorner JB Borritz M Burr H Casini A Clays E De Bacquer D Dragano NErbel R Geuskens GA Hamer M Hooftman WE Houtman IL Jockel KH KittelF Knutsson A Koskenvuo M Lunau T Madsen IE Nielsen ML Nordin MOksanen T Pejtersen JH Pentti J Rugulies R Salo P Shipley MJ Siegrist JSteptoe A Suominen SB Theorell T Vahtera J Westerholm PJ Westerlund HOrsquoreilly D Kumari M Batty GD Ferrie JE Virtanen M IPDW Long workinghours and risk of coronary heart disease and stroke a meta-analysis of 603 838men and women Lancet 20153861739ndash1746

11 Burstein B Nattel S Atrial fibrosis mechanisms and clinical relevance in atrialfibrillation J Am Coll Cardiol 200851802ndash809

12 Bhatt AG Monahan KM Fitness and the development of atrial fibrillationCirculation 20151311821ndash1823

13 Kageyama T Nishikido N Kobayashi T Kurokawa Y Kabuto M Commutingovertime and cardiac autonomic activity in Tokyo Lancet 1997350639

14 Perkiomaki J Ukkola O Kiviniemi A Tulppo M Ylitalo A Keseuroaniemi YA HuikuriH Heart rate variability findings as a predictor of atrial fibrillation in middle-agedpopulation J Cardiovasc Electrophysiol 201425719ndash724

15 Peter RH Gracey JG Beach TB Significance of fibrillatory waves and the P termi-nal force in idiopathic atrial fibrillation Ann Intern Med 1968681296ndash1300

16 Lampert R Jamner L Burg M Dziura J Brandt C Liu H Li F Donovan T SouferR Triggering of symptomatic atrial fibrillation by negative emotion J Am CollCardiol 2014641533ndash1534

17 Kivimaki M Virtanen M Kawachi I Nyberg ST Alfredsson L Batty GD BjornerJB Borritz M Brunner EJ Burr H Dragano N Ferrie JE Fransson EI Hamer MHeikkileuroa K Knutsson A Koskenvuo M Madsen IE Nielsen ML Nordin MOksanen T Pejtersen JH Pentti J Rugulies R Salo P Siegrist J Steptoe ASuominen S Theorell T Vahtera J Westerholm PJ Westerlund H Singh-Manoux A Jokela M IPD-Work consortium Long working hours socioeco-nomic status and the risk of incident type 2 diabetes meta-analysis of publishedand unpublished data from 222120 individuals Lancet Diabetes Endocrinol2014327ndash34

18 Virtanen M Jokela M Nyberg ST Madsen IE Lallukka T Ahola K Alfredsson LBatty GD Bjorner JB Borritz M Burr H Casini A Clays E De Bacquer DDragano N Erbel R Ferrie JE Fransson EI Hamer M Heikkileuroa K Jockel KHKittel F Knutsson A Koskenvuo M Ladwig KH Lunau T Nielsen ML Nordin MOksanen T Pejtersen JH Pentti J Rugulies R Salo P Schupp J Siegrist J Singh-Manoux A Steptoe A Suominen SB Theorell T Vahtera J Wagner GGWesterholm PJ Westerlund H Kivimeuroaki M Long working hours and alcohol usesystematic review and meta-analysis of published studies and unpublished individ-ual participant data BMJ 2015350g7772

19 Kivimaki M Batty GD Hamer M Ferrie JE Vahtera J Virtanen M Marmot MGSingh-Manoux A Shipley MJ Using additional information on working hours topredict coronary heart disease a cohort study Ann Intern Med 2011154457ndash463

20 Sokejima S Kagamimori S Working hours as a risk factor for acute myocardilainfarction in Japan case-control study BMJ 1998317775ndash780

21 Allan V Honarbakhsh S Casas JP Wallace J Hunter RT Schilling R Perel PMorley K Banerjee A Hemingway H Are cardiovascular risk factors also



associated with the incidence of atrial fibrillation A systematic review and fieldsynopsis of 23 factors in 32 population based cohorts of 20 million participantsThromb Haemost 2017117837ndash850

22 Goldberg D Williams P A Users Guide to the General Health QuestionnaireBerkshire Windsor UK NFER-Nelson Publishing Co 1988

23 Tunstall-Pedoe H Kuulasmaa K Amouyel P Arveiler D Rajakangas AM Pajak AMyocardial infarction and coronary deaths in the World Health OrganizationMONICA Project Registration procedures event rates and case-fatality rates in38 populations from 21 countries in four continents Circulation 199490583ndash612

24 Toren K Schioler L Soderberg M Giang KW Rosengren A The associationbetween job strain and atrial fibrillation in Swedish men Occup Environ Med201572177ndash180

25 Fransson EI Stadin M Nordin M Malm D Knutsson A Alfredsson LWesterholm PJ The association between job strain and atrial fibrillation resultsfrom the Swedish WOLF study BioMed Res Int 20152015371905

26 Larsson SC Drca N Wolk A Alcohol consumption and risk of atrial fibrillation a pro-spective study and dose-response meta-analysis J Am Coll Cardiol 201464281ndash289

27 Miller JD Aronis KN Chrispin J Patil KD Marine JE Martin SS Blaha MJBlumenthal RS Calkins H Obesity exercise obstructive sleep apnea and modifi-able atherosclerotic cardiovascular disease risk factors in atrial fibrillation J AmColl Cardiol 2015662899ndash2906

28 Bettoni M Zimmermann M Autonomic tone variations before the onset of par-oxysmal atrial fibrillation Circulation 20021052753ndash2759

29 Chen PS Chen LS Fishbein MC Lin SF Nattel S Role of the autonomic nervous sys-tem in atrial fibrillation pathophysiology and therapy Circ Res 20141141500ndash1515


CARDIOVASCULAR FLASHLIGHT doi101093eurheartjehx013Online publish-ahead-of-print 6 February 2017

Three Tesla cardiac magnetic resonance imaging in a patient with a leadlesscardiac pacemaker system

Alexander Kypta1 Hermann Blessberger1 Daniel Kiblboeck1 and Clemens Steinwender12

1Department of Cardiology Faculty of Medicine Kepler University Hospital Linz Johannes Kepler University Linz Krankenhausstrasse 9 4020 Linz Austria and2Department of Cardiology Clinic of Internal Medicine II Paracelsus Medical University of Salzburg Salzburg Austria Corresponding author Tel 14373278066220 Fax 14373278066205 Email alexanderkyptagmailcom

This is to the best of our knowledge the first re-port of cardiac magnetic resonance imaging (MRI)in a patient with a leadless cardiac pacemaker(LCP) Imaging was performed to rule out myocar-ditis in a 77-year-old male patient who had under-gone LCP implantation (MicraTM Medtronic) foratrial fibrillation with bradycardia 20 months be-fore (Panel A) After a precise check of the func-tional parameters the device was programmed tothe MRI mode (V00 with a fixed rate of 80 bpm)

The MRI was performed in a long bore 30Tesla magnet (MagnetomVR Skyra SiemensErlangen Germany) with a maximal specific ab-sorption rate of 15 Wkg During MRI the patientwas monitored continuously by electrocardio-gram and pulse oximetry The cardiac MRI showedmetallic artefacts at the apex of the heart due tothe implanted LCP in the apex of the right ven-tricle and at the sternum due to sternal wires aftercardiac surgery The LCP caused an lsquoarc-shapedrsquoartefact (in the cine images because of local fielddistortion leading to de-phasing of the transversemagnetization) However these artefacts impairedthe diagnostic quality of the cardiac MR imagesonly in a small region of the apex (Panels B Cand D)

During and after the scan no device related adverse events occurred The LCPrsquos functional parameters were stable (pacing threshold05 V and 038 V impedance 550 X and 580 X sensing 20 mV and 20 mV before and immediately after the scan respectively)

Support by the Austrian Research Promotion Agency FFG within the scope of project 853390 LaMiCellPro is gratefully acknowledged


VC The Author 2017 Published by Oxford University Press on behalf of the European Society of CardiologyThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (httpcreativecommonsorglicensesby-nc40) which permits non-commercial re-use distribution and reproduction in any medium provided the original work is properly cited For commercial re-use pleasecontact journalspermissionsoupcom


ehx324-TF1

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Long working hours as a risk factor for atrial

fibrillation a multi-cohort study

Mika Kivimeuroaki123 Solja T Nyberg2 G David Batty14 Ichiro Kawachi5

Markus Jokela6 Lars Alfredsson78 Jakob B Bjorner9 Marianne Borritz10

Hermann Burr11 Nico Dragano12 Eleonor I Fransson1314 Katriina Heikkileuroa1516

Anders Knutsson17 Markku Koskenvuo2 Meena Kumari18 Ida EH Madsen9

Martin L Nielsen19 Maria Nordin1420 Tuula Oksanen3 Jan H Pejtersen21

Jaana Pentti2 Reiner Rugulies922 Paula Salo323 Martin J Shipley1

Sakari Suominen2425 Tores Theorell14 Jussi Vahtera2526 Peter Westerholm27

Hugo Westerlund14 Andrew Steptoe1 Archana Singh-Manoux28 Mark Hamer29

Jane E Ferrie30 Marianna Virtanen3 and Adam G Tabak131 for the IPD-Work

consortium

1Department of Epidemiology and Public Health University College London WC1E 6BT London UK 2Clinicum Faculty of Medicine University of Helsinki Tukholmankatu 8 B00290 Helsinki Finland 3Finnish Institute of Occupational Health Topeliuksenkatu 41 B 00250 Helsinki Finland 4Centre for Cognitive Ageing and Cognitive EpidemiologyUniversity of Edinburgh 7 George Square EH8 9JZ Edinburgh UK 5Department of Social amp Behavioral Sciences Harvard TH Chan School of Public Health 677 HuntingtonAvenue Kresge Building 7th Floor Boston Massachusetts 02115 USA 6Department of Psychology and Logopedics Faculty of Medicine University of Helsinki Haartmaninkatu3 00014 Helsinki Finland 7Centre for Occupational and Environmental Medicine Stockholm County Council Solnaveuroagen 4 113 65 Stockholm Sweden 8Institute ofEnvironmental Medicine Nobels veuroag 13 Karolinska Institutet 171 77 Stockholm Sweden 9National Research Centre for the Working Environment Lersoslash Parkalle 105 2100Copenhagen oslash Denmark 10Bispebjerg University Hospital Copenhagen Department of Occupational and Environmental Medicine Bispebjerg Bakke 23_20F DK-2400Copenhagen NV Denmark 11Federal Institute for Occupational Safety and Health (BAuA) Noldnerstraszlige 4042 10317 Berlin Germany 12Institute of Medical SociologyMedical Faculty University of Dusseldorf Universiteuroatsstraszlige 1 D-40225 Dusseldorf Germany 13School of Health and Welfare Jonkoping University Barnarpsgatan 39 551 11Jonkoping Sweden 14Stress Research Institute Stockholm University Frescati Hagveuroag 16 A 114 19 Stockholm Sweden 15Department of Health Services Research and PolicyLondon School of Hygiene and Tropical Medicine UK 15-17 Tavistock Place WC1H 9SH London UK 16Clinical Effectiveness Unit The Royal College of Surgeons 35-43Lincolnrsquos Inn Fields WC2A 3PE London UK 17Department of Health Sciences Mid Sweden University Holmgatan 10 851 70 Sundsvall Sweden 18Institute for Social andEconomic Research University of Essex Wivenhoe Park Colchester CO4 3SQ Essex UK 19AS3 Employment AS3 Companies Hasselager Centervej 35 DK-8260 VIBY JDenmark 20Department of Psychology Umea University SE-901 87 Umea Sweden 21Danish National Centre for Social Research Herluf Trolles Gade 11 1052 Copenhagen KDenmark 22Department of Public Health and Department of Psychology University of Copenhagen Noslashrregade 10 PO Box 2177 1017 Copenhagen K Denmark23Department of Psychology University of Turku Assistentinkatu 7 20014 Turku Finland 24University of Skovde Hogskoleveuroagen 28 541 45 Skovde Sweden 25Department ofPublic Health University of Turku Joukahaisenkatu 3-5 A 20520 Turku Finland 26Turku University Hospital Kiinamyllynkatu 4-8 20521 Turku Finland 27Department of MedicalSciences Uppsala University Akademiska sjukhuset 75185 Uppsala Sweden 28Inserm U1018 Centre for Research in Epidemiology and Population Health Hopital Paul-Brousse16 avenue Paul Vaillant-Couturier Batiment 1516 94807 Villejuif Cedex France 29School of Sport Exercise and Health Sciences National Centre Sport amp Exercise MedicineLoughborough University Epinal Way Loughborough LE11 3TU UK 30School of Social and Community Medicine University of Bristol Oakfield House Oakfield Grove BristolBS8 2BN UK and 311st Department of Medicine Semmelweis University Faculty of Medicine Budapest euroUlloi ut 26 1085 Budapest Hungary

Received 3 January 2017 revised 5 April 2017 editorial decision 29 May 2017 accepted 26 June 2017 online publish-ahead-of-print 13 July 2017

See page 2629 for the editorial comment on this article (doi 101093eurheartjehx385)

Aims Studies suggest that people who work long hours are at increased risk of stroke but the association of long work-ing hours with atrial fibrillation the most common cardiac arrhythmia and a risk factor for stroke is unknown Weexamined the risk of atrial fibrillation in individuals working long hours (gt_55 per week) and those working standard35ndash40 hweek

Methodsand results

In this prospective multi-cohort study from the Individual-Participant-Data Meta-analysis in Working Populations(IPD-Work) Consortium the study population was 85 494 working men and women (mean age 434 years) with norecorded atrial fibrillation Working hours were assessed at study baseline (1991ndash2004) Mean follow-up for incident

Corresponding author Tel thorn44 207 679 8260 Fax +44 207 419 6732 Email mkivimakiuclacuk

VC The Author 2017 Published by Oxford University Press on behalf of the European Society of Cardiology

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (httpcreativecommonsorglicensesby40) which permitsunrestricted reuse distribution and reproduction in any medium provided the original work is properly cited

European Heart Journal (2017) 38 2621ndash2628 CLINICAL RESEARCHdoi101093eurheartjehx324 Atrial fibrillation





Background



Methods

















Results



All

N 5 85 494

Incident

cases N 5 1061

Non-cases

N 5 84 433

Age years

Mean 434 516 433


Sex N ()

Men 29 579 (345) 678 (639) 28 901 (342)

Women 55 915 (655) 383 (361) 55 532 (658)


High 22 555 (264) 336 (317) 22 219 (263)

Intermediate 41 570 (486) 432 (407) 41 138 (487)

Low 19 625 (230) 279 (263) 19 346 (229)

Unknown 1744 (20) 14 (13) 1730 (20)

Country N ()

UK 6649 (78) 224 (211) 6425 (76)

Denmark 12 563 (147) 161 (152) 12 402 (147)

Sweden 5551 (65) 131 (123) 5420 (64)

Finland 60 731 (710) 545 (514) 60 186 (713)















Obese 118 105 134 (117 to 154) lt00001


Smoking 249 223 115 (102 to 131) 0026


Whitehall IIc
















Discussion


















Conclusion





















































ehx324-TF1

ehx324-TF2

ehx324-TF3

ehx324-TF4




Background



Methods

















Results



All

N 5 85 494

Incident

cases N 5 1061

Non-cases

N 5 84 433

Age years

Mean 434 516 433


Sex N ()

Men 29 579 (345) 678 (639) 28 901 (342)

Women 55 915 (655) 383 (361) 55 532 (658)


High 22 555 (264) 336 (317) 22 219 (263)

Intermediate 41 570 (486) 432 (407) 41 138 (487)

Low 19 625 (230) 279 (263) 19 346 (229)

Unknown 1744 (20) 14 (13) 1730 (20)

Country N ()

UK 6649 (78) 224 (211) 6425 (76)

Denmark 12 563 (147) 161 (152) 12 402 (147)

Sweden 5551 (65) 131 (123) 5420 (64)

Finland 60 731 (710) 545 (514) 60 186 (713)















Obese 118 105 134 (117 to 154) lt00001


Smoking 249 223 115 (102 to 131) 0026


Whitehall IIc
















Discussion


















Conclusion





















































ehx324-TF1

ehx324-TF2

ehx324-TF3

ehx324-TF4










Results



All

N 5 85 494

Incident

cases N 5 1061

Non-cases

N 5 84 433

Age years

Mean 434 516 433


Sex N ()

Men 29 579 (345) 678 (639) 28 901 (342)

Women 55 915 (655) 383 (361) 55 532 (658)


High 22 555 (264) 336 (317) 22 219 (263)

Intermediate 41 570 (486) 432 (407) 41 138 (487)

Low 19 625 (230) 279 (263) 19 346 (229)

Unknown 1744 (20) 14 (13) 1730 (20)

Country N ()

UK 6649 (78) 224 (211) 6425 (76)

Denmark 12 563 (147) 161 (152) 12 402 (147)

Sweden 5551 (65) 131 (123) 5420 (64)

Finland 60 731 (710) 545 (514) 60 186 (713)















Obese 118 105 134 (117 to 154) lt00001


Smoking 249 223 115 (102 to 131) 0026


Whitehall IIc
















Discussion


















Conclusion





















































ehx324-TF1

ehx324-TF2

ehx324-TF3

ehx324-TF4












Obese 118 105 134 (117 to 154) lt00001


Smoking 249 223 115 (102 to 131) 0026


Whitehall IIc
















Discussion


















Conclusion





















































ehx324-TF1

ehx324-TF2

ehx324-TF3

ehx324-TF4


Discussion


















Conclusion





















































ehx324-TF1

ehx324-TF2

ehx324-TF3

ehx324-TF4









Conclusion





















































ehx324-TF1

ehx324-TF2

ehx324-TF3

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ehx324-TF1

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European Heart Journal , 38(34): 2621-2628 Kivimäki, M...

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