Jian Li1, Frank Pega2, Yuka Ujita3, Chantal Brisson4, Els Clays5, Alexis Descatha6, Marco M Ferrario7, Lode Godderis8, Sergio Iavicoli9, Paul A Landsbergis10, Maria-Inti Metzendorf11, Rebecca L Morgan12, Daniela V Pachito13, Hynek Pikhart14, Bernd Richter15, Mattia Roncaioli16, Reiner Rugulies17, Peter L Schnall18, Grace Sembajwe19, Xavier Trudel20, Akizumi Tsutsumi21, Tracey J Woodruff22, Johannes Siegrist23. 1. Department of Environmental Health Sciences, Fielding School of Public Health, School of Nursing, University of California, Los Angeles, United States. Electronic address: jianli2019@ucla.edu. 2. Environment, Climate Change and Health Department, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland. Electronic address: pegaf@who.int. 3. Labour Administration, Labour Inspection and Occupational Safety and Health Branch, International Labour Organization, Route des Morillons 4, 1211 Geneva, Switzerland. Electronic address: ujita@ilo.org. 4. Centre de Recherche du CHU de Québec, Université Laval, 1050 Chemin Ste-Foy, Quebec City G1S 4L8, Quebec, Canada. Electronic address: Chantal.Brisson@crchudequebec.ulaval.ca. 5. Department of Public Health and Primary Care, Ghent University, Campus University Hospital Ghent (4K3 - entrance 42), 4K3, Corneel Heymanslaan 10, B-9000 Ghent, Belgium. Electronic address: els.clays@UGent.be. 6. AP-HP (Paris Hospital), Occupational Health Unit, Poincaré University Hospital, Garches, France; Inserm Versailles St-Quentin Univ - Paris Saclay Univ (UVSQ), UMS 011, UMR-S 1168, Villejuif, France; Univ Angers, CHU Angers, Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-49000 Angers, France. Electronic address: alexis.descatha@inserm.fr. 7. Research Centre EPIMED, University of Insubria, Via O Rossi 9, 21100 Varese, Italy. Electronic address: marco.ferrario@uninsubria.it. 8. Centre for Environment and Health, KU Leuven, Leuven, Belgium; KIR Department (Knowledge, Information & Research), IDEWE, External Service for Prevention and Protection at Work, Leuven, Belgium. Electronic address: lode.godderis@kuleuven.be. 9. Inail, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, Via Fontana Candida 1, 00078 Monte Porzio Catone (Rome), Italy. Electronic address: s.iavicoli@inail.it. 10. SUNY-Downstate Health Sciences University, School of Public Health, 450 Clarkson Ave., Brooklyn, NY 11238, United States. Electronic address: paul.landsbergis@downstate.edu. 11. Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany. Electronic address: maria-inti.metzendorf@med.uni-duesseldorf.de. 12. Department of Health Research Methods, Evidence, and Impact, McMaster University, Health Sciences Centre, Hamilton, Canada. Electronic address: morganrl@mcmaster.ca. 13. Hospital Sírio-Libanês and Disciplina de Economia e Gestão em Saúde, Universidade Federal de São Paulo, 412 Barata Ribeiro, Sao Paulo, Brazil. Electronic address: pachito@uol.com.br. 14. Institute of Epidemiology and Health Care, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom. Electronic address: h.pikhart@ucl.ac.uk. 15. Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany. Electronic address: richterb@uni-duesseldorf.de. 16. Research Centre EPIMED, University of Insubria, Via O Rossi 9, 21100 Varese, Italy. Electronic address: mattia.roncaioli@gmail.com. 17. National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, DK-1014 Copenhagen, Denmark; Department of Psychology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353 Copenhagen, Denmark. Electronic address: rer@nrcwe.dk. 18. Center for Occupational and Environmental Health, University of California-Irvine, 100 Theory Way, Irvine, CA, United States. Electronic address: pschnall@workhealth.org. 19. Department of Occupational Medicine, Epidemiology and Prevention (OMEP), Donald and Barbara Zucker School of Medicine at Hofstra University, 175 Community Drive, NY 11021, United States; Department of Environmental, Occupational, and Geospatial Health Sciences, CUNY Graduate School of Public Health and Health Policy, 55 W 125th Street, New York, NY 10027, United States. Electronic address: GSembajwe@northwell.edu. 20. Centre de Recherche du CHU de Québec, Université Laval, 1050 Chemin Ste-Foy, Quebec City G1S 4L8, Quebec, Canada. Electronic address: Xavier.Trudel@crchudequebec.ulaval.ca. 21. Department of Public Health, School of Medicine, Kitasato University, 1-15-1 Kitasato, Minami, Sagamihara 252-0374, Japan. Electronic address: akizumi@kitasato-u.ac.jp. 22. Program on Reproductive Health and the Environment, University of California San Francisco, San Francisco, United States. Electronic address: Tracey.Woodruff@ucsf.edu. 23. Life Science Centre, University of Düsseldorf, Merowingerplatz 1a, Düsseldorf 40225, Germany. Electronic address: johannes.siegrist@med.uni-duesseldorf.de.
Abstract
BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing Joint Estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic data suggests that exposure to long working hours may cause ischaemic heart disease (IHD). In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from IHD that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (three outcomes: prevalence, incidence and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including MEDLINE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged < 15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies which contained an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (prevalence, incidence or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined relative risks using random-effect meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS: Thirty-seven studies (26 prospective cohort studies and 11 case-control studies) met the inclusion criteria, comprising a total of 768,751 participants (310,954 females) in 13 countries in three WHO regions (Americas, Europe and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with administrative health records (30 studies) or self-reported physician diagnosis (7 studies). The outcome was defined as incident non-fatal IHD event in 19 studies (8 cohort studies, 11 case-control studies), incident fatal IHD event in two studies (both cohort studies), and incident non-fatal or fatal ("mixed") event in 16 studies (all cohort studies). Because we judged cohort studies to have a relatively lower risk of bias, we prioritized evidence from these studies and treated evidence from case-control studies as supporting evidence. For the bodies of evidence for both outcomes with any eligible studies (i.e. IHD incidence and mortality), we did not have serious concerns for risk of bias (at least for the cohort studies). No eligible study was found on the effect of long working hours on IHD prevalence. Compared with working 35-40 h/week, we are uncertain about the effect on acquiring (or incidence of) IHD of working 41-48 h/week (relative risk (RR) 0.98, 95% confidence interval (CI) 0.91 to 1.07, 20 studies, 312,209 participants, I2 0%, low quality of evidence) and 49-54 h/week (RR 1.05, 95% CI 0.94 to 1.17, 18 studies, 308,405 participants, I2 0%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderately, clinically meaningful increase in the risk of acquiring IHD, when followed up between one year and 20 years (RR 1.13, 95% CI 1.02 to 1.26, 22 studies, 339,680 participants, I2 5%, moderate quality of evidence). Compared with working 35-40 h/week, we are very uncertain about the effect on dying (mortality) from IHD of working 41-48 h/week (RR 0.99, 95% CI 0.88 to 1.12, 13 studies, 288,278 participants, I2 8%, low quality of evidence) and 49-54 h/week (RR 1.01, 95% CI 0.82 to 1.25, 11 studies, 284,474 participants, I2 13%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderate, clinically meaningful increase in the risk of dying from IHD when followed up between eight and 30 years (RR 1.17, 95% CI 1.05 to 1.31, 16 studies, 726,803 participants, I2 0%, moderate quality of evidence). Subgroup analyses found no evidence for differences by WHO region and sex, but RRs were higher among persons with lower SES. Sensitivity analyses found no differences by outcome definition (exclusively non-fatal or fatal versus "mixed"), outcome measurement (health records versus self-reports) and risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains). CONCLUSIONS: We judged the existing bodies of evidence for human evidence as "inadequate evidence for harmfulness" for the exposure categories 41-48 and 49-54 h/week for IHD prevalence, incidence and mortality, and for the exposure category ≥55 h/week for IHD prevalence. Evidence on exposure to working ≥55 h/week was judged as "sufficient evidence of harmfulness" for IHD incidence and mortality. Producing estimates for the burden of IHD attributable to exposure to working ≥55 h/week appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates.
BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing Joint Estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic data suggests that exposure to long working hours may cause ischaemic heart disease (IHD). In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from IHD that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (three outcomes: prevalence, incidence and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including MEDLINE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged < 15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies which contained an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on IHD (prevalence, incidence or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined relative risks using random-effect meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS: Thirty-seven studies (26 prospective cohort studies and 11 case-control studies) met the inclusion criteria, comprising a total of 768,751 participants (310,954 females) in 13 countries in three WHO regions (Americas, Europe and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with administrative health records (30 studies) or self-reported physician diagnosis (7 studies). The outcome was defined as incident non-fatal IHD event in 19 studies (8 cohort studies, 11 case-control studies), incident fatal IHD event in two studies (both cohort studies), and incident non-fatal or fatal ("mixed") event in 16 studies (all cohort studies). Because we judged cohort studies to have a relatively lower risk of bias, we prioritized evidence from these studies and treated evidence from case-control studies as supporting evidence. For the bodies of evidence for both outcomes with any eligible studies (i.e. IHD incidence and mortality), we did not have serious concerns for risk of bias (at least for the cohort studies). No eligible study was found on the effect of long working hours on IHD prevalence. Compared with working 35-40 h/week, we are uncertain about the effect on acquiring (or incidence of) IHD of working 41-48 h/week (relative risk (RR) 0.98, 95% confidence interval (CI) 0.91 to 1.07, 20 studies, 312,209 participants, I2 0%, low quality of evidence) and 49-54 h/week (RR 1.05, 95% CI 0.94 to 1.17, 18 studies, 308,405 participants, I2 0%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderately, clinically meaningful increase in the risk of acquiring IHD, when followed up between one year and 20 years (RR 1.13, 95% CI 1.02 to 1.26, 22 studies, 339,680 participants, I2 5%, moderate quality of evidence). Compared with working 35-40 h/week, we are very uncertain about the effect on dying (mortality) from IHD of working 41-48 h/week (RR 0.99, 95% CI 0.88 to 1.12, 13 studies, 288,278 participants, I2 8%, low quality of evidence) and 49-54 h/week (RR 1.01, 95% CI 0.82 to 1.25, 11 studies, 284,474 participants, I2 13%, low quality of evidence). Compared with working 35-40 h/week, working ≥55 h/week may have led to a moderate, clinically meaningful increase in the risk of dying from IHD when followed up between eight and 30 years (RR 1.17, 95% CI 1.05 to 1.31, 16 studies, 726,803 participants, I2 0%, moderate quality of evidence). Subgroup analyses found no evidence for differences by WHO region and sex, but RRs were higher among persons with lower SES. Sensitivity analyses found no differences by outcome definition (exclusively non-fatal or fatal versus "mixed"), outcome measurement (health records versus self-reports) and risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains). CONCLUSIONS: We judged the existing bodies of evidence for human evidence as "inadequate evidence for harmfulness" for the exposure categories 41-48 and 49-54 h/week for IHD prevalence, incidence and mortality, and for the exposure category ≥55 h/week for IHD prevalence. Evidence on exposure to working ≥55 h/week was judged as "sufficient evidence of harmfulness" for IHD incidence and mortality. Producing estimates for the burden of IHD attributable to exposure to working ≥55 h/week appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates.
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