Tara van der Grinten, Barbara N Harding, Karin Broberg, Caisa Laurell, Anne Helene Garde, Kirsten Nabe-Nielsen, Maria Albin, Manolis Kogevinas, Roel Vermeulen, Susan Peters, Jelle Vlaanderen

Abstract

Objective: To examine the association between night-shift work and perturbations in blood metabolomics. Methods: The EPHOR study recruited night-shift and day shift workers mainly from healthcare across the Netherlands (n=98), Spain (n=386), Sweden (n=170), and Denmark (n=196). Blood metabolites were analyzed using the Nightingale Health platform. Linear mixed models, with a random intercept for study center, were used to explore associations between metabolite levels and night-shift work. Principal Component Analysis was conducted within metabolite classes (lipids, amino acids, fatty acids, key energy-related metabolites) to derive metabolic groups. Similar mixed models were used to examine the association between extracted individual scores from each component and night-shift. Analyses were adjusted for potential confounders including age, sex, origin, marital status, education, occupation, smoking, alcohol intake, physical activity, BMI, and chronotype. The False Discovery Rate was applied to account for multiple testing. Results: Compared to day workers, night-shift workers showed higher saturated fatty acid % (β = 0.50, 95% CI 0.23 to 0.77) and lower linoleic acid % (β = -0.63, CI -1.07 to -0.19), docosahexaenoic acid (DHA) % (β = -0.109, CI -0.19 to -0.03), and total polyunsaturated fatty acid (PUFA) % (β = -0.60, CI -1.06 to -0.14). Scores from a ‘key energy-related metabolites’ component (characterized by high loadings from acetoacetate and acetone) were elevated among night-shift workers (β = 0.36, CI 0.14 to 0.58). In contrast, scores from a fatty acid profile (with high loadings from unsaturation index, PUFA/MUFA, DHA) (β = -0.33, CI -0.57 to -0.08) and an amino acid profile (with high loadings from histidine and glycine) (β = -0.14, CI -0.28 to -0.00) were lower among night-shift workers. Conclusion: Night-shift work was associated with higher levels of saturated fats and ketone bodies, and lower polyunsaturated fats and specific amino acids. These findings may reflect physiological stress differences between night- and day-shift workers.

Maria Albin, Bendik Brinchmann, Merete Bugge, Tosca O.E. de Crom, Per Gustavsson, Rune Hoff, Katarina Kjellberg, Henrik Kolstad, Damien McElvenny, Ingrid Sivesind Mehlum, Anjoeka Pronk, Vivi Schlünssen, Svetlana Solovieva, Zara Stokholm, Pernilla Wiebert, Jenny Selander

Abstract

Objective The occupational exposome, encompassing a wide range of work exposures, may impact cardiovascular disease risk. However, most evidence is insufficient and does not account for co-exposures. Thus, the primary objective of this study is to investigate the contribution of occupational exposures in relation to ischemic heart disease (IHD), including myocardial infarction (MI), and stroke. Materials and Methods Five cohorts were included: the Danish Occupational Cohort with Exposure Data (DOC*X), the State of Labor Force in Finland (SLFF) cohort, Lifelines from the Netherlands, Nor-Work from Norway, and the Swedish National Cohort on Work and Health (SNOW). Yearly occupational data were linked to the European Job-Exposure Matrix (EuroJEM) to assign exposure to diesel engine exhaust, respirable crystalline silica dust, wood dust, fast breathing and heavy lifting due to physical workload, noise, low decision authority, and solar UV radiation. Discrete-time hazard models were created to investigate the impact of exposure in the previous year, and a 10-year cumulative exposure, on the risk of IHD and stroke, adjusting for age, gender, education, marital status, country of origin, and other occupational exposures. Results Preliminary results from SNOW show that after adjusting for other occupational exposures, noise and physical workload were associated with increased risk of IHD, MI, and stroke. Diesel engine exhaust was associated with an increased risk of MI only. Analyses on cumulative exposure are ongoing. Results from all cohorts will be summarized in a meta-analysis. Conclusion This study will be the first multi-national study to investigate the impact of several occupational exposures on IHD and stroke. Our findings are expected to contribute to a deeper understanding and characterization of these complex relationships. Acknowledgements This work is part of the Exposome Project for Health and Occupational Research (EPHOR), funded by the European Union’s Horizon 2020 research and innovation programme, grant agreement No 874703.