Multi-cohort study identifies social determinants of systemic inflammation over the life course

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Abstract

Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.

Abstract

Here, the authors explore the relationship between socioeconomic position (SEP) across the life course and inflammation in a multi-cohort study and show that educational attainment is most strongly related to inflammation, suggesting that socioeconomic disadvantage in young adulthood is independently associated with later life inflammation.

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Sex differences in immune responses

Sabra L. Klein, Katie Flanagan (2016)

Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.

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Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

The Emerging Risk Factors Collaboration, George Davey Smith (2011)

Summary Background Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. Methods We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease. Findings Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8·49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2·00 (95% CI 1·83–2·19) for coronary heart disease; 2·27 (1·95–2·65) for ischaemic stroke; 1·56 (1·19–2·05) for haemorrhagic stroke; 1·84 (1·59–2·13) for unclassified stroke; and 1·73 (1·51–1·98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40–59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10–12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3·90 mmol/L and 5·59 mmol/L. Compared with fasting blood glucose concentrations of 3·90–5·59 mmol/L, HRs for coronary heart disease were: 1·07 (0·97–1·18) for lower than 3·90 mmol/L; 1·11 (1·04–1·18) for 5·60–6·09 mmol/L; and 1·17 (1·08–1·26) for 6·10–6·99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors. Interpretation Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease. Funding British Heart Foundation, UK Medical Research Council, and Pfizer.

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Cohort profile: the English longitudinal study of ageing.

Andrew Steptoe, Elizabeth Breeze, James E. Banks … (2013)

The English Longitudinal Study of Ageing (ELSA) is a panel study of a representative cohort of men and women living in England aged ≥50 years. It was designed as a sister study to the Health and Retirement Study in the USA and is multidisciplinary in orientation, involving the collection of economic, social, psychological, cognitive, health, biological and genetic data. The study commenced in 2002, and the sample has been followed up every 2 years. Data are collected using computer-assisted personal interviews and self-completion questionnaires, with additional nurse visits for the assessment of biomarkers every 4 years. The original sample consisted of 11 391 members ranging in age from 50 to 100 years. ELSA is harmonized with ageing studies in other countries to facilitate international comparisons, and is linked to financial and health registry data. The data set is openly available to researchers and analysts soon after collection (http://www.esds.ac.uk/longitudinal/access/elsa/l5050.asp).

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Author and article information

Contributors

Michelle Kelly-Irving: michelle.kelly@inserm.fr

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 15 February 2019

Publication date PMC-release: 15 February 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 773

Affiliations

[1 ]ISNI 0000 0001 0723 035X, GRID grid.15781.3a, LEASP, UMR 1027, , Inserm-Université Toulouse III Paul Sabatier, ; Toulouse, 31000 France

[2 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, MRC-PHE Centre for Environment and Health, School of Public Health, Department of Epidemiology and Biostatistics, , Imperial College London, ; London, W2 1PG UK

[3 ]ISNI 0000 0001 0423 4662, GRID grid.8515.9, Psychiatric Epidemiology and Psychopathology Center, Department of Psychiatry, , Lausanne University Hospital, ; Lausanne, 1004 Switzerland

[4 ]Epidemiology Unit, ASL TO3 Piedmont Region, Grugliasco, 10095 Italy

[5 ]ISNI 0000000121901201, GRID grid.83440.3b, Department of Epidemiology and Public Health, , University College London, ; London, WC1E 6BT UK

[6 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Clinicum, Faculty of Medicine, , University of Helsinki, ; P. O. Box 20, Helsinki, FI-00014 Finland

[7 ]ISNI 0000 0001 0807 2568, GRID grid.417893.0, Epidemiology and Prevention Unit, , Fondazione IRCCS Istituto Nazionale dei Tumori, ; Milan, 20133 Italy

[8 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, Department of Clinical Medicine and Surgery, , University of Naples Federico II, ; Naples, 80131 Italy

[9 ]ISNI 0000 0004 1756 876X, GRID grid.420240.0, Piedmont Reference Centre for Epidemiology and Cancer Prevention (CPO Piemonte), ; Turin, 10126 Italy

[10 ]ISNI 0000 0001 0423 4662, GRID grid.8515.9, Institute of Social and Preventive Medicine, , Lausanne University Hospital, ; Lausanne, 1010 Switzerland

[11 ]Cancer Registry and Histopathology Department, ‘Civic – M. P. Arezzo’ Hospital, ASP Ragusa, Ragusa, 97100 Italy

[12 ]Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Torino, 10126 Italy

Author information

Raphaële Castagné http://orcid.org/0000-0003-0067-6775

Marc Chadeau-Hyam http://orcid.org/0000-0001-8341-5436

Maryam Karimi http://orcid.org/0000-0003-3301-8795

Mika Kivimäki http://orcid.org/0000-0002-4699-5627

Rosario Tumino http://orcid.org/0000-0003-2666-414X

Article

Publisher ID: 8732

DOI: 10.1038/s41467-019-08732-x

PMC ID: 6377676

PubMed ID: 30770820

SO-VID: 6af39d6d-14b5-4d2c-900e-ef79344c4ec4

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 4 July 2018

Date accepted : 28 January 2019

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Multi-cohort study identifies social determinants of systemic inflammation over the life course

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UCL: UN SDG 10 Reduced Inequalities

Most cited references 70

Sex differences in immune responses

Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

Cohort profile: the English longitudinal study of ageing.

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