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Epidemiology
Original research
White cell counts in relation to mortality in a general population of cohort study in the Netherlands: a mediating effect or not?
  1. Itziar Abete1,
  2. Yunxia Lu2,
  3. Camille Lassale3,
  4. Monique Verschuren4,
  5. Yvonne van der Schouw5,
  6. Bas Bueno-de-Mesquita6
  1. 1 Nutrition Research Center, University of Navarra, Pamplona, Spain
  2. 2 Program in Public Health, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, California, USA
  3. 3 Epidemiology and Public Health, University College London, London, UK
  4. 4 Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
  5. 5 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  6. 6 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Utrecht, The Netherlands
  1. Correspondence to Dr Yunxia Lu; yunxia.lu{at}uci.edu

Abstract

Background White cell count (WCC) is a clinical marker of inflammation. Data are limited regarding the association of total and differential WCC with risk of mortality, and its role related with smoking and body mass index (BMI).

Methods A total of 14 433 participants (4150 men; 10 283 women; average age 47.3±11.8 years) from the Dutch European Prospective Investigation into Cancer and Nutrition-Netherlands cohort were included. The associations between prediagnostic total WCC and its subtypes and risk of all-cause, cancer and cardiovascular disease (CVD) mortality were assessed. The role of WCC related with smoking and BMI on mortality was further explored. Multivariate Cox regression models were performed to estimate the HR and 95% CI.

Results After an average follow-up of 15.8 years, a total of 936 death cases were identified (466 cancer; 179 CVD; 291 other causes). Statistically significant graded associations between total WCC, and counts of lymphocytes, monocytes, neutrophils and eosinophils and risk of total mortality were observed. These associations were more apparent in current smokers. Strong associations for all-cause mortality or cancer mortality were observed in subjects with BMI ≥25 kg/m2, ever smoking and elevated WCC (HR 3.92, 95% CI 2.76 to 5.57; HR 3.93, 95% CI 2.30 to 6.72). WCC partly mediated the associations between smoking or BMI and all-cause mortality.

Conclusions Prediagnostic WCC and its subtypes are associated with all-cause, cancer and CVD mortality risk. It may play a partially mediate role on the association between smoking or obesity and mortality.

  • white cell count
  • mortality
  • smoking
  • obesity
  • mediation

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2019-030949

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    Footnotes

    • Contributors YL and IA are the correspondence authors with equal contribution. YL is acting as the submission’s guarantor. YL, IA and BB-d-M are responsible for the integrity of the work as a whole, from inception to publishing article. BB-d-M proposed the conception of the study, designed the study based on the Dutch European Prospective Investigation into Cancer and Nutrition (EPIC-NL) cohort. YL and IA performed the data analysis and drafted the manuscript; Cl participated in the data analysis, results interpretation and manuscript writing; MV, YvdS and BB-d-M are the key persons for the EPIC-NL cohort. They also contributed to conception of the study, data analysis, results interpretation and manuscript writing.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The study complies with the Declaration of Helsinki and was approved by the Institutional Review Board of the University Medical Center Utrecht (Prospect) and the Medical Ethical Committee of TNO Nutrition and Food Research (MORGEN).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data sets used for the current study are available from the Dutch European Prospective Investigation into Cancer and Nutrition (EPIC-NL) cohort on request.