European Journal of Epidemiology

, Volume 34, Issue 5, pp 471–481 | Cite as

Association of serum markers of oxidative stress with myocardial infarction and stroke: pooled results from four large European cohort studies

  • Yang Xuan
  • Martin Bobak
  • Ankita Anusruti
  • Eugène H. J. M. Jansen
  • Andrzej Pająk
  • Abdonas Tamosiunas
  • Kai-Uwe Saum
  • Bernd Holleczek
  • Xin Gao
  • Hermann Brenner
  • Ben SchöttkerEmail author


Oxidative stress contributes to endothelial dysfunction and is involved in the pathogenesis of myocardial infarction (MI) and stroke. However, associations of biomarkers of oxidative stress with MI and stroke have not yet been addressed in large cohort studies. A nested case–control design was applied in four population-based cohort studies from Germany, Czech Republic, Poland and Lithuania. Derivatives of reactive oxygen metabolites (d-ROMs) levels, as a proxy for the reactive oxygen species burden, and total thiol levels (TTL), as a proxy for the reductive capacity, were measured in baseline serum samples of 476 incident MI cases and 454 incident stroke cases as well as five controls per case individually matched by study center, age and sex. Statistical analyses were conducted with multi-variable adjusted conditional logistic regression models. d-ROMs levels were associated with both MI (odds ratio (OR), 1.21 [95% confidence interval (CI) 1.05–1.40] for 100 Carr units increase) and stroke (OR, 1.17 [95% CI 1.01–1.35] for 100 Carr units increase). TTL were only associated with stroke incidence (OR, 0.79 [95% CI 0.63-0.99] for quartiles 2–4 vs. quartile 1). The observed relationships were stronger with fatal than with non-fatal endpoints; association of TTL with fatal MI was statistically significant (OR, 0.69 [95% CI 0.51–0.93] for 100 μmol/L-increase). This pooled analysis of four large population-based cohorts suggests an important contribution of an imbalanced redox system to the etiology of mainly fatal MI and stroke events.


Oxidative stress Myocardial infarction Stroke Cardiovascular disease Cohort study 



This project was funded by a grant from the German Research Foundation (Grant No. SCHO 1545/3-1) and a scholarship from the China Scholarship Council (CSC) to Yang Xuan. The CHANCES project was funded in the FP7 framework programme of DG-RESEARCH in the European Commission (Grant No. 242,244). The CHANCES project was coordinated by the Hellenic Health Foundation, Greece. Further funding sources of participating cohorts: The ESTHER study was funded by the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany) and the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany). The HAPIEE study was funded by the Welcome Trust (064947 and 081081), the US National Institute on Ageing (R01 AG23522) and a grant from Mac Arthur Foundation. The authors are indebted to Mr. Piet Beekhof for the measurement of all oxidative stress biomarkers. We also acknowledge the work of Anne Peasey, Růžena Kubínová, Hynek Pikhart and Roman Topor-Madry in the conduct of the HAPIEE study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (DOCX 1784 kb)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Yang Xuan
    • 1
    • 2
  • Martin Bobak
    • 3
  • Ankita Anusruti
    • 1
    • 2
  • Eugène H. J. M. Jansen
    • 4
  • Andrzej Pająk
    • 5
  • Abdonas Tamosiunas
    • 6
  • Kai-Uwe Saum
    • 1
  • Bernd Holleczek
    • 7
  • Xin Gao
    • 1
    • 2
  • Hermann Brenner
    • 1
    • 2
  • Ben Schöttker
    • 1
    • 2
    • 8
    Email author
  1. 1.Division of Clinical Epidemiology and Ageing ResearchGerman Cancer Research CenterHeidelbergGermany
  2. 2.Network Aging ResearchUniversity of HeidelbergHeidelbergGermany
  3. 3.Department Epidemiology and Public HealthUniversity College LondonLondonUK
  4. 4.Centre for Health ProtectionNational Institute for Public Health and the EnvironmentBilthovenThe Netherlands
  5. 5.Faculty of Health SciencesJagiellonian University Medical CollegeKrakówPoland
  6. 6.Institute of Cardiology of LithuanianUniversity of Health SciencesKaunasLithuania
  7. 7.Saarland Cancer RegistrySaarbrückenGermany
  8. 8.Institute of Health Care and Social SciencesFOM UniversityEssenGermany

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