Association of serum markers of oxidative stress with myocardial infarction and stroke: pooled results from four large European cohort studies
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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.
KeywordsOxidative 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.
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The authors declare that they have no conflict of interest.
- 11.Li C, Zhang WJ, Choi J, Frei B. Quercetin affects glutathione levels and redox ratio in human aortic endothelial cells not through oxidation but formation and cellular export of quercetin-glutathione conjugates and upregulation of glutamate-cysteine ligase. Redox Biol. 2016;9:220–8.CrossRefGoogle Scholar
- 16.Boffetta P, Bobak M, Borsch-Supan A, Brenner H, Eriksson S, Grodstein F, et al. The Consortium on Health and Ageing: network of Cohorts in Europe and the United States (CHANCES) project—design, population and data harmonization of a large-scale, international study. Eur J Epidemiol. 2014;29:929–36.CrossRefGoogle Scholar
- 17.Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med. 2010;29:1037–57.Google Scholar
- 24.Xuan Y, Gao X, Holleczek B, Brenner H, Schöttker B. Prediction of myocardial infarction, stroke and cardiovascular mortality with urinary biomarkers of oxidative stress: Results from a large cohort study. Int J Cardiol. 2018 [epub ahead of print]. https://doi.org/10.1016/j.ijcard.2018.08.002.
- 25.Vassalle C, Botto N, Andreassi MG, Berti S, Biagini A. Evidence for enhanced 8-isoprostane plasma levels, as index of oxidative stress in vivo, in patients with coronary artery disease. Coron Artery Dis. 2003;14:213–8.Google Scholar
- 43.Pugliese G, Solini A, Bonora E, Orsi E, Zerbini G, Giorgino F, et al. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation provides a better definition of cardiovascular burden associated with CKD than the Modification of Diet in Renal Disease (MDRD) Study formula in subjects with type 2 diabetes. Atherosclerosis. 2011;218:194–9.CrossRefGoogle Scholar