Article Text
Abstract
Background and purpose Non-traditional risk factors such as chronic inflammation, oxidative stress and thrombogenic factors are believed to contribute to the excess stroke risk in chronic kidney disease (CKD) by triggering vascular injury and endothelial dysfunction. We aimed to determine how well a panel of biomarkers representative of these factors would correlate with estimated glomerular filtration rate (eGFR) in patients with recent transient ischaemic attack (TIA) or stroke. We also investigated whether eGFR would confound previously reported associations between biomarkers and mortality.
Methods We studied a panel of 16 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were log-transformed and correlated with eGFR, adjusted for age. Cox proportional hazard models were used for survival analysis.
Results Among 1297 patients with TIA or stroke, 52.7% (n=684) of patients had CKD (eGFR <60 mL/min/1.73 m2). There was a moderate correlation between log-eGFR and the log-transformed soluble tumour necrosis factor receptor-1 (R2=0.21), attenuating with adjustment for age (R2=0.12). There were moderate-to-strong correlations with markers of cardiac injury, N-terminal pro-brain natriuretic peptide and heart-type fatty acid binding protein (hFABP, R2=0.14 and 0.34, respectively). The strongest correlation after adjustment for age was between hFABP and eGFR (R2=0.20). Adjusting for eGFR did not impact any biomarker associations with mortality.
Conclusions Correlations between biomarkers related to inflammation and thrombosis with renal dysfunction in the setting of cerebrovascular events were generally modest after adjustment for age, suggesting that putative risk factors such as chronic inflammation or coagulopathy are unlikely to be important stroke mechanisms in patients with CKD.
- stroke
- blood pressure
- brain
- atherosclerosis
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Footnotes
Twitter @DearbhlaKelly4
Contributors DMK performed the statistical analysis, interpreted the data and drafted the manuscript. LL contributed to data acquisition and analysis. AIB, DLP and JMD performed the laboratory analysis and contributed to data acquisition. PR conceived and designed the study, provided supervision and funding, interpreted the data and revised the manuscript. The corresponding author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in Stroke & Vascular Neurology editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence.
Funding PR has received funding from Wellcome Trust (Grant No: 104040/Z/14/Z), the NIHR Oxford Biomedical Research Centre (Grant No: IS-BRC-1215-20008) and has received payment for membership of a randomised trial Executive Committee (Bayer). DMK has received a scholarship from the Irish Nephrology Society.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. Requests for access to data should be submitted for consideration to the OxVASC (Oxford Vascular Study) Study Director (peter.rothwell@ndcn.ox.ac.uk).