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Original Paper

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Plasma Biomarkers of Inflammation, Endothelial Function and Hemostasis in Cerebral Small Vessel Disease

Wiseman S.J.a · Doubal F.N.a · Chappell F.M.a · Valdés-Hernández M.C.a · Wang X.a · Rumley A.b · Lowe G.D.O.b · Dennis M.S.a · Wardlaw J.M.a

Author affiliations

aCentre for Clinical Brain Sciences, University of Edinburgh, and bInstitute of Cardiovascular and Medical Sciences, Royal Infirmary, University of Glasgow, Glasgow, UK

Corresponding Author

Joanna M. Wardlaw

CCBS, Chancellor's Building, Royal Infirmary of Edinburgh

49 Little France Crescent

Edinburgh, EH16 4SB (UK)

E-Mail Joanna.Wardlaw@ed.ac.uk

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Cerebrovasc Dis 2015;40:157-164

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Abstract

Background: The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It is unknown if plasma biomarkers add predictive capacity beyond age and vascular risk factors in explaining WMH. Methods: We prospectively recruited patients presenting with non-disabling ischemic stroke, classifying them clinically and with the help of MRI as lacunar or cortical. We measured biomarkers of inflammation, endothelial dysfunction and hemostasis for >1 month after stroke and compared biomarker levels between stroke subtypes. We quantitatively calculated WMH. We used multiple linear regression analysis to model WMH as a function of age, sex, hypertension and smoking (the baseline model). We fitted exploratory models using plasma biomarkers as predictor variables to assess model improvement over baseline. Results: We recruited 125 patients. The lacunar group (n = 65) had lower tissue plasminogen activator (t-PA) levels in unadjusted (7.39 vs. 8.59 ng/ml, p = 0.029) and adjusted (p = 0.035) analyses compared with the cortical group (n = 60). There were no significant differences in the other plasma biomarkers. The results for t-PA were consistent with an updated meta-analysis, although the effect remains non-significant (standardized mean difference -0.08 (95% CI -0.25 to 0.09)). The baseline regression model explained 29% of the variance in quantitative WMH (R2 0.289). Inflammatory biomarkers showed minor improvement over baseline (R2 0.291), but the other plasma biomarkers did not improve the baseline model. Conclusion: Plasma t-PA levels appear to differ between lacunar and cortical stroke subtypes, late after stroke, independent of age, sex and vascular risk factors and may reflect endothelial dysfunction. Except for a minor additional predictive effect of inflammatory markers, plasma biomarkers do not relate to WMH severity in this small stroke population.

© 2015 The Author(s) Published by S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 20, 2015
Accepted: July 06, 2015
Published online: August 08, 2015
Issue release date: September 2015

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 3

ISSN: 1015-9770 (Print)
eISSN: 1421-9786 (Online)

For additional information: https://www.karger.com/CED


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