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Plasma Biomarkers for Ischemic and Hemorrhagic Stroke Diagnosis
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Plasma Biomarkers for Ischemic and Hemorrhagic Stroke Diagnosis
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Dissertation
Plasma Biomarkers for Ischemic and Hemorrhagic Stroke Diagnosis
2017
Overview
Background: Blood biomarkers for ischemic and hemorrhagic stroke diagnosis remain elusive. Recent investigations suggested that apolipoproteins (Apo), matrix metalloproteinases (MMP), and paraoxonase-1 may be associated with stroke. We hypothesized that Apo A-I, Apo C-I, Apo C-III, MMP-3, MMP-9, and paraoxonase-1 are differentially expressed in ischemic stroke, hemorrhagic stroke, and controls. Methods: In a single center prospective observational study, consecutive stroke cases were enrolled if blood samples were obtainable within 12 hours of symptom onset. Age (+/– five years), race, and sex matched controls were recruited. Multiplex assays were used to measure protein levels. The Wilcoxon Signed Ranks Test and Mann-Whitney U Test were used to compare biomarker values between ischemic stroke patients and controls, hemorrhagic stroke patients and controls, and ischemic and hemorrhagic stroke patients. The 95% confidence intervals (CI) for the difference of two medians were calculated. Gel filtration chromatography was used to characterize HDL fractions in a subset of five case-control pairs. Results: Fourteen ischemic stroke case-control pairs and 23 intracerebral hemorrhage (ICH) case-control pairs were enrolled. Median Apo A-I levels were lower in ischemic stroke versus controls (140mg/dL vs 175mg/dL, difference 35mg/dL, 95% CI –54 to –16) , and in ischemic stroke versus ICH (140mg/dL vs 180mg/dL, difference 40mg/dL, 95% CI -57 to -23). Median paraoxonase-1 was lower in ischemic stroke compared to both ICH and matched controls. Median Apo C-I was slightly lower in ischemic stroke compared to ICH cases. There were no differences between groups for MMP-3, MMP-9, and Apo C-III. A specific HDL fraction was identified for male ICH cases and female ICH controls. Conclusion: Apo A-I and paraoxonase-1 levels may be clinically useful for ischemic stroke diagnosis and for differentiating ischemic and hemorrhagic stroke. Further evaluation of HDL fractions in stroke patients and controls, and the associated protein composition, is warranted and could lead to identification of novel biomarkers
