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Circulating levels of vascular endothelial growth factor and post-stroke long-term functional outcome

Journal article
Authors N David Åberg
Alexander Wall
Olof Anger
Katarina Jood
Ulf Andreasson
Kaj Blennow
Henrik Zetterberg
Jörgen Isgaard
Christina Jern
Johan Svensson
Published in Acta Neurologica Scandinavica
ISSN 0001-6314
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Department of Laboratory Medicine
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Language en
Links dx.doi.org/10.1111/ane.13219
Keywords cerebrovascular diseases, functional outcome, inflammation, ischemic, stroke, rehabilitation, stroke severity, strokes, vascular endothelial, growth factor, blood-brain-barrier, ischemic-stroke, genetic-variation, cerebral-ischemia, shows association, progenitor cells, vessel disease, serum, angiogenesis, classification, Neurosciences & Neurology
Subject categories Neurology, Neurochemistry

Abstract

Objectives Vascular endothelial growth factor (VEGF) acts in angiogenesis and neuroprotection, although the beneficial effects on experimental ischemic stroke (IS) have not been replicated in clinical studies. We investigated serum VEGF (s-VEGF) in the acute stage (baseline) and 3 months post-stroke in relation to stroke severity and functional outcome. Methods The s-VEGF and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in patients enrolled in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) at the acute time-point (median 4 days, N = 492, 36% female; mean age, 57 years) and at 3 months post-stroke (N = 469). Baseline stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes (3 months and 2 years) were evaluated using the modified Rankin Scale (mRS), dichotomized into good (mRS 0-2), and poor (mRS 3-6) outcomes. Multivariable logistic regression analyses were adjusted for covariates. Results The baseline s-VEGF did not correlate with stroke severity but correlated moderately with hs-CRP (r = .17, P < .001). The baseline s-VEGF was 39.8% higher in total anterior cerebral infarctions than in lacunar cerebral infarctions. In binary logistic regression analysis, associations with 3-month functional outcome were non-significant. However, an association between the 3-month s-VEGF and poor 2-year outcome withstood adjustments for age, sex, cardiovascular covariates, and stroke severity (per 10-fold increase in s-VEGF, odds ratio [OR], 2.56, 95% confidence interval [CI] 1.12-5.82) or hs-CRP (OR 2.53, CI 1.15-5.55). Conclusions High 3-month s-VEGF is independently associated with poor 2-year functional outcome but not with 3-month outcome.

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