Abstract
Serum VEGF level is regarded to be a biomarker for the diagnosis of stroke. Even though there have been published plethora of original articles describing higher blood VEGF concentrations since the 1970s, however, there is no any meta-analysis report for serum VEGF levels in the field of evidence-based medicine yet. A systematic review was performed by searching the online biomedical databases including retrieving 14 case–control studies including within-article subgroups after fulfilling the inclusion and exclusion criteria without the beginning date restriction, until 2020 for ischemic stroke patients. The Q quantity and I2% statistic index showed a high heterogeneity (84.895 and 84.687, respectively) and the random-effects model of meta-analysis was applied for further analyses. The meta-analysis on a total number of 769 stroke subjects and 621 controls found that the weighted pooled SMD for overall serum VEGF levels on different days of testing was 1.92 (95% CI, − 4.059–0.219, p value = 0.079) and the pooled SMD for overall serum VEGF levels on day 1 of testing was − 1.083 (95% CI, − 4.229–2.063, p value = 0.500). The meta-regression results demonstrated that different days of testing do not significantly affect serum VEGF concentrations in ischemic patients and actually their serum levels are time-independent. Based on the recently published studies, this meta-analysis showed that serum VEGF levels were not significantly associated with an ischemic stroke diagnosis. Thus, researchers may concern another ideal serum or cerebrospinal fluid-derived biomarker for stroke diagnosis.





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References
González RG, Hirsch JA, Koroshetz W, Lev MH, Schaefer PW (2011) Acute ischemic stroke. Springer
Mendelow A D, Lo E H, Sacco R L, Faan MMF, Wong LK (2015) Stroke: pathophysiology, diagnosis, and management, Elsevier Inc
Kini S, Memon F, Asgaonkar D (2019) Outcome in survivors of middle cerebral artery territory ischemic stroke: can it be predicted? J Assoc Phys India 6746
Hadi A, Bendriss L, Khatouri A (2018) The contribution of systematic implementation of cardiovascular explorations for the detection of cardiac sources of embolism in patients with stroke: about 230 patients. Ann Cardiol Angeiol 67(4):256–259
Farooqui AA (2013) Beneficial effects of propolis on neurological disorders. Springer, pp. 301-322
Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T (1980) Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ 58(1):113
Torres-Aleman I (2000) Serum growth factors and neuroprotective surveillance: focus on IGF-1. Mol Neurobiol 21(3):153–160
Jin KL, Mao XO, Greenberg DA (2000) Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci 97(18):10242–10247
Greenberg DA, Jin K (2013) Vascular endothelial growth factors (VEGFs) and stroke. Cell Mol Life Sci 70(10):1753–1761
Moher D, Liberati A, Tetzlaff J, Altman DG, The P G (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 6(7):e1000097
Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558
Faraone SV (2008) Interpreting estimates of treatment effects: implications for managed care. P T 33(12):700–711
Matsuo R, Ago T, Kamouchi M, Kuroda J, Kuwashiro T, Hata J, Sugimori H, Fukuda K, Gotoh S, Makihara N (2013) Clinical significance of plasma VEGF value in ischemic stroke-research for biomarkers in ischemic stroke (REBIOS) study. BMC Neurol 13(1):32
Giordano M, Ciarambino T, D’Amico M, Trotta MC, Sette D, Marinella A, Marfella R, Malatino L, Paolisso G, Adinolfi LE (2019) Circulating MiRNA-195-5p and-451a in transient and acute ischemic stroke patients in an emergency department. J Clin Med 8(2):130
Setyopranoto I, Sadewa AH, Wibowo S, Widyadharma IPE (2019) Comparison of mean VEGF-A expression between acute ischemic stroke patients and non-ischemic stroke subjects. Open Access Maced J Med Sci 7(5):747
Xue L, Chen H, Zhang T, Chen J, Geng Z, Zhao Y (2017) Changes in serum vascular endothelial growth factor and endostatin concentrations associated with circulating endothelial progenitor cells after acute ischemic stroke. Metab Brain Dis 32(2):641–648
Slevin M, Krupinski J, Slowik A, Kumar P, Szczudlik A, Gaffney J (2000) Serial measurement of vascular endothelial growth factor and transforming growth factor-β1 in serum of patients with acute ischemic stroke. Stroke 31(8):1863–1870
Mykhalojko O, Mykhalojko I (2017) Some biochemical changes in patients with acute ischemic stroke. Ukr Biochem J 89(3):31–35
Gavaghan DJ, Moore RA, McQuay HJ (2000) An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain 85(3):415–424
Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557
Geiseler SJ, Morland C (2018) The janus face of VEGF in stroke. Int J Mol Sci 19(5):1362
Kaya D, Gürsoy-Özdemir Y, Yemisci M, Tuncer N, Aktan S, Dalkara T (2005) VEGF protects brain against focal ischemia without increasing blood–brain permeability when administered intracerebroventricularly. J Cereb Blood Flow Metab 25(9):1111–1118
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The present study was approved by the Ethics Committee of Ilam University of Medical Sciences (IR.MEDILAM.REC.1398.187).
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Article highlights
• The association between serum VEGF concentrations and ischemic stroke detection was investigated using meta-analysis.
• The included studies (systematic review) were heterogeneous and the random-effects model was applied.
• The pooled SMD for overall serum VEGF levels on different days of testing was 1.92 (95% CI, − 4.059–0.219, p value = 0.079).
• The pooled SMD for overall serum VEGF levels on day 1 of testing was − 1.083 (95% CI, − 4.229–2.063, p value = 0.500).
• Based on the included studies, serum VEGF levels were not significantly associated with an ischemic stroke diagnosis.
• Researchers may concern another ideal serum or cerebrospinal fluid-derived biomarker for the near future.
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Seidkhani-Nahal, A., Khosravi, A., Mirzaei, A. et al. Serum vascular endothelial growth factor (VEGF) levels in ischemic stroke patients: a systematic review and meta-analysis of case–control studies. Neurol Sci 42, 1811–1820 (2021). https://doi.org/10.1007/s10072-020-04698-7
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DOI: https://doi.org/10.1007/s10072-020-04698-7