Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients

International Journal of General Medicine, Dec 2016

Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients Yuyun Yueniwati,1 Ni Komang Darmiastini,1 Eko Arisetijono2 1Radiology Department, Faculty of Medicine, Brawijaya University, Malang, Indonesia; 2Neurology Department, Faculty of Medicine, Brawijaya University, Malang, Indonesia Background and objectives: Atherosclerosis causes reduction of the oxygen supply to structures in the far arterial wall, provoking the release of factors that drive angiogenesis of vasa vasorum, including VEGF. Other studies have revealed the inflammatory response in atherosclerosis and the role of platelet factor 4 (PF4) as an anti-angiogenic chemokine through the inhibition of VEGF. This cross-sectional study aims at measuring the effect of atherosclerosis assessed through carotid intima-media thickness (CIMT) against plasma VEGF levels in patients with post-acute thrombotic stroke. Materials and methods: CIMT was assessed sonographically using GE Logiq S6 with 13 MHz frequency linear probe. VEGF-A plasma levels were measured using enzyme-linked immunosorbent assay (ELISA) method. Differences among variables were compared statistically. The data were analyzed using Pearson correlation. Results: A total of 25 patients with post-acute thrombotic stroke were identified in days 7 to 90. CIMT thickening was indicated in 88% of patients (1.202 ± 0.312 mm), while an increase in plasma VEGF was identified in all patients (178.28 ± 93.96 ng/mL). There was no significant correlation between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke (p=0.741). A significant correlation was recognized between CIMT and total cholesterol (p=0.029) and low-density lipoprotein (p=0.018). Conclusion: There were no significant correlations between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke. However, plasma VEGF increased in patients with thrombotic stroke. CIMT measurement is a promising noninvasive modality to assess the vascular condition of patients with stroke and diabetes, while plasma VEGF cannot specifically assess vascular condition as it can be triggered by ischemic conditions in tissues of the whole body. Keywords: atherosclerosis, CIMT, VEGF, thrombotic stroke

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Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients

International Journal of General Medicine Dovepress open access to scientific and medical research ORIGINAL RESEARCH International Journal of General Medicine downloaded from https://www.dovepress.com/ by 54.38.22.118 on 12-Jul-2018 For personal use only. Open Access Full Text Article Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post‑acute thrombotic stroke patients This article was published in the following Dove Press journal: International Journal of General Medicine 14 December 2016 Number of times this article has been viewed Yuyun Yueniwati 1 Ni Komang Darmiastini 1 Eko Arisetijono 2 1 Radiology Department, Faculty of Medicine, Brawijaya University, Malang, Indonesia; 2Neurology Department, Faculty of Medicine, Brawijaya University, Malang, Indonesia Background and objectives: Atherosclerosis causes reduction of the oxygen supply to structures in the far arterial wall, provoking the release of factors that drive angiogenesis of vasa vasorum, including VEGF. Other studies have revealed the inflammatory response in atherosclerosis and the role of platelet factor 4 (PF4) as an anti-angiogenic chemokine through the inhibition of VEGF. This cross-sectional study aims at measuring the effect of atherosclerosis assessed through carotid intima-media thickness (CIMT) against plasma VEGF levels in patients with post-acute thrombotic stroke. Materials and methods: CIMT was assessed sonographically using GE Logiq S6 with 13 MHz frequency linear probe. VEGF-A plasma levels were measured using enzyme-linked immunosorbent assay (ELISA) method. Differences among variables were compared statistically. The data were analyzed using Pearson correlation. Results: A total of 25 patients with post-acute thrombotic stroke were identified in days 7 to 90. CIMT thickening was indicated in 88% of patients (1.202 ± 0.312 mm), while an increase in plasma VEGF was identified in all patients (178.28 ± 93.96 ng/mL). There was no significant correlation between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke (p=0.741). A significant correlation was recognized between CIMT and total cholesterol (p=0.029) and low-density lipoprotein (p=0.018). Conclusion: There were no significant correlations between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke. However, plasma VEGF increased in patients with thrombotic stroke. CIMT measurement is a promising noninvasive modality to assess the vascular condition of patients with stroke and diabetes, while plasma VEGF cannot specifically assess vascular condition as it can be triggered by ischemic conditions in tissues of the whole body. Keywords: atherosclerosis, CIMT, VEGF, thrombotic stroke Introduction Correspondence: Yuyun Yueniwati Radiology Department, Faculty of Medicine, Brawijaya University, Jl Veteran Malang, 65145, Indonesia Tel +62 81 838 1800 Fax +62 341 341 808 Email 447 submit your manuscript | www.dovepress.com International Journal of General Medicine 2016:9 447–452 Dovepress © 2016 Yueniwati et al . This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/IJGM.S114577 Powered by TCPDF (www.tcpdf.org) Stroke is the leading cause of death and disability worldwide. In Indonesia, the average age of stroke patients is 58.8 years old and stroke is the leading cause of a high mortality rate in people above 50 years old.1–3 The number of stroke patients is inclined to increase every year, not only among elderly people, but also young and productive people.4 The most common type of stroke is thrombotic stroke with atherosclerosis as the most common cause.5,6 In atherosclerosis, thickening of the intima causes a decrease in the supply of oxygen to the far arterial wall, causing ischemia in blood vessels which provokes the release of factors stimulating angiogenesis of vasa vasorum, such as EPO, VEGF, and Ets-1.7 Other studies have shown the existence of inflammatory Dovepress Yueniwati et al Inclusion criteria 500 450 400 y = 26.451x + 146.41 R2 = 0.0077 350 VEGF International Journal of General Medicine downloaded from https://www.dovepress.com/ by 54.38.22.118 on 12-Jul-2018 For personal use only. 300 250 Y-Values 200 Linear (Y-Values) 150 100 50 0 0 0.5 1 CIMT 1.5 2 Figure 1 Curve of linear correlation between CIMT and plasma VEGF. Note: Demonstrates linear correlation between CIMT and plasma VEGF levels with R-value of 0.78%. Abbreviation: CIMT, carotid intima-media thickness. responses in the atherosclerotic process, such as the role of PF4 which inhibits the degradation of low-density lipoprotein (LDL), facilitating the oxidation of LDL, recruiting monocytes, and facilitating their differentiation into macrophages. In addition, platelet factors also act as an anti-angiogenic chemokine by inhibiting VEGF.8 Differences in the theory of relationship between atherosclerosis and VEGF emphasize the examination of the relationship between atherosclerosis and plasma VEGF levels assessed by carotid artery ultrasound. Angiogenesis denotes a vital process in the growth and development of tissues which also takes place in pathological conditions, such as stroke, malignancy, inflammation, and diabetes mellitus.7,8 Currently, treatment for stroke which amplifies angiogenic and neurogenic processes has been developed.9 In Indonesia, the blood test for VEGF is not yet widely available. This research aims at describing the effects of atherosclerosis examined through carotid intima-media thickness (CIMT) on the angiogenic process examined through the levels of VEGF, which seems to be able to assist clinicians in assessing vascular health, so as to provide management and selection of appropriate therapy. Methods Research subjects The research design was observational analytic. The data were collected cross-sectionally from in patients and out patients with post-acute thrombotic stroke in days 7 to 90 in Dr. Saiful Anwar General Hospital Malang, Indonesia. The research subjects were 25 patients who were chosen consecutively. 448 Powered by TCPDF (www.tcpdf.org) • Patients with clinically diagnosed post-acute thrombotic stroke identified through computed tomography scan or magnetic resonance imaging. • Patients must be willing to participate in the research (by filling in informed consent form). • For patients with loss of consciousness/Glasgow Coma S (...truncated)


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Yuyun Yueniwati, Ni Komang Darmiastini, Eko Arisetijono. Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients, International Journal of General Medicine, 2016, pp. 447-452, DOI: 10.2147/IJGM.S114577