Stroke | Association of peripheral neutrophil count with intracranial atherosclerotic stenosis | springermedicine.com

Springer Medicine

Top

Published in:

01-12-2020 | Stroke | Research article

Association of peripheral neutrophil count with intracranial atherosclerotic stenosis

Authors: Xing Zhang, Xiao-He Hou, Ya-Hui Ma, Xue-Ning Shen, Xi-Peng Cao, Jing-Hui Song, Lan Tan, Jin-Tai Yu

Published in: BMC Neurology | Issue 1/2020

Login to get access

Abstract

Background

Inflammation plays an important role in atherosclerosis but the contribution of neutrophils to this process is unclear. We sought to assess whether neutrophil count is associated with intracranial atherosclerotic stenosis (ICAS).

Methods

A total of 2847 individuals were included in our study, including 1363 with acute ischemic stroke and 1484 normal controls without stroke. The presence of ICAS was confirmed by magnetic resonance angiography. The association between neutrophil count and ICAS was evaluated by multivariable logistic regression analysis.

Results

Among 2847 individuals included in this study, individuals with ICAS had higher neutrophil counts than those without ICAS in groups with and without stroke (P < 0.0001 for stroke group, P = 0.0097 for group without stroke). The multivariable logistic regression analysis showed that the third and fourth quartiles were independent predictors of ICAS in all the subjects (Q3: OR 1.81, 95% CI 1.39–2.37, Q4: OR 2.29, 95% CI 1.70–3.10) and patients in the fourth quartile had a higher risk for the occurrence of ICAS in stroke group (Q4: OR 2.82, 95% CI 1.79–4.48). However, there was no significant association between neutrophil count and ICAS in the group without stroke.

Conclusions

The levels of circulating neutrophils were associated with the presence of ICAS. Our findings suggest that neutrophils may play a role in the pathogenesis of stroke related to ICAS and emphasize the need to develop proper strategies to control neutrophil response for the treatment of ICAS.

1.

Wang Y, Lu Z, Sun S, Yang Y, Zhang B, Kang Z, et al. Risk factors, topographic patterns and mechanism analysis of intracranial atherosclerotic stenosis ischemic stroke. Int J Neurosci. 2017;127(3):267–75. https://doi.org/10.1080/00207454.2016.1188298.CrossRefPubMed

2.

Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet. 2014;383(9913):245–54.CrossRefPubMedPubMedCentral

3.

Niu JW, Gao S, Cui LY, Peng B, Zhu YC, Ni J, et al. Intracranial atherosclerosis in Chinese young adult stroke patients. J Stroke Cerebrovasc Dis. 2014;23(6):1519–23. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.030.CrossRefPubMed

4.

Wong KS, Huang YN, Gao S, Lam WW, Chan YL, Kay R. Intracranial stenosis in Chinese patients with acute stroke. Neurology. 1998;50(3):812–3.CrossRefPubMed

5.

Bang OY. Intracranial atherosclerosis: current understanding and perspectives. J Stroke. 2014;16(1):27–35. https://doi.org/10.5853/jos.2014.16.1.27.CrossRefPubMedPubMedCentral

6.

Jander S, Sitzer M, Schumann R, Schroeter M, Siebler M, Steinmetz H, et al. Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization. Stroke. 1998;29(8):1625–30.CrossRefPubMed

7.

Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362(6423):801–9. https://doi.org/10.1038/362801a0.CrossRefPubMed

8.

Ernst E, Hammerschmidt DE, Bagge U, Matrai A, Dormandy JA. Leukocytes and the risk of ischemic diseases. JAMA. 1987;257(17):2318–24.CrossRefPubMed

9.

Shah PK. Plaque disruption and thrombosis. Potential role of inflammation and infection. Cardiol Clin. 1999;17(2):271–81.CrossRefPubMed

10.

Gown AM, Tsukada T, Ross R. Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions. Am J Pathol. 1986;125(1):191–207.PubMedPubMedCentral

11.

Jonasson L, Holm J, Skalli O, Bondjers G, Hansson GK. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis (Dallas, Tex). 1986;6(2):131–8.

12.

van der Wal AC, Das PK, van de B, Berg D, van der Loos CM, Becker AE. Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response. Lab Invest. 1989;61(2):166–70.PubMed

13.

Kaartinen M, Penttila A, Kovanen PT. Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha. Circulation. 1996;94(11):2787–92.CrossRefPubMed

14.

Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci U S A. 1989;86(8):2839–43.CrossRefPubMedPubMedCentral

15.

Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994;94(6):2493–503. https://doi.org/10.1172/jci117619.CrossRefPubMedPubMedCentral

16.

Moreno PR, Bernardi VH, Lopez-Cuellar J, Murcia AM, Palacios IF, Gold HK, et al. Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes. Circulation. 1996;94(12):3090–7.CrossRefPubMed

17.

Lombardini R, Vaudo G, Ciuffetti G. Leukocyte-endothelial cell interactions and vascular injury in the earliest preclinical stages of atherosclerosis. Haematologica. 1997;82(2):253.PubMed

18.

Mayer FJ, Gruenberger D, Schillinger M, Mannhalter C, Minar E, Koppensteiner R, et al. Prognostic value of neutrophils in patients with asymptomatic carotid artery disease. Atherosclerosis. 2013;231(2):274–80. https://doi.org/10.1016/j.atherosclerosis.2013.10.002.CrossRefPubMed

19.

Davis NE. Atherosclerosis--an inflammatory process. Journal of insurance medicine (New York, NY). 2005;37 1:72–5.

20.

Nilupul Perera M, Ma HK, Arakawa S, Howells DW, Markus R, Rowe CC, et al. Inflammation following stroke. J Clin Neurosci. 2006;13(1):1–8. https://doi.org/10.1016/j.jocn.2005.07.005.CrossRefPubMed

21.

Yamagami S, Tamura M, Hayashi M, Endo N, Tanabe H, Katsuura Y, et al. Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats. J Leukoc Biol. 1999;65(6):744–9.CrossRefPubMed

22.

Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109 23(Suppl 1):Iii27–32. https://doi.org/10.1161/01.CIR.0000131515.03336.f8.CrossRef

23.

Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653–7. https://doi.org/10.1016/j.amjcard.2008.05.006.CrossRefPubMed

24.

Buck BH, Liebeskind DS, Saver JL, Bang OY, Yun SW, Starkman S, et al. Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke. 2008;39(2):355–60. https://doi.org/10.1161/strokeaha.107.490128.CrossRefPubMed

25.

Becker KJ. Targeting the central nervous system inflammatory response in ischemic stroke. Curr Opin Neurol. 2001;14(3):349–53.CrossRefPubMed

26.

Zhu B, Liu H, Pan Y, Jing J, Li H, Zhao X, et al. Elevated neutrophil and presence of intracranial artery stenosis increase the risk of recurrent stroke. Stroke. 2018;49(10):2294–300. https://doi.org/10.1161/strokeaha.118.022126.CrossRefPubMed

27.

Ovbiagele B, Lynn MJ, Saver JL, Chimowitz MI. Leukocyte count and vascular risk in symptomatic intracranial atherosclerosis. Cerebrovascular diseases (Basel, Switzerland). 2007;24 (2–3):283–288; doi: https://doi.org/10.1159/000105681.CrossRefPubMed

28.

Chen PH, Gao S, Wang YJ, Xu AD, Li YS, Wang D. Classifying ischemic stroke, from TOAST to CISS. CNS Neurosci Ther. 2012;18(6):452–6. https://doi.org/10.1111/j.1755-5949.2011.00292.x.CrossRefPubMedPubMedCentral

29.

Chimowitz MI, Kokkinos J, Strong J, Brown MB, Levine SR, Silliman S, et al. The warfarin-aspirin symptomatic intracranial disease study. Neurology. 1995;45(8):1488–93.CrossRefPubMed

30.

Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol. 2000;21(4):643–6.PubMedPubMedCentral

31.

Qureshi AI, Caplan LR. Intracranial atherosclerosis. Lancet. 2014;383(9921):984–98. https://doi.org/10.1016/s0140-6736(13)61088-0.CrossRefPubMed

32.

Bang OY. Intracranial atherosclerotic stroke: specific focus on the metabolic syndrome and inflammation. Curr Atheroscler Rep. 2006;8(4):330–6.CrossRefPubMed

33.

Avanzas P, Arroyo-Espliguero R, Cosin-Sales J, Quiles J, Zouridakis E, Kaski JC. Multiple complex stenoses, high neutrophil count and C-reactive protein levels in patients with chronic stable angina. Atherosclerosis. 2004;175(1):151–7. https://doi.org/10.1016/j.atherosclerosis.2004.03.013.CrossRefPubMed

34.

Sirico G, Spadera L, De Laurentis M, Brevetti G. Carotid artery disease and stroke in patients with peripheral arterial disease. The role of inflammation. Monaldi Arch Chest Dis. 2009;72(1):10–7. https://doi.org/10.4081/monaldi.2009.337.CrossRefPubMed

35.

Grau AJ, Boddy AW, Dukovic DA, Buggle F, Lichy C, Brandt T, et al. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke. 2004;35(5):1147–52. https://doi.org/10.1161/01.str.0000124122.71702.64.CrossRefPubMed

36.

Chung JW, Oh MJ, Cho YH, Moon GJ, Kim GM, Chung CS, et al. Distinct roles of endothelial dysfunction and inflammation in intracranial atherosclerotic stroke. Eur Neurol. 2017;77(3–4):211–9. https://doi.org/10.1159/000460816.CrossRefPubMed

37.

Festa A, D'Agostino R Jr, Howard G, Mykkanen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the insulin resistance atherosclerosis study (IRAS). Circulation. 2000;102(1):42–7.CrossRefPubMed

38.

Stewart RA, White HD, Kirby AC, Heritier SR, Simes RJ, Nestel PJ, et al. White blood cell count predicts reduction in coronary heart disease mortality with pravastatin. Circulation. 2005;111(14):1756–62. https://doi.org/10.1161/01.cir.0000160924.73417.26.CrossRefPubMed

39.

Kannel WB, Anderson K, Wilson PW. White blood cell count and cardiovascular disease. Insights from the Framingham Study. JAMA. 1992;267(9):1253–6.CrossRefPubMed

40.

Margolis KL, Manson JE, Greenland P, Rodabough RJ, Bray PF, Safford M, et al. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative observational study. Arch Intern Med. 2005;165(5):500–8. https://doi.org/10.1001/archinte.165.5.500.CrossRefPubMed

41.

Marino F, Tozzi M, Schembri L, Ferraro S, Tarallo A, Scanzano A, et al. Production of IL-8, VEGF and Elastase by Circulating and Intraplaque Neutrophils in Patients with Carotid Atherosclerosis. PloS One. 2015;10(4):e0124565. https://doi.org/10.1371/journal.pone.0124565.CrossRefPubMedPubMedCentral

42.

Nam KW, Kwon HM, Jeong HY, Park JH, Kim SH, Jeong SM. High neutrophil to lymphocyte ratios predict intracranial atherosclerosis in a healthy population. Atherosclerosis. 2018;269:117–21. https://doi.org/10.1016/j.atherosclerosis.2017.12.035.CrossRefPubMed

43.

Turan TN, Makki AA, Tsappidi S, Cotsonis G, Lynn MJ, Cloft HJ, et al. Risk factors associated with severity and location of intracranial arterial stenosis. Stroke. 2010;41(8):1636–40. https://doi.org/10.1161/strokeaha.110.584672.CrossRefPubMedPubMedCentral

44.

Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke. 1996;27(11):1974–80. https://doi.org/10.1161/01.str.27.11.1974.CrossRefPubMed

Title: Association of peripheral neutrophil count with intracranial atherosclerotic stenosis
Authors: Xing Zhang
Xiao-He Hou
Ya-Hui Ma
Xue-Ning Shen
Xi-Peng Cao
Jing-Hui Song
Lan Tan
Jin-Tai Yu
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Stroke
Angiography
Arterial Occlusive Disease
Published in: BMC Neurology / Issue 1/2020
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-020-01641-3

Home
Congress Coverage
Clinical Collections
- Advances in Alzheimer’s
About Springer Medicine
Key Specialties