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BMC Neurology
Published in: BMC Neurology 1/2021

Open Access 01-12-2021 | Stroke | Research

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study

Authors: Zhi-bing Hu, Ze-xiong Lu, Feng Zhu, Cao-qiang Jiang, Wei-sen Zhang, Jin Pan, Ya-li Jin, Lin Xu, G. Neil Thomas, Karkeung Cheng, Taihing Lam

Published in: BMC Neurology | Issue 1/2021

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Abstract

Background

Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population.

Methods

In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke.

Results

(i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16–2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10–2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10–1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10–2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (− 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07–2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02–2.05, P = 0.04) increased risk of fatal all stroke occurrence.

Conclusions

The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.
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Literature
1.
Stroke--1989. Recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO task force on stroke and other cerebrovascular disorders. Stroke. 1989;20(10):1407–31.CrossRef
2.
Murray KN, Buggey HF, Denes A, Allan SM. Systemic immune activation shapes stroke outcome. Mol Cell Neurosci. 2013;53:14–25.PubMedCrossRef
3.
Welsh P, Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ. Associations of inflammatory and haemostatic biomarkers with poor outcome in acute ischaemic stroke. Cerebrovasc Dis. 2009;27(3):247–53.PubMedCrossRef
4.
5.
Sun W, Peacock A, Becker J, Phillips-Bute B, Laskowitz DT, James ML. Correlation of leukocytosis with early neurological deterioration following supratentorial intracerebral hemorrhage. J Clin Neurosci. 2012;19(8):1096–100.PubMedPubMedCentralCrossRef
6.
Parthasarathy S, Steinberg D, Witztum JL. The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis. Annu Rev Med. 1992;43:219–25.PubMedCrossRef
7.
Kazmierski R, Guzik P, Ambrosius W, Ciesielska A, Moskal J, Kozubski W. Predictive value of white blood cell count on admission for in-hospital mortality in acute stroke patients. Clin Neurol Neurosurg. 2004;107(1):38–43.PubMedCrossRef
8.
Algin A, Inan I. The role of radiologic, clinical and biochemical parameters in prediction of stroke mortality. Neurosciences (Riyadh). 2019;24(2):110–4.CrossRef
9.
Qu X, Shi J, Cao Y, Zhang M, Xu J. Prognostic value of white blood cell counts and C-reactive protein in acute ischemic stroke patients after intravenous thrombolysis. Curr Neurovasc Res. 2018;15(1):10–7.PubMedCrossRef
10.
Ho WM, Lin JR, Wang HH, Liou CW, Chang KC, Lee JD, et al. Prediction of in-hospital stroke mortality in critical care unit. Springerplus. 2016;5(1):1051.PubMedPubMedCentralCrossRef
11.
Brown DW, Ford ES, Giles WH, Croft JB, Balluz LS, Mokdad AH. Associations between white blood cell count and risk for cerebrovascular disease mortality: NHANES II mortality study, 1976-1992. Ann Epidemiol. 2004;14(6):425–30.PubMedCrossRef
12.
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.PubMedCrossRef
13.
Kabagambe EK, Judd SE, Howard VJ, Zakai NA, Jenny NS, Hsieh M, et al. Inflammation biomarkers and risk of all-cause mortality in the reasons for geographic and racial differences in stroke cohort. Am J Epidemiol. 2011;174(3):284–92.PubMedPubMedCentralCrossRef
14.
Wang T, Jiang CQ, Xu L, Zhang WS, Zhu F, Jin YL, et al. White blood cell count and all-cause and cause-specific mortality in the Guangzhou biobank cohort study. BMC Public Health. 2018;18(1):1232.PubMedPubMedCentralCrossRef
15.
Huh JY, Ross GW, Chen R, Abbott RD, Bell C, Willcox B, et al. Total and differential white blood cell counts in late life predict 8-year incident stroke: the Honolulu heart program. J Am Geriatr Soc. 2015;63(3):439–46.PubMedPubMedCentralCrossRef
16.
Park JK, Kim HJ, Chang SJ, Koh SB, Koh SY. Risk factors for hemorrhagic stroke in Wonju, Korea. Yonsei Med J. 1998;39(3):229–35.PubMedCrossRef
17.
Lee CD, Folsom AR, Nieto FJ, Chambless LE, Shahar E, Wolfe DA. White blood cell count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in African-American and white men and women: atherosclerosis risk in communities study. Am J Epidemiol. 2001;154(8):758–64.PubMedCrossRef
18.
Koren-Morag N, Tanne D, Goldbourt U. White blood cell count and the incidence of ischemic stroke in coronary heart disease patients. Am J Med. 2005;118(9):1004–9.PubMedCrossRef
19.
Zia E, Melander O, Bjorkbacka H, Hedblad B, Engstrom G. Total and differential leucocyte counts in relation to incidence of stroke subtypes and mortality: a prospective cohort study. J Intern Med. 2012;272(3):298–304.PubMedCrossRef
20.
Wu TH, Chien KL, Lin HJ, Hsu HC, Su TC, Chen MF, et al. Total white blood cell count or neutrophil count predict ischemic stroke events among adult Taiwanese: report from a community-based cohort study. BMC Neurol. 2013;13:7.PubMedPubMedCentralCrossRef
21.
Gillum RF, Ingram DD, Makuc DM. White blood cell count and stroke incidence and death. The NHANES I epidemiologic follow-up study. Am J Epidemiol. 1994;139(9):894–902.PubMedCrossRef
22.
Froyshov HM, Bjornerem A, Engstad T, Halvorsen DS. Elevated inflammatory markers predict mortality in long-term ischemic stroke-survivors: a population-based prospective study. Aging Clin Exp Res. 2017;29(3):379–85.PubMedCrossRef
23.
Ohira T, Shahar E, Chambless LE, Rosamond WD, Mosley TH Jr, Folsom AR. Risk factors for ischemic stroke subtypes: the atherosclerosis risk in communities study. Stroke. 2006;37(10):2493–8.PubMedCrossRef
24.
Wang L, Song Q, Wang C, Wu S, Deng L, Li Y, et al. Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: a cohort study and systematic review. J Neurol Sci. 2019;406:116445.PubMedCrossRef
25.
Freeburn JC, Wallace JM, Strain JJ, Sinnamon DG, Craig BM, Johnson D, et al. Monocyte tissue factor-like activity in post myocardial infarction patients. Br J Haematol. 1998;102(2):605–8.PubMedCrossRef
26.
Ye JK, Zhang JT, Kong Y, Xu T, Zou TT, Zhang YH, et al. Relationship between white blood cell count, neutrophils ratio and erythrocyte sedimentation rate and short clinical outcomes among patients with acute ischemic stroke at hospital admission. Zhonghua Liu Xing Bing Xue Za Zhi. 2012;33(9):956–60.PubMed
27.
Walsh KB, Sekar P, Langefeld CD, Moomaw CJ, Elkind MS, Boehme AK, et al. Monocyte count and 30-day case fatality in Intracerebral hemorrhage. Stroke. 2015;46(8):2302–4.PubMedPubMedCentralCrossRef
28.
Iso H, Cui R, Date C, Kikuchi S, Tamakoshi A, Group JS. C-reactive protein levels and risk of mortality from cardiovascular disease in Japanese: the JACC study. Atherosclerosis. 2009;207(1):291–7.PubMedCrossRef
29.
Arevalo-Lorido JC, Carretero-Gomez J, Fernandez-Recio JM, Alvarez-Oliva A, Gutierrez-Montano C, Najarro-Diez F, et al. Lowering C-reactive protein with statins after an ischemic stroke avoids mortality and readmissions. A prospective cohort study. Ann Med. 2015;47(3):226–32.PubMedCrossRef
30.
Bakhshayesh-Eghbali B, Roudbary SA, Basir Jafari S, Nabizadeh SP, Naderi-Asrami N, Sohrabnejad R. Ability of serum C-reactive protein and white blood cell cout in predicting acute schemic stroke. A short -term follow-up study. Caspian J Intern Med. 2016;7(3):206–10.PubMedPubMedCentral
31.
Lao XQ, Neil Thomas G, Jiang C, Zhang W, Adab P, Lam TH, et al. White blood cell count and the metabolic syndrome in older Chinese: the Guangzhou biobank cohort study. Atherosclerosis. 2008;201(2):418–24.PubMedCrossRef
32.
Phillips AC, Jiang CQ, Thomas GN, Lin JM, Yue XJ, Cheng KK, et al. White blood cell subsets are associated with carotid intima-media thickness and pulse wave velocity in an older Chinese population: the Guangzhou biobank cohort study. J Hum Hypertens. 2012;26(8):485–92.PubMedCrossRef
33.
Jiang C, Thomas GN, Lam TH, Schooling CM, Zhang W, Lao X, et al. Cohort profile: the Guangzhou biobank cohort study, a Guangzhou-Hong Kong-Birmingham collaboration. Int J Epidemiol. 2006;35(4):844–52.PubMedCrossRef
34.
Deng HB, Macfarlane DJ, Thomas GN, Lao XQ, Jiang CQ, Cheng KK, et al. Reliability and validity of the IPAQ-Chinese: the Guangzhou biobank cohort study. Med Sci Sports Exerc. 2008;40(2):303–7.PubMedCrossRef
35.
Chen C, Lu FC. Department of Disease Control Ministry of health PRC: the guidelines for prevention and control of overweight and obesity in Chinese adults. Biomed Environ Sci. 2004;17(Suppl):1–36.PubMed
36.
Furlan JC, Vergouwen MD, Fang J, Silver FL. White blood cell count is an independent predictor of outcomes after acute ischaemic stroke. Eur J Neurol. 2014;21(2):215–22.PubMedCrossRef
37.
Nayak AR, Kashyap RS, Kabra D, Deoras P, Purohit HJ, Taori GM, et al. Evaluation of routinely performed hematological and biochemical parameters for the prognosis of acute ischemic stroke patients. Neurol Sci. 2011;32(5):855–60.PubMedCrossRef
38.
Kammersgaard LP, Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Leukocytosis in acute stroke: relation to initial stroke severity, infarct size, and outcome: the Copenhagen stroke study. J Stroke Cerebrovasc Dis. 1999;8(4):259–63.PubMedCrossRef
39.
40.
Denes A, Ferenczi S, Kovacs KJ. Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size. J Neuroinflammation. 2011;8:164.PubMedPubMedCentralCrossRef
41.
Li T, Wu XJ, Chen XM, Wang SB, Liu KD, Xing YQ. Ankle-brachial index and brachial-ankle pulse wave velocity are risk factors for ischemic stroke in patients with type 2 diabetes. Neural Regen Res. 2017;12(11):1853–9.PubMedPubMedCentralCrossRef
42.
Proctor MJ, McMillan DC, Horgan PG, Fletcher CD, Talwar D, Morrison DS. Systemic inflammation predicts all-cause mortality: a Glasgow inflammation outcome study. PLoS One. 2015;10(3):e0116206.PubMedPubMedCentralCrossRef
43.
Jickling GC, Liu D, Ander BP, Stamova B, Zhan X, Sharp FR. Targeting neutrophils in ischemic stroke: translational insights from experimental studies. J Cerebr Blood Flow Metab. 2015;35(6):888–901.CrossRef
44.
Song SY, Zhao XX, Rajah G, Hua C, Kang RJ, Han YP, et al. Clinical significance of baseline neutrophil-to-lymphocyte ratio in patients with ischemic stroke or hemorrhagic stroke: an updated meta-analysis. Front Neurol. 2019;10:1032.PubMedPubMedCentralCrossRef
45.
Qin J, Li Z, Gong G, Li H, Chen L, Song B, et al. Early increased neutrophil-to-lymphocyte ratio is associated with poor 3-month outcomes in spontaneous intracerebral hemorrhage. PLoS One. 2019;14(2):e0211833.PubMedPubMedCentralCrossRef
46.
Giede-Jeppe A, Reichl J, Sprugel MI, Lucking H, Hoelter P, Eyupoglu IY, et al. Neutrophil-to-lymphocyte ratio as an independent predictor for unfavorable functional outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg. 2019;132(2):400–7.PubMedCrossRef
47.
Lattanzi S, Cagnetti C, Rinaldi C, Angelocola S, Provinciali L, Silvestrini M. Neutrophil-to-lymphocyte ratio improves outcome prediction of acute intracerebral hemorrhage. J Neurol Sci. 2018;387:98–102.PubMedCrossRef
48.
Ye Z, Ai X, Fang F, Hu X, Faramand A, You C. The use of neutrophil to lymphocyte ratio as a predictor for clinical outcomes in spontaneous intracerebral hemorrhage. Oncotarget. 2017;8(52):90380–9.PubMedPubMedCentralCrossRef
49.
Tao C, Hu X, Wang J, Ma J, Li H, You C. Admission neutrophil count and neutrophil to lymphocyte ratio predict 90-day outcome in intracerebral hemorrhage. Biomark Med. 2017;11(1):33–42.PubMedCrossRef
50.
Sun Y, You S, Zhong C, Huang Z, Hu L, Zhang X, et al. Neutrophil to lymphocyte ratio and the hematoma volume and stroke severity in acute intracerebral hemorrhage patients. Am J Emerg Med. 2017;35(3):429–33.PubMedCrossRef
51.
Wang F, Hu S, Ding Y, Ju X, Wang L, Lu Q, et al. Neutrophil-to-lymphocyte ratio and 30-day mortality in patients with acute Intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2016;25(1):182–7.PubMedCrossRef
52.
Zhang F, Ren Y, Fu W, Yang Z, Wen D, Hu X, et al. Predictive accuracy of neutrophil-to-lymphocyte ratio on long-term outcome in patients with spontaneous Intracerebral hemorrhage. World Neurosurg. 2019;125:e651–7.PubMedCrossRef
53.
Chamberlain AC, Turner FM, Williams EK. The evaluation of white-cell counting in radiation protection. Br J Radiol. 1952;25(292):169–76.PubMedCrossRef
54.
Metadata
Title
Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study
Authors
Zhi-bing Hu
Ze-xiong Lu
Feng Zhu
Cao-qiang Jiang
Wei-sen Zhang
Jin Pan
Ya-li Jin
Lin Xu
G. Neil Thomas
Karkeung Cheng
Taihing Lam
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Stroke
Published in
BMC Neurology / Issue 1/2021
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-021-02495-z

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