Abstract
Neutrophil counts to high-density lipoprotein cholesterol ratio (NHR) is a relatively new and readily available indicator, and our study aimed to demonstrate its relationship with short-term prognosis after intravenous thrombolysis in acute ischemic stroke (AIS) patients and to make a simple comparison with other prognostic indicators. We compared demographic and laboratory characteristics of AIS patients and healthy controls and grouped AIS patients according to NHR tertiles to contrast 3-month outcomes. Univariate and multivariate regression analyses were carried to further analyze the relationship between NHR and prognosis. Moreover, we compared the accuracy of several factors using receiver-operating characteristic curve. NHR levels of AIS patients were higher than those of healthy controls (p < 0.001). The NHR levels were significantly higher in AIS patients with poor prognosis than those with good prognosis (p = 0.001) and were higher in patients with severe stroke than those with mild stroke (p = 0.011). Multivariate logistic regression analysis indicated that elevated NHR was an independent predictor of poor outcomes (odds ratio = 4.570; 95% CI, 1.841–11.340; p = 0.001). High NHR levels were associated with poor 3-month outcomes after intravenous thrombolysis in AIS patients.
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Asberg S, Farahmand B, Hasvold P, Johansson S, Appelros P (2018) Non-cardioembolic TIA and ischemic stroke: implications of severity. Acta Neurol Scand 138:369–376. https://doi.org/10.1111/ane.12974
Bergt C, Marsche G, Panzenboeck U, Heinecke JW, Malle E, Sattler W (2001) Human neutrophils employ the myeloperoxidase/hydrogen peroxide/chloride system to oxidatively damage apolipoprotein A-I. Eur J Biochem 268:3523–3531. https://doi.org/10.1046/j.1432-1327.2001.02253.x
Buck BH, Liebeskind DS, Saver JL, Bang OY, Yun SW, Starkman S, Ali LK, Kim D, Villablanca JP, Salamon N, Razinia T, Ovbiagele B (2008) Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke 39:355–360. https://doi.org/10.1161/strokeaha.107.490128
Cagdas M, Karakoyun S, Yesin M, Rencuzogullari I, Karabag Y, Uluganyan M, Ozan Gursoy M, Artac I, Ilis D, Atalay E, Sadioglu Cagdas O (2018) The association between monocyte HDL-C ratio and SYNTAX score and SYNTAX score II in STEMI patients treated with primary PCI. Acta Cardiol Sin 34:23–30. https://doi.org/10.6515/acs.201801_34(1).20170823a
Chen Z, Huang Y, Li S, Lin J, Liu W, Ding Z, Li X, Chen Y, Pang W, Yang D, Su Z, Li J, Weng Y, Zhang X (2016) Platelet-to-white blood cell ratio: a prognostic predictor for 90-day outcomes in ischemic stroke patients with intravenous thrombolysis. J Stroke Cerebrovasc Dis 25:2430–2438. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.06.015
Chen T, Chen H, Xiao H, Tang H, Xiang Z, Wang X, Wang X, Zou H (2020) Comparison of the value of neutrophil to high-density lipoprotein cholesterol ratio and lymphocyte to high-density lipoprotein cholesterol ratio for predicting metabolic syndrome among a population in the southern coast of China. Diabetes Metab Syndr Obes 13:597–605. https://doi.org/10.2147/dmso.S238990
Cogny A, Paul JL, Atger V, Soni T, Moatti N (1994) Structural changes of high-density-lipoprotein apolipoproteins following incubation with human polymorphonuclear cells. Eur J Biochem 222:965–973. https://doi.org/10.1111/j.1432-1033.1994.tb18947.x
Cogny A, Atger V, Paul JL, Soni T, Moatti N (1996) High-density lipoprotein 3 physicochemical modifications induced by interaction with human polymorphonuclear leucocytes affect their ability to remove cholesterol from cells. Biochem J:285–292. https://doi.org/10.1042/bj3140285
Dai C, Yao X, Keeran KJ, Zywicke GJ, Qu X, Yu ZX, Dagur PK, McCoy JP, Remaley AT, Levine SJ (2012) Apolipoprotein A-I attenuates ovalbumin-induced neutrophilic airway inflammation via a granulocyte colony-stimulating factor-dependent mechanism. Am J Respir Cell Mol Biol 47:186–195. https://doi.org/10.1165/rcmb.2011-0322OC
De Nardo D, Labzin LI, Kono H, Seki R, Schmidt SV, Beyer M, Xu D, Zimmer S, Lahrmann C, Schildberg FA, Vogelhuber J, Kraut M, Ulas T, Kerksiek A, Krebs W, Bode N, Grebe A, Fitzgerald ML, Hernandez NJ, Williams BR, Knolle P, Kneilling M, Rocken M, Lutjohann D, Wright SD, Schultze JL, Latz E (2014) High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol 15:152–160. https://doi.org/10.1038/ni.2784
Enzmann G, Mysiorek C, Gorina R, Cheng YJ, Ghavampour S, Hannocks MJ, Prinz V, Dirnagl U, Endres M, Prinz M, Beschorner R, Harter PN, Mittelbronn M, Engelhardt B, Sorokin L (2013) The neurovascular unit as a selective barrier to polymorphonuclear granulocyte (PMN) infiltration into the brain after ischemic injury. Acta Neuropathol 125:395–412. https://doi.org/10.1007/s00401-012-1076-3
Eyles JL, Roberts AW, Metcalf D, Wicks IP (2006) Granulocyte colony-stimulating factor and neutrophils--forgotten mediators of inflammatory disease. Nat Clin Pract Rheumatol 2:500–510. https://doi.org/10.1038/ncprheum0291
Garcia-Bonilla L, Moore JM, Racchumi G, Zhou P, Butler JM, Iadecola C, Anrather J (2014) Inducible nitric oxide synthase in neutrophils and endothelium contributes to ischemic brain injury in mice. J Immunol 193:2531–2537. https://doi.org/10.4049/jimmunol.1400918
Huang JB, Chen YS, Ji HY, Xie WM, Jiang J, Ran LS, Zhang CT, Quan XQ (2020) Neutrophil to high-density lipoprotein ratio has a superior prognostic value in elderly patients with acute myocardial infarction: a comparison study. Lipids Health Dis 19:59. https://doi.org/10.1186/s12944-020-01238-2
Kim J, Song TJ, Park JH, Lee HS, Nam CM, Nam HS, Kim YD, Heo JH (2012) Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction. Atherosclerosis 222:464–467. https://doi.org/10.1016/j.atherosclerosis.2012.02.042
Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13:159–175. https://doi.org/10.1038/nri3399
Lee KJ, Lee JS, Jung KH (2018) Interactive effect of acute and chronic glycemic indexes for severity in acute ischemic stroke patients. BMC Neurol 18:105. https://doi.org/10.1186/s12883-018-1109-1
Lees KR, Emberson J, Blackwell L, Bluhmki E, Davis SM, Donnan GA, Grotta JC, Kaste M, von Kummer R, Lansberg MG, Lindley RI, Lyden P, Murray GD, Sandercock PA, Toni D, Toyoda K, Wardlaw JM, Whiteley WN, Baigent C, Hacke W, Howard G (2016) Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials. Stroke 47:2373–2379. https://doi.org/10.1161/strokeaha.116.013644
Libby P (2012) Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 32:2045–2051. https://doi.org/10.1161/atvbaha.108.179705
Liu H, Wang R, Shi J, Zhang Y, Huang Z, You S, Xiao G, Wang D, Cao Y (2019) Baseline neutrophil counts and neutrophil ratio may predict a poor clinical outcome in minor stroke patients with intravenous thrombolysis. J Stroke Cerebrovasc Dis 28:104340. https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104340
Maestrini I, Strbian D, Gautier S, Haapaniemi E, Moulin S, Sairanen T, Dequatre-Ponchelle N, Sibolt G, Cordonnier C, Melkas S, Leys D, Tatlisumak T, Bordet R (2015) Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology 85:1408–1416. https://doi.org/10.1212/wnl.0000000000002029
Murphy A, Woollard K, Suhartoyo A, Stirzaker R, Shaw J, Sviridov D, Chin-Dusting J (2011) Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein A-I in in vitro and in vivo models of inflammation. Arterioscler Thromb Vasc Biol 31:1333–1341. https://doi.org/10.1161/atvbaha.111.226258
Nicholls SJ, Dusting GJ, Cutri B, Bao S, Drummond GR, Rye KA, Barter PJ (2005) Reconstituted high-density lipoproteins inhibit the acute pro-oxidant and proinflammatory vascular changes induced by a periarterial collar in normocholesterolemic rabbits. Circulation 111:1543–1550. https://doi.org/10.1161/01.Cir.0000159351.95399.50
Ortiz-Munoz G, Couret D, Lapergue B, Bruckert E, Meseguer E, Amarenco P, Meilhac O (2016) Dysfunctional HDL in acute stroke. Atherosclerosis 253:75–80. https://doi.org/10.1016/j.atherosclerosis.2016.08.035
Park JS, Cha KS, Lee HW, Oh JH, Choi JH, Lee HC, Hong TJ, Jeong MH, Chae SC, Kim YJ (2019) Predictive and protective role of high-density lipoprotein cholesterol in acute myocardial infarction. Cardiol J 26:176–185. https://doi.org/10.5603/CJ.a2018.0020
Pektezel MY, Yilmaz E, Arsava EM, Topcuoglu MA (2019) Neutrophil-to-lymphocyte ratio and response to intravenous thrombolysis in patients with acute ischemic stroke. J Stroke Cerebrovasc Dis 28:1853–1859. https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.04.014
Scanu A, Luisetto R, Oliviero F, Gruaz L, Sfriso P, Burger D, Punzi L (2015) High-density lipoproteins inhibit urate crystal-induced inflammation in mice. Ann Rheum Dis 74:587–594. https://doi.org/10.1136/annrheumdis-2013-203803
Schaftenaar F, Frodermann V, Kuiper J, Lutgens E (2016) Atherosclerosis: the interplay between lipids and immune cells. Curr Opin Lipidol 27:209–215. https://doi.org/10.1097/mol.0000000000000302
Sommer CJ (2017) Ischemic stroke: experimental models and reality. Acta Neuropathol 133:245–261. https://doi.org/10.1007/s00401-017-1667-0
Wang W, Jiang B, Sun H, Ru X, Sun D, Wang L, Wang L, Jiang Y, Li Y, Wang Y, Chen Z, Wu S, Zhang Y, Wang D, Wang Y, Feigin VL (2017) Prevalence, incidence, and mortality of stroke in China: results from a nationwide population-based survey of 480 687 adults. Circulation 135:759–771. https://doi.org/10.1161/circulationaha.116.025250
Yeh PS, Yang CM, Lin SH, Wang WM, Chen PS, Chao TH, Lin HJ, Lin KC, Chang CY, Cheng TJ, Li YH (2013) Low levels of high-density lipoprotein cholesterol in patients with atherosclerotic stroke: a prospective cohort study. Atherosclerosis 228:472–477. https://doi.org/10.1016/j.atherosclerosis.2013.03.015
Yu S, Arima H, Bertmar C, Clarke S, Herkes G, Krause M (2018) Neutrophil to lymphocyte ratio and early clinical outcomes in patients with acute ischemic stroke. J Neurol Sci 387:115–118. https://doi.org/10.1016/j.jns.2018.02.002
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The study was approved by the Ethics Committee of the Third Affiliated Hospital of Wenzhou Medical University and was performed in accordance with the Declaration of Helsinki. All subjects signed a written informed consent form. The institutional approval number for the study is LZM2020033.
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Guangyong Chen, Naiping Yang, and Junli Ren are co-first author
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Chen, G., Yang, N., Ren, J. et al. Neutrophil Counts to High-Density Lipoprotein Cholesterol Ratio: a Potential Predictor of Prognosis in Acute Ischemic Stroke Patients After Intravenous Thrombolysis. Neurotox Res 38, 1001–1009 (2020). https://doi.org/10.1007/s12640-020-00274-1
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DOI: https://doi.org/10.1007/s12640-020-00274-1