Skip to main content
Top
Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

Association of fibrinogen level with early neurological deterioration among acute ischemic stroke patients with diabetes

Authors: Seong-Joon Lee, Ji Man Hong, Sung Eun Lee, Dae Ryong Kang, Bruce Ovbiagele, Andrew M. Demchuk, Jin Soo Lee

Published in: BMC Neurology | Issue 1/2017

Login to get access

Abstract

Background

Diabetes mellitus (DM) is a risk factor for early neurological deterioration (END) in acute ischemic stroke. The prothrombotic protein fibrinogen is frequently elevated in patients with diabetes, and may be associated with poorer prognoses. We evaluated whether fibrinogen is associated with END in patients with diabetes after acute ischemic stroke.

Methods

We included 3814 patients from a single hospital database admitted within 72 h of onset of ischemic stroke. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥2 within 7 days post-admission. In the total population (END, n = 661; non-END, n = 3153), univariate and multivariate analyses were performed to assess fibrinogen as an independent predictor for END. We then performed propensity score matching and univariate analyses for DM (END, n = 261; non-END, n = 522) and non-DM populations (END, n = 399; non-END, n = 798). Multiple logistic analyses were performed after matching for fibrinogen as a risk factor in each subgroup.

Results

Fibrinogen levels were higher in the END group than in the non-END group (367 ± 156 mg/dL vs. 347 ± 122 mg/dL, p = 0.002), though they were not associated with END in logistic regression analyses. Fibrinogen levels were found to be an independent predictor for END, but only in the DM population (fibrinogen levels 300–599 mg/dL, odds ratio: 1.618, 95% confidence interval: 1.037–2.525, p = 0.034, fibrinogen levels ≥600 mg/dL, 2.575, 1.018–6.514, p = 0.046; non-DM population, p = 0.393). The diabetes-fibrinogen interaction for the entire cohort was p = 0.101.

Conclusions

Elevated fibrinogen is dose-dependently associated with END in patients with diabetes following acute ischemic stroke.
Appendix
Available only for authorised users
Literature
1.
go back to reference Davalos A, Toni D, Iweins F, Lesaffre E, Bastianello S, Castillo J. Neurological deterioration in acute ischemic stroke: potential predictors and associated factors in the European cooperative acute stroke study (ECASS) I. Stroke. 1999;30(12):2631–6.CrossRefPubMed Davalos A, Toni D, Iweins F, Lesaffre E, Bastianello S, Castillo J. Neurological deterioration in acute ischemic stroke: potential predictors and associated factors in the European cooperative acute stroke study (ECASS) I. Stroke. 1999;30(12):2631–6.CrossRefPubMed
2.
go back to reference Kim BJ, Park J-M, Kang K, Lee SJ, Ko Y, Kim JG, Cha J-K, Kim D-H, Nah H-W, Han M-K, et al. Case Characteristics, Hyperacute Treatment, and Outcome Information from the Clinical Research Center for Stroke-Fifth Division Registry in South Korea. J Stroke. 2015;17(1):38–53.CrossRefPubMedPubMedCentral Kim BJ, Park J-M, Kang K, Lee SJ, Ko Y, Kim JG, Cha J-K, Kim D-H, Nah H-W, Han M-K, et al. Case Characteristics, Hyperacute Treatment, and Outcome Information from the Clinical Research Center for Stroke-Fifth Division Registry in South Korea. J Stroke. 2015;17(1):38–53.CrossRefPubMedPubMedCentral
3.
go back to reference Kamalesh M, Shen J, Eckert GJ. Long term postischemic stroke mortality in diabetes: a veteran cohort analysis. Stroke. 2008;39(10):2727–31.CrossRefPubMed Kamalesh M, Shen J, Eckert GJ. Long term postischemic stroke mortality in diabetes: a veteran cohort analysis. Stroke. 2008;39(10):2727–31.CrossRefPubMed
4.
go back to reference Megherbi SE, Milan C, Minier D, Couvreur G, Osseby GV, Tilling K, Di Carlo A, Inzitari D, Wolfe CD, Moreau T, et al. Association between diabetes and stroke subtype on survival and functional outcome 3 months after stroke: data from the European BIOMED Stroke Project. Stroke. 2003;34(3):688–94.CrossRefPubMed Megherbi SE, Milan C, Minier D, Couvreur G, Osseby GV, Tilling K, Di Carlo A, Inzitari D, Wolfe CD, Moreau T, et al. Association between diabetes and stroke subtype on survival and functional outcome 3 months after stroke: data from the European BIOMED Stroke Project. Stroke. 2003;34(3):688–94.CrossRefPubMed
5.
go back to reference Lee S-J, Hong JM, Lee M, Huh K, Choi JW, Lee JS. Cerebral Arterial Calcification Is an Imaging Prognostic Marker for Revascularization Treatment of Acute Middle Cerebral Arterial Occlusion. J Stroke. 2015;17(1):67–75.CrossRefPubMedPubMedCentral Lee S-J, Hong JM, Lee M, Huh K, Choi JW, Lee JS. Cerebral Arterial Calcification Is an Imaging Prognostic Marker for Revascularization Treatment of Acute Middle Cerebral Arterial Occlusion. J Stroke. 2015;17(1):67–75.CrossRefPubMedPubMedCentral
6.
go back to reference Barber M, Wright F, Stott DJ, Langhorne P. Predictors of early neurological deterioration after ischaemic stroke: a case-control study. Gerontology. 2004;50(2):102–9.CrossRefPubMed Barber M, Wright F, Stott DJ, Langhorne P. Predictors of early neurological deterioration after ischaemic stroke: a case-control study. Gerontology. 2004;50(2):102–9.CrossRefPubMed
7.
go back to reference Weimar C, Mieck T, Buchthal J, Ehrenfeld CE, Schmid E, Diener HC. Neurologic worsening during the acute phase of ischemic stroke. Arch Neurol. 2005;62(3):393–7.CrossRefPubMed Weimar C, Mieck T, Buchthal J, Ehrenfeld CE, Schmid E, Diener HC. Neurologic worsening during the acute phase of ischemic stroke. Arch Neurol. 2005;62(3):393–7.CrossRefPubMed
8.
go back to reference Els T, Klisch J, Orszagh M, Hetzel A, Schulte-Monting J, Schumacher M, Lucking CH. Hyperglycemia in patients with focal cerebral ischemia after intravenous thrombolysis: influence on clinical outcome and infarct size. Cerebrovasc Dis. 2002;13(2):89–94.CrossRefPubMed Els T, Klisch J, Orszagh M, Hetzel A, Schulte-Monting J, Schumacher M, Lucking CH. Hyperglycemia in patients with focal cerebral ischemia after intravenous thrombolysis: influence on clinical outcome and infarct size. Cerebrovasc Dis. 2002;13(2):89–94.CrossRefPubMed
9.
go back to reference Lansberg MG, Albers GW, Wijman CA. Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: a review of the risk factors. Cerebrovasc Dis. 2007;24(1):1–10.CrossRefPubMed Lansberg MG, Albers GW, Wijman CA. Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: a review of the risk factors. Cerebrovasc Dis. 2007;24(1):1–10.CrossRefPubMed
10.
go back to reference Demchuk AM, Morgenstern LB, Krieger DW, Linda Chi T, Hu W, Wein TH, Hardy RJ, Grotta JC, Buchan AM. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke. 1999;30(1):34–9.CrossRefPubMed Demchuk AM, Morgenstern LB, Krieger DW, Linda Chi T, Hu W, Wein TH, Hardy RJ, Grotta JC, Buchan AM. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke. 1999;30(1):34–9.CrossRefPubMed
11.
go back to reference Berger L, Hakim AM. The association of hyperglycemia with cerebral edema in stroke. Stroke. 1986;17(5):865–71.CrossRefPubMed Berger L, Hakim AM. The association of hyperglycemia with cerebral edema in stroke. Stroke. 1986;17(5):865–71.CrossRefPubMed
12.
go back to reference Candelise L, Landi G, Orazio EN, Boccardi E. Prognostic significance of hyperglycemia in acute stroke. Arch Neurol. 1985;42(7):661–3.CrossRefPubMed Candelise L, Landi G, Orazio EN, Boccardi E. Prognostic significance of hyperglycemia in acute stroke. Arch Neurol. 1985;42(7):661–3.CrossRefPubMed
13.
go back to reference Meigs JB, Mittleman MA, Nathan DM, Tofler GH, Singer DE, Murphy-Sheehy PM, Lipinska I, D'Agostino RB, Wilson PW. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA. 2000;283(2):221–8.CrossRefPubMed Meigs JB, Mittleman MA, Nathan DM, Tofler GH, Singer DE, Murphy-Sheehy PM, Lipinska I, D'Agostino RB, Wilson PW. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA. 2000;283(2):221–8.CrossRefPubMed
14.
15.
go back to reference Koenig W. Fibrin(ogen) in cardiovascular disease: an update. Thromb Haemost. 2003;89(4):601–9.PubMed Koenig W. Fibrin(ogen) in cardiovascular disease: an update. Thromb Haemost. 2003;89(4):601–9.PubMed
16.
go back to reference Ernst E. Fibrinogen as a cardiovascular risk factor--interrelationship with infections and inflammation. Eur Heart J. 1993;14 Suppl K:82–7.PubMed Ernst E. Fibrinogen as a cardiovascular risk factor--interrelationship with infections and inflammation. Eur Heart J. 1993;14 Suppl K:82–7.PubMed
17.
go back to reference Wu S, Shi Y, Wang C, Jia Q, Zhang N, Zhao X, Liu G, Wang Y, Liu L, Wang Y, et al. Glycated hemoglobin independently predicts stroke recurrence within one year after acute first-ever non-cardioembolic strokes onset in A Chinese cohort study. PLoS One. 2013;8(11):e80690.CrossRefPubMedPubMedCentral Wu S, Shi Y, Wang C, Jia Q, Zhang N, Zhao X, Liu G, Wang Y, Liu L, Wang Y, et al. Glycated hemoglobin independently predicts stroke recurrence within one year after acute first-ever non-cardioembolic strokes onset in A Chinese cohort study. PLoS One. 2013;8(11):e80690.CrossRefPubMedPubMedCentral
18.
go back to reference Kanamaru T, Suda S, Muraga K, Okubo S, Watanabe Y, Tsuruoka S, Kimura K. Albuminuria predicts early neurological deterioration in patients with acute ischemic stroke. J Neurol Sci. 2017;372:417–20.CrossRefPubMed Kanamaru T, Suda S, Muraga K, Okubo S, Watanabe Y, Tsuruoka S, Kimura K. Albuminuria predicts early neurological deterioration in patients with acute ischemic stroke. J Neurol Sci. 2017;372:417–20.CrossRefPubMed
19.
go back to reference Herrick S, Blanc-Brude O, Gray A, Laurent G. Fibrinogen. Int J Biochem Cell Biol. 1999;31(7):741–6.CrossRefPubMed Herrick S, Blanc-Brude O, Gray A, Laurent G. Fibrinogen. Int J Biochem Cell Biol. 1999;31(7):741–6.CrossRefPubMed
20.
go back to reference Forsyth CB, Solovjov DA, Ugarova TP, Plow EF. Integrin alpha(M)beta(2)-mediated cell migration to fibrinogen and its recognition peptides. J Exp Med. 2001;193(10):1123–33.CrossRefPubMedPubMedCentral Forsyth CB, Solovjov DA, Ugarova TP, Plow EF. Integrin alpha(M)beta(2)-mediated cell migration to fibrinogen and its recognition peptides. J Exp Med. 2001;193(10):1123–33.CrossRefPubMedPubMedCentral
21.
go back to reference Tousoulis D, Papageorgiou N, Androulakis E, Briasoulis A, Antoniades C, Stefanadis C. Fibrinogen and cardiovascular disease: genetics and biomarkers. Blood Rev. 2011;25(6):239–45.CrossRefPubMed Tousoulis D, Papageorgiou N, Androulakis E, Briasoulis A, Antoniades C, Stefanadis C. Fibrinogen and cardiovascular disease: genetics and biomarkers. Blood Rev. 2011;25(6):239–45.CrossRefPubMed
22.
go back to reference Schneider DJ, Taatjes DJ, Howard DB, Sobel BE. Increased reactivity of platelets induced by fibrinogen independent of its binding to the IIb-IIIa surface glycoprotein: a potential contributor to cardiovascular risk. J Am Coll Cardiol. 1999;33(1):261–6.CrossRefPubMed Schneider DJ, Taatjes DJ, Howard DB, Sobel BE. Increased reactivity of platelets induced by fibrinogen independent of its binding to the IIb-IIIa surface glycoprotein: a potential contributor to cardiovascular risk. J Am Coll Cardiol. 1999;33(1):261–6.CrossRefPubMed
23.
go back to reference Hammer MR, John PN, Flynn MD, Bellingham AJ, Leslie RD. Glycated fibrinogen: a new index of short-term diabetic control. Ann Clin Biochem. 1989;26(Pt 1):58–62.CrossRefPubMed Hammer MR, John PN, Flynn MD, Bellingham AJ, Leslie RD. Glycated fibrinogen: a new index of short-term diabetic control. Ann Clin Biochem. 1989;26(Pt 1):58–62.CrossRefPubMed
24.
go back to reference Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation reduces the susceptibility of fibrin to degradation by plasmin. Diabetes. 1983;32(7):680–4.CrossRefPubMed Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation reduces the susceptibility of fibrin to degradation by plasmin. Diabetes. 1983;32(7):680–4.CrossRefPubMed
25.
go back to reference Bobbink IW, Tekelenburg WL, Sixma JJ, de Boer HC, Banga JD, de Groot PG. Glycated proteins modulate tissue-plasminogen activator-catalyzed plasminogen activation. Biochem Biophys Res Commun. 1997;240(3):595–601.CrossRefPubMed Bobbink IW, Tekelenburg WL, Sixma JJ, de Boer HC, Banga JD, de Groot PG. Glycated proteins modulate tissue-plasminogen activator-catalyzed plasminogen activation. Biochem Biophys Res Commun. 1997;240(3):595–601.CrossRefPubMed
26.
go back to reference Lutjens A, Jonkhoff-Slok TW, Sandkuijl C, vd Veen EA, vd Meer J. Polymerisation and crosslinking of fibrin monomers in diabetes mellitus. Diabetologia. 1988;31(11):825–30.CrossRefPubMed Lutjens A, Jonkhoff-Slok TW, Sandkuijl C, vd Veen EA, vd Meer J. Polymerisation and crosslinking of fibrin monomers in diabetes mellitus. Diabetologia. 1988;31(11):825–30.CrossRefPubMed
27.
28.
go back to reference Lee AJ, Lowe GD, Woodward M, Tunstall-Pedoe H. Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease, and family history: the Scottish Heart Health Study. Br Heart J. 1993;69(4):338–42.CrossRefPubMedPubMedCentral Lee AJ, Lowe GD, Woodward M, Tunstall-Pedoe H. Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease, and family history: the Scottish Heart Health Study. Br Heart J. 1993;69(4):338–42.CrossRefPubMedPubMedCentral
29.
go back to reference Qizilbash N, Jones L, Warlow C, Mann J. Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes. BMJ. 1991;303(6803):605–9.CrossRefPubMedPubMedCentral Qizilbash N, Jones L, Warlow C, Mann J. Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes. BMJ. 1991;303(6803):605–9.CrossRefPubMedPubMedCentral
30.
go back to reference Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med. 1984;311(8):501–5.CrossRefPubMed Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med. 1984;311(8):501–5.CrossRefPubMed
31.
go back to reference Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, Kostis JB, Wilson AC, Folsom AR, Wu K, Benderly M, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294(14):1799–809.PubMed Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, Kostis JB, Wilson AC, Folsom AR, Wu K, Benderly M, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294(14):1799–809.PubMed
32.
go back to reference Kofoed SC, Wittrup HH, Sillesen H, Nordestgaard BG. Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: the Copenhagen City Heart Study. Eur Heart J. 2003;24(6):567–76.CrossRefPubMed Kofoed SC, Wittrup HH, Sillesen H, Nordestgaard BG. Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: the Copenhagen City Heart Study. Eur Heart J. 2003;24(6):567–76.CrossRefPubMed
33.
go back to reference del Zoppo GJ, Levy DE, Wasiewski WW, Pancioli AM, Demchuk AM, Trammel J, Demaerschalk BM, Kaste M, Albers GW, Ringelstein EB. Hyperfibrinogenemia and functional outcome from acute ischemic stroke. Stroke. 2009;40(5):1687–91.CrossRefPubMedPubMedCentral del Zoppo GJ, Levy DE, Wasiewski WW, Pancioli AM, Demchuk AM, Trammel J, Demaerschalk BM, Kaste M, Albers GW, Ringelstein EB. Hyperfibrinogenemia and functional outcome from acute ischemic stroke. Stroke. 2009;40(5):1687–91.CrossRefPubMedPubMedCentral
34.
go back to reference Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Sugiyama S, Saito Y, Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes Trial I. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41.CrossRefPubMed Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Sugiyama S, Saito Y, Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes Trial I. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41.CrossRefPubMed
35.
go back to reference Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840.CrossRefPubMedPubMedCentral Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840.CrossRefPubMedPubMedCentral
36.
go back to reference Hall HM, Banerjee S, McGuire DK. Variability of clopidogrel response in patients with type 2 diabetes mellitus. Diab Vasc Dis Res. 2011;8(4):245–53.CrossRefPubMed Hall HM, Banerjee S, McGuire DK. Variability of clopidogrel response in patients with type 2 diabetes mellitus. Diab Vasc Dis Res. 2011;8(4):245–53.CrossRefPubMed
37.
go back to reference Paul R, Banerjee AK, Guha S, Chaudhuri U, Ghosh S, Mondal J, Bandyopadhyay R. Study of platelet aggregation in acute coronary syndrome with special reference to metabolic syndrome. Int J Appl Basic Med Res. 2013;3(2):117–21.CrossRefPubMedPubMedCentral Paul R, Banerjee AK, Guha S, Chaudhuri U, Ghosh S, Mondal J, Bandyopadhyay R. Study of platelet aggregation in acute coronary syndrome with special reference to metabolic syndrome. Int J Appl Basic Med Res. 2013;3(2):117–21.CrossRefPubMedPubMedCentral
38.
go back to reference Hao Z, Liu M, Counsell C, Wardlaw JM, Lin S, Zhao X. Fibrinogen depleting agents for acute ischaemic stroke. Cochrane Database Syst Rev. 2012;3:CD000091. Hao Z, Liu M, Counsell C, Wardlaw JM, Lin S, Zhao X. Fibrinogen depleting agents for acute ischaemic stroke. Cochrane Database Syst Rev. 2012;3:CD000091.
39.
go back to reference Aono Y, Ohkubo T, Kikuya M, Hara A, Kondo T, Obara T, Metoki H, Inoue R, Asayama K, Shintani Y, et al. Plasma fibrinogen, ambulatory blood pressure, and silent cerebrovascular lesions: the Ohasama study. Arterioscler Thromb Vasc Biol. 2007;27(4):963–8.CrossRefPubMed Aono Y, Ohkubo T, Kikuya M, Hara A, Kondo T, Obara T, Metoki H, Inoue R, Asayama K, Shintani Y, et al. Plasma fibrinogen, ambulatory blood pressure, and silent cerebrovascular lesions: the Ohasama study. Arterioscler Thromb Vasc Biol. 2007;27(4):963–8.CrossRefPubMed
40.
go back to reference Neumann-Haefelin T, Hoelig S, Berkefeld J, Fiehler J, Gass A, Humpich M, Kastrup A, Kucinski T, Lecei O, Liebeskind DS, et al. Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. Stroke. 2006;37(10):2463–6.CrossRefPubMed Neumann-Haefelin T, Hoelig S, Berkefeld J, Fiehler J, Gass A, Humpich M, Kastrup A, Kucinski T, Lecei O, Liebeskind DS, et al. Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. Stroke. 2006;37(10):2463–6.CrossRefPubMed
Metadata
Title
Association of fibrinogen level with early neurological deterioration among acute ischemic stroke patients with diabetes
Authors
Seong-Joon Lee
Ji Man Hong
Sung Eun Lee
Dae Ryong Kang
Bruce Ovbiagele
Andrew M. Demchuk
Jin Soo Lee
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0865-7

Other articles of this Issue 1/2017

BMC Neurology 1/2017 Go to the issue