Background and Objective: Hemorrhagic transformation (HT) is a major complication of acute ischemic stroke (AIS). Serum albumin is known for its neuroprotective effects and is a marker of improved AIS patient outcomes. However, it is not known whether there is a relationship between serum albumin and HT. Methods: AIS patients admitted to the Department of Neurology of West China Hospital from 2012 to 2016 were prospectively and consecutively enrolled. Baseline characteristics were collected. HT during hospitalization was diagnosed by brain imaging. Multivariate logistic regression analysis was performed to determine the relationship between serum albumin and HT. Confounding factors were identified by univariate analysis. Stratified logistic regression analysis was performed to identify effect modifiers. Results: A total of 1996 AIS patients were recruited, of whom 135 (6.8%) developed HT. Serum albumin negatively correlated with HT. Patients in the upper serum albumin tertile (42.6–54.1 g/L) had a 46% lower risk of HT than patients in the lower tertile (19.3–39.1 g/L) after adjustment for potential confounders (OR 0.54, 95% CI 0.29–0.99, p = 0.04). Risk of HT decreased stepwise with higher serum albumin tertile (p for trend = 0.04). There was a significant interaction between serum albumin and age (p = 0.02), with no significant correlation between serum albumin and HT in patients over 60 years of age. Conclusions: Higher serum albumin is associated with lower HT risk in a dose-dependent manner in AIS patients younger than 60 years.

Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
. 2018 Mar; 137(12):e67–492.
Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al.; Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) and the GBD Stroke Experts Group. Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010.
. 2014 Jan; 383(9913): 245–54.
Jickling GC, Liu D, Stamova B, Ander BP, Zhan X, Lu A, et al. Hemorrhagic transformation after ischemic stroke in animals and humans.
J Cereb Blood Flow Metab
. 2014 Feb; 34(2): 185–99.
Álvarez-Sabín J, Maisterra O, Santamarina E, Kase CS. Factors influencing haemorrhagic transformation in ischaemic stroke.
Lancet Neurol
. 2013 Jul; 12(7): 689–705.
Boldt J. Use of albumin: an update.
Br J Anaesth
. 2010 Mar; 104(3): 276–84.
Belayev L, Saul I, Busto R, Danielyan K, Vigdorchik A, Khoutorova L, et al. Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat.
. 2005 Feb; 36(2): 326–31.
Belayev L, Pinard E, Nallet H, Seylaz J, Liu Y, Riyamongkol P, et al. Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses.
. 2002 Apr; 33(4): 1077–84.
Ginsberg MD, Hill MD, Palesch YY, Ryckborst KJ, Tamariz D. The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke—I: Physiological responses and safety results.
. 2006 Aug; 37(8): 2100–6.
Palesch YY, Hill MD, Ryckborst KJ, Tamariz D, Ginsberg MD. The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke—II: neurologic outcome and efficacy analysis.
. 2006 Aug; 37(8): 2107–14.
Dziedzic T, Pera J, Slowik A, Gryz-Kurek EA, Szczudlik A. Hypoalbuminemia in acute ischemic stroke patients: frequency and correlates.
Eur J Clin Nutr
. 2007 Nov; 61(11): 1318–22.
Che R, Huang X, Zhao W, Jiang F, Wu L, Zhang Z, et al. Low Serum Albumin level as a Predictor of Hemorrhage Transformation after Intravenous Thrombolysis in Ischemic Stroke Patients.
Sci Rep
. 2017 Aug; 7(1): 7776.
Zhang Q, Lei YX, Wang Q, Jin YP, Fu RL, Geng HH, et al. Serum albumin level is associated with the recurrence of acute ischemic stroke.
Am J Emerg Med
. 2016 Sep; 34(9): 1812–6.
Kong FY, Tao WD, Hao ZL, Liu M. Predictors of one-year disability and death in Chinese hospitalized women after ischemic stroke.
Cerebrovasc Dis
. 2010 Feb; 29(3): 255–62.
Tan G, Yuan R, Hao Z, Lei C, Xiong Y, Xu M, Liu M. Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.
J Stroke Cerebrovasc Dis
. 2017 Jan; 26(1): 230-236.
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke.
N Engl J Med
. 1995 Dec; 333(24): 1581–7.
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
. 2007 Oct; 335(7624): 806–8.
Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E, et al. Phenylpropanolamine and the risk of hemorrhagic stroke.
N Engl J Med
. 2000 Dec; 343(25): 1826–32.
Song X, Jousilahti P, Stehouwer CD, Söderberg S, Onat A, Laatikainen T, et al.; DECODE Study Group. Cardiovascular and all-cause mortality in relation to various anthropometric measures of obesity in Europeans.
Nutr Metab Cardiovasc Dis
. 2015 Mar; 25(3): 295–304.
Metzger M, Houillier P, Gauci C, Haymann JP, Flamant M, Thervet E, et al.; NephroTest Study Group. Relation between circulating levels of 25(OH) vitamin D and parathyroid hormone in chronic kidney disease: quest for a threshold.
J Clin Endocrinol Metab
. 2013 Jul; 98(7): 2922–8.
Houston DK, Tooze JA, Neiberg RH, Hausman DB, Johnson MA, Cauley JA, et al.; Health ABC Study. 25-hydroxyvitamin D status and change in physical performance and strength in older adults: the Health, Aging, and Body Composition Study.
Am J Epidemiol
. 2012 Dec; 176(11): 1025–34.
Park SY, Freedman ND, Haiman CA, Le Marchand L, Wilkens LR, Setiawan VW. Association of Coffee Consumption With Total and Cause-Specific Mortality Among Nonwhite Populations.
Ann Intern Med
. 2017 Aug; 167(4): 228–35.
Gunter MJ, Murphy N, Cross AJ, Dossus L, Dartois L, Fagherazzi G, et al. Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.
Ann Intern Med
. 2017 Aug; 167(4): 236–47.
Lee G, Andrew IS.
Goldman-Cecil Medicine.
Appendix, Reference intervals and laboratory values. 25th edition. Philadelphia: Elsevier; c2016, p. 2712-20.
Idicula TT, Waje-Andreassen U, Brogger J, Naess H, Thomassen L. Serum albumin in ischemic stroke patients: the higher the better. The Bergen Stroke Study.
Cerebrovasc Dis
. 2009; 28(1): 13–7.
Dziedzic T, Pera J, Klimkowicz A, Turaj W, Slowik A, Rog TM, et al. Serum albumin level and nosocomial pneumonia in stroke patients.
Eur J Neurol
. 2006 Mar; 13(3): 299–301.
Krueger M, Bechmann I, Immig K, Reichenbach A, Härtig W, Michalski D. Blood-brain barrier breakdown involves four distinct stages of vascular damage in various models of experimental focal cerebral ischemia.
J Cereb Blood Flow Metab
. 2015 Feb; 35(2): 292–303.
Rosell A, Cuadrado E, Ortega-Aznar A, Hernández-Guillamon M, Lo EH, Montaner J. MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke.
. 2008 Apr; 39(4): 1121–6.
Zoellner H, Höfler M, Beckmann R, Hufnagl P, Vanyek E, Bielek E, et al. Serum albumin is a specific inhibitor of apoptosis in human endothelial cells.
J Cell Sci
. 1996 Oct; 109(Pt 10): 2571–80.
Halliwell B. Albumin—an important extracellular antioxidant?
Biochem Pharmacol
. 1988 Feb; 37(4): 569–71.
Belayev L, Busto R, Zhao W, Clemens JA, Ginsberg MD. Effect of delayed albumin hemodilution on infarction volume and brain edema after transient middle cerebral artery occlusion in rats.
J Neurosurg
. 1997 Oct; 87(4): 595–601.
Belayev L, Liu Y, Zhao W, Busto R, Ginsberg MD. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window.
. 2001 Feb; 32(2): 553–60.
Nimmagadda A, Park HP, Prado R, Ginsberg MD. Albumin therapy improves local vascular dynamics in a rat model of primary microvascular thrombosis: a two-photon laser-scanning microscopy study.
. 2008 Jan; 39(1): 198–204.
Weaving G, Batstone GF, Jones RG. Age and sex variation in serum albumin concentration: an observational study.
Ann Clin Biochem
. 2016 Jan; 53(Pt 1): 106–11.
Kang MC, Kim JH, Ryu SW, Moon JY, Park JH, Park JK, et al.; Korean Society for Parenteral and Enteral Nutrition (KSPEN) Clinical Research Groups. Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study.
J Korean Med Sci
. 2018 Jan; 33(2):e10.
Zhang Z, Pereira SL, Luo M, Matheson EM. Evaluation of Blood Biomarkers Associated with Risk of Malnutrition in Older Adults: A Systematic Review and Meta-Analysis.
. 2017 Aug; 9(8): 9.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.