Association of serum albumin and relevant composite indicators with malignant brain edema after acute ischemic stroke_West China Medical Journal

Authors：

HE Haoyang ^1,2,3 , WANG Yanan ^1,2,3 , HUA Xing ^1,2,3 ,  WU Simiao ^1,2,3

1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Centre of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Institute of Brain Science and Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

WU Simiao, Email: simiao.wu@hotmail.com

Keywords：

Acute ischemic stroke; albumin; serum biomarker; malignant brain edema

DOI：

10.7507/1002-0179.202504008

Video：

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Objective To investigate the association of serum albumin and relevant composite indicators with malignant brain edema after acute ischemic stroke. Methods We screened patients with acute ischemic stroke admitted to the Department of Neurology, West China Hospital of Sichuan University between January and December 2022. The case group consisted of patients who developed malignant brain edema within 7 days of admission, while the control group consisted of patients who did not develop malignant brain edema within 7 days of admission. Multivariate logistic regression analysis was used to explore the association of serum albumin and relevant composite indicators with malignant brain edema after acute ischemic stroke. Results Finally, 428 patients were included, aged 70.00 (58.00, 82.00) years, with females accounting for 40.9% (n=175). The time from onset to admission was 10.00 (4.00, 24.00) hours. Forty-three patients (10.0%) developed malignant brain edema and were classified as the case group, and their onset time of malignant brain edema was 34.00 (22.50, 56.50) hours after the onset of the disease. Multivariate logistic regression analysis showed that the increase in the score of the baseline National Institutes of Health Stroke Scale scores [odds ratio (OR)=1.167], the combination of diabetes (OR=5.525), the treatment of thrombectomy (OR=23.875), and the neutrophil percentage-to-albumin ratio higher than the median (OR=3.806) were associated with the increased risk of malignant brain edema (P<0.05), and the successful reperfusion after thrombectomy (OR=0.120) was associated with the reduced risk of malignant brain edema (P<0.05). Conclusion A higher percentage of serum neutrophil percentage-to-albumin ratio within 24 hours of onset in patients with acute ischemic stroke is associated with an increased risk of malignant brain edema within 7 days of admission.

Citation： HE Haoyang, WANG Yanan, HUA Xing, WU Simiao. Association of serum albumin and relevant composite indicators with malignant brain edema after acute ischemic stroke. West China Medical Journal, 2025, 40(8): 1228-1233. doi: 10.7507/1002-0179.202504008 Copy

1.	Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
2.	Balami JS, Chen RL, Grunwald IQ, et al. Neurological complications of acute ischaemic stroke. Lancet Neurol, 2011, 10(4): 357-371.
3.	Wu S, Wang Y, Yuan R, et al. Clinical course, causes of worsening, and outcomes of severe ischemic stroke: a prospective multicenter cohort study. Chin Med J (Engl), 2025, 138(13): 1578-1586.
4.	Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 2019, 50(12): e344-e418.
5.	Rabinstein AA. Ischaemic brain oedema remains a major unmet need. Lancet Neurol, 2024, 23(12): 1171-1173.
6.	吳思緲, 袁若圳, 劉鳴. 應當提倡大面積腦梗死后惡性腦水腫的預防理念及其研究. 中華神經科雜志, 2020, 53(4): 244-249.
7.	Simard JM, Kent TA, Chen M, et al. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol, 2007, 6(3): 258-268.
8.	Dénes A, Ferenczi S, Kovács 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.
9.	Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: pathogenesis and clinical significance. JPEN J Parenter Enteral Nutr, 2019, 43(2): 181-193.
10.	Zhu HJ, Sun YY, Du Y, et al. Albumin-seeking near-infrared-II probe evaluating blood-brain barrier disruption in stroke. J Nanobiotechnology, 2024, 22(1): 742.
11.	Manolis AA, Manolis TA, Melita H, et al. Low serum albumin: a neglected predictor in patients with cardiovascular disease. Eur J Intern Med, 2022, 102: 24-39.
12.	中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性腦卒中診治指南 2018. 中華神經科雜志, 2018, 51(9): 666-682.
13.	Lin Y, Lin Y, Yue J, et al. The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in critically ill patients with acute myocardial infarction. BMC Cardiovasc Disord, 2022, 22(1): 115.
14.	Zuo L, Dong Y, Liao X, et al. Low HALP (hemoglobin, albumin, lymphocyte, and platelet) score increases the risk of post-stroke cognitive impairment: a multicenter cohort study. Clin Interv Aging, 2024, 19: 81-92.
15.	Xu M, Wu Z, Wu B, et al. Lactate dehydrogenase-to albumin ratio (LAR) is associated with early-onset cognitive impairment after acute ischemic stroke. J Clin Neurosci, 2022, 106: 61-65.
16.	Ha JW, Pyo JY, Ahn SS, et al. Predictive potential of albumin-alkaline phosphatase ratio for cerebrovascular accident in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Ann Clin Biochem, 2023, 60(3): 184-190.
17.	Cui R, Wang YL, Tao YL, et al. Platelet to albumin ratio is an independent indicator for disease activity in ankylosing spondylitis. Clin Rheumatol, 2023, 42(2): 407-413.
18.	Liu J, Ye B, Su D, et al. Evaluation of laboratory predictors for intravenous immunoglobulin resistance and coronary artery aneurysm in Kawasaki disease before and after therapy. Clin Rheumatol, 2023, 42(1): 167-177.
19.	Derya O, Onur UK, Miray E, et al. Fibrinogen to albumin ratio’s prognostic value in ischemic stroke patients who underwent mechanical thrombectomy. Ideggyogy Sz, 2024, 77(5/6): 167-176.
20.	Ye Y, Chen W, Gu M, et al. Serum globulin and albumin to globulin ratio as potential diagnostic biomarkers for periprosthetic joint infection: a retrospective review. J Orthop Surg Res, 2020, 15(1): 459.
21.	Wu S, Wang Y, Yuan R, et al. Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling. EClinicalMedicine, 2023, 59: 101977.
22.	郭文, 王璐, 劉鳴. 急性腦梗死后惡性腦水腫患者炎癥指標動態變化研究. 華西醫學, 2022, 37(6): 816-822.
23.	Zawiah M, Khan AH, Farha RA, et al. Assessing the predictive value of neutrophil percentage to albumin ratio for ICU admission in ischemic stroke patients. Front Neurol, 2024, 15: 1322971.
24.	Thorén M, Azevedo E, Dawson J, et al. Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis. Stroke, 2017, 48(9): 2464-2471.
25.	Chen Z, Xie D, Li Y, et al. Neutrophil albumin ratio is associated with all-cause mortality in stroke patients: a retrospective database study. Int J Gen Med, 2022, 15: 1-9.
26.	Yang Y, Ding R, Li T, et al. Elevated neutrophil-percentage-to-albumin ratio predicts increased all-cause and cardiovascular mortality in hypertensive patients: evidence from NHANES 1999-2018. Maturitas, 2025, 192: 108169.
27.	Jiang X, Andjelkovic AV, Zhu L, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol, 2018, 163-164: 144-171.
28.	Jayaraj RL, Azimullah S, Beiram R, et al. Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation, 2019, 16(1): 142.
29.	Kenne E, Erlandsson A, Lindbom L, et al. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice. J Neuroinflammation, 2012, 9: 17.
30.	Jiang N, Moyle M, Soule HR, et al. Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats. Ann Neurol, 1995, 38(6): 935-942.
31.	Lu HT, Zhao JG, Li MH, et al. Application of albumin prior to delayed thrombolysis reduces brain edema and blood brain barrier permeability in an embolic stroke model. Brain Res, 2012, 1438: 75-84.
32.	Belayev L, Zhao W, Pattany PM, et al. Diffusion-weighted magnetic resonance imaging confirms marked neuroprotective efficacy of albumin therapy in focal cerebral ischemia. Stroke, 1998, 29(12): 2587-2599.
33.	Zhou H, Wang A, Meng X, et al. Low serum albumin levels predict poor outcome in patients with acute ischaemic stroke or transient ischaemic attack. Stroke Vasc Neurol, 2021, 6(3): 458-466.
34.	Ginsberg MD, Palesch YY, Hill MD, et al. High-dose albumin treatment for acute ischaemic stroke (ALIAS) part 2: a randomised, double-blind, phase 3, placebo-controlled trial. Lancet Neurol, 2013, 12(11): 1049-1058.

1. Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
2. Balami JS, Chen RL, Grunwald IQ, et al. Neurological complications of acute ischaemic stroke. Lancet Neurol, 2011, 10(4): 357-371.
3. Wu S, Wang Y, Yuan R, et al. Clinical course, causes of worsening, and outcomes of severe ischemic stroke: a prospective multicenter cohort study. Chin Med J (Engl), 2025, 138(13): 1578-1586.
4. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 2019, 50(12): e344-e418.
5. Rabinstein AA. Ischaemic brain oedema remains a major unmet need. Lancet Neurol, 2024, 23(12): 1171-1173.
6. 吳思緲, 袁若圳, 劉鳴. 應當提倡大面積腦梗死后惡性腦水腫的預防理念及其研究. 中華神經科雜志, 2020, 53(4): 244-249.
7. Simard JM, Kent TA, Chen M, et al. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol, 2007, 6(3): 258-268.
8. Dénes A, Ferenczi S, Kovács 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.
9. Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: pathogenesis and clinical significance. JPEN J Parenter Enteral Nutr, 2019, 43(2): 181-193.
10. Zhu HJ, Sun YY, Du Y, et al. Albumin-seeking near-infrared-II probe evaluating blood-brain barrier disruption in stroke. J Nanobiotechnology, 2024, 22(1): 742.
11. Manolis AA, Manolis TA, Melita H, et al. Low serum albumin: a neglected predictor in patients with cardiovascular disease. Eur J Intern Med, 2022, 102: 24-39.
12. 中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性腦卒中診治指南 2018. 中華神經科雜志, 2018, 51(9): 666-682.
13. Lin Y, Lin Y, Yue J, et al. The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in critically ill patients with acute myocardial infarction. BMC Cardiovasc Disord, 2022, 22(1): 115.
14. Zuo L, Dong Y, Liao X, et al. Low HALP (hemoglobin, albumin, lymphocyte, and platelet) score increases the risk of post-stroke cognitive impairment: a multicenter cohort study. Clin Interv Aging, 2024, 19: 81-92.
15. Xu M, Wu Z, Wu B, et al. Lactate dehydrogenase-to albumin ratio (LAR) is associated with early-onset cognitive impairment after acute ischemic stroke. J Clin Neurosci, 2022, 106: 61-65.
16. Ha JW, Pyo JY, Ahn SS, et al. Predictive potential of albumin-alkaline phosphatase ratio for cerebrovascular accident in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Ann Clin Biochem, 2023, 60(3): 184-190.
17. Cui R, Wang YL, Tao YL, et al. Platelet to albumin ratio is an independent indicator for disease activity in ankylosing spondylitis. Clin Rheumatol, 2023, 42(2): 407-413.
18. Liu J, Ye B, Su D, et al. Evaluation of laboratory predictors for intravenous immunoglobulin resistance and coronary artery aneurysm in Kawasaki disease before and after therapy. Clin Rheumatol, 2023, 42(1): 167-177.
19. Derya O, Onur UK, Miray E, et al. Fibrinogen to albumin ratio’s prognostic value in ischemic stroke patients who underwent mechanical thrombectomy. Ideggyogy Sz, 2024, 77(5/6): 167-176.
20. Ye Y, Chen W, Gu M, et al. Serum globulin and albumin to globulin ratio as potential diagnostic biomarkers for periprosthetic joint infection: a retrospective review. J Orthop Surg Res, 2020, 15(1): 459.
21. Wu S, Wang Y, Yuan R, et al. Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling. EClinicalMedicine, 2023, 59: 101977.
22. 郭文, 王璐, 劉鳴. 急性腦梗死后惡性腦水腫患者炎癥指標動態變化研究. 華西醫學, 2022, 37(6): 816-822.
23. Zawiah M, Khan AH, Farha RA, et al. Assessing the predictive value of neutrophil percentage to albumin ratio for ICU admission in ischemic stroke patients. Front Neurol, 2024, 15: 1322971.
24. Thorén M, Azevedo E, Dawson J, et al. Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis. Stroke, 2017, 48(9): 2464-2471.
25. Chen Z, Xie D, Li Y, et al. Neutrophil albumin ratio is associated with all-cause mortality in stroke patients: a retrospective database study. Int J Gen Med, 2022, 15: 1-9.
26. Yang Y, Ding R, Li T, et al. Elevated neutrophil-percentage-to-albumin ratio predicts increased all-cause and cardiovascular mortality in hypertensive patients: evidence from NHANES 1999-2018. Maturitas, 2025, 192: 108169.
27. Jiang X, Andjelkovic AV, Zhu L, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol, 2018, 163-164: 144-171.
28. Jayaraj RL, Azimullah S, Beiram R, et al. Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation, 2019, 16(1): 142.
29. Kenne E, Erlandsson A, Lindbom L, et al. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice. J Neuroinflammation, 2012, 9: 17.
30. Jiang N, Moyle M, Soule HR, et al. Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats. Ann Neurol, 1995, 38(6): 935-942.
31. Lu HT, Zhao JG, Li MH, et al. Application of albumin prior to delayed thrombolysis reduces brain edema and blood brain barrier permeability in an embolic stroke model. Brain Res, 2012, 1438: 75-84.
32. Belayev L, Zhao W, Pattany PM, et al. Diffusion-weighted magnetic resonance imaging confirms marked neuroprotective efficacy of albumin therapy in focal cerebral ischemia. Stroke, 1998, 29(12): 2587-2599.
33. Zhou H, Wang A, Meng X, et al. Low serum albumin levels predict poor outcome in patients with acute ischaemic stroke or transient ischaemic attack. Stroke Vasc Neurol, 2021, 6(3): 458-466.
34. Ginsberg MD, Palesch YY, Hill MD, et al. High-dose albumin treatment for acute ischaemic stroke (ALIAS) part 2: a randomised, double-blind, phase 3, placebo-controlled trial. Lancet Neurol, 2013, 12(11): 1049-1058.

West China Medical Journal

Association of serum albumin and relevant composite indicators with malignant brain edema after acute ischemic stroke

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