SYSTEMATIC REVIEW article

Front. Neurol., 20 October 2025

Sec. Neurological Biomarkers

Volume 16 - 2025 | https://doi.org/10.3389/fneur.2025.1594258

Prognostic assessment of acute ischemic stroke by systemic immune-inflammatory index: a comprehensive meta-analysis of multidimensional outcomes

  • YJ

    Yanhong Jiang 1

  • YC

    Yifan Cui 1

  • XH

    Xiaojie Hu 2

  • JL

    Jiaying Lian 3

  • XQ

    Xueying Qin 4

  • XW

    Xingchen Wang 1,2*

  • XM

    Xuran Ma 1*

  • 1. The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China

  • 2. Department of Neurology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China

  • 3. Department of Neurology, Quzhou Traditional Chinese Medicine Hospital, Quzhou, China

  • 4. The First Clinical Medical College, Beijing University of Traditional Chinese Medicine, Beijing, China

Abstract

Introduction:

Our study aimed to quantify the predictive ability of the Systemic Immune-inflammatory Index (SII) for predicting the prognosis and multidimensional complications in acute ischemic stroke (AIS) patients. The primary outcome was poor prognosis, and secondary outcomes included mortality, severity, hemorrhagic transformation/symptomatic intracerebral hemorrhage, stroke-associated pneumonia/poststroke pneumonia, early neurological deterioration, post-stroke depression, progression or recurrence, and other adverse outcomes.

Methods:

We searched 15 databases from their establishment to 13 October 2024 and selected cohort or case-control analyses that analyzed the association of continuous or categorized SII as exposures with the above adverse outcomes of AIS populations.

Results:

The results showed that 78 studies with 40,682 participants were included in meta-analyses. Continuous SII values were significantly higher in poor prognosis groups than in controls (SMD = 248.13, 95% CI: 198.77 to 297.50; p = 0.000). Poor prognosis incidences rose with higher continuous SII values (OR = 1.004, 95% CI: 1.002 to 1.005; p = 0.000). More patients in High SII groups had poor prognosis (RR = 1.95, 95% CI: 1.66 to 2.28; p = 0.000). The risk of poor prognosis was higher in the high SII groups, though this was not statistically significant (OR = 1.007, 95% CI: 0.998 to 1.015; p = 0.120).

Discussion:

In conclusion, our study found that continuous SII and high SII were associated with poor prognosis of AIS and various complications. Given the accessibility and low cost of SII, integrating it into prognostic scores merits further research for better clinical choices.

Systematic review registration:

PROSPERO (CRD42024586414), https://www.crd.york.ac.uk/PROSPERO/view/CRD42024586414.

1 Introduction

Acute ischemic stroke (AIS), a prominent form of stroke, ranks as the primary cause of disability and mortality on a global scale (1). Given its high prevalence, there is an urgent need for a simple, accurate, and inexpensive prognostic biomarker to better predict AIS outcomes. Systemic Immune-Inflammatory Index (SII) is an inflammatory indicator calculated as Neutrophil ×Platelets/Lymphocyte, which reflects the balance between the body’s inflammatory response and immune state and the state of coagulation. There were three systematic reviews that reported on SII’s predictive value in the prognosis of AIS, but all were published early and flawed in design, with few included studies (2–4). The purpose of this study was to conduct a thorough literature search and pool data on the prognostic ability of SII for outcomes of AIS, including poor prognosis, mortality, severity, complications like hemorrhagic transformation (HT)/symptomatic intracerebral hemorrhage (sICH), stroke-associated pneumonia (SAP)/poststroke pneumonia (PSP), early neurological deterioration (END), post-stroke depression (PSD), progression/recurrence, and other complications.

2 Materials and methods

There were two researchers who independently conducted the entire process under MOOSE (4), with the review protocol deposited in PROSPERO (CRD42024586414). There were 15 databases searched from their establishment to 13 October 2024: PubMed, Embase, Cochrane, EBSCO, Scopus, OVID, Web of Science, CNKI, Wanfang, VIP, Sinomed, Clinical Trials, WHO-ICTRP, Chictr, and DANS EASY. AIS search subject terms included “Brain Infarction,” “Brain Ischemia,” “Cerebral Arterial Diseases,” “Cerebral Infarction,” “Cerebrovascular Disorders,” “Stroke,” and free terms included 122. SII terms included six terms (Search criteria, strategies, and results as shown in Supplementary material 1).

After eliminating duplicate reports, the remaining studies’ titles and abstracts were screened to assess their appropriateness for inclusion. Subsequently, the previously selected papers were evaluated for eligibility, data obtained, and bias risk evaluated by the Newcastle-Ottawa Scale (NOS) using the full text. Another two researchers independently conducted the abovementioned processes, and any disagreements were resolved by consulting a third guide researcher.

Eligible articles were cohort or case–control analyses analyzing the relationship between SII and AIS adverse outcomes, including poor prognosis, mortality, severity, and complications such as HT/sICH, SAP/PSP, END, PSD, progression/recurrence, and others. The inclusion criteria were as follows: 1. Population: Patients of AIS and its complications (any diagnostic criteria); 2. Required data: Continuous SII value of poor prognosis/death/mild severity/HT/SAP/END/PSD/progression or recurrence/other complications groups versus the corresponding control groups; sample size of outcomes’ events, adjusted odds ratio (aOR)/adjusted hazard ratio (aHR) of outcomes, and National Institute of Health Stroke Scale (NIHSS) in High SII groups versus Low SII groups; SII cut-off values and area under curve (AUC) of receiver operating characteristic (ROC) curves. 3. Exclusion criteria were as follows: duplicate publications, obviously incorrect data, mismatched research types, and low quality (NOS ≤ 4) (When studies provided sample sizes of outcomes’ events for high- and low-SII groups, HIGH SII was defined as the highest SII group, and LOW SII was the sum of the other groups. For aOR/aHR or NIHSS data, HIGH SII was defined as the highest SII group, and LOW SII was the lowest SII group).

We assessed the association between SII and AIS adverse outcomes using mean difference (MD), Relative Risk (RR), and pooled aOR/aHR. Using Stata 14.0, we considered a p-value < 0.05 significant, quantified heterogeneity with I2 and p value of Cochran’s Q statistics, applied the random-effects model for high heterogeneity, and checked for bias with funnel plots and Begg/Egger tests.

3 Results

3.1 General results

Literature search and studies included the initial search, which resulted in 1646 total studies, 670 studies that remained to be screened after removing duplicates, and 99 studies that remained for full-text assessment. Finally, 79 studies (1, 5–82) remained to be included in the systematic review, and 78 studies remained to be included in the meta-analysis (1, 5–33, 35–82) except Wang SN 2024 (34). Details of the process are shown in Figure 1. A summary of the main characteristics of the 78 studies is presented in Table 1; the rating of the quality of the evidence by NOS is presented in Table 2.

Figure 1

Table 1

No.ReferencesStudy designNOSRegionPopulationType of AISEntry timeParticipants (M/F)Age-year (Mean ± SD)/[Median(IQR)]Medical & medication historyBlood samplingFollowed-upOutcomes
Cohort studies
1Wang N 2024 (13)R-S9ChinaChanghai Hospital of Naval Medical UniversityAIS with IVT2016.01–2020.12466 (291/175)65.5①②③⑤⑥Before IVT (Within 4.5 h of Symptom Onset)90dACDE
2Zhang LL 2024 (15)R-S9Chinathe First Affiliated Hospital of Soochow UniversityAIS with Atherosclerotic Plaque in Responsible Carotid Artery2020.01–2022.06202 (147/55)Vulnerable groups 65.13 ± 10.53/Stable groups 64.57 ± 11.28①②③④⑮⑱Within 24 h of Admission1mosJ
3Wei 2024 (16)R-S9ChinaSecond Hospital of Tianjin Medical UniversityAIS with IVT2019.03–2021.05221 (138/83)68.0 ± 12.1①②③④⑤⑥⑮⑯Before The Bolus of IVT3mosABCDE
4Zhang MK 2024 (32)R-S9ChinaXuan Wu Hospital, affiliated to Capital Medical UniversityAIS with EVT & fDNI2017.01–2020.04352 (250/102)DNI groups 60.89 ± 11.63/Non-DNI groups 64.81 ± 11.85①②③④⑤⑥Before EVT90dJ
5Yang Y 2024 (5)R-S8ChinaBeijing Friend-ship Hospital, Capital Medical UniversityAIS with ICA severe stenosis and SAP2020.1–2023.6342 (171/171)65.2 ± 10.2/66.3 ± 11.1①②③④⑤⑥⑦⑮⑯⑱⑲The Next Morning (5:00 a.m.) after Admission120dBC
6Cao 2024 (8)R-S8ChinaXuanwu Hospital of Capital Medical UniversityAnterior Circulation AIS-LVO with EVT2018.12–2022.12482 (323/159)65 (56–72)①②③④⑤⑥⑮⑯Admission or the first day post-EVT90dAD
7Arslan 2024 (6)R-S7TurkeyIstanbul Kanuni Sultan Süleyman Training and Research HospitalCritical AIS in ICU2020–2022198 (95/103)70 (56–86)①②④⑤⑧NR28dAB
8Zhu 2024 (7)R-S7ChinaNantong Third People’s HospitalAIS NOT EVT or IVT2019.09–2024.02306 (191/115)FPG groups 68.761 ± 10.763, PPG groups 75.327 ± 8.911①②③④⑤⑥⑫⑮⑯⑱Within 1 h of Admission30dAG
9Zhao 2024 (17)R-S7ChinaWuxi People’s HospitalAIS with IVTNR197 (125/72)FPG 68.18 ± 10.09/PPG 67.69 ± 8.75①②⑤Within 4.5 h of Symptom OnsetNRA
10Guoqing 2024 (18)R-S7ChinaPeople’s Hospital of Xinjiang Uygur Autonomous RegionAIS with IVT2021.06–2023.06122 (65/57)58 (54, 63)①②Before The Bolus of IVT6mosA
11Ma L 2024 (21)R-S7Chinathe Second Affiliated Hospital of Anhui Medical UniversityACI with IVT2021.09–2023.09199 (130/69)62.96 ± 13.00①②⑤⑥⑮⑱Before IVT3mosAEG
12Huang H 2024 (29)R-S7Chinathe First People’s Hospital of SuqianMinor Stroke Due to Anterior Circulation AIS-LVO2021.11–2023.12132 (85/47)68 (58–77)①②③④⑤⑥⑮⑯⑱⑲㉒340 (228 ~ 572)Min after Onset24 hE
13Misirlioglu 2024 (10)R-S6TurkeyGaziosmanpasa Education and Research HospitalAIS2019.01–2023.061,350 (710/640)64.38 ± 16.43①②③④⑤Within 24 h of Stroke OnsetNRB
14Mengting 2024 (20)R-S6ChinaXishan People’s Hospital of WuxiACI with IVT2022.01–2023.12174 (111/63)FPG groups 68 (57, 76)/PPG groups74 (66, 81)①②③④⑤⑥⑮⑱Before and 24 h after IVTDischargeA
15Zhouquan 2024 (23)R-S6Chinathe Second People’s Hospital of ChengduAIS with IVT2022.03–2023.03213 (125/88)67.5 ± 20.5①②⑤Admission3mosA
16Jiaxiang 2024 (25)R-S6ChinaNanjing Drum Tower HospitalAIS with IVT2020.01–2022.12185 (104/81)END groups 80 (70, 84)/Non-END groups 73 (66, 80)①②③⑤⑥NR3mosE
17Zhang J 2024 (27)R-S5ChinaThe Affiliated Hospital of Chengde Medical CollegeAIS2023.01–2023.12115 (81/34)PIS groups 61.83 ± 10.89/Non-PIS groups 64.06 ± 9.92①②④⑤Within 24 h of Admission7dJ
18Haimei 2024 (30)R-S5ChinaTaizhou People’s HospitalAIS2022.01–2022.12259 (159/100)SAP groups 71.00 (61.00, 81.00)/Non-SAP groups 70.00 (58.00, 77.25)①②④⑤NR7dF
19Lijun 2024 (31)R-S5ChinaThe First Affiliated Hospital of Naval Medical UniversityAIS2022.08–2022.1280 (58/22)27–84①②③④⑥The Day After Admission90dG
20(1)Huang SW 2024 (1) (1)R-M8Chinathe First Affiliated Hospital of Wenzhou Medical UniversityAIS without IVT2020.1–2020.121,268 (835/433)67 (59–76)①②④⑤⑥Within 24 h of Admission1yABJ
20(2)Huang SW 2024 (1) (2)R-M8Chinathe Third Affiliated Hospital of Wenzhou Medical UniversityAIS without IVT2020.1–2020.12536 (341/195)69 (60–78)①②④⑤⑥Within 24 h of Admission1yABJ
20(3)Huang SW 2024 (1) (3)R-M8ChinaBothAIS without IVT2020.1–2020.12650 (391/259)75.00 (68.00–81.00)①②④⑤⑥Within 24 h of Admission1yABJ
21Lee 2024 (12)P-S8KoreaSoonchunhyang University School of MedicineAIS2019.01–2021.12697 (405/292)4 SII groups:69.4 ± 13.3/67.1 ± 13.1/68.8 ± 13.8/71.4 ± 14.1①②⑤⑨⑩⑭⑰⑱⑲Within 1 h after Admission7dACEI
22Cheng 2024 (9)P-S8Chinathe First People’s Hospital of YanchengAIS2022.01–2023.03332 (203/129)68 (58–76)①②④⑤⑬The Next Morning3mosJ
23Hao 2024 (11)P-S7ChinaPeople’s Hospital of Zhengzhou UniversityAIS with IVT2020.01–2022.08121 (78/43)63.8 ± 12.9①②④⑥⑬⑲⑳Within 24 h after Ischemic Stroke OnsetDischargeJ
24Chen GJ 2024 (14)P-M8China111 hospitals(Clinical trials NCT03370939)AIS with EVT2017.11–2019.031,002 (660/342)65 (55–72)①②④⑤The First Test on Admission & before EVT90dAC
25Fernández-Garza 2023 (35)R-S9MexicoUniversity Hospital “Dr. José Eleuterio González”AIS2018.01–2019.06145 (97/48)61.5 ± 12.75①②③⑥⑲Within 24 h of Admission90dAG
26Ma 2023 (37)R-S9ChinaJiangsu Province Hospital of Chinese MedicineAIS with IVT2019.09–2022.12190 (122/68)70.389 ± 11.675①②④⑤⑥⑮⑯⑱㉒㉓Within 24 h of Admission3mosABI
27Zhao 2023 (38)R-S8ChinaHebei general hospitalAIS with IVT2017.09–2022.08281 (168/113)66 (56–73)①②③④⑤⑥Before IVT3mosAE
28Hu 2023 (39)R-S8AmericaMIMIC-IV(the Beth Israel Deaconess Medical Center)AIS Admitted to the ICU2008–2019463 (221/242)71.68 ± 16.29②④⑦⑧⑩⑪NRDischargeB
29Zhang 2023 (40)R-S8ChinaChanghai HospitalAIS with EVT2019.01–2019.12248 (160/188)67.19 ± 11.47①②③④⑤㉔On Admission90 ± 14dF
30Chu 2023 (41)R-S8ChinaMinhang Hospital of Fudan UniversityMild AIS with IVT2017.01–2022.05240 (81/159)66.00 (60.00–73.35)①②⑤Before IVT3mosA
31Gao 2023 (54)R-S8ChinaHuai’an First People’s HospitalAIS with IVT2019.07–2022.07352 (240/112)66.46 ± 12.00①②⑤⑥The Morning after Admission36 hD
32Wang S 2023 (36)R-S7Chinathe First Affiliated Hospital of Soochow UniversityAIS with IVT2017.01–2022.08717 (485/232)68 (58–75)①②③⑤⑥⑮⑯⑰NR3mosA
33Zhou 2023 (46)R-S7ChinaThe Affiliated Hospital of Guilin Medical CollegeAIS2020.01–2020.12208 (143/65)63.3 ± 11.3①②③④⑤Within 24 h of Admission3mosAC
34Xiao 2023 (43)R-S6ChinaGuangzhou First People’s HospitalAIS with PFO2021.02–2021.12100 (78/22)PFO groups 50.48 ± 8.86/Non-PFO groups 54.00 ± 10.30①②③NRNRJ
35Dan-dan 2023 (44)R-S6ChinaAffiliated Hospital of Xuzhou Medical UniversityElderly AIS with IVT2019.08–2022.02347 (228/119)60–93 (70.12 ± 7.71)①②⑤⑥NR3mosAD
36Shao 2023 (47)R-S6ChinaLianyungang Second People’s HospitalAcute Lacunar Infarction2021.01–2022.06172 (112/60)BG-EPVS mild groups 63.35 ± 11.46/BG-EPVS Moderate-to-Severe groups 69.16 ± 10.13①②The Morning after Admission7dJ
37Wang X 2023 (48)R-S6Chinathe First Affiliated Hospital of Shihezi University Medical CollegeAIS with EVT2019.01–2022.12682 (481/201)65.00(55.00, 76.00)①②NR90dA
38Song 2023 (49)R-S6ChinaWafangdian Third HospitalACI2021.01–2022.05310 (200/110)62.58 ± 10.27①②③④⑤Within 24 h of Admission1mosHJ
39Wang YL 2023 (50)R-S6ChinaJianping County Hospital of traditional Chinese medicineACI with IVT2021.05–2022.09100 (40/60)64.24 ± 9.22①②④⑥NR3mosA
40Liu HT 2023 (51)R-S6ChinaNorthern Jiangsu People’s HospitalAIS with AF & IVT2018.10–2022.11514 (285/229)AF-S groups 73.2 ± 10.2/Non-AF-S groups 66.1 ± 11.1①②④⑤⑥⑮⑯Before IVT; Morning of The Second Day after Admission90dADJ
41Dong 2023 (53)R-S6ChinaBaoji Municipal Central HospitalAIS-LVO with EVT2017.12–2022.06219 (122/97)39–83 (61 ± 9)①②③④⑤Immediately after Admission90dJ
42Huixin 2023 (55)R-S6ChinaXuanwu HospitalALVOS with EVT2019.01–2021.01426 (282/144)65 (57, 74)①②③④⑤⑥Before EVT90dA
43Liu YY 2023 (56)R-S6ChinaThe Fifth Affiliated Hospital of Zhengzhou UniversityAIS2021.03–2022.1022 (NR)NR①②④⑥⑮⑱The Morning after Admission90dA
44Su 2023 (57)R-S6ChinaNanchong Mental Health Center of Sichuan ProvinceAIS with IVT2021.01–2022.08Model 272 (143/129); Verification 112 (54/58)63.02 ± 11.27①④NR3mosJ
45Lin 2023 (42)P-S7ChinaShunde Hospital of Southern Medical UniversityAIS2022.01–2022.09177 (121/56)FPG groups 63.04 ± 12.26/PPG groups 63.17 ± 13.44①②③④⑥㉔Within 24 h On The Day of Admission90dAGJ
46Wang ZT 2023 (52)P-S7Chinathe First Affiliated Hospital of China Medical UniversityAIS with IVT2020.09–2022.09324 (219/105)65 (58, 71)①②④⑤Before IVT90dAE
47Li 2023 (45)P-S6ChinaXianyang Hospital of Yan’an UniversityAnterior Circulation AIS2020.10–2022.10110 (83/2762.03 ± 10.54NRWithin 24 h3mosA
48Zhang 2022 (59)R-S9Chinathe First People’s Hospital of YanchengAIS with Carotid Atherosclerotic Plaque2020.06–2021.03131 (98/33)61.86 ± 12.37①②④⑥⑮⑱Within 24 h of Admission1monCJ
49Liu 2022 (69)R-S9ChinaYantai Yuhuangding HospitalAIS2020.08–2021.08266 (160/106)Mild groups 64.2 ± 10.0/Moderate-to-severe groups 66.2 ± 12.1①②⑤⑮⑯Within 24 h after Onset90dADG
50Wu 2022 (61)R-S8AmericaMIMIC-IV(the Beth Israel Deaconess Medical Center)AIS2008–20191,181 (600/581)69.1 ± 15.6①②③④⑤⑧⑩⑪⑫⑭⑮⑯㉔The First Test Results At Icu.30d&90dB
51Yang 2022 (64)R-S8ChinaWest China HospitalAIS-LVO with EVT2017.01–2021.01379 (199/180)71 (58–78)①②③⑤⑰⑱Immediately Upon Arrival At The Emergency RoomNRCD
52Li 2022 (58)R-S7ChinaHuizhou Central People’s HospitalLAO-AIS after EVT2020.01–2022.01173 (118/55)56.9 ± 8.9①②③④⑤In The Emergency Department Or Within 1D of AdmissionNRJ
53Wenli Z 2022 (71)R-S7ChinaNanjing Municipal First HospitalAcute Stroke with EVT2018.01–2020.0688 (52/36)67.39 ± 28.21①②③⑤NR3mosAJ
54Lin 2022 (63)R-S6ChinaNRAIS2017.01–2019.06526 (277/249)Definite AF groups 68.08 ± 12.16/Non-AF groups 78.61 ± 9.65①②④⑥⑲⑳During Hospitalization, after Fasting For At Least 12 hDischargeJ
55Zhou 2022 (65)R-S6ChinaThe Affiliated Hospital of Guilin Medical UniversityAIS2020.01–2020.12208 (143/65)63.3 ± 11.3①②③④⑤Within 24 h3mosA
56Ma 2022 (68)R-S6ChinaUrumqi Friendship HospitalAIS with IVT2020.05–2021.0863 (33/30)65.0 ± 11.0NRBefore IVT90dA
57Laiyun Z 2022 (70)R-S6ChinaThe Affiliated Hospital of Xuzhou Medical UniversityYoung ACI2019.03–2021.03182 (152/30)FPG groups 40.00 (35.00, 44.00)/PPG groups 39.00 (34.00, 43.00)①②Within 24 h of Admission3mosAG
58Chen 2022 (66)R-S5China TaiwanTaipei Tzu Chi HospitalAIS2011.01–2021.043,402 (72 IHIS+3,330 OHIS) (1959/1443)IHIS groups 75.3 (65.6–81.9)/OHIS groups 71.8 (61.7–81.5)①②③④⑤⑥⑦⑩Emergency Department Arrival/During Acute Attack of Stroke at WardDischargeAB
59Adiguzel 2022 (67)R-S5TurkeyHacettepe University Neurology Intensive Care and Stroke UnitSevere AIS(NIHSS>10)2019–2021205 (85/120)71 ± 15①②⑤⑧⑨⑰㉔Within The First 12H after Stroke OnsetDischarge/3mosABFJ
60Ji 2022 (62)R-M8ChinaJinling Hospital & Yijishan HospitalAnterior Circulation LVOS with EVT2014.01–2018.12/2015.09–2021.07675 (402/273)67.1 ± 11.4①②⑤Within The First 24 h after Admission90dAJ
61Wang 2022 (60)P-M8China201 hospitals(CNSR-III)AISNR9,107 (6343/2764)61.9 ± 11.1①②③④⑤⑥NR90d&1yABI
62Zhong 2021 (79)R-S8Chinathe First Affiliated Hospital of Kunming Medical UniversityAIS2017.02–2020.04238 (131/107)FPG groups 60.47 ± 13.25/PPG groups 68.86 ± 13.19①②③④⑤⑥⑧⑲㉔Within 24 h of Admission3mosAFG
63Weng 2021 (75)R-S8Chinathe Third Affiliated Hospital of Wenzhou Medical UniversityAIS with IVT2016.02–2019.04216 (136/80)68.5 (59.25–76)①②③④⑤⑥Within 24 h after Admission3mosACG
64Wei 2021 (76)R-S8Chinathe General Hospital of the Eastern Theater CommandAIS2017.07–2017.12116 (87/29)62.09 ± 12.42NRAIS groups Admission/Control groups Fasted For More Than 12 h2yIJ
65Li LH 2021 (74)R-S7China TaiwanTaipei Veterans General HospitalAIS within 3 h2016.01–2018.12277 (157/120)73.2 ± 13.4②③④Emergency Department Arrival1yJ
66Cheng 2021 (77)R-S6ChinaThe Affiliated Hospital of Xuzhou Medical UniversityAIS2020.01–2020.12305 (200/105)SAP groups 75.77 ± 10.19//Non-SAP groups 61.68 ± 12.31①②③④⑤⑥㉑㉔Within 24 h of Admission7dF
67Yi 2021 (73)R-M7KoreaSoonchunhyang University Bucheon Hospital & St. Vincent’s HospitalLAO-AIS with ET2015.01–2020.09440 (260/180)FPG groups 68.0 (13.4)/PPG groups 72.6 (11.7)①②③④⑤⑥On Admission3mosACDJ
68Hu 2021 (72)P-S9Chinathe First Affiliated Hospital of Wenzhou Medical UniversityAIS2014–2017432 (272/151)62.58 ± 10.27①②③④The Morning after Admission, 05:00–08:001monCHJ
69Wei 2021 (76)P-S6ChinaAffiliated Beijing Shijitan Hospital of Capital Medical UniversityACI2018.03–2019.02220 (137/83)60 ~ 93 (73.86 ± 8.58)①②③④⑤⑥⑧Within 24 h of AdmissionDischargeF
70Zhao 2020 (81)R-S8ChinaSubei People’s Hospital of Jiangsu ProvinceACI2019.01–2019.07140 (84/56)68.20①②④Within The First 24 h after Admission.0.5yA
71Chu 2020 (82)R-S6China TaiwanTaipei Tzu Chi HospitalAIS2010.05–2020.022,543 (1469/1074)70.8 ± 13.5①②③④⑥⑦⑩Arrival In The Emergency RoomAt DischargeAJ
72Ceng 2020 (80)P-S9Chinathe First Affiliated Hospital of Zhengzhou UniversityAIS2015.01–2017.12SAP 1155 (NR);3 Month 1,106 (NR);1 Year 1,074 (721/434)Non-SAP groups 59.51 ± 12.30/SAP groups 65.65 ± 13.22①②③④⑤⑥Within 24 h3mos&1yABF
Case–control studies
73Dong 2024 (28)R-S8ChinaBaoji Central HospitalAIS2019.02–2021.02307 (159/148)PSD groups 59.52 ± 10.04/Non-PSD groups 61.76 ± 9.96①②③④⑤Early Morning after Admission (05:00 ~ 08:00)30dH
74Zheng 2024 (33)R-S6ChinaThe Affiliated Hospital of Putian UniversityMassive Cerebral Infarction within 48 h2019.01–2021.1182 (52/30)FPG groups 68 (61.5, 80.5)/PPG groups 70 (57.5, 76)①②⑤⑥Within 24 h of AdmissionDischargeADFJ
75Zhou 2024 (19)R-S6ChinaWujin Hospital, Affiliated to Jiangsu UniversityAIS2020.01–2022.12238 (161/77)SAP groups 77.57 ± 8.69/Non-SAP groups 76.57 ± 9.36①②④Within 24 h of Admission7dF
76Tianlu 2024 (24)R-S6Chinathe First Affiliated Hospital of Harbin Medical UniversityAIS2020.01–2023.06236 (143/93)NR①②㉑NR7dF
77Yu 2024 (77)R-S6ChinaChina-Japan Union Hospital of Jilin UniversityAIS with EVT2021.01–2023.08150 (103/47)68 (59, 72)①②④⑤⑥NRNRD
78Niu 2024 (26)R-S5ChinaLijin County Central HospitalAIS with IVT2021.07–2023.07150 (83/67)HT groups 49.63 ± 9.52/Non-HT groups 50.89 ± 9.66The Next MorningNRD

Characteristics of studies investigating the relationship between SII and AIS.

ACI, Acute Cerebral Infarction; AF, Atrial fibrillation; AF-S, Atrial fibrillation Stroke; AIS, Acute Ischemic Stroke; AIS-LVO, Acute Ischemic Stroke with Large Vessel Occlusion; ALVOS, Acute Large Vessel Occlusive Stroke; BG-EPVS, Basal Ganglia-Enlarged Perivascular Spaces; BG-EPVS, Basal Ganglia Region Enlarged Perivascular Spaces; CNSR-III, China National Stroke Registry III; CSO-EPVS, Central Semi-ovale Region Enlarged Perivascular Spaces; DNI, Delayed Neurological Improvement; END, Early Neurological Deterioration; EVT, Endovascular Treatment; FPE, First Pass Effect; FPG, Favorable Prognosis groups; HT, Hemorrhagic Transformation; ICA, Internal Carotid Artery; IHIS, In-hospital Ischemic Stroke; IS, Ischemic Stroke; LAO-AIS, Large Artery Occlusion-Acute Ischemic Stroke; LAA, Large Artery Atherosclerosis; LVOS, Large-vessel Occlusive Stroke; MCE, Malignant Cerebral Edema; MIMIC-IV, Medical Information Mart for Intensive Care-IV; MT, mechanical thrombectomy; NOS, Newcastle–Ottawa Scale; NIHSS, National Institutes of Health Stroke Scale; NR, Not Reported; OHIS, Out-of-hospital Ischemic Stroke; PCI, Progressive Cerebral Infarction; PFO, Patent Foramen Ovale; PPG, Poor Prognosis groups; PSCI, Post-stroke Cognitive Impairment; PSD, Post-stroke Depression; PSP, Poststroke Pneumonia; PIS, Progressive Ischemic Stroke; R, Retrospective; SAP, Stroke-Associated Pneumonia; SHS, Stroke-heart Syndrome; SII, Systemic Immune-inflammation Index; sICH, Symptomatic Intracerebral Hemorrhage; IVT, Intravenous Thrombolysis; ICU, Intensive Care Unit; fDNI, Failure of Delayed Neurological Improvement.

R, Retrospective; P, Prospective; S, Single-center; M, Multi-center. M, Male; F, Female; h, hours; d, day; y, year; mon, month; mos, months; w, week.

① Hypertension; ② Diabetes; ③ Dyslipidaemia; ④ Heart Diseases (Coronary Heart Disease/Heart Failure/Myocardial Infarction, etc.); ⑤ Atrial Fibrillation; ⑥ Previous Cerebrovascular Diseases (Stroke/TIA, etc.); ⑦ Kidney Diseases; ⑧ Respiratory Diseases (Asthma/Chronic Obstructive Pulmonary Disease, etc.); ⑨ Infections; ⑩ Cancer; ⑪ Dementia; ⑫ Peripheral Arterial Diseases; ⑬ Carotid Diseases (Carotid Plaque/Carotid Atherosclerosis/Carotid Artery Stenosis, etc.); ⑭ Other Diseases; ⑮ Antiplatelets; ⑯ Anticoagulants; ⑰ Antithrombotics; ⑱ Statins; ⑲ IVT; ⑳ EVT; ㉑ Antibiotics; ㉒ Antihypertensive Drugs; ㉓ Hypoglycemic Drugs; ㉔ Other Drugs or Therapies.

A, Poor Prognosis; B, Mortality; C, Admission NIHSS; D, HT/sICH; E, END; F, SAP/PSP; G, AIS Severity; H, PSD; I, Stroke Progression/Recurrence; J, Others.

Table 2

Cohort studies
No.StudyTotalSelectionComparabilityOutcome
12341123
Representativeness of the exposed cohortSelection of the non-exposed cohortAscertainment of exposureDemonstration that outcome of interest was not present at start of studyComparability of cohorts on the basis of the design or analysisAssessment of outcomeWas follow-up long enough for outcomes to occurAdequacy of follow-up of cohorts
1Yang Y 2024 (5)8☆☆×
2Huang SW 2024 (1)8☆☆×
3Arslan 2024 (6)7×
4Zhu 2024 (7)7☆☆××
5Cao 2024 (8)8☆☆×
6Cheng 2024 (9)8☆☆×
7Misirlioglu 2024 (10)6××
8Hao 2024 (11)7×☆☆×
9Lee 2024 (12)8☆☆×
10Wang N 2024 (13)9☆☆
11Chen GJ 2024 (14)8×☆☆
12Zhang LL 2024 (15)9☆☆
13Wei 2024 (16)9☆☆
14Zhao 2024 (17)7×
15Guoqing 2024 (18)7×
16Mengting 2024 (20)6××
17Zhouquan 2024 (23)6××
18Jiaxiang 2024 (25)6××
19Ma L 2024 (21)7×
20Zhang J 2024 (27)5×××
21Huang H 2024 (29)7×
22Haimei 2024 (30)5×××
23Lijun 2024 (31)5×××
24Zhang MK 2024 (32)9☆☆
25Lin 2023 (42)7×
26Xiao 2023 (43)6☆☆×××
27Dan-dan 2023 (44)6××
28Zhou 2023 (46)7×
29Shao 2023 (47)6××
30Wang X 2023 (48)6××
31Song 2023 (49)6××
32Wang YL 2023 (50)6×
33Liu HT 2023 (51)6c×
34Wang ZT 2023 (52)7☆☆××
35Dong 2023 (53)6××
36Gao 2023 (54)8☆☆×
37Huixin 2023 (55)6×××
38Liu YY 2023 (56)6×
39Su 2023 (57)6××
40Fernández-Garza 2023 (35)9☆☆
41Wang S 2023 (36)7×
42Ma 2023 (37)9☆☆
43Zhao 2023 (38)8☆☆×
44Hu 2023 (39)8☆☆×
45Zhang 2023 (40)8
46Chu 2023 (41)8
47Li 2023 (45)6××
48Ma 2022 (68)6××
49Liu 2022 (69)9☆☆
50Laiyun Z 2022 (70)6××
51Wenli Z 2022 (71)7×
52Li 2022 (58)7×
53Zhang 2022 (59)9☆☆
54Wang 2022 (60)8☆☆×
55Wu 2022 (61)8☆☆×
56Ji 2022 (62)8☆☆×
57Lin 2022 (63)6×
58Yang 2022 (64)8☆☆×
59Zhou 2022 (65)6×
60Chen 2022 (66)5×××
61Adiguzel 2022 (67)5×××
62Wei L 2021 (76)6☆☆×××
63Cheng 2021 (77)6××
64Zhong 2021 (79)8☆☆×
65Hu 2021 (72)9☆☆
66Yi 2021 (73)7×
67Li LH 2021 (74)7×
68Weng 2021 (75)8☆☆×
69Wei-shi 2021 (78)8☆☆×
70Ceng 2020 (80)9☆☆
71Zhao 2020 (81)8☆☆×
72Chu 2020 (82)6××
73Wang SN 2024 (34)4××××
Case–control studies
No.StudyTotalSelectionComparabilityExposure
12341123
Adequate case-definitionRepresentativeness of the casesSelection of controlsDefinition of controlsComparability of cases and controls on the basis of the design or analysisAscertainment of exposureSame Method of ascertainment for cases and controlsNon-response rate
1Zheng 2024 (33)6××
2Zhou 2024 (19)6××
3Tianlu 2024 (24)6××
4Yu 2024 (77)6××
5Niu 2024 (26)5×××
6Dong 2024 (28)8☆☆×

Quality assessment based on the Newcastle–Ottawa Scale (NOS).

*Wang SN 2024 (34) was excluded from the meta-analysis because of low quality (Nos ≤ 4). The meanings of the ☆, ☆☆, and × can be found at the official instruction website of the NOS scale: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

3.2 Study characteristics

This systematic review and meta-analysis encompassed 40,682 individuals; the sample size ranged from a minimum of 22 (56) to a maximum of 9,107 (60). Not all studies reported the sex distribution and age data, preventing the accurate calculation of these data. Geographically, 68 studies were conducted in China (1, 5, 7–9, 11, 13–33, 36–38, 40–60, 62–65, 68–72, 75–81), 11 studies were conducted in other states or area including Turkey (n = 3) (6, 10, 67), China Taiwan (n = 3) (66, 74, 82), America (n = 2) (61), Korea (n = 2) (12, 73), Mexico (n = 1) (35). Moreover, studies (1, 5–8, 10, 13, 15–33, 35–41, 43, 44, 46–51, 53–59, 61–71, 73–75, 77–79, 81, 82) were retrospective, and 11 studies (9, 11, 12, 14, 42, 45, 52, 60, 72, 76, 80) were prospective. At the same time, 73 studies (5–13, 15–33, 35–59, 61, 63–72, 74–82) were single-center, and 5 studies (1, 14, 60, 62, 73) were multi-center. The number of studies reporting data on outcomes were as follows: poor prognosis (n = 43) (1, 6–8, 12–14, 16–18, 20, 21, 23, 33, 35–38, 41, 42, 44–46, 48, 50–52, 55, 56, 60, 62, 65–71, 73, 75, 79–82), mortality (n = 12) (1, 5, 6, 10, 16, 37, 39, 60, 61, 66, 67, 80), severity (n = 9) (7, 21, 31, 35, 42, 69, 70, 75, 79), HT/sICH (n = 12) (8, 13, 16, 22, 26, 33, 44, 51, 54, 64, 69, 73), END (n = 8) (12, 13, 16, 21, 25, 29, 38, 52), SAP/PSP (n = 10) (19, 24, 30, 33, 40, 67, 76, 77, 79, 80), PSD (n = 3) (28, 49, 72), progression/recurrence (n = 4) (12, 37, 60, 78), admission NIHSS (n = 11) (5, 12–14, 16, 46, 59, 64, 72, 73, 75), and other complications (n = 25) (1, 9, 11, 15, 27, 32, 33, 42, 43, 47, 49, 51, 53, 57–59, 62, 63, 67, 71–74, 78, 82).

3.3 Predictive value of SII for AIS poor prognosis (primary outcome)

3.3.1 Predictive value of continuous SII for AIS poor prognosis

A total of 32 studies (1, 6–8, 14, 16–18, 20, 21, 23, 33, 35–38, 41, 42, 48, 50, 51, 55, 66–71, 73, 79, 81, 82), which included 42 designs and involved 14,915 AIS patients, were included. Among them, 6,198 patients were in the poor prognosis groups, and 8,717 were in the favorable prognosis groups. A total of 16 studies (8, 14, 16, 17, 23, 36, 37, 42, 50, 55, 68–71, 73, 79) with 20 designs adopted the guideline-recommended 3-month modified Rankin Scale (mRS) 3–6 as the poor prognostic criterion (83). Ultimately, 26 studies came from China (1, 7, 8, 14, 16–18, 20, 21, 23, 33, 36–38, 41, 42, 48, 50, 51, 55, 68–71, 79, 81), and 6 from other countries and regions (6, 35, 66, 67, 73, 82). In the meantime, 12 studies mentioned IVT (16–18, 20, 21, 23, 36, 38, 41, 50, 51, 68), 6 mentioned EVT (8, 14, 48, 55, 71, 73), and 14 used pure medication therapy (1, 6, 7, 33, 35, 37, 42, 66, 67, 69, 70, 79, 81, 82). I2 = 89.9% > 50%, Q statistics p = 0.000, indicating a high level of heterogeneity among 42 designs. Meta-regression was conducted with effect size (ES) as the dependent variable and the 5 possible sources of heterogeneity (mRS rating, follow-up time, treatment modality, regional distribution, and mRS rating + follow-up time) as independent variables. The meta-regression results showed that for the 5 independent variables, all p-values were > 0.05 (0.444; 0.380; 0.275; 0.745; 0.643), indicating that the heterogeneity was not related to these 5 factors, and the source of heterogeneity needs to be further explored. Random-effects model showed the baseline SII value was significantly higher in poor prognosis groups (SMD = 248.13, 95% CI: 198.77 to 297.50, p = 0.000, Figure 2A), meaning that the SII value of the poor prognosis groups was 248.13 × 109/L higher than that of the favourable prognosis groups significantly. Figure 3A shows the funnel plot was asymmetric, Begg p = 0.319 > 0.05, Egger p = 0.004 < 0.05, indicating a slight publication bias in the 42 designs. After applying the trim-and-fill method, the significance of the overall effect size and the heterogeneity did not change, suggesting that publication bias did not distort the conclusions of this meta-analysis (Figure 3B).

Figure 2

Figure 3

A total of fourteen studies (6, 14, 16–18, 20, 21, 23, 45, 50, 52, 69, 79, 81), with 15 designs, evaluated the aORs of continuous SII in predicting AIS poor prognosis. High heterogeneity was found (I2 = 90.9%, Q-statistic, p = 0.000). Meta-regression indicated that neither follow-up time nor treatment modality was a source of heterogeneity (p = 0.578; 0.489). Figure 2B shows a trend: with an increase in continuous SII, the incidence of poor prognosis may be slightly higher (OR = 1.004, 95% CI: 1.002 to 1.005, p = 0.000). The funnel plot in Figure 3C shows a specific publication bias in the 15 designs (Begg p = 0.020, Egger p = 0.834). The trim-and-fill analysis showed that the number of imputed missing studies was negligible, and the adjusted effect size (OR = 1.003, 95% CI: 1.002 to 1.005, p = 0.000) was almost consistent with the unadjusted one (Figure 3D).

Additionally, 2 studies involved aORs of SII per 1 standard deviation (SD) to predict AIS poor prognosis. Chen GJ 2024 (14) reported aOR = 1.241 (95% CI: 1.051 to 1.465), and Huang SW 2024 (1) reported aOR = 1.191 (95% CI: 1.006 to 1.410), indicating that for every 1 SD increase in SII, the likelihood of a poor prognosis increases in AIS patients.

3.3.2 Predictive value of categorized SII for AIS poor prognosis

A total of 10 studies (12–14, 16, 44–46, 60, 65, 75), with 11 designs, provided data on the sample size of poor/favorable prognosis patients in both high and low SII groups; all criteria of poor prognosis were mRS 3–6. Among 21,719 patients, 5,761 were in high SII groups, and 15,958 were in low SII groups. High heterogeneity was noted (I2 = 92.9%, Q statistics p = 0.000), and meta-regression showed follow-up time, regional distribution, and treatment modality were not sources of heterogeneity (p = 0.590; 0.459; 0.593). Subgroup analysis by treatment modality in Figure 2C revealed less within-group heterogeneity. A random-effects model for all designs indicated RR = 1.95 (95% CI: 1.66 to 2.28, p = 0.000), meaning patients with High SII were 1.95 times more likely to have a poor prognosis significantly. The almost symmetrical funnel plot (Begg p = 0.876, Egger p = 0.134) suggests that there is no expected publication bias, as shown in Figure 3E.

A total of 16 studies (1, 8, 12, 14, 32, 35, 37, 38, 46, 51, 60, 62, 65, 70, 75, 80) with 19 designs reported aORs of categorized SII in predicting poor prognosis. Among them, CAO 2024 (8) with 2 designs was removed as its aOR = 1.000 (95% CI: 1.000 to 1.000) made log-conversion in STATA difficult. The remaining studies had substantial heterogeneity (I2 = 92.8%, Q-statistic p = 0.000). Meta-regression showed that four variables (follow-up time, regional distribution, treatment modality, and mRS rating+follow-up time) were not the source of heterogeneity (p = 0.866; 0.893; 0.710; 0.949 > 0.05). Figure 2D shows that the random-effects model pooled OR = 1.007 (95% CI: 0.998 to 1.015, p = 0.120), indicating a higher but non-significantly poor prognosis risk in the high SII groups compared to the low SII groups. Funnel plots for the 17 designs were symmetrical, and bias tests (Begg p = 0.760, Egger p = 0.833) suggested likely no publication bias in the designs (Figure 3F).

3.4 Predictive value of SII for AIS secondary outcomes (mortality, severity, HT/sICH, END, PSD, progression/recurrence, and other complications)

3.4.1 Continuous SII

  • Continuous SII values were listed in both the death, mild severity, HT/sICH, SAP/PSP, END, PSD, Progression/Recurrence groups, and the corresponding control groups, including 5 (5, 6, 16, 66, 67), 6 (21, 31, 42, 69, 70, 79), 8 (8, 22, 26, 33, 44, 51, 54, 69), 10 (19, 24, 30, 33, 40, 67, 76, 77, 79, 80), 7 (13, 16, 21, 25, 29, 38, 52), and 3 (28, 49, 72), 1 (27) studies. The baseline SII value was significantly higher in the death groups, SMD = [369.889 (95% CI: 274.957 to 464.822), p = 0.000, I2 = 0.0%, Q statistics p = 0.545, fixed, Figure 4A; Begg p = 0.707, Egger p = 0.150, Figure 5A]; mild severity groups SMD = [−366.98 (95% CI: −524.43 to −209.53), p = 0.000, I2 = 87.7%, Q statistics p = 0.000, random, Figure 4D; Begg p = 1.000, Egger p = 0.166, Figure 5D]; HT/sICH groups [Excluding NIU 2024 (26), one design of Gao 2023 (54) and one design of Cao 2024 (8), SMD = 444.540 (95% CI: 377.566 to 511.514), p = 0.000, I2 = 0.0%, Q statistics p = 0.502, fixed, Figure 4F; Begg p = 0.371, Egger p = 0.274, Figure 5E]; SAP/PSP (Excluding Tianlu 2024 (24), SMD = 634.39 (95% CI: 556.60 to 712.18), p = 0.000, I2 = 32.8%, Q statistics p = 0.156, fixed, Figure 4J; Begg p = 0.34, Egger p = 0.311, Figure 5G]; END (Excluding Wang ZT 2023 (52), SMD = 255.72 (95% CI: 186.61 to 324.83), p = 0.000, I2 = 51.1%, Q statistics p = 0.069, fixed, Figure 4L; Begg p = 0.707, Egger p = 0.536, Figure 5H]; PSD SMD = [73.21(95% CI: 59.41 to 87.01), p = 0.000, I2 = 7.2%, Q statistics p = 0.341, fixed, Figure 4P]; Progression/Recurrence groups [Progression/Recurrence groups SII = 557.00 (345.00, 832.88); Non-Progression/Recurrence groups SII = 420.63 (310.58, 546.48), p = 0.011].

  • Adjusted ORs of continuous SII in predicting AIS mortality, mild severity, HT/sICH, SAP/PSP, and END were reported in 2 (6, 16), 5 (7, 21, 42, 69, 79), 4 (22, 26, 54, 69), 4 (19, 24, 77, 79), and 5 (16, 21, 25, 29, 52) studies. Except for severity, the incidence of adverse outcomes could be higher with an increase significantly in continuous SII, Mortality pooled OR = [2.592 (95% CI: 1.046 to 6.421), p = 0.040]; severity pooled OR = [1.001(95% CI: 0.998 to 1.003), p = 0.718, I2 = 88.0%, Q statistics p = 0.000, random, Figure 4E]; HT/sICH pooled OR = [1.001 (95% CI: 0.999 to 1.002), p = 0.000, I2 = 90.2%, Q statistics p = 0.000, random, Figure 4G]; SAP/PSP pooled OR = [1.46 (95% CI: 1.05 to 2.03), p = 0.000, I2 = 74.7%, Q statistics p = 0.008, random, Figure 4K]; END pooled OR = [1.003 (95% CI: 0.999 to 1.008), p = 0.123, I2 = 93.6%, Q statistics p = 0.000, random, Figure 4M].

  • Huang SW 2024 (1) mentioned SII per 1 SD to predict mortality, aHR = 1.195 (95% CI: 1.072 to 1.332), p = 0.001. Yang 2022 (64) mentioned SII per 10 SD to predict HT/sICH, aOR = 1.005 (95% CI: 1.002 to 1.008), p = 0.002.

Figure 4

Figure 5

3.4.2 Categorized SII

  • The sample size of death, HT/sICH, END, progression/recurrence patients in both High SII vs. Low SII groups was listed, including 6 (5, 16, 37, 39, 60, 61), 3 (13, 16, 73), 3 (12, 13, 16), 3 (12, 37, 60) studies. The sample size of adverse outcomes patients of high SII groups were significantly higher than low SII groups, death pooled RR = [2.26 (95% CI: 2.01 to 2.55, p = 0.000, I2 = 0%, Q statistics p = 0.649, fixed, Figure 4B; Begg p = 0.076, Egger p = 0.036, Figure 5B]; HT/sICH pooled RR = [1.41 (95% CI: 1.06 to 1.88), p = 0.019, I2 = 0.0%, Q statistics p = 0.808, fixed, Figure 4H; Begg p = 0.734, Egger p = 0.601, Figure 5F]; END pooled RR = [2.07 (95% CI: 1.66 to 2.59), p = 0.000, I2 = 0.0%, Q statistics p = 0.402, fixed, Figure 4N]; Progression/Recurrence pooled RR = [1.39 (95% CI: 1.25 to 1.54), p = 0.000, I2 = 0.0%, Q statistics p = 0.490, fixed, Figure 4R].

  • Adjusted ORs of categorized SII in predicting AIS mortality, severity, HT/sICH, SAP/PSP, END, PSD, Progression/Recurrence were reported in 2 (5, 80), 1 (35), 4 (8, 44, 51, 64), 2 (76, 80), 3 (12, 13, 38), 3 (28, 49, 72), and 1 (27) studies. Except for END, the risk of adverse outcomes in high SII groups was significantly higher than in low SII groups, mortality pooled OR = [Ceng 2020 (80) ① 90d: 7.332 (95% CI: 1.608 to 33.419, p = 0.01; ② 1y: 5.15 (95% CI: 1.918 to 13.841), p = 0.001; Yang Y 2024 (5) 4.671(95% CI: 1.379 to 15.826), p = 0.013]; severity pooled OR = [7.462 (95% CI: 1.666 to 33.333), p = 0.009]; HT/sICH pooled OR = [Excluding CAO 2024 (8), 3.04 (95% CI: 0.84 to 8.99), p = 0.000, I2 = 93.4%, Q statistics p = 0.000, random, Figure 4I]; SAP/PSP pooled OR = [Ceng 2020 (80) 6.803 (95% CI: 3.251 to 14.236), p = 0.000; Wei 2021 (76) 0.999 (95% CI: 0.998 to 1.000), p = 0.060], END pooled OR = [1.74(95% CI: 0.82 to 3.68), p = 0.150, I2 = 85.1%, Q statistics p = 0.001, random, Figure 4O]; PSD pooled OR = [2.34 (95% CI: 1.81 to 3.07), p = 0.000, I2 = 0.0%, Q statistics p = 0.891, fixed, Figure 4Q]; Progression/Recurrence pooled OR = [1.003(95% CI: 1.000485 to 1.005), p = 0.017].

  • Adjusted HRs of categorized SII in predicting AIS mortality were reported in 4 studies (1, 39, 60, 61), pooled HR = 2.45 (95% CI: 2.00 to 3.01, p = 0.000, I2 = 0.0%, Q statistics p = 0.954, fixed, Figure 4C; Begg p = 0.707, Egger p = 0.589, Figure 5C).

  • A total of 11 studies (5, 12–14, 16, 46, 59, 64, 72, 73, 75) provided data on the value of Admission NIHSS in both high SII and low SII groups, NIHSS in high SII groups were significantly higher, pooled SMD = 2.365 (95% CI: 1.178 to 3.552, p = 0.003, I2 = 92.94%, Q statistics p = 0.000, random, Figure 4S; Begg p = 0.350, Egger p = 0.242, Figure 5I).

3.5 Other complications

A total of 17 studies (1, 9, 11, 15, 32, 42, 43, 47, 51–53, 57–59, 62, 71, 78) listed continuous/categorized SII aORs/aHRs in other complication groups studied, as shown in Table 3. A total of 13 studies (9–11, 15, 33, 43, 47, 51, 57, 62, 63, 70, 78) listed continuous SII values in other complications groups were studied, as shown in Table 4.

Table 3

No.StudyIndicators (continuous SII/HIGH SII)OutcomesaOR/aHR(95% CI)
1Huang SW 2024 (1) (1)High SII vs. Low SIIFunctional Dependency2.894 (1.093, 7.659)
2Huang SW 2024 (1) (2)High SII vs. Low SIIStroke-associated Infection2.655 (1.490, 4.731)
3Cheng 2024 (9)High SII vs. Low SIIPost-stroke Cognitive Impairment10.369 (4.460, 24.107)
4Liu HT 2023 (51)High SII vs. Low SIIAtrial fibrillation Stroke1.116 (1.024, 1.438)
5Zhang 2022 (59) (1)High SII vs. Low SIIVulnerable Plaques Presence2.242 (1.378, 4.024)
6Zhang 2022 (59) (2)High SII vs. Low SIIRuptured Fibrous Caps3.462 (2.031, 6.074)
7Li 2022 (58)High SII vs. Low SIIDecompressive craniectomy3.579 (1.360, 9.422)
8Zhang LL 2024 (15) (1)Continuous SIIPresence of Vulnerability Plaques5.013 (2.671, 8.472)
9Zhang LL 2024 (15) (2)Continuous SIIPresence of Ulcerative Plaques5.017 (3.010, 8.023)
10Hao 2024 (11)Continuous SIIStroke-heart Syndrome5.089 (1.981, 15.74)
11Dong 2023 (53)Continuous SIIFirst Pass Effect0.895 (0.801, 0.971)
12Wang ZT 2023 (52)Continuous SIIEarly Neurological Improvement0.998 (0.997, 0.999)
13Shao 2023 (47)Continuous SIIBasal Ganglia-Enlarged Perivascular Spaces Severity1.004 (1.001, 1.008)
14Lin 2023 (42)Continuous SIIGood Prognosis (90d/mRS 0–2)1.000 (0.999, 1.001)
15Xiao 2023 (43)Continuous SIIPatentForamenOvale0.99 (0.98, 1.01)
16Su 2023 (57)Continuous SIIVascular Dementia1.006 (1.002, 1.010)
17Ji 2022 (62)Continuous SIIMalignant Cerebral Edema1.209 (1.034, 1.413)
18Wenli Z 2022 (71)Continuous SIIIneffective Recanalization3.731 (1.641, 10.602)
19Huang SW 2024 (1) (3)SII (per 1 SD)Functional Dependency1.224 (1.040, 1.441)
20Huang SW 2024 (1) (4)SII (per 1 SD)Stroke-associated Infection1.349 (1.139, 1.598)
21Zhang MK 2024 (32)SII (per 200 Units)Failure of Delayed Neurological Improvement1.065 (1.001, 1.132)
22Wei 2021 (76)continuous SIIFavorable Prognosis (Non-cerebrovascular Diseases Recurrence/2y)1.284 (1.105, 1.493)

Continuous/categorized SII aORs/aHRs in other complications.

Only the effect size of the Wei2021 literature is aHR, and the rest are aORs. As shown in columns 3 and 4 of Table 3, four aOR/aHR (95% CI) data are mentioned in the literature by Huang SW (1). (1) represents the aOR/aHR (95% CI) with “High SII vs. Low SII” as the Indicator and “Functional Dependency” as the Outcome. (2) represents the aOR/aHR (95% CI) with “High SII vs. Low SII” as the Indicator and “Stroke-associated Infection” as the Outcome. (3) represents the aOR/aHR (95% CI) with “SII (per 1 SD)” as the Indicator and “Functional Dependency” as the Outcome. (4) represents the aOR/aHR (95% CI) with “SII (per 1 SD)” as the Indicator and “Stroke-associated Infection” as the Outcome.

Table 4

No.ComplicationsStudyGroup 1Group 2Group 3
nSII [M (Q1, Q3]/ ± snSII [M (Q1, Q3]/ ± snSII [M(Q1, Q3]/ ± s
1&2AF-S/Non-AF-SLiu HT 2023 (51)144759 (516, 1,549)370480 (379, 1,081)
Lin 2022 (63)173802.29 (473.08, 1390.30)353562.50 (379.73, 1040.33)
3Plaque: Vulnerable/StableZhang LL 2024 (15)144684.6 (553.2, 819.7)58407.1 (293.4, 601.9)
4Cerebral Herniation /Non-Cerebral HerniationZheng 2024 (33)72184.13 (1849.47, 4724.67)751336.41 (833.34, 2242.55)
5SHS/Non-SHSHao 2024 (11)241,100 (700, 1,500)97500 (400, 800)
6PFO /Non-PFOXiao 2023 (43)50613.08 ± 202.0350411.64 ± 157.81
7Vascular Dementia /Non-Vascular DementiaSu 2023 (57)56579.35 ± 122.32216503.46 ± 122.41
8MCE/Non-MCEJi 2022 (62)1322,460 ± 1,8605431,570 ± 1,300
9PSCI/Non-PSCICheng 2024 (9)193587.75 (337.42, 988.95)139345.66 (248.44, 572.89)
10BG-EPVS Severity: Mild /Moderate–SevereShao 2023 (47)57466.16 (336.69, 603.12)115652.63 (463.75, 903.16)
11CSO-EPVS Severity: Mild/Moderate–SevereShao 2023 (47)100579.45 (418.36, 775.58)72581.75 (391.48, 751.26)
11Aetiology: Small Vessels/Large Vessels
/Other Etiologies
Misirlioglu 2024 (10)794871.04 (650.62, 1102.69)396898.17 (565.27, 1165.79)160243.34 (142.97, 367.66)
12Infarct Focus Volume: Small/Medium/LargeLaiyun Z 2022 (70)77565.13 (369.81, 741.89)75696.25 (441.22, 1072.71)301187.28 (730.05, 2251.80)
13Recurrent Cerebrovascular Disease (Ischemic Stroke/Hemorrhagic Stroke/Transient Ischemic Attack)Wei 2021 (76)241190.65 (439.77, 2290.33)92426.35 (311.45, 769.23)

Continuous SII values in other complication groups and the corresponding control groups.

AF-S, Atrial Fibrillation Stroke; SHS, Stroke-heart Syndrome; PFO, patent foramen ovale; MCE, Malignant Cerebral Edema; PSCI, Post-stroke Cognitive Impairment; BG-EPVS, Basal Ganglia-Enlarged Perivascular Spaces; CSO-EPVS, Central Semi-ovale Region Enlarged Perivascular Spaces.

3.6 SII cut-off values and AUC of ROC curves

A total of 51 studies (5, 6, 8, 9, 11–13, 15–21, 24–29, 32, 33, 35–39, 43, 44, 46, 47, 49–52, 54, 56, 58, 62, 65, 66, 68–70, 72, 73, 76, 77, 79, 80, 82) listed cut-off values, AUC (95% CI), sensitivity, and specificity of ROC curves, as shown in Table 5.

Table 5

No.StudyOutcomesAUC (95% CI)SII Cut-offSensitivity (%)Specificity (%)
1. Poor prognosis
1Zheng 2024 (33)Poor Prognosis (Discharge)0.721 (0.561, 0.881)1,19292.344.9
2Mengting 2024 (20)Poor Prognosis (Discharge)0.821 (0.746, 0.896)753.6887.274.8
3Chu 2020 (82)Poor Prognosis (Discharge)NR651NRNR
4(1)Ma 2022(1) (68)Poor Prognosis (3mos)0.714 (0.514, 0.914)97475.085.7
4(2)Ma 2022(2) (68)Poor Prognosis (3mos)0.688 (0.504, 0.871)69510062.5
5(1)Ceng 2020(1) (80)Poor Prognosis (3mos)0.612 (NR, NR)5556849.9
6Zhao 2024 (17)Poor Prognosis (3mos)0.779 (0.715, 0.843)NRNRNR
7Cao 2024 (8)Poor Prognosis (3mos)0.633 (0.583, 0.683)1617.4260.664.1
8Liu YY 2023 (56)Poor Prognosis (3mos)0.848 (0.634, 1.000)1103.22NRNR
9Wang ZT 2023 (52)Poor Prognosis (3mos)0.702 (0.642, 0.762)848.762.572.3
10Liu HT 2023 (51)Poor Prognosis (3mos)0.701 (0.611, 0.790)64485.258.9
11Liu 2022 (69)Poor Prognosis (3mos)0.880 (0.836, 0.924)449.7683.767.3
12Ma 2023 (37)Poor Prognosis (3mos)0.715 (0.546, 0.826)392.90387.946.5
13Wang YL 2023 (50)Poor Prognosis (3mos)0.880 (0.804, 0.957)1012.0690.879.2
14Zhouquan 2024 (23)Poor Prognosis (3mos)0.715 (0.6550, 0.776)868.5555.784.0
15Yi 2021 (73)Poor Prognosis (3mos)0.679 (0.643, 0.745)853NRNR
16Zhou 2023 (46)Poor Prognosis (3mos)0.657 (0.572, 0.742)802.870.958.2
17Zhou 2022 (65)Poor Prognosis (3mos)0.657 (0.572, 0.742)802.870.958.2
18Laiyun Z 2022 (70)Poor Prognosis (3mos)0.789 (0.712, 0.866)781.474.574.0
19Zhao 2023 (38)Poor Prognosis (3mos)0.787 (0.731, 0.843)621.6871.775.4
20Wang S 2023 (36)Poor Prognosis (3mos)0.598 (0.552, 0.645)582.7556553
21Zhong 2021 (79)Poor Prognosis (3mos)0.702 (0.635, 0.769)58073.169.7
22Wei 2024 (16)Poor Prognosis (3mos)0.717 (0.646, 0.788)504.9970.969.6
23Ma L 2024 (21)Poor Prognosis (3mos after Discharge)0.826 (0.755, 0.898)781.1696.252.5
24Arslan 2024 (6)Poor Prognosis (28d)0.645 (0.568, 0.722)1,14650.578.8
25Fernández-Garza 2023 (35)Poor Prognosis (30d)0.634 (0.528, 0.741)621.16173.651.0
26Guoqing 2024 (18)Poor Prognosis (6mos)0.841 (0.759, 0.924)880.5363.4195.06
5(2)Zeng 2020(2) (80)Poor Prognosis (1y)0.662 (NR, NR)856.4643.975.5
2. Mortality
1(1)Chen 2022(1) (66)Mortality (Discharge)NR1,051NRNR
1(2)Chen 2022(2) (66)Mortality (Discharge)0.707 (NR, NR)2,12050.091.4
2Hu 2023 (39)Mortality (Discharge)0.65 (0.62, 0.68)NRNRNR
3Wei 2024 (16)Mortality (3mos)0.703 (0.582, 0.825)524.4778.959.9
4(1)Ceng 2020(1) (80)Mortality (3mos)0.765 (NR, NR)915.0370.476.6
4(2)Ceng 2020(2) (80)Mortality (1y)0.725 (NR, NR)887.2560.875.4
5Yang Y 2024 (5)Mortality (120d)0.830 (0.710, 0.949)666.3172.792.0
3. HT/sICH
1Niu 2024 (26)HT0.604 (0.506, 0.701)NR27.6043.20
2Zheng 2024 (33)HT0.659 (0.541, 0.776)1721.791458.371.7
3Liu 2022 (69)HT0.857 (0.808, 0.907)728.0379.282.6
4Dan-dan 2023 (44)HT0.784 (0.715, 0.853)72173.170.5
5Liu HT 2023 (51)HT0.82 (0.747, 0.889)706.383.753.2
6(1)Gao 2023(1) (54)HT0.610 (0.535, 0.686)488.486947
6(2)Gao 2023(2) (54)sICH0.739 (0.636, 0.842)846.567077
7Cao 2024 (8)sICH0.707 (0.639, 0.776)1817.837065
8Wei 2024 (16)sICH0.517 (0.279, 0.754)NRNRNR
4. END
1Huang H 2024 (29)END0.798 (0.709, 0.888)854.7680.778.2
2Jiaxiang 2024 (25)END0.658 (0.558, 0.758)768.20663.469.4
3Wang N 2024 (13)END0.61 (0.54, 0.69)591.6358.164.6
4Lee 2024 (12)END0.702 (0.620, 0.784)588.9NRNR
5Wei 2024 (16)END0.708 (0.631, 0.785)504.9970.762.6
6Zhao 2023 (38)END0.601 (0.473, 0.730)NRNRNR
7Wang ZT 2023 (52)END0.845 (0.772, 0.918)1,42971.993.5
5. SAP
1Zhou 2024 (19)SAP0.807 (0.751, 0.855)846.5574.5879.17
2Tianlu 2024 (24)SAP0.723 (0.643, 0.802)1179.5662.5079.44
3Zhong 2021 (79)SAP0.742 (0.673, 0.812)70073.966.9
4Cheng 2021 (77)SAP0.843 (0.798, 0.882)885.0579.585.0
5Wei L 2021 (76)SAP0.801 (0.742, 0.852)NRNRNR
6Ceng 2020 (2) (80)SAP0.762 (0.736, 0.787)901.0668.6778.00
6. PSD
1Dong 2024 (28)PSD0.765 (0.709, 0.820)478.1875.767.6
2Song 2023 (49)PSD0.827 (0.736, 0.918)NRNRNR
3Hu 2021 (72)PSD0.579 (0.517, 0.641)565.7NRNR
7. Moderate to Severe Disability(mRS3-5)
1Ceng 2020(1) (80)mRS3-5(90d)0.557 (NR, NR)1148.426.887
2Ceng 2020(2) (80)mRS3-5(1y)0.575 (NR, NR)1179.432588.4
8. AIS Severity
1Fernández-Garza 2023 (35)AIS Severity0.693 (0.599, 0.786)623.72373.567.3
9. Others
1Shao 2023 (47)Moderate—Severe BG-EPVS0.717 (0.638, 0.796)686.3547.891.2
2Ji 2022 (62)Malignant Cerebral Edema0.69 (0.66, 0.73)2,1445580
3Zhang MK 2024 (32)Failure of Delayed Neurological Improvement0.861 (0.816, 0.907)696.165NRNR
4Wang ZT 2023 (52)Early neurological improvement0.58 (0.511, 0.648)639.955.857.3
5Li 2022 (58)Decompressive Craniectomy0.649 (NR, NR)2505.75575.8
6Zheng 2024 (33)Cerebral Herniation0.794 (0.636, 0.953)179885.768
7Xiao 2023 (43)Patent Foramen Ovale0.777 (0.674, 0.861)476.47070
8Zhang LL 2024 (15)Ulcerative Plaque0.895 (NR, NR)537.493.389.2
9Hao 2024 (11)Stroke-heart Syndrome0.767 (0.6443, 0.8892)85766.6783.51
10Zhang J 2024 (27)Progressive Ischemic Stroke0.656 (0.535, 0.778)737.62440.092.9
11Cheng 2024 (9)Post-stroke Cognitive Impairment0.659 (0.600, 0.717)676.8344.682.0

SII cut-off values and AUC of ROC curves.

SII, Systemic Immune-inflammation Index; AUC, Area Under the Curve; NR, Not Reported; AIS, Acute Ischemic Stroke; HT, Hemorrhagic Transformation; sICH, Symptomatic Intracerebral Hemorrhage; END, Early Neurological Deterioration; SAP, Stroke-Associated Pneumonia; PSD, Post-stroke Depression; mRS, Modified Rankin Scale; BG-EPVS, Basal Ganglia Region Enlarged Perivascular Spaces; h, hours; d, day; y, year; mos, month(s); w, week.

4 Discussion

In this study, we conducted a comprehensive systematic review and meta-analysis to explore the link between SII and AIS. A total of 40,682 individuals from 78 studies (1, 5–33, 35–82) were involved in the meta-analysis, while 79 studies (1, 5–82) were included in the systematic review.

The principal findings of this study are as follows: (1) The continuous SII values in poor prognosis, death, moderate–severe severity, HT/sICH, SAP/PSP, END, PSD, Progression/Recurrence groups were significantly higher than those in favorable prognosis, survival, mild severity, non-HT/sICH, non-SAP/PSP, non-END, non-PSD, no-progression/recurrence groups. (2) The incidence of poor prognosis, mortality, moderate–severe severity, HT/sICH, SAP/PSP, and END could be higher with an increase in continuous SII, significantly higher except for the incidence related to severity. (3) The sample size of poor prognosis, death, HT/sICH, END, progression/recurrence patients of high SII groups was significantly higher than that of low SII groups. (4) The risk of mortality, severity, HT/sICH, SAP/PSP, END, PSD, Progression/Recurrence in high SII groups was higher than in low SII groups, significantly higher except for the risks of poor prognosis and END. (5) The Admission NIHSS in AIS patients with high SII groups was significantly higher than in low SII groups.

From a pathophysiological perspective, the body’s immune-inflammatory response is activated following the onset of AIS. SII, a biomarker of systemic immune inflammation, has an elevated SII level that often implies an exacerbated inflammatory response, triggering a cascade of adverse events (84). Inflammatory cells infiltrate the brain tissue, releasing diverse inflammatory factors that disrupt the blood–brain barrier, exacerbate brain edema, and intensify neurological damage (83). Additionally, high SII levels are associated with platelet activation and aggregation, promoting thrombosis, aggravating cerebral ischemia, and influencing AIS prognosis, mortality, severity, END, progression, and recurrence (2–4). Patients in high SII groups are at a significantly higher risk of developing HT (64), likely due to high-SII-induced vascular endothelial damage, increased vascular permeability, and blood component exudation. Patients in High SII groups are also more susceptible to PSD (72), as the inflammatory response interferes with neurotransmitter synthesis, metabolism, and release, leading to an imbalance in neurotransmitters like 5-hydroxytryptamine and dopamine. Moreover, high SII levels, reflecting a perturbed immune-inflammatory state, increase the risk of SAP by reducing the body’s resistance and making it more vulnerable to pulmonary infections (76, 80).

Our study boasts noteworthy strengths. First, given that the concept of the SII was first proposed by Chinese researchers (84), we specifically retrieved several Chinese databases as sources. This effort significantly broadened the scope of our system review. The search strategy we implemented was more sophisticated. For the research on AIS, our search keywords included 6 subject terms and 122 free terms, effectively reducing the probability of missed or inaccurate retrievals. By incorporating studies from more recent years, we broadened the scope further, guaranteeing the inclusion of the latest research findings. Moreover, our analysis encompassed additional outcomes, such as SAP/PSP, END, and PSD, which were integrated into the meta-analysis for the first time, facilitating a more multi-dimensional assessment.

There are several limitations to our study. First, language is a constraint, as we only included literature in Chinese and English, while relevant studies in other languages may contain valuable information, affecting the generalizability and comprehensiveness of the findings. Second, due to the variability of cut-offs of SII used in different studies, we could not determine a consensus on the best cut-off value based on our analysis, which may limit clinical guidance. Third, although we used various methods to assess and deal with heterogeneity, some analysis results still have high heterogeneity, which may affect the accuracy and reliability of pooled effect values, reducing the persuasiveness of the findings. Sources of heterogeneity may include differences in study participants (age, sex, nationality, etc.), differences in study design (prospective cohort studies, retrospective cohort studies, and case–control studies), differences in interventions (different treatments, drug use, etc.), differences in SII grouping criteria (time of blood sampling and instruments), and differences in outcome measures (definitions and evaluation tools).

This result suggests that SII levels may represent an important diagnostic and prognostic tool for AIS complications in clinical practice. Monitoring and treatment should be strengthened for patients with higher SII levels, and more active measures should be taken to control the inflammatory response and clotting state. However, the role of SII in predicting poor prognosis, mortality, severity, and a variety of other complications is not fully understood.

In summary, high SII levels are linked to poor AIS prognosis and multiple complications, and SII may function as a cost-effective prognostic biomarker. Evaluating the role of SII in therapeutic decision-making is necessary, as our preliminary results suggest its potential to reflect clinical conditions and assist decision-makers. However, more research, especially large-sample and multi-center studies, is needed to better understand the utility of SII through dynamic monitoring.

Statements

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Author contributions

YJ: Data curation, Methodology, Writing – original draft, Investigation. YC: Formal analysis, Writing – original draft, Data curation. XH: Investigation, Data curation, Supervision, Writing – original draft. JL: Writing – original draft, Formal analysis, Data curation. XQ: Investigation, Writing – original draft. XW: Conceptualization, Supervision, Funding acquisition, Writing – review & editing. XM: Writing – review & editing, Conceptualization.

Funding

The author(s) declare that financial support was received for the research and/or publication of this article. XW was supported by the Natural Science Foundation of Shandong Province (Grant Number: ZR2020MH156) and the National Famous Old Chinese Medicine Experts Inheritance Studio Construction Project (Grant Number: National Chinese Medicine Human Education Letter [2022] No. 75).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The authors declare that no Gen AI was used in the creation of this manuscript.

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Supplementary material

The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2025.1594258/full#supplementary-material

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Summary

Keywords

acute ischemic stroke, systemic immune-inflammatory index, poor prognosis, prognostic biomarker, meta-analysis

Citation

Jiang Y, Cui Y, Hu X, Lian J, Qin X, Wang X and Ma X (2025) Prognostic assessment of acute ischemic stroke by systemic immune-inflammatory index: a comprehensive meta-analysis of multidimensional outcomes. Front. Neurol. 16:1594258. doi: 10.3389/fneur.2025.1594258

Received

08 April 2025

Accepted

29 August 2025

Published

20 October 2025

Volume

16 - 2025

Edited by

Pradeep Kumar, All India Institute of Medical Sciences, Delhi, India

Reviewed by

Murat Mert Atmaca, University of Health Sciences, Türkiye

Yang Liu, Fudan University, China

Updates

Copyright

*Correspondence: Xingchen Wang, Xuran Ma,

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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