Is Bilirubin Associated with the Severity of Ischemic Stroke? A Dose Response Meta-Analysis

Song, Yumeng; Zhang, Xiaohong; Li, Chaoxiu; Xu, Shengwen; Zhou, Baosen; Wu, Xiaohua

doi:10.3390/jcm11123262

Cited by 5 publications

(5 citation statements)

References 26 publications

(47 reference statements)

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“…In addition to diagnostic value, we investigated the prognostic value of bilirubin subtypes in ischemic stroke. Our results determined that the direct and total bilirubin levels were positively correlated with the ischemic stroke severity, consistent with the systematic review of Ghojazadeh et al's (2020) study and Song et al's (2022) study. Song et al also established that bilirubin is linear with ischemic stroke severity and trial sequential analysis found that the sample size for this study is sufficient.…”

Section: Discussionsupporting

confidence: 91%

“…However, there is strong evidence that bilirubin has anti-inflammatory, antioxidant, and neuroprotective properties ( Thakkar et al, 2019 ). Previous meta-analyses suggested that a higher total level of bilirubin was related to a lower stroke prevalence and had a significant association with stroke severity, indicating that bilirubin might be involved in the progression of stroke ( Zhong et al, 2019 ; Song et al, 2022 ). Recently, however, there has been no definitive consensus on the relationship of bilirubin levels with stroke risk ( Page et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Association between bilirubin levels with incidence and prognosis of stroke: A meta-analysis

et al. 2023

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ObjectiveBilirubin has anti-inflammatory, antioxidant, and neuroprotective properties, but the association between bilirubin and stroke remains contentious. A meta-analysis of extensive observational studies on the relationship was conducted.MethodsStudies published before August 2022 were searched in PubMed, EMBASE, and Cochrane Library. Cohort, cross-sectional and case-control studies that examined the association between circulating bilirubin and stroke were included. The primary outcome included the incidence of stroke and bilirubin quantitative expression level between stroke and control, and the secondary outcome was stroke severity. All pooled outcome measures were determined using random-effects models. The meta-analysis, subgroup analysis, and sensitivity analysis were performed using Stata 17.ResultsA total of 17 studies were included. Patients with stroke had a lower total bilirubin level (mean difference = −1.33 μmol/L, 95% CI: −2.12 to −0.53, P < 0.001). Compared with the lowest bilirubin level, total odds ratio (OR) of the highest bilirubin for the occurrence of stroke was 0.71 (95% CI: 0.61–0.82) and ischemic stroke was 0.72 (95% CI: 0.57–0.91), especially in cohort studies with accepted heterogeneity (I2 = 0). Serum total and direct bilirubin levels were significantly and positively associated with stroke severity. A stratified analysis based on gender showed that the total bilirubin level in males correlated with ischemic stroke or stroke, which was not noted in females.ConclusionWhile our findings suggest associations between bilirubin levels and stroke risk, existing evidence is insufficient to establish a definitive association. Better-designed prospective cohort studies should further clarify pertinent questions (PROSPERO registration number: CRD42022374893).

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Association between bilirubin levels with incidence and prognosis of stroke: A meta-analysis

et al. 2023

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“…Of note, the prognostic values of bilirubin in stroke are controversial, since bilirubin exhibits both neuroprotective and neurotoxic effects. At least two studies validated that TBIL and DBIL levels were significantly and positively associated with stroke severity [71,73]. Moreover, Ouyang et al [74] demonstrated that elevated levels of serum TBIL, DBIL and IBIL were significantly associated with poor functional outcomes in patients with AIS or TIA at 3-month and 1-year follow-ups.…”

Section: Discussionmentioning

confidence: 97%

A Nomogram for Predicting the Recurrence of Acute Non-Cardioembolic Ischemic Stroke: A Retrospective Hospital-Based Cohort Analysis

Shao

Zhang

et al. 2023

Brain Sciences

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Non-cardioembolic ischemic stroke (IS) is the predominant subtype of IS. This study aimed to construct a nomogram for recurrence risks in patients with non-cardioembolic IS in order to maximize clinical benefits. From April 2015 to December 2019, data from consecutive patients who were diagnosed with non-cardioembolic IS were collected from Lanzhou University Second Hospital. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection. Multivariable Cox regression analyses were used to identify the independent risk factors. A nomogram model was constructed using the “rms” package in R software via multifactor Cox regression. The accuracy of the model was evaluated using the receiver operating characteristic (ROC), calibration curve, and decision curve analyses (DCA). A total of 729 non-cardioembolic IS patients were enrolled, including 498 (68.3%) male patients and 231 (31.7%) female patients. Among them, there were 137 patients (18.8%) with recurrence. The patients were randomly divided into training and testing sets. The Kaplan–Meier survival analysis of the training and testing sets consistently revealed that the recurrence rates in the high-risk group were significantly higher than those in the low-risk group (p < 0.01). Moreover, the receiver operating characteristic curve analysis of the risk score demonstrated that the area under the curve was 0.778 and 0.760 in the training and testing sets, respectively. The nomogram comprised independent risk factors, including age, diabetes, platelet–lymphocyte ratio, leukoencephalopathy, neutrophil, monocytes, total protein, platelet, albumin, indirect bilirubin, and high-density lipoprotein. The C-index of the nomogram was 0.752 (95% CI: 0.705~0.799) in the training set and 0.749 (95% CI: 0.663~0.835) in the testing set. The nomogram model can be used as an effective tool for carrying out individualized recurrence predictions for non-cardioembolic IS.

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Section: Introductionmentioning

confidence: 99%

“…Stroke is considered the second leading cause of death worldwide and remains a significant cause of disability in both developed and developing countries (1). Ischemic stroke accounts for almost 70% of all stroke cases (1). There is a rich literature available substantiating that prolonged sleep onset latency (PSOL) and age can determine stroke severity (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

The effect of the interaction of sleep onset latency and age on ischemic stroke severity via inflammatory chemokines

Zhou,

Han,

et al. 2024

Front. Neurol.

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ObjectiveProlonged sleep onset latency (PSOL) and age have been linked to ischemic stroke (IS) severity and the production of chemokines and inflammation, both of which contribute to IS development. This study aimed to explore the relationship between chemokines, inflammation, and the interplay between sleep onset latency (SOL) and age in influencing stroke severity.MethodsA cohort of 281 participants with mild to moderate IS was enrolled. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and SOL was recorded. Serum levels of macrophage inflammatory protein-1alpha (MIP-1α), macrophage inflammatory protein-1beta (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured.ResultsNIHSS scores of middle-aged participants with PSOL were significantly higher than those with normal sleep onset latency (NSOL) (p = 0.046). This difference was also observed when compared to both the elderly with NSOL (p = 0.022), and PSOL (p < 0.001). Among middle-aged adults with PSOL, MIP-1β exhibited a protective effect on NIHSS scores (β = −0.01, t = −2.11, p = 0.039, R2 = 0.13). MIP-1α demonstrated a protective effect on NIHSS scores in the elderly with NSOL (β = −0.03, t = −2.27, p = 0.027, R2 = 0.12).ConclusionThis study reveals a hitherto undocumented association between PSOL and IS severity, along with the potential protective effects of MIP-1β in mitigating stroke severity, especially among middle-aged patients.

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Is Bilirubin Associated with the Severity of Ischemic Stroke? A Dose Response Meta-Analysis

Cited by 5 publications

References 26 publications

Association between bilirubin levels with incidence and prognosis of stroke: A meta-analysis

Association between bilirubin levels with incidence and prognosis of stroke: A meta-analysis

A Nomogram for Predicting the Recurrence of Acute Non-Cardioembolic Ischemic Stroke: A Retrospective Hospital-Based Cohort Analysis

The effect of the interaction of sleep onset latency and age on ischemic stroke severity via inflammatory chemokines

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