Prognostic Value of Inflammatory and Cardiovascular Biomarkers for Prediction of 90-Day All-Cause Mortality after Acute Ischemic Stroke—Results from the Linz Stroke Unit Study

Dieplinger, Benjamin; Bocksrucker, Christoph; Egger, Margot; Eggers, Christian; Haltmayer, Meinhard; Mueller, Thomas

doi:10.1373/clinchem.2016.269969

Cited by 52 publications

(49 citation statements)

References 25 publications

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“…In line with previous reports suggesting a multimarker approach to improve outcome prediction in AIS patients [27], our data indicate that calprotectin either alone or even better when combined with CRP and NLR could improve the overall prediction of 3-month mortality in AIS, suggesting that an elevated in ammatory state may contribute to the mortality in AIS patients. Though, the predictive capacity of this multimarker approach in our cohort and the robust results on K-fold internal cross-validation, it will need further external validation in other cohorts of AIS patients.…”

Section: Discussionsupporting

confidence: 91%

Calprotectin predicts mortality after ischemic stroke and is present in the thrombus

Marta-Enguita¹,

Navarro-Oviedo²,

Rubio-Baines³

et al. 2020

Preprint

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Background- Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi.Methods- Among the 748 patients treated at a comprehensive stroke centre between 2015-2017, 413 patients with confirmed acute ischemic injury were evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3-months (defined as modified Rankin Scale<2), and intracranial haemorrhage (ICH) after stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n=44). Results- Higher calprotectin levels were associated with 3-month mortality and ICH, while lower calprotectin levels were documented in patients with 3-month FI. After adjusting for potential confounders, plasma calprotectin levels remained associated with 3-month mortality [OR (95%CI); 3.06, (1.67-5.61)]. Patients with calprotectin≥2.26 µg/mL were 4-times more likely to die [OR 3.98, (1.88-8.41)]. Likewise, Neutrophil-Lymphocyte Ratio (NLR) and C-Reactive Protein (CRP) were also associated with 3-month mortality [OR 1.98, (1.17-3.35); and 1.39, (1.02-1.89) respectively]. A multimarker approach demonstrated that patients with increased calprotectin, CRP and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p=0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p<0.002); leukocytes (0.45, p<0.01) and neutrophil elastase (0.70, p<0.001) thrombi content. Conclusions- Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. Presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation and further studies are needed to determine its influence in resistance to reperfusion.

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Section: Discussionsupporting

confidence: 91%

Calprotectin predicts mortality after ischemic stroke and is present in the thrombus

Marta-Enguita¹,

Navarro-Oviedo²,

Rubio-Baines³

et al. 2020

Preprint

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“…Additionally, sST2 levels were found to independently correlate with 90-day mortality and hemorrhagic transformation after AIS [9]. However, the predictive value of sST2 for all-cause mortality 90 days after ischemic stroke showed no statistical significance after multivariate adjustment [10]. Our data supported and further reported the independent predictive value of sST2 for long-term prognosis after TIA/ischemic stroke (composite adverse events and a combination of major disability and death at 1 year).…”

Section: Discussionsupporting

confidence: 74%

“…Elevated sST2 is also associated with increased risk of hemorrhagic transformation, 90-day poor functional outcomes, and higher mortality after acute ischemic stroke (AIS) [8,9]. However, results have been mixed, with another study reporting that sST2 offered no prognostic value for 90-day all-cause mortality after AIS in multivariate analysis [10]. The present study aimed to investigate the predictive value of serum sST2 for long-term prognostic outcomes in a cohort of patients with TIA/ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study

Tian¹,

Guo²,

Wang³

et al. 2019

Preprint

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Background: Soluble ST2 (sST2) is a novel inflammation marker for the prediction of adverse outcomes in patients with cardiovascular disease and diabetes mellitus. The aim of the present study was to examine the predictive value of serum sST2 for prognostic outcomes in patients with transient ischemic attack (TIA)/ischemic stroke.Methods: Patients within 24 h after symptom onset were prospectively enrolled based on the TIA/ischemic stroke database of the First Affiliated Hospital of Zhengzhou University. The 1-year prognostic outcomes were composite adverse events (including ischemic and hemorrhagic stroke, myocardial infarction, and all-cause death) and a combination of major disability and death [modified Rankin Scale (mRS), 3-6]. Cox proportional hazard and logistic regression models were used to evaluate the association between serum sST2 and TIA/ischemic stroke prognosis. The C statistic, net reclassiﬁcation index (NRI), and integrated discrimination index (IDI) were used to present improvement in risk classification.Results: Serum sST2 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores. Kaplan-Meier analysis indicated a significantly different risk in composite adverse events between patients with higher and those with lower levels of sST2 ( P =0.006). Serum sST2 was an independent predictor for composite adverse events (HR: 2.517, 95% CI: 1.279-4.956, P =0.008) and major disability or death (OR: 3.126, 95% CI: 1.452-6.728, P =0.004) after multivariate adjustment. The addition of the sST2 to the NIHSS score significantly improved the predictive value for prognostic outcomes in patients with TIA/ischemic stroke (C statistic: 0.021, IDI: 1.91%, P =0.042 for composite adverse events; NRI: 32.82%, P =0.042 for major disability or death).Conclusions: Serum sST2 levels were positively associated with the severity of TIA/ischemic stroke and could independently predict composite adverse events and major disability or death, indicating that sST2 may be a potential prognostic marker for TIA/ischemic stroke.

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“…The elevated sST2 has also been shown to be related to worse outcome and higher mortality after AIS [17]. However, the conclusions from another study in a large cohort of AIS patients revealed that serum sST2 may not be a strong and independent prognostic marker for AIS mortality [18]. To date, the relationship between circulating levels of sST2, stroke severity, and post-ischemic inflammation has not been well elucidated.…”

Section: Introductionmentioning

confidence: 99%

Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke

Chen¹,

Ao²,

Yu³

et al. 2018

Clin. Lab.

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Background: Soluble ST2 (sST2) receptor is secreted and detectable in human serum, which acts as a decoy receptor for interleukin (IL)-33 to prevent IL-33-mediated Th2 immune responses. Recently, elevated serum sST2 has been found to be a novel biomarker in cardiovascular diseases such as heart failure and atherosclerosis. Here, we studied the role of sST2 in acute ischemic stroke (AIS) and its relationship with several inflammatory markers. Methods: The study included 112 patients with first-ever acute ischemic stroke, who were admitted within 48 hours after stroke onset. The serum levels of sST2 and IL-33 were measured with ELISA and the severity of AIS patients was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The cerebral infarct volume was calculated according to the Pullicino formula based on the cranial CT scan or MRI. High-sensitivity C-reactive protein (hs-CRP) and serum amyloid A protein (SAA) were measured using the latex-enhanced immunoturbidimetric assay. Results: The serum sST2 level was significantly increased in patients with AIS compared to the control patients without AIS. In addition, the concentration of serum sST2 increased with the infarct volume and the severity of AIS evaluated based on the NIHSS score. Furthermore, the sST2 level correlated positively with the inflammatory marker hs-CRP. Conclusions: Our study suggests that sST2 may be used as a novel diagnostic and predicting inflammatory marker in AIS.

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Prognostic Value of Inflammatory and Cardiovascular Biomarkers for Prediction of 90-Day All-Cause Mortality after Acute Ischemic Stroke—Results from the Linz Stroke Unit Study

Abstract: In this large cohort of patients with acute ischemic stroke, IL-6 and NT-proBNP at admission were strong and independent prognostic markers for 90-day all-cause mortality, and provided complementary prognostic information to the routinely used stroke severity score NIHSS.

Cited by 52 publications

References 25 publications

Calprotectin predicts mortality after ischemic stroke and is present in the thrombus

Calprotectin predicts mortality after ischemic stroke and is present in the thrombus

Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study

Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke

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