Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke

Abstract

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 center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively 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 24 h. 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 < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44). Results Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13–4.73)]. Patients with calprotectin ≥ 2.26 μg/mL were 4 times more likely to die [OR 4.34 (1.95–9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87–0.95) vs 0.89 (0.85–0.93); p < 0.05]. 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) thrombus 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. The 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.

Predictors and Prognosis of Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke Patients Without Thrombolysis: Analysis of Data From the Chinese Acute Ischemic Stroke Treatment Outcome Registry

“…Finally, all the patients were recruited in China. The rate of receiving intravenous thrombolysis and endovascular treatment, as well as the mortality were relatively lower than other studies in the western countries ( 2 , 41 – 44 ). Hence, caution is needed when generalizing our results to other populations.…”

Plasma Calprotectin Is Predictive for Short-Term Functional Outcomes of Acute Ischemic Stroke

“…These lines of evidence imply that calprotectin might play a pivotal role in the pathogenesis of cardiovascular diseases. Although previous animal studies have demonstrated that calprotectin could promote neuroinflammation and exacerbate the pathology of AIS ( 20 ), limited evidence is available in human studies, with only two studies investigated the association between calprotectin and prognosis of stroke ( 21 , 22 ). Specifically, Guo et al investigated the association between baseline calprotectin levels and 3-month functional outcomes of AIS.…”

“…Guo et al found that high plasma calprotectin levels at baseline were associated with increased risks of poor clinical outcomes at 3 months after AIS ( 21 ). It is suggested that plasma calprotectin, along with other inflammatory factors, is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with AIS with poor outcomes after AIS ( 22 ). These findings along with ours imply that calprotectin might serve as a valid prognostic biomarker of AIS.…”

Elevated Circulating Levels of Phenylacetylglutamine in Stroke Patients With T2D Are Linked to Specific Gut Microbiota

“…A study showed that neutrophils (NE) mediated in ammation to amplify cerebral microvascular damage in the early stage of T2D, resulting in more severe brain edema and nerve damage after ischemia [20]. Furthermore, NE also participated in in ammatory damage by releasing neutrophil extracellular traps (NETs), which are network structures of DNA bers, composed of histones and active particles [21,22].…”