Elsevier

Journal of Critical Care

Volume 26, Issue 6, December 2011, Pages 608-612
Journal of Critical Care

Outcomes
Plasma gelsolin levels and 1-year mortality after first-ever ischemic stroke

https://doi.org/10.1016/j.jcrc.2011.02.007Get rights and content

Abstract

Purpose

Plasma gelsolin depletion has been associated with poor outcome of critically ill patients. We sought to investigate change in plasma gelsolin level after ischemic stroke and to evaluate its relation with disease outcome.

Materials and Methods

Fifty healthy controls and 172 patients with first-ever ischemic stroke were included. Plasma samples were obtained within 24 hours from stroke onset. Its concentration was measured by enzyme-linked immunosorbent assay.

Results

Plasma gelsolin level in stroke patients was significantly decreased compared with healthy controls. A multivariate analysis showed that plasma gelsolin level was an independent predictor for 1-year mortality (odds ratio, 0.945; 95% confidence interval [CI], 0.918-0.974; P = .0002) and negatively associated with National Institutes of Health Stroke Scale (NIHSS) score (t = −4.802, P < .001) and plasma C-reactive protein level (t = −4.197, P < .001). A receiver operating characteristic curve identified that a baseline plasma gelsolin level less than 52.0 mg/L predicted 1-year mortality of patients with 73.0% sensitivity and 65.2% specificity (area under curve [AUC], 0.738; 95% CI, 0.666-0.802). The predictive value of the gelsolin concentration was similar to that of NIHSS score (AUC, 0.742; 95% CI, 0.670-0.806; P = .940). Gelsolin improved the AUC of NIHSS score to 0.814 (95% CI, 0.747-0.869; P = .032).

Conclusions

Plasma gelsolin level is a useful, complementary tool to predict mortality after ischemic stroke.

Introduction

Plasma gelsolin is an actin-binding plasma protein that is part of an “actin-scavenging” system that buffers potentially harmful actin molecules released from injured tissues [1]. The consistent observation of lowered levels of plasma gelsolin in diverse states of acute injury and inflammation, such as hepatic failure, malaria, acute lung injury, myonecrosis, and cardiac injury [2], [3], [4], [5], has led to a hypothesis that it participates in the clearance of actin from the circulation [1]. Further studies have revealed that critical extents of plasma gelsolin depletion in patients subjected to trauma, burns, major surgery, or hematopoietic stem cell transplantation are correlated with poor outcomes, including death [6], [7], [8]. In addition, the finding that plasma gelsolin binds inflammatory mediators such as platelet-activating factor and lysophosphatidic acid suggests that its physiological function may be to localize inflammation and blunt its systemic effects and that extensive plasma gelsolin depletion due to actin exposure after injury allows inflammatory mediators to cause widespread tissue damage [9].

It is evidenced that gelsolin knockout mice have largely increased cerebral lesion volumes after brain ischemia [10]. A recent study reported that plasma gelsolin is decreased and correlated with the rate of decline in Alzheimer disease [11]. However, there is a paucity of data available on circulating plasma gelsolin concentration in ischemic stroke. We therefore undertook a study to determine whether plasma gelsolin is decreased in the circulation of humans with ischemic stroke and if plasma gelsolin decrease is correlated with outcomes in these patients.

Section snippets

Study population

All patients admitted between September 2007 and July 2009 with a presumable diagnosis of first-ever ischemic stroke were prospectively evaluated for inclusion in the study. Exclusion criteria from the study were concurrent renal or hepatic insufficiency, malignancy and recent infection, surgery, or major trauma. Renal insufficiency was defined as creatinine clearance less than 80 mL/min. Hepatic insufficiency was defined as Child-Pugh classification score higher than 5. Recent infection was

Patients characteristics

During the recruitment period, 219 patients were admitted, with an initial diagnosis of first-ever ischemic stroke, 181 (82.7%) patients fulfilled the inclusion criteria, and adequate data on admission and follow-up were available for 172 individuals (94 men and 78 women) (78.5%) who were finally included in the analysis. The median age was 70 years (range, 60-82 years). On admission, the median NIHSS score was 10 (range, 1-37). Table 1 summarized the other baseline demographic data,

Discussion

In this study, we report for the first time that plasma gelsolin levels of patients with ischemic stroke were significantly lower than our controls and that low plasma gelsolin levels are strongly associated with clinical severity and outcome in these patients.

The mechanism of plasma gelsolin's actions is poorly understood. Gelsolin was first discovered as an intracellular protein involved in actin dynamics [12]. Plasma gelsolin was subsequently identified as a secreted isoform of the

Conclusions

This study suggests that plasma gelsolin is depleted after ischemic stroke. Plasma gelsolin level is a valuable marker of ischemic stroke and correlated with severity of ischemic stroke and 1-year mortality.

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