Persistently elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker in post-cardiac-arrest patients

Abstract

Predicting the prognosis of comatose, post-cardiac-arrest patients is a complex problem in clinical practice. There are several established methods to foretell neurological outcome; however, further prognostic markers are needed. HSP70 (HSPA1A), which increases rapidly in response to severe stress (among others after ischemic or hypoxic events), is a biomarker of cell damage in the ischemic brain and spinal cord. We hypothesized that HSP70 might be a reliable predictor of mortality in post-cardiac-arrest patients. The aim of this study was to analyze the role of extracellular HSP70 in the systemic inflammatory response over time, as well as the predictive value in cardiac arrest patients. Here, we show that the elevation of HSP70 levels in resuscitated patients and their persistence is an independent predictor of 30-day mortality after a cardiac arrest. Forty-six cardiac arrest patients were successfully cooled to 32-34 degrees C for 24 h, and followed up for 30 days. Twenty-four patients (52.2 %) were alive by the end of follow-up, and 22 patients (47.8 %) died. Forty-six patients with stable cardiovascular disease served as controls. Extracellular HSP70 (measured by ELISA in blood samples) was elevated in all resuscitated patients (1.31 [0.76-2.73] and 1.70 [1.20-2.37] ng/ml for survivors and non-survivors, respectively), compared with the controls (0.59 [0.44-0.83] ng/ml). HSP70 level decreased significantly in survivors, but persisted in non-survivors, and predicted 30-day mortality regardless of age, sex, complications, and the APACHE II score. Extracellular HSP70 could prove useful for estimating prognosis in comatose post-cardiac-arrest patients.