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

Abstract

Predicting the prognosis of comatose, postcardiac-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-cardiacarrest 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°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 nonsurvivors, 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.

Circulating mitochondrial stress 70 protein/mortalin and cytosolic Hsp70 in blood: Risk indicators in colorectal cancer

“…Serum Hsp70 levels in healthy individuals (median, 25–75 percentile) were determined in our two earlier studies. Young (nonpregnant) women had 0.29 (0.20–0.35) ng/ml serum Hsp70 and healthy adults had 0.59 (0.43–0.89) ng/ml serum Hsp70 …”

The detection and role of heat shock protein 70 in various nondisease conditions and disease conditions: a literature review

“…In Kaplan-Meier survival analyses, HSP70 levels greater than the median were associated with significantly increased mortality, and multivariate survival models have shown that HSP70 levels greater than the median are an independent predictor of 5-year mortality in HF (Jenei et al 2013a). However, extracellular HSP70 levels are significantly decreased in survivors, whereas they persist in nonsurvivors, predicting 30-day mortality regardless of age, sex, complications, or APAC HE II score (Jenei et al 2013b). Thus, HSP70 might be a useful marker for estimating survival in patients with HF and in determining the prognosis of comatose postcardiac arrest patients.…”

Acute exercise boosts cell proliferation and the heat shock response in lymphocytes: correlation with cytokine production and extracellular-to-intracellular HSP70 ratio

“…Not unexpectedly, serum eHSP72 concentrations are positively correlated with inflammation markers in humans [e.g. C-reactive protein, monocyte count, and TNF-α (Mayer and Bukau 2005;Njemini et al 2004)], being regarded as a prognostic marker of the progression of immune-related diseases (Terry et al 2004(Terry et al , 2006, clinical status and death (Gelain et al 2011;Genth-Zotz et al 2004;Jenei et al 2013aJenei et al , 2013b. Consequently, the ratio between eHSP70 and iHSP70 (R = [eHSP70]/[iHSP70]) correlates with organismal immunoinflammatory balance, whereas the rate of variation in R ratios between different conditions (a.k.a.…”