Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest

Background: An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome. Methods: Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24h Sequential Organ Failure Assessment (SOFA) score≥12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed. Results: Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48% (133 of 276) to 1year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24h SOFA and cardiovascular SOFA score (p<0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p<0.0001; AUC=0.70±0.04, p=0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p<0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p<0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74±0.04 (p<0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076-2.399], p=0.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834-1.596], p=0.387). Conclusions: Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.