title: Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest.
abstract: 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 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h 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 1 year 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 48 h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h 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.
authors: Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Giuseppe
authors: G
authors: Ristagno
authors: Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Serge
authors: S
authors: Masson
authors: Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
authors: Marjaana
authors: M
authors: Tiainen
authors: Division of Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland.
authors: Stepani
authors: S
authors: Bendel
authors: Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Roberto
authors: R
authors: Bernasconi
authors: Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Topeliuksenkatu 5, PL 266, 00029 HUS, Helsinki, Finland.
authors: Tero
authors: T
authors: Varpula
authors: Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Valentina
authors: V
authors: Milani
authors: Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Topeliuksenkatu 5, PL 266, 00029 HUS, Helsinki, Finland.
authors: Jukka
authors: J
authors: Vaahersalo
authors: Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Michela
authors: M
authors: Magnoli
authors: DIAneering - Diagnostics Engineering & Research, Heidelberg, Germany.
authors: Eberhard
authors: E
authors: Spanuth
authors: Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Simona
authors: S
authors: Barlera
authors: Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Roberto
authors: R
authors: Latini
authors: Department of Intensive Care, Tampere University Hospital, Tampere, Finland.
authors: Sanna
authors: S
authors: Hoppu
authors: Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Topeliuksenkatu 5, PL 266, 00029 HUS, Helsinki, Finland.|Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland.
authors: Ville
authors: V
authors: Pettilä
authors: Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Topeliuksenkatu 5, PL 266, 00029 HUS, Helsinki, Finland. markus.skrifvars@hus.fi.|Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. markus.skrifvars@hus.fi.
authors: Markus B
authors: MB
authors: Skrifvars
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D006323:Heart Arrest / Q000453:epidemiology / Q000401:mortality*; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration / Q000706:statistics & numerical data; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D011379:Prognosis; D012372:ROC Curve; D011971:Receptors, Immunologic / Q000032:analysis* / Q000097:blood; D012151:Resuscitation / Q000401:mortality
chemical_list: D011971:Receptors, Immunologic; C116128:heparin-binding protein receptor
keywords: Cardiac arrest; Heparin-binding protein; Outcome; Post resuscitation