title: Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide.
abstract: BACKGROUND
  Inflammation in acute coronary syndrome (ACS) can identify those at greater long-term risks for heart failure (HF) and death. The present study assessed the performance of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) (cytokines involved in the activation and recruitment of leukocytes) in addition to known biomarkers [e.g., N-terminal pro-brain natriuretic peptide (NT-proBNP)] for predicting HF and death in an ACS population.
  
  
  METHODS
  In a cohort of 216 ACS patients, NT-proBNP (Elecsys; Roche) and IL-6, IL-8, and MCP-1 (evidence investigator; Randox) were measured in serial specimens collected early after symptom onset (n = 723). We collected at least 2 specimens from each participant: an early specimen (median 2 h; interquartile range 2-4 h) and a later specimen (9 h; 9-9 h), and used the later specimens' biomarker concentrations for risk stratification.
  
  
  RESULTS
  An increase in both IL-6 and NT-proBNP was observed but not for IL-8 or MCP-1 early after pain onset. Kaplan-Meier analysis demonstrated that individuals with increased NT-proBNP (>183 ng/L) or cytokines (IL-6 > 6.4 ng/L; above upper limit of normal for IL-8 or MCP-1) had a greater probability of death or HF in the following 8 years (P <0.05). In a Cox proportional hazard model adjusted for both CRP and troponin I, increased IL-6, MCP-1, and NT-proBNP remained significant risk factors. Combining all 3 biomarkers resulted in a higher likelihood ratio for death or HF than models restricted to any 2 of these biomarkers.
  
  
  CONCLUSIONS
  IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, highlighting the importance of identifying leukocyte activation and recruitment in ACS patients.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. kavsakp@mcmaster.ca
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kavsak
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Ko
authors.forename: Alice M
authors.initials: AM
authors.lastname: Newman
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: Viliam
authors.initials: V
authors.lastname: Lustig
authors.forename: Andrew R
authors.initials: AR
authors.lastname: MacRae
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain