title: Prognostic relevance of baseline pro- and anti-inflammatory markers in STEMI: an APEX AMI substudy.
abstract: BACKGROUND
  Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro- and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown.
  
  
  METHODS
  In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI).
  
  
  RESULTS
  Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03-1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06-1.23; p<0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12-1.41;p<0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76-0.98; p<0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p<0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p<0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value.
  
  
  CONCLUSIONS
  Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP.
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA; Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: sv9@ualberta.ca.
authors: Sean
authors: S
authors: van Diepen
authors: L Kristin
authors: LK
authors: Newby
authors: Renato D
authors: RD
authors: Lopes
authors: Amanda
authors: A
authors: Stebbins
authors: Vic
authors: V
authors: Hasselblad
authors: Stefan
authors: S
authors: James
authors: Matthew T
authors: MT
authors: Roe
authors: Justin A
authors: JA
authors: Ezekowitz
authors: David J
authors: DJ
authors: Moliterno
authors: Franz-Josef
authors: FJ
authors: Neumann
authors: Craig
authors: C
authors: Reist
authors: Kenneth W
authors: KW
authors: Mahaffey
authors: Judith S
authors: JS
authors: Hochman
authors: Christian W
authors: CW
authors: Hamm
authors: Paul W
authors: PW
authors: Armstrong
authors: Christopher B
authors: CB
authors: Granger
authors: Pierre
authors: P
authors: Theroux
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D002170:Canada / Q000453:epidemiology; D002423:Cause of Death / Q000639:trends; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000150:complications / Q000628:therapy; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D012770:Shock, Cardiogenic / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D057127:Single-Chain Antibodies / Q000627:therapeutic use*; D013548:Sweden / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D010446:Peptide Fragments; D057127:Single-Chain Antibodies; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; C402724:pexelizumab
keywords: Inflammation; Myocardial infarction; Prediction models