Prognostic relevance of baseline pro- and anti-inflammatory markers in STEMI: an APEX AMI substudy

Int J Cardiol. 2013 Oct 3;168(3):2127-33. doi: 10.1016/j.ijcard.2013.01.004. Epub 2013 Feb 8.

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.

Keywords: Inflammation; Myocardial infarction; Prediction models.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism*
  • Canada / epidemiology
  • Cause of Death / trends
  • Double-Blind Method
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Heart Failure / blood
  • Heart Failure / epidemiology
  • Heart Failure / etiology
  • Humans
  • Inflammation / blood
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / complications
  • Myocardial Infarction / therapy
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Percutaneous Coronary Intervention / methods*
  • Predictive Value of Tests
  • Prognosis
  • Shock, Cardiogenic / blood
  • Shock, Cardiogenic / epidemiology
  • Shock, Cardiogenic / etiology
  • Single-Chain Antibodies / therapeutic use*
  • Sweden / epidemiology
  • United States / epidemiology

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Peptide Fragments
  • Single-Chain Antibodies
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein
  • pexelizumab