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

• Published in: International journal of cardiology Vol. 168; no. 3; pp. 2127 - 2133
• Main Authors: van Diepen, Sean, Newby, L. Kristin, Lopes, Renato D., Stebbins, Amanda, Hasselblad, Vic, James, Stefan, Roe, Matthew T., Ezekowitz, Justin A., Moliterno, David J., Neumann, Franz-Josef, Reist, Craig, Mahaffey, Kenneth W., Hochman, Judith S., Hamm, Christian W., Armstrong, Paul W., Granger, Christopher B., Theroux, Pierre
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 03.10.2013; Elsevier Ireland Ltd; Elsevier
• Subjects: Aged; Antibodies, Monoclonal, Humanized - therapeutic use; Biological and medical sciences; Biomarkers - blood; Bones, joints and connective tissue. Antiinflammatory agents; C-Reactive Protein - metabolism; Canada - epidemiology; Cardiology. Vascular system; Cardiovascular; Cause of Death - trends; Coronary heart disease; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Germany - epidemiology; Heart; Heart Failure - blood; Heart Failure - epidemiology; Heart Failure - etiology; Humans; Inflammation; Inflammation - blood; Male; Medical sciences; Middle Aged; Myocardial infarction; Myocardial Infarction - blood; Myocardial Infarction - complications; Myocardial Infarction - therapy; Myocarditis. Cardiomyopathies; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; Percutaneous Coronary Intervention - methods; Pharmacology. Drug treatments; Prediction models; Predictive Value of Tests; Prognosis; Shock, Cardiogenic - blood; Shock, Cardiogenic - epidemiology; Shock, Cardiogenic - etiology; Single-Chain Antibodies - therapeutic use; Sweden - epidemiology; United States - epidemiology; Myocardial infarction; Prediction models; Inflammation; Prognosis; Antiinflammatory agent; Prediction; Biological marker; Cardiovascular disease; Coronary heart disease; Myocardial disease; Relevance; Models; Cardiology; Predictive factor; Apex
• ISSN: 0167-5273; 1874-1754; 1874-1754
• DOI: 10.1016/j.ijcard.2013.01.004

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. 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). 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. 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.