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

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.