Temporal changes in biomarkers and their relationships to reperfusion and to clinical outcomes among patients with ST segment elevation myocardial infarction.

Abstract

Coronary plaque rupture mediating acute ST segment elevation myocardial infarction (STEMI) is associated with a systemic inflammatory response. Whether early temporal changes in inflammatory biomarkers are associated with angiographic and electrocardiographic markers of reperfusion and subsequent clinical outcomes is unclear. In the APEX-AMI biomarker substudy, 376 patients with STEMI had inflammatory biomarkers measured at the time of hospital presentation and 24h later. The primary outcome was the 90-day composite of death, shock, or heart failure. Secondary reperfusion outcomes were (1) worst least residual ST segment elevation (ST-E: <1mm, 1 to <2mm, ≥2mm) and (2) post-percutaneous coronary intervention (PCI) TIMI flow grade (0/1/2 vs 3) and TIMI myocardial perfusion grade (TMPG 0/1 vs 2/3). The 90-day incidence of death, shock or heart failure was 21.3% in this cohort. Electrocardiographic reperfusion (worst residual ST-E <1mm, 1 to <2mm, ≥2mm) was associated with differences in 24h change in N-terminal proB-type natriuretic peptide (NT-proBNP) (1192.8, 1332.5, 1859.0ng/mL; p=0.043) and the pro-inflammatory cytokines Interleukin (IL)-6 (14.0, 13.6, 22.1pg/mL; p=0.016), IL-12 (-0.5, -0.9, -0.1pg/mL; p=0.013), and tumor necrosis factor α (TNFα) (1.0, 0.6, 3.6pg/mL; p=0.023). Angiographic reperfusion (TMPG 0/1 vs 2/3) was associated with changes in median NT-proBNP (2649.3, 1382.7ng/mL; p=0.002) and IL-6 (28.7, 15.1; p=0.040). After adjustment for baseline covariates, the 24h change in the pro-inflammatory cytokine TNFα [hazard ratio (HR) 0.49; 95% CI 0.26-0.95; p=0.035] and the anti-inflammatory cytokine IL 10 (HR 1.41; 95% CI 1.06-1.87; p=0.018) were independently associated with the primary composite outcome. Successful coronary reperfusion was associated with less systemic inflammatory response and greater temporal inflammatory changes were independently associated with higher 90-day composite of death, shock, or heart failure. These findings provide support for an association between success of reperfusion, an acute STEMI inflammatory response and subsequent clinical outcomes.