Interleukin-8 and other neutrophil-related biomarkers are associated with 1-year mortality in patients with acute myocardial infarction

Abstract

Abstract Background Interleukin-8 (IL-8) triggers early inflammatory responses upon tissue injury, activating neutrophils that release neutrophil extracellular traps with cell-free DNA (cfDNA) and myeloperoxidase (MPO). Injury upon acute myocardial infarction (AMI) induces an early excessive inflammatory response. The value of IL-8 and neutrophil-related biomarkers for AMI patient outcomes is incompletely understood. Methods AMI patients sampled ≤ 24 h after symptom onset were included from SPUM-ACS cohort. One hundred twelve cases with all-cause mortality or recurrent AMI within 1 year were matched 1:1 to event-free controls by age, sex, AMI subtype, symptom onset time, and recruiting sites. Results Cases showed higher IL-8 (median: 66.82 vs. 41.24 pg/mL; p = 0.001), cfDNA (393.9 vs. 223.8 ng/mL; p < 0.001), MPO (683.4 vs. 602.2 ng/mL; p = 0.030), and neutrophil-to-lymphocyte ratio (NLR) than controls (6.22 vs. 4.76; p = 0.013). IL-8 and cfDNA were higher in the death subgroup than recurrent AMI (IL-8: 71.16 vs. 51.52 pg/mL; p = 0.026; cfDNA: 420.5 vs. 239.7 ng/mL; p = 0.030). Notably, IL-8 peaked in the hyper-acute phase (< 6 h), earlier than high-sensitivity troponin T (hsTnT). This aligned with its associations with death or recurrent AMI (OR = 1.62; p = 0.021), death (OR = 2.14; p = 0.019), and early presenters (< 6 h, OR = 2.65; p = 0.008) after adjusting for confounders (estimated glomerular filtration rate [eGFR], high-sensitivity C-reactive protein [hsCRP], N-terminal pro-B-type natriuretic peptide [NT-proBNP], and hsTnT). IL-8, along with cfDNA, NLR, and hsCRP clustered in patients with increased Killip Class and worse outcomes. Conclusions IL-8 and neutrophil-related biomarkers were associated with 1-year mortality in AMI patients, especially in the hyper-acute phase. Clinical trial registration NCT01000701. Graphical Abstract IL-8 level is associated with 1-year mortality in patients with AMI. IL-8 and neutrophil-related biomarkers were measured in 112 AMI case–control pairs within 24 h of symptom onset from the SPUM-ACS cohort. After adjusting for key confounders (eGFR, hsTnT, NT-proBNP, and hsCRP), elevated IL-8 levels were independently associated with 1-year composite outcome (all-cause mortality or recurrent AMI: OR 1.62; p = 0.021), all-cause mortality alone (OR 2.14; p = 0.019), and showed the strongest association in early presenters within the hyper-acute phase (< 6 h, OR 2.65; p = 0.008). Difference of IL-8 levels within case–control pair peaked during hyper-acute phase, elevating earlier than hsTnT, which rose progressively across later symptom onset time windows. The temporal panel shows the mean within-pair difference in standardized, log-transformed IL-8 and hsTnT by symptom onset window, as in Fig. 3B. AMI, acute myocardial infarction; eGFR, estimated glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein; hsTnT, high-sensitivity troponin T; IL, interleukin; NT-proBNP, N-terminal pro-B-type natriuretic peptide; OR, odds ratio.