In patients with acute myocardial infarction interleukin-8 levels are related to impaired renal function and predict recurrent infarction or death at 1-year follow-up - a case-control study

Abstract

Abstract Introduction Acute myocardial infarction (AMI) induces a surge of inflammatory cytokines. IL-8, secreted by endothelial cells and monocyte-macrophages, rapidly recruits immune cells to the infarcted tissue. Previous studies in chronic kidney disease reported IL-8 to be associated with an increased inflammatory burden. Little is known about the diagnostic and prognostic value of IL-8 plasma levels in patients with AMI. Purpose We aimed to explore the diagnostic and prognostic value of IL-8 plasma levels in AMI patients. Methods Patients with AMI (STEMI and NSTEMI) were included from the SPUM-ACS cohort selecting a time window <24 h from symptom onset to blood sampling before PCI. Patients with malignancies or on immunosuppressive therapies were excluded. 160 patients with recurrent AMI or death within 1-year follow-up (cases) were compared to 160 counterparts with favorable outcome matched for age, sex, AMI subtype, and pain onset time (controls). 45 healthy blood donors (HD) without cardiovascular disease were added as an age- and sex-matched reference group. Heparin-plasma was used for Mesoscale U Plex cytokine analyses. The median and interquartile ranges (IQR) were compared using the non-parametric Kruskal-Wallis test. Relation of baseline characteristics to IL-8 levels within cases and controls was assessed with linear regression analyses. Kaplan-Meier curves were computed, selecting the cut-off value in consideration of the overall median IL-8 level. Results Cases (median=59.5, IQR=112.0 pg/mL) showed higher IL-8 plasma levels than HD (median=38.6, IQR=25.1 pg/mL, p=0.0006, Figure 1). Cases also had higher plasma IL-8 levels compared to controls (median=41.2, IQR=51.7 pg/mL, p=0.0006, Figure 1). Considering the median IL-8 level (50.1 pg/ml) as cut-off, cases with higher IL-8 had higher rates of recurrent MI or all-cause death than those with lower IL-8 levels within one year (log-rank p=0.002, Figure 2) with divergence between the subgroups seen early within the first two months. After correction for possible confounding factors (BMI, hypertension history, dyslipidaemia, diabetes, smoking, use of statins, LDL, Troponin, LVEF, and NT-proBNP), eGFR (estimated glomerular filtration rate) remained the only predictor for increased IL-8 (SRC: -0.178, p=0.016) in AMI patients. Conclusions In patients with AMI increased IL-8 levels predict subsequent MI or death at one-year follow-up. Lower eGFR is related to elevated IL-8 levels. Patients with AMI may thus profit from early IL-8 blocking therapies, particularly in the setting of impaired renal function.