Abstract
BackgroundWe aimed to assess associations between circulating IL‐18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS).Hypothesis and MethodsPlasma IL‐18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT‐hs, NT‐proBNP, cystatin C, CRP‐hs, and GDF‐15).ResultsMedian IL‐18 concentrations at baseline, discharge, 1 month, and 6 months were 237, 283, 305, and 320 ng/L (n = 16 636). Male sex, obesity, diabetes, and plasma levels of cystatin C, GDF‐15, and CRP‐hs were independently associated with higher IL‐18 levels. Higher baseline IL‐18 levels were associated with the composite endpoint and with CV death (hazard ratio [HR] 1.05, 95% confidence interval [95% CI] 1.02‐1.07 and HR 1.10, 95% CI 1.06‐1.14, respectively, per 25% increase of IL‐18 levels). Associations remained significant after adjustment for clinical variables but became non‐significant after adjustment for all biomarkers (HR 1.01, 95% CI 0.98‐1.04 and HR 1.04, 95% CI 1.00‐1.08, respectively). There were no associations with sMI.ConclusionsIn ACS patients, IL‐18 concentrations increased after the acute event and remained increased for 6 months. Baseline IL‐18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers.
Highlights
Inflammation is important for the development of atherosclerosis and inflammatory mediators synergistically amplify traditional risk factors of cardiovascular (CV) disease.[1]
Interleukin-18 (IL-18), a member of the IL-1 cytokine superfamily, is a pleiotropic inflammatory cytokine expressed in several cells including macrophages and endothelial cells.[5]
In patients with acute coronary syndromes (ACS), the IL-18 concentration increased during the first month after the acute event and remained at similar level at 6 months
Summary
Inflammation is important for the development of atherosclerosis and inflammatory mediators synergistically amplify traditional risk factors of cardiovascular (CV) disease.[1]. Interleukin-18 (IL-18), a member of the IL-1 cytokine superfamily, is a pleiotropic inflammatory cytokine expressed in several cells including macrophages and endothelial cells.[5] Increased circulating IL-18 concentrations have been associated with coronary artery disease and an increased risk for cardiovascular (CV) morbidity and mortality.[6,7] IL-18 has been detected in atherosclerotic plaques and has been proposed to destabilize coronary plaques leading to subsequent thrombotic events.[3] the importance of circulating IL-18 in patients with ACS is not well documented.[8]. We aimed to assess associations between circulating IL-18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS). Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT-hs, NT-proBNP, cystatin C, CRP-hs, and GDF-15). Baseline IL-18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers
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