Prognostic significance of IL-18 in acute coronary syndrome patients

Abstract

Background: After acute coronary syndrome (ACS), inflammation aids healing but may harm the heart. Interleukin (IL)-18 and IL-1β are pivotal proinflammatory cytokines released during pyroptosis, a process that initiates and sustains inflammation. This study aimed to evaluate the levels of circulating IL-18 and IL-1β during the progression of ACS and to determine their association with subsequent clinical events in ACS patients.

Hypothesis: Circulating levels of IL-18 and IL-1β are associated with subsequent clinical events in ACS patients.

Methods: Employing immunoassays, we examined plasma levels of IL-1β and IL-18 in 159 ACS patients and matched them with 159 healthy controls. The primary composite endpoint included recurrent unstable angina, myocardial infarction, heart failure exacerbation, stroke, or cardiovascular death.

Results: ACS patients exhibited a significant increase in plasma IL-18 levels, measuring 6.36 [4.46-9.88] × 10² pg/mL, in contrast to the control group with levels at 4.04 [3.21-4.94] × 10² pg/mL (p < 0.001). Conversely, plasma levels of IL-1β remained unchanged compared to the control group. Following a 25-month follow-up, IL-18 levels exceeding the median remained an important prognostic factor for adverse clinical events in ACS patients (hazard ratio = 2.37, 95% confidence interval: 1.14-4.91, p = 0.021). Besides, IL-18 displayed a nonlinear association with adverse clinical events (p nonlinear = 0.044). Subgroup analysis revealed that the correlation between IL-18 and the risk of adverse clinical events was not significantly affected by factors such as age, sex, history of diabetes, smoking, Gensini score, or ACS type (all p interaction >0.05).

Conclusion: IL-18 appears to hold potential as a predictive marker for anticipating clinical outcomes in patients with ACS.

Keywords: acute coronary syndrome; adverse clinical events; inflammation; interleukin-18; interleukin-1β; prognosis.

Figure 1

Kaplan−Meier curves depict adverse clinical events in relation to IL‐18 levels within ACS. The curves represent the occurrence of adverse clinical events over a 25‐month follow‐up, categorized by high and low IL‐18 levels. ACS, acute coronary syndrome.

Figure 2

Multivariable adjusted hazard ratios (HR) for adverse clinical events according to levels of IL‐18 on a continuous scale. Solid purple lines are multivariable adjusted HR, with dashed purple lines showing 95% confidence intervals derived from restricted cubic spline regressions with four knots. The median of IL‐18 6.36 × 10² pg/mL was selected as the reference level. Yellow histograms show the fraction of the population with different levels of IL‐18(10² pg/mL). Adjusted for age, gender, diabetes, hypertension, LVEF, NTproBNP, hsCTnT, LVPW, Gensini scores, and CRP. CRP, C‐reactive protein; LVEF, left ventricular ejection fraction; LVPW, left ventricular posterior wall.

Figure 3

IL‐18 as a predictor of adverse clinical events occurrence in different subgroups. The HR (hazard ratio) values for each subgroup were adjusted for age, gender, hypertension, diabetes, and LVEF. *Statistically significant. AMI, acute myocardial infarction; LVEF, left ventricular ejection fraction; UA, unstable angina.