Interleukin-1B and ST2L/IL-33R and risk of clinical outcomes in patients with multi-vessel disease

Background Interleukin-1β (IL-1β) is a pro-inflammatory cytokine, and its abnormal expression has a significant adverse effect on myocardial remodeling and cardiac function Recent studies have demonstrated that monoclonal antibodies targeting IL-1β can significantly improve the clinical outcomes of coronary artery disease (CAD). Similar to IL-1β, as a member of the IL-1 cytokine family, IL-33 has been identified as a poor prognostic factor in numerous diseases. IL-33 mainly exerts its cellular functions by binding to transmembrane ST2 receptor (ST2L) which also known as IL-33 receptor (IL-33R). ST2L/IL-33R holds potential in the identification of cardiovascular risks. However, in the complex cardiovascular disease like multi-vessel disease (MVD), the association between IL-1β and ST2L/IL-33R and long-term prognosis remains unclear. Method This study is a secondary analysis of a large-sample, prospective, multicenter, observational cohort study which included 18701 patients diagnosed with CAD. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), including all-cause mortality, myocardial infarction, revascularization, and stroke. Cox regression analysis was performed to study the associations between IL-1β and ST2L/IL-33R and 2-year MACCE, using 3 models: IL-1β and ST2L/IL-33R as continuous variables after natural logarithmic transformation (Ln), both IL-1β and ST2L/IL-33R as categorical variables, and the categories of the combination. Results This study examined 1058 patients with MVD after percutaneous coronary intervention (62.5±10.7 years of age and 75.8% male). The median IL-1β and ST2L/IL-33R concentration was 0.07 pg/ml (IQR: 0.06 to 0.21) and 17.45 (IQR: 12.45 to 27.33) ng/ml, separately, and there was a positive correlation between IL-1β and ST2L/IL-33R (ρ = 0.29; p < 0.001). The analysis for tertiles of IL-1β (adjusted HR: 2.09; 95% CI: 1.33 to 3.27; p = 0.001) and ST2L/IL-33R (adjusted HR: 1.53; 95% CI: 1.00 to 2.34; p = 0.049) revealed the adjusted risk of MACCE was significantly higher in the highest tertile group compared with the lowest tertile group. After multivariate adjustment, when considering Ln(IL-1β) and Ln(ST2L/IL-33R) separately as continuous variables, both IL-1β and ST2L/IL-33R retained statistically significant predictors. Moreover, the analysis of combination demonstrated that patients with high IL-1β and low ST2L/IL-33R (adjusted HR: 1.63; 95% CI: 1.00 to 2.65; p = 0.049), as well as those with high IL-1β and high ST2L/IL-33R (adjusted HR: 2.13; 95% CI: 1.37 to 3.33; p = 0.001), had a significantly higher risk of MACCE, compared with those with low IL-1β and low ST2L/IL-33R. Notably, the risk was highest in patients with high IL-1β and high ST2L/IL-33R. Conclusion This study report that IL-1β and ST2L/IL-33R have prognostic implications for multivessel disease (MVD), and there is a synergistic effect between IL-1β and ST2L/IL-33R in increasing the risk of poor prognosis.