Synergistic Effect of Interleukin-1beta and Cholesterol Efflux Capacity on Outcomes in Acute Myocardial Infarction Patients

Background Low cholesterol efflux capacity and elevated levels of Interleukin-1ß (IL-1ß) are both associated with residual cardiovascular risk in patients with acute myocardial infarction (MI) and may be used as new biomarkers to identify patients at higher cardiovascular risk. Both pathways are currently evaluated as new therapeutic targets in ongoing clinical trials. Objectives We evaluated potential synergetic effect of cholesterol efflux capacity and IL-1ß on recurrent major cardiovascular events (MACE) at one-year in patients with acute ST-segment elevation MI who underwent primary percutaneous coronary intervention. Methods Cholesterol efflux capacity and IL-1ß were measured among 2012 ST-segment elevation MI patients enrolled in a prospective cohort. The association of these biomarkers with the primary outcome of MACE (MI, Stroke, or cardiovascular death) was evaluated at one-year follow-up using a multivariate-cox proportional regression analysis. In addition, in-vitro analysis of anti-atherogenic properties of HDL particles was also performed. Results Patients with both, a reduced cholesterol efflux capacity and an elevated level of IL-1b, exhibited the highest risk of recurrent MACE at one year compared to patients with both high cholesterol efflux capacity and low IL-1b (adjusted HR: 3.28; 95% CI: 1.83 to 5.89, p<0.0001) (Figure). In this high-risk subgroup, patients exhibited HDL particles defective for ABCA1-dependent efflux capacity with enhanced pro-inflammatory activity as a potential explanation for our clinical findings. Conclusion Defective cholesterol efflux capacity and elevated IL-1β increase synergistically the residual cardiovascular risk in MI patients.