Background and Aims

Low Cholesterol efflux capacity (CEC) and elevated levels of IL-1Beta (IL-1β) are strongly and independently associated with cardiovascular outcomes after Myocardial Infarction (MI). Both pathways are currently evaluated as new therapeutic targets in ongoing clinical trials. Animal studies demonstrated that alteration of cholesterol efflux leads to IL-1ß production, suggesting that defective CEC triggers inflammation.

The present study aims to evaluate (1) potential synergetic effect of CEC and IL-1β on recurrent major cardiovascular events (MACE) at one-year after a first MI and (2) the capacity of HDL particles to activate inflammation according to the risk of recurrent MACE.

Methods

CEC and IL-1B levels were measured among 2012 ST-segment elevation MI patients. The association of these biomarkers with the primary outcome of MACE was evaluated at one-year follow-up using a multivariate-cox analysis. In-vitro analyses of HDL functions including anti-inflammatory properties and CEC was evaluated in human THP-1 macrophages.

Results

Patients exhibited both reduced CEC and an elevated level of IL-1β displayed an increased risk of recurrent MACE at one year compared to patients with both high CEC and low IL-1β. HDL particles isolated from highest risk patients exhibited a reduced CEC from macrophages, as well as higher pro-inflammatory properties, as compared to patients at lower risk of recurrent MACE.

Conclusions

Defective CEC and elevated IL-1B increase synergistically the residual cardiovascular risk in MI patients. HDL particles from patients at highest risk of recurrent MACE after MI exhibit defective biological activities. These latter patients may benefit from a dual therapeutic approach targeting both CEC and inflammation.