Defective biological activities of high-density lipoprotein identify patients at highest risk of recurrent cardiovascular event.

Abstract

Aims: Low cholesterol efflux capacity (CEC) 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.

Methods and results: We evaluated potential synergetic effect of CEC and IL-1ß on recurrent major adverse cardiovascular events (MACE) at 1 year in 2012 patients with acute ST-segment elevation MI who underwent primary percutaneous coronary intervention. In addition, we evaluated the contribution to residual risk of HDL biological functions from 20 patients of the two extreme subgroups, focusing on CEC and anti-inflammatory properties. Patients with MACE during the first year after the MI had significantly lower serum CEC as compared with those without recurrent events and higher level of IL-1ß, and both associations were confirmed after multivariate analysis. We found an inverse relationship between CEC and circulating levels of the inflammatory marker IL-1ß, defining a very high risk (low CEC/high IL-1ß) and a low risk (high CEC/low IL-1ß) group of patients. Patients combining low CEC/high IL-1ß exhibited the highest risk of recurrent MACE at 1 year showing an additive prognostic value of these biomarkers, regardless of all the other clinical or biological factors. In this very high-risk subgroup, patients exhibited reduced HDL efflux capacity and defective ABCA1 and SR-BI with enhanced pro-inflammatory activity as a potential explanation for our clinical findings.

Conclusion: Impaired CEC and elevated IL-1β synergistically increase the residual cardiovascular risk in MI patients, which could be explained by reduced HDL efflux capacity and enhanced HDL pro-inflammatory activity.