Low-density lipoprotein quality determines mortality risk in patients with acute coronary syndromes

Low-density lipoprotein (LDL)-cholesterol (LDL-C) undoubtedly promotes atherosclerotic cardiovascular disease (ASCVD), with changes in LDL electronegativity modulating its pro-atherogenic/pro-thrombotic effects. Whether such alterations associate with adverse outcomes in patients with acute coronary syndromes (ACS), a patient population at particularly high cardiovascular risk, remains unknown. In this case-cohort analysis, members of the Center for Molecular Cardiology identified LDL electronegativity as a completely novel risk factor of adverse events in patients with a recent ACS. Indeed, reduced low-density lipoprotein electronegativity associated independently with mortality risk at 30 days and 1 year after the acute event and superseded several risk factors for the prediction of 1-year death, including LDL-C. Moreover, when added to the GRACE risk score, it enhanced the discriminatory performance of the score, with LDL particles of different electronegativity showing a distinct lipidome, with potential implications for their athero-/thrombogenicity.

We conclude that reductions in LDL electronegativity are linked to alterations of the LDL lipidome, associate with all-cause and cardiovascular mortality beyond established risk factors, and represent a novel risk factor for adverse outcomes in patients with ACS. These associations warrant further validation in independent cohorts. Fully study results are now available in the latest issue of Atherosclerosis.