Abstract 4360857: Changes in Lipoprotein(a) and Oxidized Phospholipids Are Associated with Myocardial Inflammation but Not Systemic Inflammatory Markers Following an Acute Myocardial Infarction

Abstract

Background: Lipoprotein(a) [Lp(a)] is a major carrier of the pro-inflammatory oxidized phospholipids on apo-B containing lipoproteins (OxPL-apoB). In the OCEAN(a) DOSE trial olpasiran reduced Lp(a) and OxPL-apoB but not hs-CRP or IL-6, markers of systemic inflammation. The investigators proposed that the lack of a systemic effect could be explained by low baseline levels of systemic inflammation in the patients with stable disease and that there might be an anti-inflammatory impact in the setting of a local inflammatory milieu. We examined the associations between the changes of Lp(a), OxPL-apoB, hs-CRP, and IL-6, and the changes of local myocardial inflammation from hospitalization to 30 days in patients with an acute myocardial infarction (MI). Research Objective: To determine the association of changes in Lp(a), OxPL-apoB, hsCRP, and IL-6 with the changes in local myocardial inflammation following an MI. Methods: Fifty-five patients from the EVACS I and II trials with an acute MI were randomized to evolocumab, a PCSK9 inhibitor known to reduce Lp(a) levels or placebo and underwent 18 F-FDG PET imaging during hospitalization and at 30 days. Myocardial inflammation was quantified using a fixed threshold method, calculating SUV total as the total uptake within voxels exceeding 50% of the maximum SUV. Blood samples were collected at both timepoints, and the changes were correlated with changes in SUV total . Results: Mean age was 57±13 years, 36% were women and 22% were Black individuals. SUV total decreased and Lp(a) remained stable with evolocumab, while SUV total remained unchanged and Lp(a) increased with placebo over 30 days. The changes in SUV total correlated with the changes in Lp(a) (r=0.45, p<0.001) and OxPL-apoB (r=0.30, p=0.039) but not with the changes in hs-CRP or IL-6. The changes in hs-CRP and IL-6 were also not associated with the changes in Lp(a) or OxPL-apoB. After adjusting for baseline SUV total and treatment group, changes in Lp(a) independently predicted changes in myocardial inflammation (β=1.18, p=0.024), with a twofold increase in Lp(a) corresponding to an approximately 2.3-fold rise in SUV total . Conclusion: Changes in myocardial inflammation after an acute MI were associated with changes in Lp(a) and OxPL-apoB but not with indices of systemic inflammation. These findings support a pathophysiologic role for Lp(a)-associated OxPLs in myocardial inflammation and highlight the potential for Lp(a) targeted therapies in the early post-MI period.