Abstract Body (Do not enter title and authors here): 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 ¹⁸F-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.