Abstract 17162: High Lp(a) is Associated With Activation of the Arachidonic Acid Pathway

Abstract

Introduction: High lipoprotein(a) [Lp(a)] is associated with increased platelet aggregation, inflammation and cardiovascular events. Eicosanoids such as eicosapentaenoic acid (EPA) and arachidonic acid (AA) have anti- and pro-inflammatory effects, respectively. In this cross-sectional study, we explored the associations between eicosanoids, Lp(a), and oxidized phospholipids on apolipoprotein B (oxPL:apoB). Hypothesis: Increased platelet aggregation and inflammation associated with high Lp(a) levels may be due to relative EPA and AA levels. Methods: Consecutive outpatients with known Lp(a) levels seen in an outpatient cardiology practice between April 2021 to April 2023 underwent repeat testing for Lp(a) and measurement of OxPL:apoB, EPA and AA levels. OxPL:apoB was measured using chemiluminescent immunoassay. Fatty acid measurements were done via column chromatography/mass spectrometry. Lp(a), OxPL-apoB, EPA, and AA were log e -transformed to satisfy the assumption of normality. Results: We enrolled 238 patients with a mean age of 56.5 ± 13.5 years (46% being female, 69% white, 10% black, 14% Asian). Statin therapy was used in 66%, and mean LDL-C was 87.3 ± 47.5 mg/dL. Median (IQR) Lp(a), OxPL:apoB, AA, and AA:EPA ratio was 167.7 (57.3-233.5) nmol/L, 2.3 (1.2-3.9) nmol/L, 287.3 (234.8-350.2) ug/mL, and 10.3 (6.1-14.9), respectively. Lp(a) correlated with OxPL:apoB (r=0.48, p<0.0001). In multivariate analysis adjusting for age, race, sex, hypertension, LDL-C, statin use and PCSK9 inhibitor use, log-Lp(a) was associated with AA (p=0.002) and log-AA:EPA (p=0.02), but not associated with log-EPA (p=0.19). LogOxPL:apoB was associated with log AA (p=0.03). Conclusion: Higher Lp(a) levels are associated with elevated AA levels, suggesting a pathway by which Lp(a) may contribute to increased platelet aggregation and inflammation in patients with high Lp(a).