763: Aspirin-triggered Lipoxin A4 is Diminished in Obese Pregnant Women at Risk for Developing Preeclampsia

Low-dose aspirin (LDA) has been recommended in high risk pregnancies for preeclampsia (PE) prevention, but the precise mechanism of action is not known. LDA has a direct impact on the lipoxin (LX) circuit by triggering the biosynthesis of endogenous epimers of LX, termed aspirin-triggered 15-epi-LXA4, that share the potent anti-inflammatory actions of LX. Obesity is associated with low-grade systemic inflammation and a known risk factor for preeclampsia. Therefore, we investigated the influence of obesity on plasma 15-epi-LXA4 levels in high risk women treated with LDA. This was a secondary analysis of a prospective multi-centered study investigating the effect of LDA (60 mg) administration in women at high risk for PE. Maternal plasma samples were drawn at 2 time points: before LDA intake between 13-26 weeks and between 24-28 weeks (at least 2 weeks after starting daily LDA). Patients were stratified by body mass index (non-obese, BMI < 30; obese, BMI ≥30). Plasma 15-epi-LXA4 levels were measured by sandwich ELISA (range 0-20 ng/ml; sensitivity 0.625 ng/ml). Values were analyzed by Shapiro-Wilk test for normality and median levels were calculated by Mann-Whitney U test. Percent change for pre- and post- LDA was calculated. A total of 63 patients were included in the analysis: 42 (56%) and 21 (34%) in the non-obese (BMI < 30) and obese (BMI ≥30) groups, respectively. Absolute levels of 15-epi-LXA4 were significantly lower in obese compared to non-obese women prior to starting LDA (1.288 [IQR] 0.794 - 2.048 ng/mL vs 1.90 [1.216 - 2.511] ng/mL; p=0.03). Obese women manifested a higher percent change of 15-epi-LXA4 after daily use of LDA compared to non-obese women (11.7 [-11.9 - 76.5%] vs -3.31 [-16.962 - 9.158%]; p=0.04). (Figure 1) Obese women have lower absolute levels of 15-epi-LXA4 compared to non-obese women. Daily use of LDA increases biosynthesis of 15-epi-LXA4 in obese women compared to non-obese women at high risk for developing PE. These data suggest a possible mechanism of action for LDA in obese women for PE prevention.