(422) Are aspirin-inducible Lipoxin (LXA4) concentrations correlated with Biomarkers for Endothelial Dysfunction?

Placental growth factor (PLGF) and soluble intercellular adhesion molecule-1 (sICAM) are biomarkers for endothelial growth and damage. Lipoxins (LXA₄) are eicosanoids involved in elimination of reactive oxygen species, inhibition of neutrophil chemotaxis, and correlated with inflammatory cytokines, also affected by aspirin exposure in pregnancy.

Study Design:

This was a secondary analysis of a randomized trial enrolling patients at high risk for pre-eclampsia by USPSTF criteria. A convenience control group was also recruited without risk factors during the same interval. Dosing began prior to 16 weeks' gestation in the high-risk patients, who were treated with either 81 mg or 162 mg of aspirin. Serum specimens were collected at enrollment and at 28-32 weeks.

Results:

160 patients were included: 56 were controls, 47 received 81mg, and 57 assigned to 162mg. See Table 1. In low-risk control patients, LXA₄ and PLGF concentrations were significantly inversely related during the first trimester (p=0.0008, Figure 1a); but conversely, a positive correlation was seen between LXA4 and PLGF in the third trimester (p=0.02, Figure 1b). For high-risk patients, no correlation between LXA₄ and PLGF was seen at either time point. There was no correlation with sICAM and LXA₄ during the first or third trimester in either the low-risk or high-risk subpopulations (p >0.05). The high-risk patients with hypertension, pre-gestational diabetes or history of preterm pre-eclampsia were examined separately. No correlation between LXA₄ and PLGF, or LXA₄ and sICAM was noted at any time point in these subpopulations but the sample sizes were limited for particular comparisons (p >0.05).

Conclusion:

In low-risk patients, PLGF and LXA₄ are related during pregnancy. These data do not suggest a mechanism of LDA to alter biomarkers of endothelial growth or damage, but a beta-error is possible. The group of patients at high-risk for pre-eclampsia are diverse, which may further limit observed relationships related to these measures.