Lipoxin concentration in high-risk participants taking aspirin: a potential mechanism of action

Lipoxins are endogenous inflammatory mediators that are shown to be upregulated with aspirin (ASA) exposure in several populations. Our objective was to describe lipoxin levels in high-risk women at baseline and with ASA exposure. This open-label randomized trial recruited participants defined as high risk for pre-eclampsia per the USPSTF major criteria. Participants were randomized to 81mg or 162mg of ASA prophylaxis and analyzed based on dose exposure or grouped as high-risk ASA-exposed. A separate cohort recruited simultaneously of low-risk patients without major criteria served as controls. Serum samples were obtained at 11-16 and 28-32 weeks’ gestation. Lipoxin (LXA4) and C-reactive protein (CRP) in maternal plasma were quantified using Cayman Lipoxin A4 ELISA and hsCRP protein enzyme immunoassay. We utilized t-tests and simple linear regression. 56 low risk and 104 high-risk participants were included (47 taking 81mg; 57 taking 162mg ASA). Demographic characteristics differed between groups as expected (Table 1). CRP was significantly correlated with LXA4 concentration at enrollment for the total population (P=0.03) and was higher in high risk participants (P=.04). LXA4 concentrations were significantly lower in high-risk vs. low-risk participants at enrollment (P< 0.0001, Table 2). Over the midtrimester, Lipoxin concentrations decreased for both low and high-risk groups, but this decline was significantly lower in the aspirin-exposed patients, P=.007. This change in LXA4 concentration, termed delta, was not correlated with CRP concentration in the third trimester or with a change in CRP between enrollment and the third trimester suggesting an independent action related to aspirin exposure. In pregnancy, aspirin exposure appears to preserve lipoxin concentration suggesting a possible mechanism of action for prophylaxis. This observation is consistent with other populations treated with this medication outside of obstetrics.View Large Image Figure ViewerDownload Hi-res image Download (PPT)