Aspirin has a gender-dependent impact on Antiinflammatory 15-epi-lipoxin A4 formation -: A randomized human trial

Objective - Aspirin blocks thromboxane production that contributes to its well-appreciated antiplatelet action. Aspirin also initiates the biosynthesis of novel antiinflammatory mediators from arachidonic acid, namely aspirin-triggered 15-epi-lipoxin A(4). We recently conducted a double-blinded clinical trial with healthy subjects in whom low-dose aspirin (81 mg daily) significantly increased aspirin-triggered 15-epi-lipoxin A(4) and concomitantly inhibited thromboxane. Here, we assessed whether plasma aspirin - triggered 15-epi-lipoxin A(4) was age or gender dependent in subjects taking low-dose aspirin. Methods and Results - A total of 128 subjects were allocated to: placebo, 81, 325, or 650 mg daily aspirin for an 8-week period. Plasma thromboxane B-2 and aspirin-triggered 15-epi-lipoxin A(4) were assessed from blood collected at baseline and the conclusion of the trial. We then performed a post-trial analysis in the group receiving low-dose aspirin. In female subjects, we found a positive correlation between age and aspirin-triggered 15-epi-lipoxin A(4) (increase of 0.37 ng/mL per decade), and a negative correlation was observed in men (decrease of 0.29 ng/mL per decade). These trends were significantly different from each other (P = 0.045). Conclusions - Low-dose aspirin has a gender-specific impact on aspirin-triggered 15-epi-lipoxin A(4) production, which may contribute to the gender-dependent clinical benefits of aspirin. Also, they may provide a molecular rationale for low-dose aspirin therapies in elderly women to reduce inflammation-related disorders.