on November 17, 2005
Published online before print November 17, 2005, doi: 10.1161/01.ATV.0000196729.98651.bf
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Submitted on September 8, 2005
Accepted on November 3, 2005
Aspirin Has A Gender-Dependent Impact on Antiinflammatory 15-Epi-Lipoxin A4 Formation. A Randomized Human Trial
Nan Chiang ;
From the Center for Experimental Therapeutics and Reperfusion Injury (N.C., C.N.S.), Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Cardiovascular Disease Prevention and the Donald W. Reynolds Center for Cardiovascular Research (P.M.R.), and Department of Medicine (S.H.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.
* To whom correspondence should be addressed. E-mail: cnserhan{at}zeus.bwh.
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-lipoxinA4. 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-lipoxinA4 and concomitantly inhibited thromboxane. Here, we assessed whether plasma aspirin-triggered 15-epi-lipoxinA4 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 thromboxaneB2 and aspirin-triggered 15-epi-lipoxinA4 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-lipoxinA4 (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-lipoxinA4 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.
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