Abstract 16658: Greater Post-Aspirin Residual Platelet Aggregation is Associated With Increased Risk of Incident Acute Coronary Syndromes in Healthy Individuals
Background: Platelet aggregation plays an essential role in the pathogenesis of acute coronary syndrome (ACS). Aspirin (ASA), as an inhibitor of the cyclooxygenase-1 (COX-1) and thromboxane-dependent platelet activation pathways, is the mainstay of primary chemoprophylaxis. However, studies have demonstrated that persons still experience an ACS event while on ASA, suggesting that variation in indirect COX-1 pathways may contribute to clinical outcomes. We determined the extent to which an increased risk of incident ACS would be observed in healthy individuals with residual platelet aggregation in an important indirect COX-1 pathway following ASA.
Methods: 1507 apparently healthy individuals with a family history of premature coronary artery disease were enrolled for 2-week therapy with of ASA 81 mg/day. At the end of second week, whole blood impedance aggregometry after collagen-mediated (5ug/mL) platelet aggregation was used to measure maximal platelet aggregation. ACS events during follow-up were adjudicated from medical records by 3 independent reviewers.
Results: At baseline, the mean (SD) age was 46.3 (11.5) years; 57% female; 37% African American; 23% current smokers, 34% hypertensive, and 8% diabetes. During follow-up (mean 5[1.8] years), there were 26 ACS events. Post-ASA residual collagen-mediated platelet aggregation was greater in participants who had an ACS compared with those without ACS (28.5 ohms vs. 24.0 ohms, p<0.001). In an age, sex, race, and cardiovascular risk factors (LDL cholesterol, current smoking, diabetes, and hypertension) adjusted model, one ohm difference in residual collagen-mediated platelet aggregation was strongly associated with a 7% increase in the hazard of an ACS event (HR = 1.07, 95%CI = 1.02 to 1.11, p = 0.002).
Conclusions: Healthy subjects with greater residual collagen-mediated platelet aggregation in an indirect COX-1 pathway after ASA therapy are at significantly higher risk of ACS than subjects with lower aggregation. Platelet aggregation pathways not directly inhibited by ASA may play an important role in the pathogenesis of ACS.
- © 2011 by American Heart Association, Inc.