Abstract 5012: Metabolic Syndrome Associates With Resistance to Aspirin in Patients With Coronary Artery Disease
The ability of aspirin to acetylate cyclooxygenase (COX) ex vivo depends on the oxidation state of the enzyme. This suggests that clinical phenotypes associated with increased endogenous platelet activation, which generates lipid hydroperoxides in the platelet, may impair aspirin’s efficacy. Accordingly, we hypothesized that resistance to aspirin would be associated with metabolic syndrome based on evidence for increased in vivo platelet activation in this condition. We prospectively enrolled patients with coronary artery disease (CAD), who were taking aspirin as part of their outpatient regimen, and provided aspirin 81mg daily for 2 weeks. We optimized compliance with a telephone call mid-study and a pill count. The primary outcome was serum thromboxane B2 (sTxB2) measured by GC/MS, which reflects aspirin’s pharmacological effect. Of 137 patients who completed the study with sufficient data for analysis, the mean age was 65±9 y, blood pressure 126/73, and body mass index 30±5.7 kg/m2; nearly all (99%) had a diagnosis of hypertension and 39 (29%) were diabetic. Ninety (66%) received enteric-coated aspirin (ECASA) and 47 (34%) received chewable aspirin. Twelve patients with sTxB2 >13ng/ml were characterized as resistant to aspirin, as this represented <95% inhibition of the mean sTxB2 levels determined in 60 aspirin-naïve healthy volunteers. All of these resistant patients had metabolic syndrome as defined by the AHA. Exploring this association further in a linear model, we found that the presence of metabolic syndrome significantly associated with higher sTxB2 (log-transformed) (P=0.011), adjusted for age, sex, and formulation of aspirin. In a second linear model, no significant associations were found with the individual components of the metabolic syndrome, indicating that the presence of these components in concert was required to predict incomplete response to aspirin. Although the use of ECASA associated with higher sTxB2 in both linear models (P=0.013), the formulation of aspirin did not correlate with sTxB2 > 13ng/ml. These data suggest that the metabolic syndrome contributes to inadequate platelet inhibition by aspirin in patients with CAD.