Abstract 12704: The Antiplatelet Effect of Aspirin is Impaired by Serum Lipids in Patients With Diabetes Mellitus
Introduction: The antiplatelet action of acetylsalicylic acid (ASA) is variable. We studied whether the inhibition of thromboxane (TX) synthesis by ASA is altered in patients with diabetes, a condition often associated with increased serum concentrations of nonesterified free fatty acids (NEFA).
Methods: Adult patients (n=43) with type 1 or 2 diabetes were included (age range 19-69 years). Venous blood was drawn after overnight fasting and allowed to coagulate (30 min, 37°C) in the presence of 0, 30 and 100 µmol/L ASA. Platelet-derived TX was measured by immunoassay. NEFA were determined by the ACS-ACOD assay. Moreover, arachidonic acid-induced aggregation and flow cytometry were used to determine whether NEFA or lipoproteins (LDL, VLDL, HDL) interfere with platelet inhibition by ASA in vitro.
Results: In diabetic patients, the inhibition of TX synthesis by ASA (30 and 100 µmol/L) largely varied between subjects (30 µmol/L: range 2-92 %, median 15.4 %; 100 µmol/L: range 0-25 %, median 0.9 %). The patients were divided into 'poor' (inhibition less than median) or 'good' responders (equal & greater median) according to TX inhibition by 30 µmol/L ASA. NEFA concentrations were lower in serum of good compared with poor responders (0.6±0.1 vs. 1.0±0.2 mmol/L, p=0.01). This led us to hypothesize that NEFA may interfere with platelet inhibition by ASA. Indeed, subsequent measurements with platelets from healthy donors demonstrated that biologically relevant NEFA concentrations (e.g. palmitic and oleic acid) interfere with platelet inhibition by ASA, suggesting that NEFA compete with ASA at the active site of platelet cyclooxygenase (COX-1). P-selectin expression (flow cytometry) also revealed an impaired platelet inhibition by ASA in the presence of NEFA. Moreover, both LDL (100 mg/dL) and HDL (30 mg/dL) significantly (p<0.05) attenuated the inhibition of platelet aggregation by ASA (ASA alone: 100±0 %, ASA+LDL: 56±6 %, ASA+HDL: 73±7 %). VLDL did not interfere with ASA.
Conclusions: Increased serum concentrations of NEFA are associated with an impaired inhibition of platelet TX synthesis by ASA in blood samples of diabetic patients. This may be explained by an interaction of NEFA and lipoproteins (LDL, HDL) with the antiplatelet effect of ASA.
- © 2011 by American Heart Association, Inc.