Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects

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Abstract
OBJECTIVE: Platelet aggregation responses to acetylsalicylic acid (ASA) show considerable interindividual variation, the causes of which are largely unknown. We determined whether variation in insulin action is associated with that of ASA on platelets. SUBJECTS: In all, 10 nonobese (age 503 y, BMI 251 kg/m2) and 11 obese (age 522 y, BMI 321 kg/m2) subjects. MEASUREMENTS: Insulin sensitivity of glucose uptake was determined by the euglycemic insulin clamp technique. Platelet aggregation responses to four doses of arachidonic acid (AA) and adenosine diphosphate (ADP) were assessed in platelet-rich plasma before and 1 h after ingestion of 50 mg ASA using Born's turbidometric aggregometer. RESULTS: Whole-body insulin sensitivity (M-value 0–180 min) was 36% lower in the obese (4.50.6) than the nonobese (7.10.6 mg/kg min, PP=0.016 for ANOVA). ADP-induced aggregation at high doses (2 and 3 mol/l) was also less inhibited in the obese group. In vivo insulin sensitivity (r=-0.68, Pr=0.58, P<0.01 for 1 mmol/l AA) were closely correlated with residual aggregation after ASA administration. CONCLUSION: These data demonstrate that obese insulin-resistant subjects have a blunted response to platelet-inhibitory effect of ASA. If this blunted effect is of a single dose of ASA preserved in continuous use, it could contribute to the increased risk of atherothrombosis in insulin-resistant individuals.