Effect of obesity and serum leptin level on clopidogrel resistance

Clopidogrel inhibits platelet aggregation by blockade of platelet adenosine diphosphate (ADP) P2Y12 receptor. Leptin is the obesity gene product, and its serum level increases with obesity. Platelets have leptin receptors on their surfaces. Hyperleptinemia may induce ADP-mediated platelet aggregation. It has been proposed that clopidogrel effect could be diminished with high serum leptin levels. The aim of the present trial was to further investigate the relationship between serum leptin level and clopidogrel resistance.

A total of 100 subjects who underwent percutaneous coronary intervention were enrolled. Two groups were organized according to presence of clopidogrel resistance, and serum leptin levels were compared. Threshold for clopidogrel resistance and hyperleptinemia were accepted as ≥P2Y12 reaction unit (PRU) 240 and ≥15 ng/mL leptin, respectively. Body mass index (BMI) of 30 kg/m2 or greater was considered obese.

A total of 37% of patients were considered clopidogrel-resistant. Comparison of groups revealed significantly higher clopidogrel resistance (p=0.017) and PRU levels (p=0.001) in hyperleptinemic patients. No significant difference in serum leptin levels (p=0.116) was found. Increased clopidogrel resistance was observed in patients with BMI >30 kg/m2 (p=0.015).

Clopidogrel resistance is more common in obese and hyperleptinemic patients. Dosage should be individualized in these populations.