title: Obesity is associated with poor response to clopidogrel and an increased susceptibility to protease activated receptor-1 mediated platelet activation.
abstract: Obesity is associated with a prothrombotic state resulting from increased thrombin generation, platelet hyper-reactivity, and decreased fibrinolysis. Data on the influence of obesity on clopidogrel-mediated platelet inhibition are conflicting and limited to platelet function tests. Moreover, there are no data on thrombin-inducible platelet activation in obese patients. We therefore investigated response to clopidogrel therapy and protease activated receptor (PAR)-1 mediated platelet activation in obese and nonobese patients undergoing angioplasty and stenting for cardiovascular disease. The vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, multiple electrode aggregometry (MEA) with adenosine diphosphate (ADP), and surface expressions of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to ADP and thrombin receptor activating peptide (TRAP)-6 were assessed in 71 obese and 245 nonobese patients. Obesity was independently associated with higher residual platelet reactivity by the VASP assay and MEA ADP, and with platelet surface expressions of P-selectin and activated GPIIb/IIIa in response to ADP (all P ≤ 0.04). Further, high on-treatment residual ADP-inducible platelet reactivity by the VASP assay and by MEA ADP were significantly more frequent in obese patients compared with nonobese patients (both P ≤ 0.04). Finally, PAR-1 mediated platelet activation as assessed by expression of P-selectin and activated GPIIb/IIIa in response to TRAP-6 was significantly more pronounced in obese patients than in patients without obesity (both P ≤ 0.02). In conclusion, obese patients undergoing angioplasty and stenting exhibit a diminished response to clopidogrel and an increased susceptibility to TRAP-6 inducible platelet activation.
authors: Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria. thomas.gremmel@meduniwien.ac.at
authors: Thomas
authors: T
authors: Gremmel
authors: Sabine
authors: S
authors: Steiner
authors: Daniela
authors: D
authors: Seidinger
authors: Renate
authors: R
authors: Koppensteiner
authors: Simon
authors: S
authors: Panzer
authors: Christoph W
authors: CW
authors: Kopp
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D017130:Angioplasty / Q000009:adverse effects; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D019007:P-Selectin / Q000097:blood; D010750:Phosphoproteins / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000097:blood*; D015607:Stents / Q000009:adverse effects; D013927:Thrombosis / Q000097:blood* / Q000209:etiology* / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D057170:Translational Research, Biomedical; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D044463:Receptor, PAR-1; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine