title: Relation between atherosclerosis risk factors and aspirin resistance in a primary prevention population.
abstract: Resistance to inhibition of platelet function by aspirin may contribute to future myocardial infarction and stroke. Adverse cardiovascular outcomes have been associated with aspirin resistance on several different platelet function assays, including the level of urinary 11-dehydro thromboxane B2 (Tx-M), platelet aggregation to arachidonic acid and adenosine diphosphate, and closure time on the platelet function analyzer-100. We examined the concordance of these aspirin-resistance assays and their relation to cardiovascular risk factors in a primary prevention population. Asymptomatic patients (n = 1,311) at increased risk for coronary heart disease were evaluated before and after 2 weeks of aspirin (81 mg/day). Aspirin resistance was defined according to published criteria for these 3 assays of platelet function. Subjects were characterized for the presence of atherosclerosis risk factors. Agreement among the 3 assays was poor. Only 5 patients met aggregation criteria for aspirin resistance. Attenuated suppression of urinary Tx-M by aspirin was associated with a greater atherosclerotic risk profile and Framingham risk score in multivariable regression analysis. Aspirin resistance by platelet function analyzer-100 was associated only with increased von Willebrand factor levels and not with atherosclerotic risk profile. In conclusion, in a primary prevention population, different published criteria for aspirin resistance classify distinct groups of patients as aspirin resistant with very little overlap. Higher Tx-M, which reflects decreased suppression of thromboxane production in vivo, is the only criterion associated with atherosclerosis risk factors, suggesting that this measurement may represent the most relevant approach for identifying asymptomatic subjects whose aspirin treatment will "fail."
authors.affiliation: Division of Cardiac Surgical Intensive Care, Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. nfaraday@jhmi.edu
authors.forename: Nauder
authors.initials: N
authors.lastname: Faraday
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Yanek
authors.forename: Jesus Enrique
authors.initials: JE
authors.lastname: Herrera-Galeano
authors.forename: Jodi B
authors.initials: JB
authors.lastname: Segal
authors.forename: Taryn F
authors.initials: TF
authors.lastname: Moy
authors.forename: Paul F
authors.initials: PF
authors.lastname: Bray
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000097:blood / Q000517:prevention & control* / Q000652:urine; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D012307:Risk Factors; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D014914:Whole Blood Coagulation Time
chemical_list: D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C049235:11-dehydro-thromboxane B2; D001241:Aspirin