Circulation. 2002;105:1650-1655
Published online before print March 25, 2002, doi: 10.1161/01.CIR.0000013777.21160.07
Published online before print March 25, 2002, doi: 10.1161/01.CIR.0000013777.21160.07
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(Circulation. 2002;105:1650.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events
From the Department of Medicine, University of Western Australia, Thrombosis and Haemophilia Unit, Royal Perth Hospital, Perth, Australia (J.W.E.); Hamilton Civic Hospitals Research Centre, Hamilton, Canada (J.H., J.I.W.); the Department of Medicine, McMaster University, Hamilton, Canada (J.H., J.I.W., S.Y.); Hemostasis Reference Laboratory, Hamilton Civic Hospitals, Hamilton, Canada (M.J.); the Biostatistics Department, Princess Margaret Hospital, Toronto, Canada (Q.Y.); and Population Health Institute, McMaster University, Hamilton, Canada (S.Y.).
Correspondence to Dr John Eikelboom, Thrombosis and Haemophilia Unit, Royal Perth Hospital, Wellington Street, Perth Box X2213 GPO, Perth WA 6897, Australia. E-mail john.eikelboom{at}health.wa.gov.au
Background— We studied whether aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population.
Methods and Results— Baseline urine samples were obtained from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Using a nested case-control design, we measured urinary 11-dehydro thromboxane B2 levels, a marker of in vivo thromboxane generation, in 488 cases treated with aspirin who had myocardial infarction, stroke, or cardiovascular death during 5 years of follow-up and in 488 sex- and age-matched control subjects also receiving aspirin who did not have an event. After adjustment for baseline differences, the odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of 11-dehydro thromboxane B2, with patients in the upper quartile having a 1.8-times-higher risk than those in the lower quartile (OR, 1.8; 95% CI, 1.2 to 2.7; P=0.009). Those in the upper quartile had a 2-times-higher risk of myocardial infarction (OR, 2.0; 95% CI, 1.2 to 3.4; P=0.006) and a 3.5-times-higher risk of cardiovascular death (OR, 3.5; 95% CI, 1.7 to 7.4; P<0.001) than those in the lower quartile.
Conclusions— In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity.
Key Words: aspirin • thromboxane • atherosclerosis • myocardial infarction • stroke
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