Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long-Term Outcome After Cardiac Surgery.

BACKGROUND: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome. METHODS AND RESULTS: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11-dehydrothromboxane B CONCLUSIONS: Long-term nonplatelet thromboxane generation after coronary artery bypass graft surgery is a novel risk factor for 5-year adverse outcome, including death. In contrast, nonplatelet thromboxane generation in the early postoperative period appears to be driven predominantly by inflammation and did not independently predict long-term clinical outcome

A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.

BACKGROUND: Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PlA2, of the gene encoding glycoprotein IIIa in kindreds with a high prevalence of premature myocardial infarction. METHODS: To investigate the relation between the PlA2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infarction or unstable angina and 68 inpatient controls without known heart disease. The groups were matched for age, race, and sex. We used two methods to determine the PlA genotype: reverse dot blot hybridization and allele-specific restriction digestion. RESULTS: The prevalence of PlA2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P=0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of PlA2 was 50 percent, a value that was 3.6 times that among control subjects under 60 years of age (13.9 percent, P=0.002). Among subjects with the PlA2 polymorphism, the odds ratio for having a coronary event was 2.8 (95 percent confidence interval, 1.2 to 6.4). In the patients less than 60 years of age at the onset of disease, the odds ratio was 6.2 (95 percent confidence interval, 1.8 to 22.4). CONCLUSIONS: We observed a strong association between the PlA2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years

Non-Platelet Thromboxane Generation is an Independent Predictor of Late-Term Mortality After Coronary After Bypass Graft Surgery

Aim Non-platelet thromboxane generation, measured by urinary 11-dehydroTXB2 in subjects on aspirin therapy, has been shown to be independently associated with vein graft thrombosis 6 months after coronary artery bypass graft (CABG) surgery. We investigated its ability to predict, along with other patient demographic, clinical and laboratory factors, late-term outcome after CABG surgery. Methods:We analyzed data from 293 subjects enrolled in the multicenter Reduction in Graft Occlusion Rates study who were on aspirin therapy and survived to graft patency assessment 6 months after CABG surgery. The primary endpoint was the composite of mortality, myocardial infarction (MI), stroke and repeat revascularization with mortality as a secondary endpoint. Post-operative events prior to the 6 month evaluation (194±30 days) were excluded. Proportional hazard Cox survival modeling was used to assess determinants of outcome. Predictors reaching significance (unadjusted p Results: There were 67 primary endpoints, including 26 mortalities, during a mean follow-up period of 1566±484 days. Independent predictors of outcome on multivariate modeling are shown below. Conclusions: Non-platelet thromboxane generation 6-months after CABG surgery is a significant independent predictor of late-term events, including mortality