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Background: We tested the hypothesis that genetic variation in thrombotic and inflammatory pathways is independently associated with long-term mortality after coronary artery bypass graft (CABG) surgery., Methods and Results: Two separate cohorts of patients undergoing CABG surgery at a single institution were examined, and all-cause mortality between 30 days and 5 years after the index CABG was ascertained from the National Death Index. In a discovery cohort of 1018 patients, a panel of 90 single-nucleotide polymorphisms (SNPs) in 49 candidate genes was tested with Cox proportional hazard models to identify clinical and genomic multivariate predictors of incident death. After adjustment for multiple comparisons and clinical predictors of mortality, the homozygote minor allele of a common variant in the thrombomodulin (THBD) gene (rs1042579) was independently associated with significantly increased risk of all-cause mortality (hazard ratio, 2.26; 95% CI, 1.31 to 3.92; P=0.003). Six tag SNPs in the THBD gene, 1 of which (rs3176123) in complete linkage disequilibrium with rs1042579, were then assessed in an independent validation cohort of 930 patients. After multivariate adjustment for the clinical predictors identified in the discovery cohort and multiple testing, the homozygote minor allele of rs3176123 independently predicted all-cause mortality (hazard ratio, 3.6; 95% CI, 1.67 to 7.78; P=0.001)., Conclusions: In 2 independent cardiac surgery cohorts, linked common allelic variants in the THBD gene are independently associated with increased long-term mortality risk after CABG and significantly improve the classification ability of traditional postoperative mortality prediction models.

Background: There are little data regarding outcomes in patients with angina and severe coronary artery disease (CAD) treated with medical management. Using the Duke Databank of Cardiovascular Disease, we describe the prevalence and long-term outcomes of patients with angina and multivessel CAD treated medically after catheterization., Methods: Patients undergoing catheterization for angina (chest pain without recent revascularization or myocardial infarction) with severe CAD (>or=75% stenosis in >or=2 epicardial vessels) were identified (n = 8,555). One and five year outcomes in the 32% (n = 2,776) of patients who did not receive revascularization in the 30 days after catheterization were described. Predictors of 1-year death, cardiac rehospitalization, and late revascularization in this population were identified., Results: The population had a median age of 66, were mostly male, had significant comorbidities, and most had prior revascularization. Outcomes were poor at 1 and 5 years: death (11% and 37%), cardiac rehospitalization (29% and 61%), and late revascularization (10% and 27%). The cumulative rate of death, myocardial infarction, late revascularization, or cardiac rehospitalization occurred in 38% at 1 year and 76% at 5 years. Prior coronary artery bypass grafting was the only variable independently associated with protection from death, cardiac rehospitalization, and late revascularization., Conclusions: Medical management after catheterization is a common in patients with severe CAD and angina. Of patients treated with medical management, one third will have a recurrent cardiac event within the first year highlighting the poor outcomes and high utilization of resources by this patient population.

Despite the established benefits of antiplatelet agents in coronary artery disease (CAD), many appropriate patients are not receiving them. We investigated the prevalence of and factors associated with aspirin use and nonuse within a large referral population with CAD. The goal was to identify an approach to increase the use of antiplatelet agents by such patients. We surveyed a subset (n = 2,694) of a large CAD referral population (n = 16,174) to determine the use of aspirin and factors associated with its use or nonuse. The subset was made up of all of the CAD referral population who were considered nonusers of aspirin and a 5% sample of those considered aspirin users. We then extrapolated survey data to the overall population to estimate how many eligible patients were not taking antiplatelet agents. In all, 1,626 (63%) of the surviving patients responded to the survey. Of these, 948 (58%) reported taking aspirin, and 678 (42%) reported no aspirin use. The extrapolated rate of aspirin use in the overall population was 85%. Of 2,367 nonusers, 998 (42%, or 6% of the overall cohort) were eligible for antiplatelet agents but were not taking such therapy. Although the rate of aspirin use in this population was higher than previously reported, an estimated 6% of eligible patients were not receiving antiplatelet therapy.

Despite substantial evidence that antiplatelet therapy saves lives and reduces adverse events in patients with coronary artery disease (CAD), use of the most widely available and lowest cost antiplatelet agent, aspirin, continues to be disappointingly low. In a large database of patients with known CAD, we (1) explored trends in the use of aspirin over time, (2) characterized patients most likely to take aspirin regularly, and (3) estimated the effectiveness of aspirin use by examining long-term outcomes. Using patients entered in the Duke Databank for Cardiovascular Diseases, we explored the use of aspirin from 1969 to 1999. More than 25,000 patients were sent a questionnaire that included several questions about medication use, including 1 question specifically about aspirin. Patients who failed to respond to the questionnaire received a follow-up telephone call. Aspirin use increased substantially over the most recent 4 years in the study, from 59% in 1995 to 81% in 1999. Predictors of aspirin use included younger age, male sex, being a nonsmoker, and having had a myocardial infarction or revascularization procedure. Patients who never took aspirin had a risk ratio for death of 1.85 compared with patients who regularly took aspirin. Despite the well-known beneficial effects of aspirin, too many patients without contraindications to aspirin fail to take it regularly. The health care system currently lacks effective methods to ensure that patients who have CAD have adequate follow-up concerning aspirin use.