Nonplatelet thromboxane generation is associated with impaired cardiovascular performance and mortality in heart failure.

Nonplatelet thromboxane generation, stimulated largely by oxidative stress, is a novel mortality risk factor in individuals with coronary artery disease. Though inversely associated with left ventricular ejection fraction (LVEF), a potential role in the pathobiology of heart failure (HF) remains poorly defined. Nonplatelet thromboxane generation and oxidative stress were assessed by measuring urine thromboxane-B2 metabolites (TXB2-M) and 8-isoPGF2α by ELISA in 105 subjects taking aspirin and undergoing right heart catheterization for evaluation of HF, valve disease, or after transplantation. Multivariable logistic regression and survival analyses were used to define associations of TXB2-M to invasive measures of cardiovascular performance and 4-year clinical outcomes. TXB2-M was elevated (>1,500 pg/mg creatinine) in 46% of subjects and correlated with HF severity by New York Heart Association (NYHA) functional class and brain natriuretic peptide level, modestly with LVEF, but not with HF etiology. There was no association of oxidative stress to HF type or etiology but a trend with NYHA functional class. Multiple invasive hemodynamic parameters independently associated with TXB2-M after adjustment for oxidative stress, age, sex, and race with pulmonary effective arterial elastance (Ea pulmonary), reflective of right ventricular afterload, being the most robust on hierarchical analysis. Similar to Ea pulmonary, elevated urinary TXB2-M is associated with increased risk of death (adjusted HR = 2.15, P = 0.037) and a combination of death, transplant, or mechanical support initiation (adjusted HR = 2.0, P = 0.042). Nonplatelet TXA2 thromboxane generation is independently associated with HF severity reflected by invasive measures of cardiovascular performance, particularly right ventricular afterload, and independently predicted long-term mortality risk.NEW & NOTEWORTHY Nonplatelet thromboxane generation in heart failure is independently associated with risk of death, transplant, or need for mechanical support. Measurement of urine thromboxane metabolites using a clinically available assay may be a useful surrogate for invasive measurement of cardiovascular hemodynamics and performance that could provide prognostic information and facilitate tailoring of therapy in patients with heart failure. Inhibiting thromboxane generation or its biological effects is a potential strategy for improving cardiovascular performance and outcomes in heart failure.

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 B2 (11-dhTXB2), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, and death alone. 11-dhTXB2 measured 3 days after surgery did not independently predict outcome, whereas 11-dhTXB2 >450 pg/mg creatinine measured 6 months after surgery predicted the composite end point (adjusted hazard ratio, 1.79; P=0.02) and death (adjusted hazard ratio, 2.90; P=0.01) at 5 years compared with lower values. Additional modeling revealed 11-dhTXB2 measured early after surgery associated with several markers of inflammation, in contrast to 11-dhTXB2 measured 6 months later, which highly associated with oxidative stress. 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.

Medicaid coverage and access to publicly funded opiate treatment.

This observational study examines changes in access to methadone maintenance treatment following Oregon's decision to remove substance abuse treatment from the Medicaid benefit for an expansion population. Access was compared before and after the benefit change for two cohorts of adults addicted to opiates presenting for publicly funded treatment. Propensity score analysis helped model some selective disenrollment from Medicaid that occurred after the benefit change. Logistic regression was used to compare access to methadone by cohort controlling for client characteristics. Opiate users presenting for publicly funded treatment after the change were less than half as likely (OR = 0.40) to be placed in an opiate treatment program compared to the prior year. Further analysis revealed that those with no recent treatment history were less likely to present for treatment after the benefit change. These results have implications for states considering Medicaid cuts, especially if the anticipated increases in illegal activity, emergency room utilization, unemployment, and mortality can be demonstrated.

The impact of managed care on publicly funded outpatient adolescent substance abuse treatment: service use and six-month outcomes in Oregon and Washington.

This study assessed the impact of managed care on publicly funded adolescent substance abuse treatment by comparing differences in service utilization and outcomes across prospective samples from two states: Oregon, which uses managed care practices in service financing and delivery, and Washington, which does not. One hundred and six adolescents from Washington and 94 from Oregon, who entered outpatient substance abuse treatment in 1998 and 1999, completed self-report surveys about their substance use before and after receiving treatment (follow-up rate = 75 percent). In addition, clinical chart reviews conducted at the 6-month follow-up assessed the type and amount of treatment these adolescents received during the study period. It was found that service utilization and treatment outcomes were comparable across the two state samples. The evidence presented here suggests that managed care is capable of delivering substance abuse treatment services of comparable quality to state-administered substance abuse treatment services.

Oregon's transition to a managed care model for Medicaid-funded substance abuse treatment: steamrolling the glass menagerie.

The approval of a Health Care Financing Administration (now called Centers for Medicare and Medicaid Services) 1115 Medicaid waiver in Oregon allowed the state to design and implement an expanded publicly funded health care system, the Oregon Health Plan (OHP). Integral to OHP is the administration of physical and behavioral health services, including outpatient substance abuse treatment, through contracted managed care organizations. The two overarching changes to the outpatient substance abuse treatment system were expanded Medicaid eligibility and new operating procedures for the outpatient substance abuse treatment system. The authors used grounded theory to examine the effects of this transition on the treatment system, with an emphasis on the experiences of treatment providers.

Integration and its discontents: substance abuse treatment in the Oregon Health Plan.

With the creation of the Oregon Health Plan (OHP) in 1994, Oregon placed its Medicaid program under a managed care system. This paper examines the managed care practices of seven health plans serving OHP enrollees between 1996 and 1998. Results indicated that the original vision of integrating substance abuse treatment services with physical care for OHP enrollees evolved into a multilayered, carved-out approach. Factors working against integration included changes in the administration and management of the chemical dependency benefit, financial losses by health plans, and lack of training and incentives for physicians to refer clients to substance abuse treatment.