from University of Pittsburgh application) This reapplication proposes to extend the follow-up of the Women's Ischemia Syndrome Evaluation (WISE) patients for a minimum of 5 years and is being submitted jointly with the applications, """"""""Altered Renin Angiotensin System as a Mechanism for Coronary Microvascular Dysfunction in Women"""""""" (C. Pepine PI) and """"""""Immunologic Basis For Coronary Disease in Women"""""""" (S.Reis OI). The WISE contract began in September 1996 as a 4-center study to 1) optimize symptom evaluation and diagnostic testing for ischemic heart disease in women: 2) explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenoses: and 3) evaluate the influence of reproductive hormones on symptoms and diagnostic test response. An extensive contemporary database has been assembled on 936 women referred for coronary angiography because of suspected ischemia. Data include demographic, clinical, symptomatic, functional, and psychosocial variables. Coronary angiography and ventriculography data, brachial artery reactivity testing, ECG monitoring, and blood determinations are all assessed by core laboratories, Site-specific-innovative technologies have been used to develop potential markers of myocardial ischemia. We seek to 1) Determine the incremental long- term prognostic value of novel testing developed in WISE: 2) Develop sex- specific incremental outcome models to evaluate the prognostic value of female reproductive variables: 3) Assess the incremental cost effectiveness and resource of the WISE innovative testing techniques as compared with traditional tests: 4) Continue ongoing analyses and ancillary projects, collaborate with other WISE investigators' R01s submitted in this cluster and maintain a WISE database and infrastructure to facilitate further investigations into the mechanisms underlying ischemia syndromes in women. To address these aims, a longer follow-up is necessary. Follow-up will consist of annual telephone contacts by experienced site coordinators. WISE will continue to use the well-established methods to implement study coordination, data management, quality control, statistical analyses, and manuscript preparation. Cox regression models will be used to analysis events with demographics risk factors, diagnostic testing and reproductive factors considered as explanatory variables. A hybrid decision model will be used that compares resource use patterns and sums cost estates. The results of these studies will enhance our understanding of both the significance and pathophysiology of ischemic heart disease in women and serve as a foundation for diagnostic and therapeutic clinical trials aimed at reducing disease- related morbidity and mortality.
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