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Cardiovascular Risk in Women With Non-Specific Chest Pain (from the Women's Health Initiative Hormone Trials)

  • Jennifer G. Robinson
    Correspondence
    Corresponding author: Tel: 319-384-5040; fax: 319-384-5004
    Affiliations
    Department of Epidemiology, University of Iowa, Iowa City, Iowa

    Department of Medicine, University of Iowa, Iowa City, Iowa
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  • Robert Wallace
    Affiliations
    Department of Epidemiology, University of Iowa, Iowa City, Iowa

    Department of Medicine, University of Iowa, Iowa City, Iowa
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  • Marian Limacher
    Affiliations
    Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida
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  • Hong Ren
    Affiliations
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
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  • Barbara Cochrane
    Affiliations
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
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  • Sylvia Wassertheil-Smoller
    Affiliations
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
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  • Judith K. Ockene
    Affiliations
    Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
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  • Patricia L. Blanchette
    Affiliations
    Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Manoa, Hawaii
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  • Marcia G. Ko
    Affiliations
    Division of Women's Health, Mayo Clinic, Scottsdale, Arizona
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  • Author Footnotes
    † Conflicts of interest: Dr. Robinson has received grants from Abbott Laboratories, Abbott Park, Illinois; AstraZeneca, Wilmington, Delware; Bristol-Myers Squibb, New York, New York; GlaxoSmithKline, Research Triangle Park, North Carolina; Hoffman-La Roche, Nutley Park, New Jersey; Merck & Company, Whitehouse Station, New Jersey; Pfizer, New York, New York; Procter & Gamble, Cincinnati, Ohio; Daiichi Sankyo, Parsippany, New Jersey; Schering-Plough, Kenilworth, New Jersey; and Takeda Pharmaceutical Company, Osaka, Japan. Dr. Robinson has received speaker honoraria for education programs from Merck & Company and Pfizer. Dr. Robinson has received honoraria from Reliant Pharmaceuticals, Liberty Corner, New Jersey. Dr. Robinson is a consultant and advisory board member for Merck & Company. Dr. Wallace has received grants and research funding from the National Institutes of Health, Bethesda, Maryland, and Pfizer. Dr. Wallace is a consultant for Merck & Company. Dr. Wallace is a member of the Clinical Trial Monitoring Board for Novartis, East Hanover, New Jersey. Dr. Limacher has received a research grant from Boehringer Ingelheim, Ridgefield, Connecticut.
    ‡ A list of participating investigators and institutions is provided in the Appendix.
      Women discharged with diagnoses of nonspecific chest pain (NSCP) may be at increased risk for subsequent coronary artery disease (CAD) events. The influence of hormone therapy on NSCP is unknown. The Women's Health Initiative (WHI) enrolled postmenopausal women aged 50 to 79 years. The duration of follow-up was 7.1 years in the WHI Estrogen-Alone trial (E-Alone) and 5.6 years in the WHI Estrogen Plus Progestin trial (E+P). After excluding women with previous cardiovascular disease, 9,427 women in E-Alone and 15,105 women in E+P were included in this analysis. NSCP, defined as having a primary hospital discharge diagnosis of NSCP by International Classification of Diseases, Ninth Revision, code, was reported in 322 women in E-Alone and 249 in E+P. Risks for subsequent CAD events were estimated using intent-to-treat Cox proportional-hazards models stratified by clinic and adjusted for age and other risk factors. In the fully adjusted models of the combined trials, women with NSCP had a twofold greater risk for subsequent nonfatal CAD events, including nonfatal myocardial infarction (2.3% vs 1.7%, hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.11 to 3.98), revascularization (3.5% vs 2.6%, HR 1.99, 95% CI 1.20 to 3.30), and hospitalized angina (3.7% vs 2.3%, HR 2.39, 95% CI 1.46 to 3.92). Hormone therapy did not appear to have a significant effect on either the incidence of NSCP hospitalizations (E-Alone: HR 1.04, 95% CI 0.81 to 1.32; E+P: HR 0.78, 95% CI 0.59 to 1.02) or the risk for a subsequent CAD event. In conclusion, a hospitalization for NSCP doubles the risk for a subsequent CAD event in postmenopausal women over the next 5 to 7 years and identifies them as candidates for aggressive risk factor treatment.
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