Detection of Silent Myocardial Ischemia in Asymptomatic Diabetic Subjects

The DIAD study

  1. Frans J.Th. Wackers, MD1,
  2. Lawrence H. Young, MD1,
  3. Silvio E. Inzucchi, MD2,
  4. Deborah A. Chyun, PHD3,
  5. Janice A. Davey, MSN1,
  6. Eugene J. Barrett, MD4,
  7. Raymond Taillefer, MD5,
  8. Steven D. Wittlin, MD6,
  9. Gary V. Heller, MD7,
  10. Neil Filipchuk, MD8,
  11. Samuel Engel, MD9,
  12. Robert E. Ratner, MD10,
  13. Ami E. Iskandrian, MD11 and
  14. for the Detection of Ischemia in Asymptomatic Diabetics (DIAD) Investigators*
  1. 1Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
  2. 2Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
  3. 3Yale University School of Nursing, New Haven, Connecticut
  4. 4Department of Medicine/Endocrinology, University of Virginia, Charlottesville, Virginia
  5. 5Department of Nuclear Medicine, University of Montreal, Montreal, Canada
  6. 6Department of Medicine/Endocrinology, University of Rochester, Rochester, New York
  7. 7Hartford Hospital, Hartford, Connecticut
  8. 8Cardiology Consultants, Calgary, Canada
  9. 9Soundview Research Associates, Norwalk, Connecticut
  10. 10MedStar Research Institute, Washington, DC
  11. 11Department of Medicine/Cardiovascular Disease, University of Alabama, Birmingham, Alabama
  1. Address correspondence and reprint requests to Frans J. Th. Wackers, MD, Yale University School of Medicine, Section of Cardiovascular Medicine, 333 Cedar St., Fitkin-3, New Haven, CT 06520. E-mail: frans.wackers{at}yale.edu

Abstract

OBJECTIVE—To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines.

RESEARCH DESIGN AND METHODS—In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50–75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission–computed tomography myocardial perfusion imaging.

RESULTS—A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio [OR] 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion (n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia.

CONCLUSIONS—Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.

Footnotes

  • *

    ↵* A complete list of the Detection of Ischemia in Asymptomatic Diabetes (DIAD) Investigators can be found in the appendix.

  • F.J.Th.W. has received honoraria and consulting fees from Bristol-Myers Squibb Medical Imaging and Fujisawa; has received grant/research support from Bristol-Myers Squibb Medical Imaging, Fujisawa, AstraZeneca, and Mitsubishi; and has served on advisory boards for AstraZeneca and Mitsubishi. L.H.Y., D.A.C., J.A.D., and S.D.W. have received grant/research support from Bristol-Myers Squibb Medical Imaging and Fujisawa. S.E.I. has received honoraria and grant/research support from Bristol-Myers Squibb Medical Imaging. R.T. holds stock in and has received grant/research support from Bristol-Myers Squibb Medical Imaging. S.E. has received grant/research support from Bristol-Myers Squibb Medical Imaging. R.E.R. holds stock in and has received grant/research support from Bristol-Myers Squibb Medical Imaging. A.E.I. has received honoraria from Fujisawa and grant/research support from CV Therapeutics, Fujisawa, Berlex, and Amersham.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted May 5, 2004.
    • Received February 9, 2004.
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  1. doi: 10.2337/diacare.27.8.1954 Diabetes Care August 2004 vol. 27 no. 8 1954-1961
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