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(Circulation. 2004;109:2993-2999.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Prognosis in Women With Myocardial Ischemia in the Absence of Obstructive Coronary Disease

Results From the National Institutes of Health–National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE)

B. Delia Johnson, PhD; Leslee J. Shaw, PhD; Steven D. Buchthal, PhD; C. Noel Bairey Merz, MD; Hee-Won Kim, PhD; Katherine N. Scott, PhD; Mark Doyle, MD; Marian B. Olson, MS; Carl J. Pepine, MD; Jan den Hollander, MD; Barry Sharaf, MD; William J. Rogers, MD; Sunil Mankad, MD; John R. Forder, PhD; Sheryl F. Kelsey, PhD; Gerald M. Pohost, MD

From the Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa (B.D.J., M.B.O., S.F.K.); Atlanta Cardiovascular Research Institute, Atlanta, Ga (L.J.S.); Center for Nuclear Imaging Research, University of Alabama at Birmingham (S.B., J.D.H.); Women’s Health Program, Cedars Sinai Hospital, Los Angeles, Calif (C.N.B.M.); the University of Florida, Gainesville (H.W.K., C.J.P., K.N.S.); Veterans Affairs Medical Center, Gainesville, Fla (K.N.S.); Rhode Island Hospital, Providence (B.S.); the University of Alabama at Birmingham Medical Center, Birmingham (W.J.R.); Western Pennsylvania Allegheny Hospital, Pittsburgh (S.M.); and Keck School of Medicine, University of Southern California, Los Angeles (J.R.F., G.M.P.).

Correspondence to Gerald M. Pohost, MD, Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, 1355 San Pablo St, AHC 117, Los Angeles, CA 90089-9231. E-mail Pohost{at}usc.edu

Received July 17, 2003; de novo received November 20, 2003; revision received March 4, 2004; accepted March 15, 2004.

Background— We previously reported that 20% of women with chest pain but without obstructive coronary artery disease (CAD) had stress-induced reduction in myocardial phosphocreatine–adenosine triphosphate ratio by phosphorus-31 nuclear magnetic resonance spectroscopy (abnormal MRS), consistent with myocardial ischemia. The prognostic implications of these findings are unknown.

Methods and Results— Women referred for coronary angiography for suspected myocardial ischemia underwent MRS handgrip stress testing and follow-up evaluation. These included (1) n=60 with no CAD/normal MRS, (2) n=14 with no CAD/abnormal MRS, and (3) n=352 a reference group with CAD. Cardiovascular events were death, myocardial infarction, heart failure, stroke, other vascular events, and hospitalization for unstable angina. Cumulative freedom from events at 3 years was 87%, 57%, and 52% for women with no CAD/normal MRS, no CAD/abnormal MRS, and CAD, respectively (P<0.01). After adjusting for CAD and cardiac risk factors, a phosphocreatine–adenosine triphosphate ratio decrease of 1% increased the risk of a cardiovascular event by 4% (P=0.02). The higher event rate in women with no CAD/abnormal MRS was primarily due to hospitalization for unstable angina, which is associated with repeat catheterization and higher healthcare costs.

Conclusions— Among women without CAD, abnormal MRS consistent with myocardial ischemia predicted cardiovascular outcome, notably higher rates of anginal hospitalization, repeat catheterization, and greater treatment costs. Further evaluation into the underlying pathophysiology and possible treatment options for women with evidence of myocardial ischemia but without CAD is indicated.

Key Words: prognosis • women • cost-benefit analysis • magnetic resonance imaging • spectroscopy

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