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)

Circulation. 2004 Jun 22;109(24):2993-9. doi: 10.1161/01.CIR.0000130642.79868.B2. Epub 2004 Jun 14.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analysis*
  • Aged
  • Angina, Unstable / epidemiology
  • Cardiac Catheterization / statistics & numerical data
  • Cohort Studies
  • Coronary Angiography
  • Coronary Stenosis
  • Cost-Benefit Analysis
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hand Strength
  • Health Care Costs
  • Heart Failure / epidemiology
  • Heart Failure / etiology
  • Hospitalization / statistics & numerical data
  • Humans
  • Life Tables
  • Magnetic Resonance Spectroscopy
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Ischemia / economics
  • Myocardial Ischemia / epidemiology*
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / mortality
  • Myocardial Ischemia / pathology
  • Myocardium / chemistry
  • Outcome Assessment, Health Care
  • Phosphocreatine / analysis*
  • Prognosis
  • Risk Factors
  • Stroke / epidemiology
  • United States / epidemiology


  • Phosphocreatine
  • Adenosine Triphosphate