Adverse Outcomes Among Women Presenting With Signs and Symptoms of Ischemia and No Obstructive Coronary Artery Disease: Findings From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Angiographic Core Laboratory

Study Questions:

Do outcomes differ among women with signs and symptoms of ischemia, but no obstructive coronary artery disease (CAD)?


Data from the WISE (Women’s Ischemia Syndrome Evaluation) study were used for the present analysis. The WISE study cohort consisted of 917 women presenting with symptoms and/or signs of ischemic heart disease undergoing coronary angiography. Exclusion criteria for WISE included any contraindication to provocative stress testing; thus, enrolled subjects almost exclusively had stable symptoms including typical, atypical, and nonanginal chest pain. Myocardial ischemia was defined as an ischemic response on any noninvasive tests. An angiographic severity score was prospectively developed, assigning points for any stenosis weighted by stenosis severity, location, and collaterals, and was then tested for prediction for adverse outcome in 917 women, over a median of 9.3 years. The primary outcomes included first occurrence of cardiovascular death or nonfatal myocardial infarction. Hospitalization for angina was a secondary outcome.


A total of 917 women had angiograms acceptable for core laboratory analysis and follow-up data. Outcome information was collected for 883 of the women, at a median of 6.0 years. The National Death Index search resulted in outcome information on a total of 917 women and extended follow-up for mortality only, to a median of 9.3 years (median interquartile range, 8.6-10 years). Cardiovascular death or myocardial infarction at 10 years occurred in 6.7%, 12.8%, and 25.9% of women with no, nonobstructive, and obstructive CAD (p < 0.0001), respectively. Cumulative 10-year cardiovascular death or myocardial infarction rates showed progressive, near-linear increases for each WISE CAD severity score range of 5, 5.1-10, 10.1-20, 20.1-50, and >50. The optimal threshold in the WISE severity score classifications for predicting cardiovascular mortality was >10 (e.g., 5.0-10 vs. 10.1-89), with both a sensitivity and specificity of 0.64 and an area under the curve of 0.64 (p = 0.02, 95% confidence interval, 0.59-0.68).


The investigators concluded that among women with signs and symptoms of ischemia, nonobstructive CAD is common and associated with adverse outcomes over the longer term. The new WISE angiographic score appears to be useful for risk prediction in this population.


These data suggest that the WISE angiographic score may provide clinically useful information. Further validation in other populations is warranted.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Coronary Artery Disease, Myocardial Infarction, Women, Myocardial Ischemia, Follow-Up Studies, Coronary Angiography, Chest Pain, Cardiovascular Diseases, Confidence Intervals, United States

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