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 WISE Study of Women and Heart Disease Yields Important Findings on Frequently Undiagnosed Coronary Syndrome 
by National Institutes of Health - 1/31/2006
In as many as 3 million U.S. women with coronary heart disease, cholesterol plaque may not build up into major blockages, but instead spreads evenly throughout the artery wall. As a result, diagnostic coronary angiography reveals that these women have ?clear? arteries — no blockages — incorrectly indicating low risk. Despite this, many of these women have a high risk for heart attack, according to newly published research from the National Institutes of Health.

In women with this condition, called coronary microvascular syndrome, plaque accumulates in very small arteries of the heart, causing narrowing, reduced oxygen flow to the heart, and pain that can be similar to that of people with blocked arteries, but the plaque does not show up when physicians use standard tests. As a result, many women go undiagnosed, according to findings from the National Heart, Lung, and Blood Institute?s (NHLBI) Women?s Ischemia Syndrome Evaluation (WISE) study. Insights from the study are published in a special supplement to the February 6 issue of the Journal of the American College of Cardiology, available online January 31.

"When a diagnosis of this condition is missed, women are not treated for their angina and high cholesterol and they remain at high risk for having a heart attack," said NHLBI Director Elizabeth G. Nabel, M.D. "This study and the high prevalence of coronary microvascular dysfunction demonstrate that we must think out of the box when it comes to the evaluation and diagnosis of heart disease in women."

The National Institutes of Health initiated WISE in 1996 to increase scientific knowledge about ischemic heart disease in women. WISE aimed to develop accurate diagnostic approaches for ischemic heart disease detection in women, to better understand the ways in which heart disease develops in women including the significance of ischemia without coronary blockages in women, and to evaluate the influence of hormones, on ischemic heart disease development and diagnosis.

'So much of our understanding of the underpinnings of heart disease and heart attack, and the basis for our standard methods of diagnosis and treatment are the result of research conducted on men,? said C. Noel Bairey Merz, Cedars-Sinai Medical Center and the WISE study chairperson. ?Through clinical experience, many critical questions arose about how the disease may manifest differently in women, and how diagnostic techniques may need to be used differently in order to prevent more heart attacks and save lives."

WISE investigators found that the majority of women with ?clear? angiography who are not diagnosed will continue to have symptoms, a declining quality of life, and repeated hospitalizations and tests.

"Through WISE, we have made tremendous progress toward better understanding of heart disease in women. Too often women are tested again and again, go untreated, and still have high risk for heart attacks," said George Sopko, MD, NHLBI project officer for WISE. "As clinicians we must systematically examine women for evidence of any blockages and initiate intensive treatment for their risk factors."

Authors of six review papers providing insight on WISE conclude that the study has provided the groundwork for additional controlled clinical studies of diagnostic tools and treatments in women with ischemic heart disease.

Additional study conclusions from WISE appear in the same JACC edition:

  • Identifying Candidates for Exercise Stress Testing: Using the evaluative tool Duke Activity Status Index (DASI) in women with heart disease symptoms prior to stress testing can help determine who would be eligible for an exercise stress test versus a stress test using intravenous medications to increase the heart load instead of exercise. Current guidelines offer physicians little guidance on how to identify women who would not be able to sufficiently complete the exercise test. The DASI has been previously validated as a useful tool for determining functional capacity.

  • Low Coronary Flow and Scores on Function Test Indicate Poor Outcomes: Women who have low DASI scores also have lower coronary flow velocity, a combination which may explain the poor outcomes seen for women with heart disease but no blocked arteries.

  • Role of Pre-menopausal Hypertension in Disease Risk: Women who have high blood pressure before menopause, especially high systolic blood pressure, should be considered at a higher risk and treated accordingly.


To interview a scientist about this study, contact the NHLBI Communications Office at (301) 496-4236.

NHLBI is part of the National Institutes of Health (NIH), the Federal Government?s primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services. NHLBI press releases and other materials including information about women and heart disease are available online at

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

Provided by National Institutes of Health on 1/31/2006
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