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Women's Ischemia Syndrome Evaluation (WISE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00000554
Recruitment Status : Completed
First Posted : October 28, 1999
Last Update Posted : April 4, 2014
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE October 27, 1999
First Posted Date  ICMJE October 28, 1999
Last Update Posted Date April 4, 2014
Study Start Date  ICMJE May 2001
Actual Primary Completion Date April 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Women's Ischemia Syndrome Evaluation (WISE)
Official Title  ICMJE Not Provided
Brief Summary To evaluate innovative diagnostic methods that will improve the diagnostic reliability of cardiovascular testing in evaluation of ischemic heart disease in women. Innovative approaches proposed include physiologic or functional measurements such as impaired metabolism, perfusion, or endothelial function as well as assessment of epicardial coronary arteries by angiography. Other objectives include developing safe, accurate, and cost effective diagnostic approaches for evaluating women with suspected ischemic heart disease, and determining the frequency of myocardial ischemia in the absence of significant epicardial coronary stenosis, as well as the frequency of non-ischemic or non-cardiac chest pain. A key aspect of the WISE study is to determine whether evidence of myocardial ischemia occurs in the absence of obstructive coronary disease.
Detailed Description


Cardiovascular disease exacts a heavy burden on the health of women. Ischemic heart disease claims the lives of nearly 250,000 women in the United States each year. Recognition of ischemic heart disease in women is a major challenge to the primary care physician. Diagnosis of ischemic heart disease requires recognition of clinical symptoms such as chest pain, or events such as a myocardial infarction, which are evaluated by a physician who will confirm the diagnosis with objective tests. Unfortunately, both symptom recognition and diagnostic tests confuse rather than confirm a diagnosis of myocardial ischemia in women. Chest pain syndromes suspicious for myocardial ischemia are common in women. Noninvasive diagnostic methods which often confirm the diagnosis and assess disease severity in men are less reliable in women. This lack of objective data to support the diagnosis of chronic or acute myocardial ischemia may influence the physician's decision to further evaluate women at risk. With precision in diagnosis, efforts to optimize therapies are hampered.

The detection of epicardial coronary atherosclerosis is a major objective in clinical cardiology. The utility of this approach is well established. However, although the presence of atherosclerosis is sufficient to cause myocardial ischemia, whether significant ischemia or risk of ischemia exists in the absence of angiographic epicardial stenosis, is not known and may be important for women.

Recent progress in understanding the pathophysiology of myocardial ischemia provides a more complex causal pathway than the heretofore notion of fixed atherosclerotic obstructions in passive conduits. Diseased arteries which may appear angiographically normal as well as arteries with fixed obstructions can respond to vasomotor influences with a detrimental amount of vasoconstriction. The endothelium generates vasoactive and anticoagulant factors that are important mediators of thrombosis. Cycling hormones may further influence these complex interactions. Methods which do not rely solely on fixed obstruction of epicardial arteries are not only possible but may be useful to recognize early atherosclerosis or, for example, endothelial dysfunction which places the patient at risk for untoward coronary events.

The concept for the study was developed by the Cardiology Advisory Committee in collaboration with staff and was approved by the May 1993 National Heart, Lung, and Blood Advisory Council. The Request for Proposals was released in April 1994.


The Women's Ischemia Syndrome Evaluation (WISE) was a four center study designed to evaluate ischemic heart disease and its pathophysiology in women. WISE testing focused on three areas: 1) optimizing symptom evaluation and diagnostic testing for ischemic heart disease; 2) exploring mechanisms for symptoms and evidence of myocardial ischemia in the absence of epicardial coronary artery disease; 3) evaluating the influence of reproductive hormones on symptoms and diagnostic test response. The WISE core data base included demographic and clinical data, symptom and psychosocial variables, coronary angiography and ventriculography data, blood lipoprotein/homocysteine/lipid peroxidation/genetic/hormone/ phytoestrogen analysis, brachial artery reactivity testing, and resting/ambulatory electrocardiographic (ECG) monitoring. Site specific complementary methods included physiologic and functional cardiovascular assessments of myocardial perfusion and metabolism, ventriculography, endothelial vascular function and coronary angiography. Women were followed for at least one year to assess clinical events and symptom status. In the Phase I (1996-7), a pilot phase, 256 women were studied. Phase II has completed enrolling 1008 women in the study. The WISE study defined contemporary and comprehensive state-of-the-art diagnostic testing to evaluate women with suspected ischemic heart disease, and explore sex specific ischemic heart disease pathophysiology.

The study has been renewed through April, 2005 to extend patient follow-up for a minimum of five years. Dr. Kelsey (U01HL64829) of the Data Coordinating Center at the University of Pittsburgh will continue the follow-up, develop sex-specific incremental outcome models to evaluate the prognostic value of female reproductive variables, assess cost effectiveness of the WISE testing techniques, and continue data analyses. Dr. Reis (U01HL64914) will study the immunologic basis of coronary disease in women, focusing on the role of inflammation and cytokine production. He will measure several cytokines and cytokine-related proteins and genotypes in approximately 900 stored samples from WISE participants. Dr. Pepine (U01HL64924) will study the renin angiotensin system in coronary microvascular dysfunction, focusing on whether polymorphisms of the renin-angiotensin/kallikrein-kinin systems and beta-adrenergic receptors polymorphisms are associated with abnormal coronary microvascular function determined by coronary flow reserve measurements.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Primary Purpose: Diagnostic
Condition  ICMJE
  • Angina Pectoris
  • Cardiovascular Diseases
  • Coronary Disease
  • Heart Diseases
  • Myocardial Ischemia
Intervention  ICMJE
  • Procedure: Angiography, MRI, Dobutamine-Stress Echocardiography, PET,
  • Procedure: Myocardial Contrast Echo, Coronary Flow and Vasomotor Testing
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2007
Actual Primary Completion Date April 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE Women over the age of 18 who have suspected ischemic heart disease.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00000554
Other Study ID Numbers  ICMJE 98
U01HL064829 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University of Pittsburgh
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE University of Pittsburgh
Original Study Sponsor  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Investigator: Sheryl Kelsey University of Pittsburgh
Investigator: Carl Pepine University of Florida
Investigator: Steven Reis University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP