Women's Ischemia Syndrome Evaluation (WISE)
This study is no longer recruiting patients.
Purpose
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.
Condition
|
Treatment or Intervention |
Phase |
Angina Pectoris Cardiovascular Diseases Coronary Disease Heart Diseases Myocardial Ischemia
|
Procedure: Angiography, MRI, Dobutamine-Stress Echocardiography, PET, Procedure: Myocardial Contrast Echo, Coronary Flow and Vasomotor Testing
|
Phase III
|
MedlinePlus related topics: Angina; Circulatory Disorders; Coronary Disease; Heart Diseases; Heart Diseases--Prevention
Study Type: Interventional
Study Design: Diagnostic
Further Study Details:
Study start: August 1996;
Study completion: April 2005
BACKGROUND: 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.
DESIGN NARRATIVE: 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.
Eligibility
Ages Eligible for Study:
15 Years and above,
Genders Eligible for Study:
Female
Women over the age of 18 who have suspected ischemic heart disease.
Location
Information
Study chairs or principal investigators
Sheryl Kelsey, University of Pittsburgh
Carl Pepine, University of Florida
Steven Reis, University of Pittsburgh
Steven Reis, University of Pittsburgh
More Information
Publications
Merz CN, Kelsey SF, Pepine CJ, Reichek N, Reis SE, Rogers WJ, Sharaf BL, Sopko G. The Women's Ischemia Syndrome Evaluation
(WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol. 1999 May;33(6):1453-61.
Reis SE, Holubkov R, Lee JS, Sharaf B, Reichek N, Rogers WJ, Walsh EG, Fuisz AR, Kerensky R, Detre KM, Sopko G, Pepine CJ.
Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no
obstructive coronary disease. Results from the pilot phase of the Women's Ischemia Syndrome Evaluation (WISE) study. J Am
Coll Cardiol. 1999 May;33(6):1469-75.
Lewis JF, Lin L, McGorray S, Pepine CJ, Doyle M, Edmundowicz D, Holubkov R, Pohost G, Reichek N, Rogers W, Sharaf BL, Sopko
G, Merz CN. Dobutamine stress echocardiography in women with chest pain. Pilot phase data from the National Heart, Lung and
Blood Institute Women's Ischemia Syndrome Evaluation (WISE). J Am Coll Cardiol. 1999 May;33(6):1462-8.
Bittner V, Olson M, Kelsey SF, Rogers WJ, Bairey Merz CN, Armstrong K, Reis SE, Boyette A, Sopko G. Effect of coronary angiography
on use of lipid-lowering agents in women: a report from the Women's Ischemia Syndrome Evaluation (WISE) study. For the WISE
Investigators. Am J Cardiol. 2000 May 1;85(9):1083-8.
Bairey Merz CN, Olson M, McGorray S, Pakstis DL, Zell K, Rickens CR, Kelsey SF, Bittner V, Sharaf BL, Sopko G. Physical activity
and functional capacity measurement in women: a report from the NHLBI-sponsored WISE study. J Womens Health Gend Based Med.
2000 Sep;9(7):769-77.
Olson MB, Kelsey SF, Bittner V, Reis SE, Reichek N, Handberg EM, Merz CN. Weight cycling and high-density lipoprotein cholesterol
in women: evidence of an adverse effect: a report from the NHLBI-sponsored WISE study. Women's Ischemia Syndrome Evaluation
Study Group. J Am Coll Cardiol. 2000 Nov 1;36(5):1565-71.
Rutledge T, Reis SE, Olson M, Owens J, Kelsey SF, Pepine CJ, Reichek N, Rogers WJ, Merz CN, Sopko G, Cornell CE, Matthews
KA. Psychosocial variables are associated with atherosclerosis risk factors among women with chest pain: the WISE study.
Psychosom Med. 2001 Mar-Apr;63(2):282-8.
Sharaf BL, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, Sopko G, Kelsey SF, Holubkov R, Olson M, Miele NJ, Williams
DO, Merz CN. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored
Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory). Am J Cardiol. 2001 Apr 15;87(8):937-41; A3.
Reis SE, Holubkov R, Conrad Smith AJ, Kelsey SF, Sharaf BL, Reichek N, Rogers WJ, Merz CN, Sopko G, Pepine CJ. Coronary microvascular
dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI
WISE study. Am Heart J. 2001 May;141(5):735-41.
Rutledge T, Reis SE, Olson M, Owens J, Kelsey SF, Pepine CJ, Reichek N, Rogers WJ, Merz CN, Sopko G, Cornell CE, Sharaf B,
Matthews KA. History of anxiety disorders is associated with a decreased likelihood of angiographic coronary artery disease
in women with chest pain: the WISE study. J Am Coll Cardiol. 2001 Mar 1;37(3):780-5.
Merz NB, Johnson BD, Kelsey PSF, Reis SE, Lewis JF, Reichek N, Rogers WJ, Pepine CF, Shaw LJ. Diagnostic, prognostic, and
cost assessment of coronary artery disease in women. Am J Manag Care. 2001 Oct;7(10):959-65.
Wild RA, Reis SE. Estrogens, progestins, selective estrogen receptor modulators, and the arterial tree. Am J Obstet Gynecol.
2001 Apr;184(5):1031-9. Review.
Holubkov R, Karas RH, Pepine CJ, Rickens CR, Reichek N, Rogers WJ, Sharaf BL, Sopko G, Merz CN, Kelsey SF, McGorray SP, Reis
SE. Large brachial artery diameter is associated with angiographic coronary artery disease in women. Am Heart J. 2002 May;143(5):802-7.
Reis SE, Olson MB, Fried L, Reeser V, Mankad S, Pepine CJ, Kerensky R, Merz CN, Sharaf BL, Sopko G, Rogers WJ, Holubkov R.
Mild renal insufficiency is associated with angiographic coronary artery disease in women. Circulation. 2002 Jun 18;105(24):2826-9.
Bairey Merz CN, Olson MB, Johnson BD, Bittner V, Hodgson TK, Berga SL, Braunstein GD, Pepine CJ, Reis SE, Sopko G, Kelsey
SF. Cholesterol-lowering medication, cholesterol level, and reproductive hormones in women: the women's ischemia syndrome
evaluation (WISE). Am J Med. 2002 Dec 15;113(9):723-7.
Chen Q, Reis SE, Kammerer CM, McNamara DM, Holubkov R, Sharaf BL, Sopko G, Pauly DF, Merz CN, Kamboh MI. Association between
the Severity of Angiographic Coronary Artery Disease and Paraoxonase Gene Polymorphisms in the National Heart, Lung, and Blood
Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study. Am J Hum Genet. 2003 Jan;72(1):13-22.
Bairey Merz CN, Johnson BD, Sharaf BL, Bittner V, Berga SL, Braunstein GD, Hodgson TK, Matthews KA, Pepine CJ, Reis SE, Reichek
N, Rogers WJ, Pohost GM, Kelsey SF, Sopko G. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal
women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol. 2003 Feb 5;41(3):413-9.
Rutledge T, Reis SE, Olson M, Owens J, Kelsey SF, Pepine CJ, Reichek N, Rogers WJ, Bairey-Merz CN, Sopko G, Cornell CE, Matthews
KA. Socioeconomic status variables predict cardiovascular disease risk factors and prospective mortality risk among women
with chest pain. The WISE Study. Behav Modif. 2003 Jan;27(1):54-67.
Marroquin OC, Holubkov R, Edmundowicz D, Rickens C, Pohost G, Buchthal S, Pepine CJ, Sopko G, Sembrat RC, Meltzer CC, Reis
SE. Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: implications
for clinical practice. Am Heart J. 2003 Apr;145(4):628-35.
Holubkov R, Pepine CJ, Rickens C, Reichek N, Rogers WJ, Sharaf BL, Sopko G, Merz CN, Kelsey SF, Olson M, Smith KM, Reis SE.
Electrocardiogram abnormalities predict angiographic coronary artery disease in women with chest pain: results from the NHLBI
WISE Study. Clin Cardiol. 2002 Dec;25(12):553-8.
Chen Q, Reis SE, Kammerer CM, McNamara DM, Holubkov R, Sharaf BL, Sopko G, Pauly DF, Bairey Merz CN, Kamboh MI. APOE polymorphism
and angiographic coronary artery disease severity in the Women's Ischemia Syndrome Evaluation (WISE) study. Atherosclerosis.
2003 Jul;169(1):159-67.
Chen Q, Reis SE, Kammerer C, Craig WY, LaPierre SE, Zimmer EL, McNamara DM, Pauly DF, Sharaf B, Holubkov R, Bairey Merz CN,
Sopko G, Bontempo F, Kamboh MI. Genetic variation in lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) gene
and the risk of coronary artery disease. Circulation. 2003 Jul 1;107(25):3146-51. Epub 2003 Jun 16.
Johnson BD, Kip KE, Marroquin OC, Ridker PM, Kelsey SF, Shaw LJ, Pepine CJ, Sharaf B, Bairey Merz CN, Sopko G, Olson MB, Reis
SE; National Heart, Lung, and Blood Institute. Serum amyloid A as a predictor of coronary artery disease and cardiovascular
outcome in women: the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation.
2004 Feb 17;109(6):726-32.
Marroquin OC, Kip KE, Kelley DE, Johnson BD, Shaw LJ, Bairey Merz CN, Sharaf BL, Pepine CJ, Sopko G, Reis SE; Women's Ischemia
Syndrome Evaluation Investigators. Metabolic syndrome modifies the cardiovascular risk associated with angiographic coronary
artery disease in women: a report from the Women's Ischemia Syndrome Evaluation. Circulation. 2004 Feb 17;109(6):714-21.
Kip KE, Marroquin OC, Kelley DE, Johnson BD, Kelsey SF, Shaw LJ, Rogers WJ, Reis SE. Clinical importance of obesity versus
the metabolic syndrome in cardiovascular risk in women: a report from the Women's Ischemia Syndrome Evaluation (WISE) study.
Circulation. 2004 Feb 17;109(6):706-13.
von Mering GO, Arant CB, Wessel TR, McGorray SP, Bairey Merz CN, Sharaf BL, Smith KM, Olson MB, Johnson BD, Sopko G, Handberg
E, Pepine CJ, Kerensky RA; National Heart, Lung, and Blood Institute. Abnormal coronary vasomotion as a prognostic indicator
of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome
Evaluation (WISE). Circulation. 2004 Feb 17;109(6):722-5.
Olson MB, Bairey Merz CN, Shaw LJ, Mankad S, Reis SE, Pohost GM, Smith KM, McGorray SP, Cornell CE, Kelsey SF; NHLBI-Sponsored
WISE Study. Hormone replacement, race, and psychological health in women: a report from the NHLBI-Sponsored WISE Study.
J Womens Health (Larchmt). 2004 Apr;13(3):325-32.
Arant CB, Wessel TR, Olson MB, Bairey Merz CN, Sopko G, Rogers WJ, Sharaf BL, Reis SE, Smith KM, Johnson BD, Handberg E, Mankad
S, Pepine CJ; National Heart, Lung, and Blood Institute Women's Ischemia Syndrome Evaluation Study. Hemoglobin level is
an independent predictor for adverse cardiovascular outcomes in women undergoing evaluation for chest pain: results from the
National Heart, Lung, and Blood Institute Women's Ischemia Syndrome Evaluation Study. J Am Coll Cardiol. 2004 Jun 2;43(11):2009-14.
Johnson BD, Shaw LJ, Buchthal SD, Bairey Merz CN, Kim HW, Scott KN, Doyle M, Olson MB, Pepine CJ, den Hollander J, Sharaf
B, Rogers WJ, Mankad S, Forder JR, Kelsey SF, Pohost GM; National Institutes of Health-National Heart, Lung, and Blood Institute.
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. Epub 2004 Jun 14.
Wessel TR, Arant CB, Olson MB, Johnson BD, Reis SE, Sharaf BL, Shaw LJ, Handberg E, Sopko G, Kelsey SF, Pepine CJ, Merz NB.
Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women. JAMA.
2004 Sep 8;292(10):1179-87.
Study ID Numbers:
98
Record last reviewed:
September 2004
Record first received:
October 27, 1999
ClinicalTrials.gov Identifier:
NCT00000554Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-14