|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 1999; 33:1453-1461 © 1999 by the American College of Cardiology Foundation |
* Division of Cardiology, Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
Department of Medicine, University of California School of Medicine, Los Angeles, California, USA
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Division of Cardiology, Department of Medicine, University of Florida, Gainesville, Florida, USA
|| Division of Cardiology, Department of Medicine, Allegheny General Hospital, MCP-Hahnemann School of Medicine, Pittsburgh, Pennsylvania, USA
¶ Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
# Division of Cardiology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
** Rhode Island Hospital, Providence, Rhode Island, USA
Division of Heart and Vascular Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
Manuscript received June 26, 1998; revised manuscript received December 3, 1998, accepted January 21, 1999.
Reprint requests and correspondence: Dr. C. Noel Bairey Merz, c/o WISE Coordinating Center, University of Pittsburgh, 127 Parran Hall, Graduate School of Public Health, 130 DeSoto St., Pittsburgh, Pennsylvania 15261
 |
Abstract |
|---|
 Top Abstract MethodsResultsDiscussionAppendix: WISE participantsReferences |
|---|
The Women’s Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute–sponsored, four-center study designed to: 1) optimize symptom evaluation and diagnostic testing for ischemic heart disease; 2) explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenoses, and 3) evaluate the influence of reproductive hormones on symptoms and diagnostic test response.
BACKGROUND
Accurate diagnosis of ischemic heart disease in women is a major challenge to physicians, and the role reproductive hormones play in this diagnostic uncertainty is unexplored. Moreover, the significance and pathophysiology of ischemia in the absence of significant epicardial coronary stenoses is unknown.
METHODS
The WISE common core data include demographic and clinical data, symptom and psychosocial variables, coronary angiographic and ventriculographic data, brachial artery reactivity testing, resting/ambulatory electrocardiographic monitoring and a variety of blood determinations. Site-specific complementary methods include physiologic and functional cardiovascular assessments of myocardial perfusion and metabolism, ventriculography, endothelial vascular function and coronary angiography. Women are followed for at least 1 year to assess clinical events and symptom status.
RESULTS
In Phase I (1996–1997), a pilot phase, 256 women were studied. These data indicate that the WISE protocol is safe and feasible for identifying symptomatic women with and without significant epicardial coronary artery stenoses.
CONCLUSIONS
The WISE study will define contemporary diagnostic testing to evaluate women with suspected ischemic heart disease. Phase II (1997–1999) is ongoing and will study an additional 680 women, for a total WISE enrollment of 936 women. Phase III (2000) will include patient follow-up, data analysis and a National Institutes of Health WISE workshop.
| ||||||||||
Accurate and timely diagnosis of ischemic heart disease in women is a major challenge to physicians. At least three problematic areas exist:
The Women’s Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute–sponsored, four-center study designed to address ischemic heart disease recognition and diagnosis. The primary objectives of the WISE are: 1) to improve diagnostic testing for ischemic heart disease in women, including symptom evaluation tools, risk assessment algorithms and noninvasive imaging techniques; 2) to study pathophysiologic mechanisms and prognosis in women with chest pain and abnormal diagnostic testing for myocardial ischemia in the absence of epicardial coronary artery stenoses, and 3) to evaluate the influence of cyclical hormones, menopausal status and reproductive hormone levels on symptoms and diagnostic testing results.
|
Methods |
|---|
|
TopAbstractMethodsResultsDiscussionAppendix: WISE participantsReferences |
|---|
|
|
Study recruitment and inclusion/exclusion criteria. Women are eligible for participation if they are older than 18 years of age and are undergoing a clinically indicated coronary angiogram as part of their regular medical care for chest pain symptoms or suspected myocardial ischemia. Major exclusion criteria include comorbidity which compromises one-year follow-up, pregnancy, contraindications to provocative diagnostic testing, cardiomyopathy, New York Heart Association class IV congestive heart failure, recent myocardial infarction, significant valvular or congenital heart disease and a language barrier to questionnaire testing. Women with recent coronary angioplasty or coronary bypass surgery or who undergo these procedures after angiography but before their WISE testing are also excluded.
Common core protocol. All participants have data collected uniformly for a Common Core Protocol, as outlined in Figure 1. To characterize symptoms, WISE compares a questionnaire of known diagnostic validity in women (15) to a new symptom questionnaire specifically developed for women (Hodgson and Berry, personal communication, August 1996). Questions regarding initial response to symptoms and health seeking behavior are included. Symptoms provoked during testing procedures are assessed using a uniform tool. Psychosocial assessment includes indicators of hostility/cynicism (16), typical depression (17), panic (18), avoidance (19), autonomic perception (20), reward dependence (21), trait anxiety (22), social support (23) and quality of life.
|
Coronary angiography as assessed by a core laboratory includes quantification of epicardial coronary artery size, quantification of left ventricular ejection fraction and qualitative and quantitative assessment as to the presence, severity and complexity of epicardial coronary artery stenoses, using a previously published coronary severity score (24). The following definitions are used for coronary artery group categorization: normal/minimal disease = <20% stenosis; mild = 20% to 49% stenosis; significant = 
50% stenosis in any one major epicardial coronary artery. Resting ECGs are interpreted by a core laboratory, using gender-specific interpretative criteria for left ventricular hypertrophy (25). Data are also being collected, when available, from routine clinical stress testing, including nuclear perfusion imaging, performed before WISE enrollment.
Ambulatory ECG monitoring is performed for 24 to 48 h according to previously described methods (26), using an all-digital recording system (27,28) with electronic transfer of the data to a core laboratory for analysis and interpretation. Brachial artery reactivity testing for both endothelium-dependent and endothelium-independent vasomotion is performed using standard techniques (29), with data analysis by a core laboratory.
Follow-up. Women’s Ischemia Syndrome Evaluation participants are contacted at six weeks and then annually to assess symptom status, menstrual status and occurrence of cardiovascular events, including death, nonfatal myocardial infarction, coronary angioplasty, coronary bypass surgery, cardiac transplantation and hospitalization for unstable angina.
Specific protocols. The testing protocol methods are organized below according to the three main WISE study goals. When testing is performed at more than one site, a uniform protocol is used. Interpretation of all studies is performed by masked observers for both qualitative and quantitative analysis.
Goal: to improve diagnostic testing for ischemic heart disease in women
The innovative diagnostic tests selected for the WISE represent the best technologic advances in ischemic heart disease detection currently available. An emphasis was placed on selection of techniques which might obviate difficulties relevant to women, such as breast imaging artifact (magnetic resonance imaging [MRI]-coronary angiography, MRI perfusion imaging and sestamibi single photon emission computed tomography [SPECT] perfusion imaging), as well as techniques commonly available currently (dobutamine stress echocardiography and exercise stress testing).
Magnetic resonance imaging coronary angiography imaging
Magnetic resonance imaging coronary angiography depicts both anatomic features and flow effects of epicardial coronary artery stenoses using a 1.5-T Siemens Vision (Schaumberg, Illinois) with echo-planar capability. The patient is supine in a phased array thoracic coil for approximately 40 min, with the need for breath-holding eliminated. Depending on cardiac cycle length, 5 to 11 views per cycle are obtained. Tomographic slice thickness is 2 mm and stacks of 16 to 24 images are taken at a time, which can be viewed as obtained or put into a three-dimensional volume in any orientation desired for qualitative analysis. Image quantitation is performed with compound and curved plane reslicing and three-dimensional projection images.
Magnetic resonance imaging perfusion imaging
Magnetic resonance imaging myocardial perfusion imaging is performed using "first pass" gadolinium–diethylenetriaminepenta-acetic acid and a 1.5-T Philips ACS Gyroscan system (Best, The Netherlands). Cardiac scout images (two- and four-chamber views) are acquired in two orthogonal planes and dynamic imaging is initiated just before the bolus of gadolinium and continues for 64 heartbeats. The BRISK (30) and interpolated keyhole (31) imaging sequences developed by one of the sites (University of Alabama at Birmingham) allow up to three or four near-simultaneous short-axis images to be acquired during each cardiac cycle. Imaging of left ventricular function is also performed. Qualitative defects by MRI are determined by describing regional signal intensity with that of the region containing the highest signal intensity in predefined regions. Quantitative analysis uses plots of MR signal intensity versus location about the circumference of the short-axis image.
Sestamibi SPECT imaging
Sestamibi SPECT myocardial imaging is performed at baseline and during dipyridamole infusion. Myocardial perfusion images are obtained on a 64 x 64 matrix using a single-head Siemens Orbitor SPECT camera (Schaumberg, Illinois) with a high resolution parallel-hole collimator for sestamibi imaging. Imaging is performed every 5° for 40 s over a 180° arc. Rest and dipyridamole images with sestamibi are obtained 1 h after injection. Qualitative and quantitative analyses are performed, the latter using gender-specific normal limits.
Dobutamine stress echocardiography
After acquisition of baseline images in standard views, dobutamine stress echocardiography is performed using published methodology (32). Image analysis includes calculation of a wall motion score index, which is the total score divided by the number of segments visualized and scored.
Exercise stress ECG
After standard 12-lead ECG recordings and blood pressure measurements at rest, the Asymptomatic Cardiac Ischemia Pilot treadmill exercise protocol is performed, since it provides continuous "ramp-like" increases in work, using previously published methods (26). Reports of symptoms, including chest pain or discomfort, are carefully elicited and recorded along with level of perceived exertion using the Borg scale (33).
Goal: to study pathophysiologic mechanisms for ischemia in the absence of epicardial coronary artery stenoses
Testing protocols were designed to determine the prevalence of this syndrome in women with normal or mild stenoses using a reference standard test for ischemia (MR spectroscopy) and to explore the pathophysiologic mechanisms involved (microvascular coronary flow reserve and endothelial function testing).
Magnetic resonance spectroscopic study
31Phosporus MR spectroscopy is a nonimaging direct biochemical assessment of phosphocreatine, adenosine triphosphate and inorganic phosphate metabolites. The patient is placed supine in a Philips 1.5-T ACS MRI system (Best, The Netherlands), and the positioning of the 31P surface coil over the heart is confirmed. After acquisition of a control spectrum at rest, the subject squeezes and holds a handgrip at 30% of maximum force for approximately 7 min, during which time a second spectrum is obtained. After the period of exercise, the subject is allowed to recover, another spectrum is collected and the study is complete. Spectral data are processed at a core laboratory using Philips software, and include phosphocreatine/adenosine triphosphate ratios and rate–pressure products during all phases as well as average dynamometer output for the exercise phase.
Microvascular coronary flow reserve
In women with normal or mild stenoses, the left anterior descending coronary artery is uniformly studied. When appropriate, the artery suspected as causing the abnormal diagnostic test response is studied. After administration of systemic heparin, a 0.014- to 0.018-in. (0.036 to 0.046 cm) Doppler-tipped guide wire is advanced into the target vessel, as previously described (14). After baseline recordings, adenosine (18 µg diluted in 2 ml saline followed by 5 ml saline flush) is hand-injected as a bolus via the coronary guiding catheter, and recordings are repeated. Time-averaged peak coronary blood flow velocity is assessed at baseline and after intracoronary adenosine and nitroglycerin (200 µg). One site (University of Pittsburgh) is also assessing this during a speech mental stress task and intravenous adenosine. A cineangiogram is performed immediately after measurement of coronary blood flow velocity. Quantitative coronary angiography is performed off-line to quantify epicardial coronary cross-sectional area 5.2 mm distal to the guide wire tip. Coronary flow reserve is computed as the ratio of post- to preadenosine average peak velocity (14). Volumetric blood flow calculations, using coronary lumen diameter measured from the angiograms, is also performed using previously reported techniques (34). The ratio of flow during each intervention (speech task, intracoronary and intravenous adenosine, intracoronary nitroglycerin) to baseline is used as a standard to define coronary vasomotion in the studied women.
Coronary artery endothelial function
Two minutes after completion of maximum flow reserve (described above), repeat baseline recordings are made. The infusion catheter is primed with low dose (10–6M) acetylcholine (0.036 µg/ml). Acetylcholine is then infused at a rate of 2 ml/min for 3 min. Three minutes after the beginning of the infusion, blood flow velocity, ECG and pressure recordings are obtained, and a left coronary cineangiogram is recorded using hand-injected low osmolar, nonionic contrast material. The same volumes of contrast material and the same optimal projection are used for each angiogram. High dose (10–4M) acetylcholine (3.5 µg/ml) is then infused and after 3 min all recordings and an angiogram are repeated. Five minutes after this, coronary flow velocity and coronary angiography are obtained. Intracoronary nitroglycerin (150 µg) is given as a bolus from a glass syringe through the guide catheter. After 1 min, coronary angiography is performed. Nitroglycerin is given last as a direct acting dilator to counteract any residual vasoconstrictive effects of acetylcholine and to assure a reference angiogram for analysis of maximal coronary lumen diameter at each coronary segment of interest.
Positron emission tomography imaging
Baseline myocardial perfusion is quantified in each of the three coronary artery distributions by 13N-NH3–positron emission tomography imaging using standard techniques (35,36). Twenty millicuries of 13N-NH3 is injected at rest, during a continuous infusion of intravenous adenosine (140 µg/kg/min), and during performance of a mental stress speech task. The speech task uses predetermined stress-provoking scenarios (37), and consists of a 2-min preparation period followed by a 3-min speech. The first several minutes of temporal data acquired as 13N-NH3 is distributed in the blood and myocardium are analyzed by a previously validated two-compartment model to quantify myocardial blood flow (38,39).
Goal: to evaluate the influence of menopausal status and reproductive hormone levels on diagnostic testing results
This testing is designed to assess diagnostic test reproducibility in women, determine sources of variability, such as cyclical reproductive hormones, and investigate the influence of reproductive hormonal status and hormone therapy on diagnostic test response and symptomatic status.
Hormonal status determination
The hormonal status determination developed for WISE uses both historical and single sampling blood hormonal characterization (Fig. 2). Premenopausal women also undergo menstrual cycle phase (follicular, luteal, menstrual) determination using estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone levels, at the time of WISE testing. Information regarding hormone therapy, including estrogenic, progestational and androgenic agents taken within 24 h of each WISE test are recorded.
|
Plan of analysis. The planned WISE analyses based on the three main study goals are outlined.
Goal: to improve diagnostic testing for ischemic heart disease in women
Analyses will determine the sets of characteristics and test results (symptom characterization, diagnostic techniques, reproductive hormone status and level) that optimally predict presence or absence of significant epicardial coronary artery stenoses, as well as outcomes (cardiac events and symptom status) during follow-up. Preliminary modeling for this has begun with data from patients entered into Phase I. This allows for assessment of necessity for transforming data, and assessment of stability of the models by comparing the model for Phase I with the model for Phase II, and provides focus for analyses to be performed when all data are available. Estimates of sensitivity, specificity and predictive accuracy from derived indexes will have 95% confidence intervals no wider than ±7%, based on a minimum clinically defined subgroup sample size of 200 for specific diagnostic tests. Due to the referral nature of this symptomatic population, selection bias(es) will be present which will probably influence conclusions regarding the various tests’ diagnostic accuracy.
Goal: to study pathophysiologic mechanisms and prognosis of myocardial ischemia in the absence of epicardial coronary artery disease
Women with evidence of myocardial ischemia by 31P MR spectroscopy in the absence of significant epicardial coronary artery stenoses will be compared with women without evidence of myocardial ischemia, as well as with women with significant epicardial coronary artery stenoses according to physiologic measures such as coronary flow reserve and endothelial function. Hormonal status, symptoms and psychosocial characteristics will also be compared to explore potential pathophysiologic mechanisms of myocardial ischemia in the absence of epicardial coronary artery stenoses. Prediction of cardiovascular events, as previously defined, during the 1- to 3-year follow-up will include comparison of those with and without significant epicardial coronary artery stenoses and/or myocardial ischemia. The estimated population of 200 participants with myocardial ischemia by MR spectroscopy is expected to have a relatively low annual event rate (<2%) compared with the approximately 300 participants with significant epicardial coronary artery disease with an estimated cumulative event rate of 20%. Since these rates are not likely to provide sufficient power to detect meaningful differences in prognosis by baseline assessment, an extension in the long-term follow-up of WISE participants is being planned.
Goal: to evaluate the influence of menopausal status and reproductive hormone levels on diagnostic testing results
Reproductive hormonal status (premenopausal, perimenopausal, postmenopausal and hormone replacement therapy) and serum hormone levels will be analyzed as to their influence on diagnostic test accuracy and reproducibility. Reproductive status and hormone levels will be analyzed as to their influence on symptoms, as well as measures of coronary flow, endothelial function and myocardial ischemia measured by 31P MR spectroscopy. These measures will be compared among hormonal status groups using analysis of variance with factors of hormonal status and diagnostic test results. Diameter change will also be related directly to estrogen levels as well as to symptoms, the presence and magnitude of myocardial perfusion abnormalities, coronary arterial microvascular and endothelial testing and hormonal status using scatterplots and regression analyses.
|
Results |
|---|
|
TopAbstractMethodsResultsDiscussionAppendix: WISE participantsReferences |
|---|
Characteristics for the initial 308 WISE participants are listed in Table 3. These women with suspected ischemic heart disease are compared with previously described populations of women, including healthy women from the Framingham Study (40), healthy postmenopausal women from the Postmenopausal Estrogen/Progestin Interventions study (41) and postmenopausal women with established ischemic heart disease from the Heart and Estrogen/Progestin Replacement Study (42). Table 3 documents that the WISE protocol identifies a group of women with a constellation of cardiac risk factors greater than that seen in both healthy women and women with established ischemic heart disease. Notably, minority recruitment is good at 21%.
|
Characterization of the chest pain symptoms revealed that 35% reported typical angina, 60% reported atypical angina and 45% reported daily/almost daily symptoms. Ninety-one percent of the participants had a low functional capacity of <8 metabolic equivalents, measured by the Duke Activity Score Index (43). Comorbid conditions are frequent and included history of treatment for depression (26%), autoimmune disease (20%), weight cycling (>10 lbs [>4.54 kg] >3 times) (32%) and polycystic ovary disease (8%).
Coronary angiography results in the first 323 WISE participants revealed that 31% of the participants have significant coronary artery stenoses (50%) in any major coronary artery, 32% have mild stenoses (20% to 49%) and 37% have no (<20%) stenoses. The cumulative frequency distribution of the severity scores in the WISE participants is depicted in Figure 3, and demonstrates that 50% have a low severity score <10. The average left ventricular ejection fraction is 68% (range 23% to 86%), and the majority (87%) are greater than 50%.
|
|
Discussion |
|---|
|
TopAbstractMethodsResultsDiscussionAppendix: WISE participantsReferences |
|---|
Summary. Previous evidence suggests that gender-specific differences exist in ischemic heart disease symptoms, detection and management. The WISE study is: 1) defining new, comprehensive diagnostic strategies to evaluate women with suspected ischemic heart disease; 2) exploring the pathophysiology and significance of ischemia in the absence of epicardial coronary stenoses, and 3) evaluating the role of reproductive hormones on symptoms and diagnostic test response. Phase II of the WISE is in progress.
|
Appendix: WISE participants |
|---|
|
TopAbstractMethodsResultsDiscussionAppendix: WISE participantsReferences |
|---|
University of Alabama at Birmingham, Birmingham
William J. Rogers, MD (PI), Gerald M. Pohost, MD (CoI), Alfred A. Bartolucci, PhD (CoI), Vera Bittner, MD (CoI), Joseph R. Logic, MD (CoI), Steven Buchthal, PhD (CoI), Carol E. Cornell, PhD (CoI), Jan A. Denhollander, PhD (CoI), Marc Doyle, PhD (CoI), Anthon R. Fuisz, MD (CoI), Edward T. Martin, MD (CoI), Thomas D. Paine, MD (CoI), Michelle L. Robbin, MD (CoI), Lindsey Tauxe (CoI), Edward G. Walsh, PhD, MSPH (CoI), Kathy Clay, RN(C), William C. Gamble III, RN(C), Kathleen Armstrong, RN(C)
University of Florida, Gainesville
Carl J. Pepine, MD (PI), Jannet Lewis, MD (CoI), Lang Lin, MD (CoI), Eileen Handberg-Thurmond, PhD (CoI), Rick Kerensky, MD (CoI), Keith Stone, MD (CoI), Susan McGorray, PhD (CoI), Alix Baxter, MD (CoI), Alice Boyette (C)
University of Pittsburgh
Steven E. Reis, MD (PI), Katherine Detre, MD, DrPH (CoPI), Richard Holubkov, PhD (CoI), Flordeliza Villanueva, MD (CoI), Jane Owens, PhD (CoI), Karen Matthews, PhD (consultant), Janine Flory, PhD (CoI), A.J. Conrad Smith, MD (CoI), Daniel Edmundowicz, MD (CoI), David Townsend, PhD (CoI), Carolyn Meltzer, MD (CoI), Kathleen Zell, BSN (C), Cheryl Rickens, RN(C)
Coordinating Center—University of Pittsburgh
Sheryl F. Kelsey, PhD (PI), Katherine M. Detre, MD, DrPH (CoI), Richard Holubkov, PhD (CoI), Tanya Kenkre, MPH(C), Marian Olson, MS(C), B. Delia Johnson, PhD(C)
Core Angiography Laboratory—Rhode Island Hospital
Barry L. Sharaf, MD (PI), David O. Williams, MD (CoI), Nicholas Miele (C)
National Heart, Lung and Blood Institute Project Officers
George Sopko, MD, Paul Albert, PhD, Gail Pearson, MD, Donna Berkowitz (contract C), William Stevens (contract C), Doug Frye (contract C)
Study Chair—Cedars-Sinai Medical Center, Los Angeles
C. Noel Bairey Merz, MD (PI)
Data and Safety Monitoring Board
Bernard J. Gersh, MD (Chair), Robert O. Bonow, MD, Richard O. Cannon III, MD, Katherine Stoney, PhD, Madison Powers, PhD, JD, Erica Brittain, PhD
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractMethodsResultsDiscussionAppendix: WISE participantsReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  L. J. Shaw, C. N. Bairey Merz, R. Azziz, F. Z. Stanczyk, G. Sopko, G. D. Braunstein, S. F. Kelsey, K. E. Kip, R. M. Cooper-DeHoff, B. D. Johnson, et al. Postmenopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health--National Heart, Lung, and Blood Institute Sponsored Women's Ischemia Syndrome Evaluation J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1276 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rutledge, S. E. Linke, M. B. Olson, J. Francis, B. D. Johnson, V. Bittner, K. York, C. McClure, S. F. Kelsey, S. E. Reis, et al. Social Networks and Incident Stroke Among Women With Suspected Myocardial Ischemia Psychosom Med, April 1, 2008; 70(3): 282 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Vaccarino, C. McClure, B. D. Johnson, D. S. Sheps, V. Bittner, T. Rutledge, L. J. Shaw, G. Sopko, M. B. Olson, D. S. Krantz, et al. Depression, the Metabolic Syndrome and Cardiovascular Risk Psychosom Med, January 1, 2008; 70(1): 40 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Vaccarino, B. D. Johnson, D. S. Sheps, S. E. Reis, S. F. Kelsey, V. Bittner, T. Rutledge, L. J. Shaw, G. Sopko, and C. N. Bairey Merz Depression, Inflammation, and Incident Cardiovascular Disease in Women With Suspected Coronary Ischemia: The National Heart, Lung, and Blood Institute Sponsored WISE Study J. Am. Coll. Cardiol., November 20, 2007; 50(21): 2044 - 2050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Rosenfeld State of the Heart: Building Science to Improve Women's Cardiovascular Health Am. J. Crit. Care., November 1, 2006; 15(6): 556 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Shaw, C. N. B. Merz, C. J. Pepine, S. E. Reis, V. Bittner, K. E. Kip, S. F. Kelsey, M. Olson, B. D. Johnson, S. Mankad, et al. The Economic Burden of Angina in Women With Suspected Ischemic Heart Disease: Results From the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation Circulation, August 29, 2006; 114(9): 894 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rutledge, S. E. Reis, M. B. Olson, J. Owens, S. F. Kelsey, C. J. Pepine, S. Mankad, W. J. Rogers, C. N. B. Merz, G. Sopko, et al. Depression Symptom Severity and Reported Treatment History in the Prediction of Cardiac Risk in Women With Suspected Myocardial Ischemia: The NHLBI-Sponsored WISE Study. Arch Gen Psychiatry, August 1, 2006; 63(8): 874 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Johnson, L. J. Shaw, C. J. Pepine, S. E. Reis, S. F. Kelsey, G. Sopko, W. J. Rogers, S. Mankad, B. L. Sharaf, V. Bittner, et al. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women's Ischaemia Syndrome Evaluation (WISE) study Eur. Heart J., June 2, 2006; 27(12): 1408 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N. Bairey Merz, B. D. Johnson, G. D. Braunstein, C. J. Pepine, S. E. Reis, M. Paul-Labrador, G. Hale, B. L. Sharaf, V. Bittner, G. Sopko, et al. Phytoestrogens and Lipoproteins in Women J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2209 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Rutledge, S. E. Reis, M. Olson, J. Owens, S. F. Kelsey, C. J. Pepine, S. Mankad, W. J. Rogers, G. Sopko, C. E. Cornell, et al. Depression is associated with cardiac symptoms, mortality risk, and hospitalization among women with suspected coronary disease: the NHLBI-sponsored WISE study. Psychosom Med, March 1, 2006; 68(2): 217 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Pepine Ischemic Heart Disease in Women J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S1 - S3. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Shaw, M. B. Olson, K. Kip, S. F. Kelsey, B. D. Johnson, D. B. Mark, S. E. Reis, S. Mankad, W. J. Rogers, G. M. Pohost, et al. The Value of Estimated Functional Capacity in Estimating Outcome: Results From the NHBLI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S36 - S43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Handberg, B. D. Johnson, C. B. Arant, T. R. Wessel, R. A. Kerensky, G. von Mering, M. B. Olson, S. E. Reis, L. Shaw, C. N. Bairey Merz, et al. Impaired Coronary Vascular Reactivity and Functional Capacity in Women: Results From the NHLBI Women's Ischemia Syndrome Evaluation (WISE) Study J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S44 - S49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Gierach, B. D. Johnson, C. N. Bairey Merz, S. F. Kelsey, V. Bittner, M. B. Olson, L. J. Shaw, S. Mankad, C. J. Pepine, S. E. Reis, et al. Hypertension, Menopause, and Coronary Artery Disease Risk in the Women's Ischemia Syndrome Evaluation (WISE) Study J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S50 - S58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Jacobs Women, Ischemic Heart Disease, Revascularization, and the Gender Gap: What Are We Missing? J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S63 - S65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Quyyumi Women and Ischemic Heart Disease: Pathophysiologic Implications From the Women's Ischemia Syndrome Evaluation (WISE) Study and Future Research Steps J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S66 - S71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Triola, M. B. Olson, S. E. Reis, P. Rautaharju, C. N. B. Merz, S. F. Kelsey, L. J. Shaw, B. L. Sharaf, G. Sopko, and S. Saba Electrocardiographic Predictors of Cardiovascular Outcome in Women: The National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study J. Am. Coll. Cardiol., July 5, 2005; 46(1): 51 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Olson, D. S. Krantz, S. F. Kelsey, C. J. Pepine, G. Sopko, E. Handberg, W. J. Rogers, G. L. Gierach, C. K. McClure, C. N. B. Merz, et al. Hostility Scores Are Associated With Increased Risk of Cardiovascular Events in Women Undergoing Coronary Angiography: A Report from the NHLBI-Sponsored WISE Study Psychosom Med, July 1, 2005; 67(4): 546 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Rutledge, S. E. Reis, M. Olson, J. Owens, S. F. Kelsey, C. J. Pepine, S. Mankad, W. J. Rogers, C. N. Bairey Merz, G. Sopko, et al. Social Networks Are Associated With Lower Mortality Rates Among Women With Suspected Coronary Disease: The National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation Study Psychosom Med, November 1, 2004; 66(6): 882 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
