doi: 10.1161/01.CIR.0000116205.96440.FE
(Circulation. 2004;109:805-807.)
© 2004 American Heart Association, Inc.
AHA/NHLBI Conference Proceedings |
Women’s Ischemic Syndrome Evaluation
Current Status and Future Research Directions: Report of the National Heart, Lung and Blood Institute Workshop*: October 2–4, 2002 : Executive Summary
Key Words: AHA Scientific Statements • women • ischemia • cardiovascular diseases
The WISE workshop was convened to review results from the Women’s Ischemic Syndrome Evaluation (WISE) study and other studies of ischemic heart disease to examine the nature and scope of gender differences in both chronic and acute cardiac ischemia, in terms of clinical manifestations, detection, and treatment. The purpose of the workshop was to provide recommendations to National Heart, Lung and Blood Institute that (1) address the need for improved diagnosis of ischemia and coronary artery disease (CAD) in women; (2) explore strategies for improved translation of promising research results into clinical practice; and (3) assess opportunities for effective educational strategies, including further refinement of the key messages for women with regard to risk factors and heart attack symptoms.
Workshop Objectives
- To identify opportunities and needs in current state-of-the-art knowledge in gender differences in manifestation and detection of ischemia and CAD in women.
- To identify opportunities and provide recommendations on gender-based education for health professionals, patients, and the public.
- To recommend future research directions in ischemia and CAD in women.
CAD in women continues to be a major public health problem that represents a leading cause of death and disability.1–3 Among US women, more than a quarter of a million deaths per year are attributed to CAD, and this figure is expected to increase in the first decades of the 21st century as our population ages. The increased prevalence of obesity and diabetes in women is also expected to contribute to this increase in CAD. Women have a higher frequency of angina/chest pain than men; however, women have a lower prevalence of obstructive CAD compared with men with similar symptoms.4–6 Nevertheless, young women with obstructive CAD experience a significantly worse outcome compared with men with regard to prognosis after myocardial infarction,7 and older women with obstructive CAD often have greater comorbidities that influence their outcome adversely after acute myocardial infarction or myocardial revascularization than do men.8–11 Women presenting with acute coronary syndromes (ACS) are also less likely to receive effective acute diagnostic and treatment strategies than men.12–14
More women develop and die from CAD than from all forms of cancer combined3; yet most women consider CAD only a remote health risk. Moreover, when women develop obstructive CAD they have a greater functional expression of their disease and disability compared with men. A majority of women without obstructive CAD at coronary angiography continue to have symptom-related disability and consume considerable healthcare resources,15–17 in part because the pathophysiology of ischemia in women is incompletely understood and gender-specific diagnostic and treatment strategies are underdeveloped.
Diagnostic evaluation of women with suspected myocardial ischemia and CAD continues to be a major challenge. It is well appreciated that there are gender differences in reporting of pain, including but not limited to chest pain. It has been demonstrated since the 1970s that chest pain in women is less likely to be associated with flow-limiting coronary stenoses than chest pain in men.4–6 Gender differences in endogenous pain-modulatory systems may contribute to differences in pain perception. The diagnosis of ischemia influences prognosis differently in various clinical ischemic syndromes. For example, in unstable angina the detection of ischemia indicates the likelihood of persistence or recurrence of plaque instability and hence carries much more severe prognostic implications than in chronic stable angina. On the other hand, angina in patients with normal coronary angiograms is not associated with increased short-term risk of infarction or sudden cardiac death. Newer technologies allow for identification of abnormalities in vascular function and structure, not identifiable by coronary angiogram, which in turn can cause or contribute to development of myocardial ischemia. Magnetic resonance spectroscopy and gadolinium cardiac magnetic resonance imaging may identify patients whose chest pain is due to myocardial ischemia without obstructive CAD.18,19 The WISE study and others have suggested that chest pain without flow-limiting lesions by angiography may be associated with endothelial dysfunction and impaired coronary flow reserve.19,20 Preliminary data suggest that coronary microvascular dysfunction is associated with an increased rate of hospitalization for chest pain, poor quality of life, and ongoing healthcare costs.
Better understanding of gender differences in manifestation and detection of myocardial ischemia is a critical initial step to improve outcomes for women. Gender differences also impact our understanding of heart disease as a result of population selection bias. National Heart, Lung and Blood Institute–supported studies such as WISE offer opportunities for both translation and charting new research and educational strategies. Improved understanding of gender differences in ischemic presentation, diagnosis, and management is needed to communicate meaningful messages to the public, patients, and the healthcare community.
The workshop participants recommended that there is a need to develop a unified and comprehensive gender-specific strategy for cardiovascular research and education for women targeting the following areas:
- Improve understanding of pathology and pathophysiology of gender differences in ischemic heart disease. This includes studies of: (a) established and novel risk factors, the metabolic syndrome, the physiology of endogenous reproductive hormones, and evaluation of endothelial function; (b) role of endothelial dysfunction in producing obstructive macrovascular CAD, myocardial ischemia (as assessed by a reference standard), chronic chest pain syndromes, and ACS; and (c) genetic factors, proteomics, the menstrual cycle and reproductive status, pain threshold/perception, neurohormonal control, and behavioral and psychosocial factors and myocardial ischemia.
- Improve understanding of symptom description and diagnostic tools. This includes: (a) evaluation of symptom complexes in women with chest discomfort related to obstructive CAD, in those with nonobstructive CAD, and in those with chest pain and normal coronary angiograms; (b) development and validation of improved diagnostic methods to detect myocardial ischemia in women, including incremental impact of diagnostic strategies on outcomes; and (c) development of community-based studies to assess prodromal symptoms in patients with ACS, including those who do not survive, to determine whether there are gender-related differences in ACS warning symptoms and in their timing.
- Conduct gender-specific clinical investigation. This includes: (a) pooling of existing databases and (b) development of prospective clinical studies designed to evaluate gender differences in diagnostic tests, natural history, and treatment outcomes, including symptom control and cost-effectiveness. It is strongly recommended that all existing and new investigation outcome datasets be stratified by gender.
- Investigate mechanisms for adverse cardiovascular events occurring in the early phase after initiation of hormone replacement therapy. This includes: (a) factors, ranging from genetics/pharmacogenetics to lifestyle, contributing to these adverse outcomes; (b) alternative formulations or means of delivery of hormone replacement therapy that might improve safety; and (c) putative versus beneficial effects of estrogens.
- Promote translation research. This includes research designed to apply existing, proven prevention, diagnostic, and treatment strategies for acute and chronic ischemic heart disease more effectively in women through education targeted to both the lay and professional communities. This is of particular importance in racial and ethnic minority populations.
Appendix
Workshop Task Force
Chairpersons
Noel Bairey Merz, MD; Robert O. Bonow, MD
Participants
Robert S. Balaban, PhD; Jie J. Cao, MD; Robert M. Califf, MD; Richard O. Cannon, III, MD; John G. Canto, MD; Peter Collins, MD; George A. Diamond, MD; John R. Finnegan, Jr, PhD; Nieca Goldberg, MD; Robert J. Goldberg, PhD; David Gordon, MD, PhD; Mary M. Hand, RN, MSPH; David M. Herrington, MD; Sharonne N. Hayes, MD; Mark A. Hlatky, MD; Judith Hsia, MD; Willa A. Hsueh, MD; B. Delia Johnson, PhD; Paula A. Johnson, MD; Sheryl F. Kelsey, PhD; Ronald Klein, MD, MPH; Robert Langer, MD, MPH; Amir Lerman, MD; Jannet F. Lewis, MD; Terry Long; Teri A. Manolio, MD, PhD; Attilio Maseri, MD; Jean McSweeney, RN, PhD; Elizabeth G. Nabel, MD; Lori Mosca, MD, MPH; Patrice Desvigne Nickens, MD; Steven E. Nissen, MD; Pamela Ouyang, MD; Carl J. Pepine, MD; Gerald M. Pohost, MD; Rita F. Redberg, MD, MSc; Steven E. Reis, MD; Jacques E. Rossouw, MD; A. Richey Sharrett, PhD; Harry P. Selker, MD; Leslee J. Shaw, PhD; David S. Sheps, MD; George Sopko, MD, MPH; Marcia L. Stefanick, PhD; Russell P. Tracy, PhD; Viola Vaccarino, MD, PhD; Renu Virmani, MD; and David D. Waters, MD
Footnotes
The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This paper represents a summary of a scientific conference sponsored by the National Heart, Lung and Blood Institute on October 2–4, 2002. The opinions expressed in this paper are those of the authors and do not necessarily represent those of the editor or the American Heart Association.
The publication of this statement was approved by the American Heart Association Science Advisory and Coordinating Committee on December 5, 2003. A single reprint is available by calling 800-242-8721 (US only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX 75231-4596. Ask for reprint No. 71-0277. To purchase additional reprints: up to 999 copies, call 800-611-6083 (US only) or fax 413-665-2671; 1000 or more copies, call 410-528-4121, fax 410-528-4264, or e-mail kgray@lww.com. To make photocopies for personal or educational use, call the Copyright Clearance Center, 978-750-8400.
*Members of the Workshop Task Force are listed in the Appendix. 
Sections 1 through 6 of the Conference Proceedings and Perspective can be found in the online-only version of the February 17, 2004, issue of Circulation at http://www.circulationaha.org (Circulation. 2004;109:e44–e46; e47–e49; e50–e52; e53–e55; e56–e58; e59–e61; and e62–e63).
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