The NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) has documented a high prevalence of coronary vascular dysfunction in women with symptoms and evidence of ischemia with no obstructive CAD. The condition is associated with an adverse prognosis and healthcare costs similar to obstructive CAD, there are an estimated 2-3 million women with existent disease, and a projected 100,000 new cases annually. This places the prevalence, morbidity and costs of coronary vascular dysfunction higher than all female reproductive cancers combined. Prospective testing of a noninvasive approach for diagnosis and prognosis is needed as critical next steps toward translation of our findings into clinical care. Using a prospective cohort design with follow-up, we aim to investigate: 1) Abnormal cardiac magnetic resonance imaging (CMRI) predicts abnormalities in coronary reactivity testing (CRT);2) Persistent cardiac magnetic resonance imaging (CMRI) abnormalities at 1-year follow-up predict persistent symptoms of ischemia;3) CMRI predicts adverse outcomes, and thus can be used as an outcome in future therapeutic trials. The baseline study visit will include a physical exam and elicitation of medical history, symptoms, lifestyle and functional characteristics, and psychosocial status. We will recruit 375 women undergoing coronary angiography for suspected ischemia with no obstructive CAD. All 375 will undergo baseline CMRI imaging, and a subgroup of 200 will undergo repeat one-year follow-up CMRI. An additional subgroup of 200 women with no coronary stenosis >20% in any epicardial coronary artery will undergo CRT. Women will be contacted annually to measure outcome of symptoms, coronary events, and associated costs. Established WISE core laboratories and clinical sites will be used. Documentation of the link between invasive CRT and noninvasive CMRI imaging, and the prognostic value of this measure for symptoms and adverse outcomes, will provide a platform for clinical trials to test therapeutic interventions in appropriately powered studies. Potential therapeutic trials being planned include anti-ischemia therapies, such as ranolazine and dipyridamole, as well as novel interventions, such as erythropoietin and stem-cell therapy, targeting coronary vascular function. Results of the application will provide practicing physicians with the ability to translate these findings to clinical care to improve IHD outcomes in women using a noninvasive assessment strategy.

Public Health Relevance

Registry data indicate that most women with coronary vascular dysfunction remain untreated with evidence-based care. Further investigation into approaches to the noninvasive assessment coronary vascular dysfunction is needed to improve clinical care and lower health care cost for women.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Sleep Epidemiology (CASE)
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Sopko, George
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Cedars-Sinai Medical Center
Los Angeles
United States
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Humphries, K H; Izadnegahdar, M; Sedlak, T et al. (2017) Sex differences in cardiovascular disease - Impact on care and outcomes. Front Neuroendocrinol 46:46-70
Jain, Ankur; Elgendy, Islam Y; Al-Ani, Mohammad et al. (2017) Advancements in pharmacotherapy for angina. Expert Opin Pharmacother 18:457-469
Bairey Merz, C Noel; Pepine, Carl J; Walsh, Mary Norine et al. (2017) Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade. Circulation 135:1075-1092
Eastwood, Jo-Ann; Taylor, Doris A; Johnson, B Delia et al. (2017) Premature atherosclerosis in premenopausal women: Does cytokine balance play a role? Med Hypotheses 109:38-41
Landes, Sofy; Dela Cruz, Sherwin; Wei, Janet et al. (2017) Cold Pressor Stress Cardiac Magnetic Resonance Myocardial Flow Reserve Is Not Useful for Detection of Coronary Endothelial Dysfunction in Women with Signs and Symptoms of Ischemia and No Obstructive CAD. PLoS One 12:e0169818
Kenkre, Tanya S; Malhotra, Pankaj; Johnson, B Delia et al. (2017) Ten-Year Mortality in the WISE Study (Women's Ischemia Syndrome Evaluation). Circ Cardiovasc Qual Outcomes 10:
Shufelt, Chrisandra; Elboudwarej, Omeed; Johnson, B Delia et al. (2016) Carotid artery distensibility and hormone therapy and menopause: the Los Angeles Atherosclerosis Study. Menopause 23:150-7
Weng, Liming; Taylor, Kent D; Chen, Yii-Der Ida et al. (2016) Genetic loci associated with nonobstructive coronary artery disease in Caucasian women. Physiol Genomics 48:12-20
Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel (2016) Stroke in women: Where are we in 2015? Trends Cardiovasc Med 26:89-91
Enkhmaa, Davaasambuu; Wall, Danielle; Mehta, Puja K et al. (2016) Preeclampsia and Vascular Function: A Window to Future Cardiovascular Disease Risk. J Womens Health (Larchmt) 25:284-91

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