Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 73, Issue 6, Pages 684-693Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2018.11.040
Keywords
cardiovascular outcome; coronary flow reserve; coronary reactivity; endothelial function; microvasculature
Categories
Funding
- Ruth L. Kirschstein Institutional National Research Service Award Training Grant [T32HL007745]
- National Heart, Lung, and Blood Institute from the National Institute on Aging [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, U0164829, U01 HL649141, U01 HL649241, K23HL105787, T32HL69751, R01 HL090957, 1R03AG032631]
- GCRC from the National Center for Research Resources [M01-RR00425]
- National Center for Advancing Translational Sciences [UL1TR000124, UL1TR001427]
- Gustavus and Louis Pfeiffer Research Foundation, Danville, New Jersey
- Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California
- Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania
- QMED, Inc., Laurence Harbor, New Jersey
- Edythe L. Broad Women's Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California
- Constance Austin Women's Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California
- Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles
- Society for Women's Health Research (SWHR), Washington, DC
- Linda Joy Pollin Women's Heart Health Program, Cedars-Sinai Medical Center, Los Angeles, California
- Erika Glazer Women's Heart Health Project, Cedars-Sinai Medical Center, Los Angeles, California
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BACKGROUND Currently as many as one-half of women with suspected myocardial ischemia have no obstructive coronary artery disease (CAD), and abnormal coronary reactivity (CR) is commonly found. OBJECTIVES The authors prospectively investigated CR and longer-term adverse cardiovascular outcomes in women with and with no obstructive CAD in the National Heart, Lung, and Blood Institute-sponsored WISE (Women's Ischemia Syndrome Evaluation) study. METHODS Women (n = 224) with signs and symptoms of ischemia underwent CR testing. Coronary flow reserve and coronary blood flow were obtained to test microvascular function, whereas epicardial CR was tested by coronary dilation response to intracoronary (IC) acetylcholine and IC nitroglycerin. All-cause mortality, major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, stroke, and heart failure), and angina hospitalizations served as clinical outcomes over a median follow-up of 9.7 years. RESULTS The authors identified 129 events during the follow-up period. Low coronary flow reserve was a predictor of increased MACE rate (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.01 to 1.12; p = 0.021), whereas low coronary blood flow was associated with increased risk of mortality (HR: 1.12; 95% CI: 1.01 to 1.24; p = 0.038) and MACE (HR: 1.11; 95% CI: 1.03 to 1.20; p = 0.006) after adjusting for cardiovascular risk factors. In addition, a decrease in cross-sectional area in response to IC acetylcholine was associated with higher hazard of angina hospitalization (HR: 1.05; 95% CI: 1.02 to 1.07; p < 0.0001). There was no association between epicardial IC-nitroglycerin dilation and outcomes. CONCLUSIONS On longer-term follow-up, impaired microvascular function predicts adverse cardiovascular outcomes in women with signs and symptoms of ischemia. Evaluation of CR abnormality can identify those at higher risk of adverse outcomes in the absence of significant CAD. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554) (c) 2019 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.
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