Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women

doi:10.1016/j.jacc.2018.11.040

Journal of the American College of Cardiology

Volume 73, Issue 6, 19 February 2019, Pages 684-693

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Abstract

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)

Central Illustration

Key Words

cardiovascular outcome

coronary flow reserve

coronary reactivity

endothelial function

microvasculature

Abbreviations and Acronyms

CAD

coronary artery disease

CBF

coronary blood flow

CFR

coronary flow reserve

confidence interval

coronary reactivity

CSA

cross-sectional area

heart failure

hazard ratio

intracoronary

IC-Ach

intracoronary acetylcholine

IC-NTG

intracoronary nitroglycerin

MACE

major adverse cardiovascular events

myocardial infarction

Cited by (0)

: Dr. AlBadri is supported by Ruth L. Kirschstein Institutional National Research Service Award Training Grant T32HL007745. This work was also supported by the National Heart, Lung, and Blood Institute contracts N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, K23HL105787, T32HL69751, R01 HL090957, and 1R03AG032631 from the National Institute on Aging, GCRC grant M01-RR00425 from the National Center for Research Resources, the National Center for Advancing Translational Sciences grants UL1TR000124 and UL1TR001427, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, New Jersey, The Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, California, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania, and QMED, Inc., Laurence Harbor, New Jersey, the Edythe L. Broad and the Constance Austin Women’s Heart Research Fellowships, Cedars-Sinai Medical Center, Los Angeles, California, the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, The Society for Women’s Health Research (SWHR), Washington, DC, The Linda Joy Pollin Women’s Heart Health Program, and the Erika Glazer Women’s Heart Health Project, Cedars-Sinai Medical Center, Los Angeles, California. This work is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or National Institutes of Health. Dr. Bairey Merz has been a speaker for Abbott Diagnostics and served on the board of directors for iRhythm. Dr. Bittner has received institutional contracts to serve as a steering committee member for Sanofi; as a national trial coordinator for AstraZeneca, DalCor, and Esperion; as a trial coinvestigator for Amgen; and as a site principal investigator for AstraZeneca and Bayer; and has served on advisory boards for Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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