Coronary Microvascular Reactivity to Adenosine Predicts Adverse Outcome in Women Evaluated for Suspected Ischemia: Results From the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) Study

doi:10.1016/j.jacc.2010.01.054

Journal of the American College of Cardiology

Volume 55, Issue 25, 22 June 2010, Pages 2825-2832

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Objectives

We investigated whether coronary microvascular dysfunction predicts major adverse outcomes during follow-up among women with signs and symptoms of ischemia.

Background

Altered coronary reactivity occurs frequently in women evaluated for suspected ischemia, and the endothelium-dependent component is linked with adverse outcomes. Possible links between endothelium-independent microvascular coronary reactivity and adverse outcomes remain uncertain.

Methods

As part of the National Heart, Lung and Blood Institute-sponsored WISE (Women's Ischemia Syndrome Evaluation), we investigated relationships between major adverse outcomes and baseline coronary flow reserve (CFR) after intracoronary adenosine in 189 women referred to evaluate suspected ischemia.

Results

At a mean of 5.4 years, we observed significant associations between CFR and major adverse outcomes (death, nonfatal myocardial infarction, nonfatal stroke, or hospital stay for heart failure). An exploratory receiver-operator characteristic analysis identified CFR <2.32 as the best discriminating threshold for adverse outcomes (event rate 26.7%; and ≥2.32 event rate 12.2%; p = 0.01). Lower CFR was associated with increased risk for major adverse outcomes (hazard ratio: 1.16, 95% confidence interval: 1.04 to 1.30; p = 0.009). This held true among the 152 women without obstructive coronary artery disease (CAD) (hazard ratio: 1.20, 95% confidence interval: 1.05 to 1.38; p = 0.008). The CFR significantly improved prediction of adverse outcomes over angiographic CAD severity and other risk conditions.

Conclusions

Among women with suspected ischemia and atherosclerosis risk factors, coronary microvascular reactivity to adenosine significantly improves prediction of major adverse outcomes over angiographic CAD severity and CAD risk factors. These findings suggest that coronary microvessels represent novel targets for diagnostic and therapeutic strategies to predict and limit adverse outcomes in women. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554)

Key Words

adverse outcomes

ischemia

microcirculation

women

Abbreviations and Acronyms

CAD

coronary artery disease

CFR

coronary flow reserve

CHF

congestive heart failure

confidence interval

cardiovascular

hazard ratio

left ventricular

MBF

myocardial blood flow

myocardial infarction

ROC

receiver-operator characteristic

Cited by (0)

: This work was supported by contracts from the NHLBI, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, T32HL69751; GCRCgrant MO1-RR00425from the National Center for Research Resources; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, New Jersey; The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania; QMED, Inc., Laurence Harbor, New Jersey; and The Women's Guild of Cedars-Sinai Medical Center, the Edythe L. Broad Women's Heart Research Fellowship; and the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, California. Dr. Pepine has received research grants and an educational grant from Pfizer. Dr. Bairey Merz has served as a consultant for Strategy Group, BSP, and Kendle Internation, Inc.; has served on the advisory board of Novartis; has served on the External Review Panel of Karolinska Institute; was the NHLBI DSMB chair of the University of Pittsburgh; has performed grant reviewing for Pfizerand the NHLBI; has received lecture honorarium from Northwestern University, University of California, Davis, Abbott Laboratories, CV Therapeutics, Boehringer Ingelheim, American College of Physicians, ProMedica, Mayo Clinic, and Merck; and owns stock in Boston Scientific, Medtronic, Johnson & Johnson, and Teva Pharmaceuticals.