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