Coronary Microvascular Reactivity to Adenosine Predicts Adverse Outcome in Women Evaluated for Suspected Ischemia
Key result
Lower CFR links to ~16% higher risk of major adverse outcomes.
- HR 1.16
- 95% CI 1.04-1.30
- P=0.009
- n=189
Why the study?
Altered coronary reactivity occurs frequently in women with suspected ischemia, but links between endothelium-independent microvascular coronary reactivity and adverse outcomes remained uncertain.
Does coronary microvascular dysfunction (measured by CFR after intracoronary adenosine) predict major adverse outcomes in women with suspected ischemia?
Key Points
- This research aims to determine if coronary microvascular dysfunction can predict major adverse outcomes in women with suspected ischemia.
- Evaluated 189 women referred for suspected ischemia as part of the WISE study.
- Assessed baseline coronary flow reserve after intracoronary adenosine administration.
- Conducted a receiver-operator characteristic analysis to establish the best predictive threshold for adverse outcomes.
- CFR <2.32 predicted major adverse outcomes with an event rate of 26.7%; CFR ≥2.32 had an event rate of 12.2%, p=0.01.
- Lower CFR was associated with a 16% increased risk of adverse outcomes (HR: 1.16, 95% CI: 1.04-1.30, p=0.009).
Study Design
Type
Cohort (n=189)
Structured PICO
Does coronary microvascular dysfunction (measured by CFR after intracoronary adenosine) predict major adverse outcomes in women with suspected ischemia?
P
Population
189 women referred for evaluation of suspected ischemia, followed for a mean of 5.4 years.
E
Exposure
Coronary flow reserve (CFR) measurement after intracoronary adenosine
C
Comparator
Higher CFR (≥2.32) vs Lower CFR (<2.32)
O
Outcome
Major adverse outcomes (composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospital stay for heart failure)composite
Main Result
Hazard Ratio: 1.16 (95% CI 1.04–1.3)
Absolute Event Rate: 26.7% vs 12.2%
p-value: p=0.009
Coronary microvascular dysfunction, indicated by a CFR <2.32 after intracoronary adenosine, significantly predicts major adverse cardiovascular outcomes in women with suspected ischemia.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“So much of our understanding of the underpinnings of heart disease and heart attack, and the basis for our standard methods of diagnosis and treatment are the result of research conducted on men. Through clinical experience, many critical questions arose about how the disease may manifest differently in women, and how diagnostic techniques may need to be used differently in order to prevent more heart attacks and save lives.”
“Through WISE, we have made tremendous progress toward better understanding of heart disease in women. Too often women are tested again and again, go untreated, and still have high risk for heart attacks. As clinicians we must systematically examine women for evidence of any blockages and initiate intensive treatment for their risk factors.”
“In women with normal or near-normal coronary angiograms, blood vessels that inappropriately constrict when they should dilate indicate risk for cardiac events. We think this is due to damage of the lining of the blood vessel wall that is part of the early process of atherosclerosis. Our findings increase our confidence that this is an important factor in patients at risk for vascular disease.”
Implication
May aid risk stratification in women with suspected ischemia; leaves open whether reactivity testing should guide diagnostics or therapy.
Abstract
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 >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. 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).
Discussion
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Cite This Study
Pepine et al. (2010) conducted a cohort in suspected ischemia (n=189). Coronary flow reserve <2.32 vs. Coronary flow reserve ≥2.32 was evaluated on major adverse outcomes (death, nonfatal myocardial infarction, nonfatal stroke, or hospital stay for heart failure) (HR 1.16, 95% CI 1.04-1.30, p=0.009). Lower coronary flow reserve was associated with increased risk of major adverse outcomes (HR 1.16; 95% CI 1.04-1.30; P=0.009), with rates of 26.7% vs 12.2% for CFR <2.32 vs ≥2.32.