September 18, 2013Open Access
Brachial Artery Constriction during Brachial Artery Reactivity Testing Predicts Major Adverse Clinical Outcomes in Women with Suspected Myocardial Ischemia: Results from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study
Key Result
Brachial artery constriction during reactivity testing independently predicted an almost two-fold increased risk of major adverse cardiovascular events (HR 1.96) in women with suspected myocardial ischemia.
Study Design
Type
Cohort (n=377)
Multicenter
Yes
Structured PICO
Does brachial artery constriction during brachial artery reactivity testing predict major adverse clinical outcomes in women with suspected myocardial ischemia?
P
Population
377 women with suspected myocardial ischemia referred for coronary angiography, followed for a median of 9.5 years.
E
Exposure
Brachial artery constriction (BAC) defined as >4.8% artery constriction following release of the blood pressure cuff during brachial artery reactivity testing (BART).
C
Comparator
No brachial artery constriction (BAC ≤4.8%) during brachial artery reactivity testing.
O
Outcome
Major adverse events (MACE) including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure.composite
Brachial artery constriction following hyperemia is a novel risk marker that independently predicts a nearly two-fold increased risk of major adverse cardiovascular events in women with suspected myocardial ischemia.
Main Result
Hazard Ratio: 1.96 (95% CI 1.12–3.43)
Absolute Event Rate: 39% vs 22%
p-value: p=0.018
Limitations
- Causality cannot be determined or implied due to the observational study design
- Results may not be generalizable to non-angiographic populations of women
- Small BAC subgroup size with few major adverse events limits statistical power
- BART was not timed to a specific time in the menstrual cycle in premenopausal women
- Unable to conclude with certainty whether BAC represents true flow-mediated constriction or simply a failure to dilate
- Lack of repeated scans to test the reproducibility of the BAC measurement
Abstract
BACKGROUND: Limited brachial artery (BA) flow-mediated dilation during brachial artery reactivity testing (BART) has been linked to increased cardiovascular risk. We report on the phenomenon of BA constriction (BAC) following hyperemia. OBJECTIVES: To determine whether BAC predicts adverse CV outcomes and/or mortality in the women's ischemic Syndrome Evaluation Study (WISE). Further, as a secondary objective we sought to determine the risk factors associated with BAC. METHODS: We performed BART on 377 women with chest pain referred for coronary angiography and followed for a median of 9.5 years. Forearm ischemia was induced with 4 minutes occlusion by a cuff placed distal to the BA and inflated to 40mm Hg > systolic pressure. BAC was defined as >4.8% artery constriction following release of the cuff. The main outcome was major adverse events (MACE) including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure. RESULTS: BA diameter change ranged from -20.6% to +44.9%, and 41 (11%) women experienced BAC. Obstructive CAD and traditional CAD risk factors were not predictive of BAC. Overall, 39% of women with BAC experienced MACE vs. 22% without BAC (p=0.004). In multivariate Cox proportional hazards regression, BAC was a significant independent predictor of MACE (p=0.018) when adjusting for obstructive CAD and traditional risk factors. CONCLUSIONS: BAC predicts almost double the risk for major adverse events compared to patients without BAC. This risk was not accounted for by CAD or traditional risk factors. The novel risk marker of BAC requires further investigation in women.