Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women

Abstract

Background-Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. Methods and Results-As part of the Women's Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (⌬CSA) in response to acetylcholine (Pϭ0.0006) and nitroglycerin (Pϭ0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (Pϭ0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %⌬CSA with acetylcholine (Pϭ0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %⌬CSA with acetylcholine remained a significant predictor (Pϭ0.006). Conclusions-In

Gender Differences on Brachial Flow‐mediated Dilation and Carotid Intima‐media Thickness for Prediction of Spontaneous Cardiovascular Events

“…Nevertheless, age, but not the extent of CAD, was also shown to be associated with increased risk of spontaneous cardiovascular events in women. As shown in the Women's Ischemia Syndrome Evaluation (WISE) study, 15 coronary endothelial dysfunction predicted cardiovascular events independent of cardiovascular risk factors and the severity of CAD during long-term follow-up. In this study, women without CAD had an 8-fold risk of cardiovascular events compared with men.…”

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study

“…Endothelial dysfunction and/or coronary microvascular dysfunction are mechanisms of ischemia observed in many women who have no obstructive CAD 19, 32. Autopsy data show that young women (aged <50 years) who died from myocardial infarction have more erosions and microemboli versus the overt plaque rupture typically seen in men 33.…”

Reduced Survival in Patients with “Coronary Microvascular Disease”

“…10 The Women and Ischemia Syndrome Evaluation (WISE) group reported that impaired coronary vasomotor response to acetylcholine, chest pain, or abnormal myocardial energy metabolism detected with magnetic resonance spectroscopy was associated with an increased risk of coronary events, including angina, myocardial infarction, heart failure, hospital admissions, and increased health care costs. 6,8,12,14 But there are no mortality data and WISE study is restricted to women.…”

“…Smaller studies (n ¼ 157 to 163) have suggested an increased risk of adverse short-term outcomes and significant decrease in quality of life and high health care costs. [6][7][8][9][10][11][12][13][14] However, its impact on survival is not known. We evaluated survival of this group of patients in comparison to age-and gender-matched population and those with significant epicardial coronary artery disease (CAD).…”