Prevalence of Coronary Endothelial and Microvascular Dysfunction in Women with Symptoms of Ischemia and No Obstructive Coronary Artery Disease Is Confirmed by a New Cohort: The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD).
R David Anderson, John W Petersen, Puja K Mehta, Janet Wei, B Delia Johnson, Eileen M Handberg, Saibal Kar, Bruce Samuels, Babak Azarbal, Kamlesh Kothawade, Sheryl F Kelsey, Barry Sharaf, Leslee J Shaw, George Sopko, C Noel Bairey Merz, Carl J Pepine
Author Information
R David Anderson: University of Florida, Gainesville, Florida, USA. ORCID
John W Petersen: University of Florida, Gainesville, Florida, USA.
Puja K Mehta: Emory University School of Medicine, Atlanta, Georgia, USA.
Janet Wei: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
B Delia Johnson: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Eileen M Handberg: University of Florida, Gainesville, Florida, USA.
Saibal Kar: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Bruce Samuels: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Babak Azarbal: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Kamlesh Kothawade: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Sheryl F Kelsey: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Barry Sharaf: Rhode Island Hospital, Providence, Rhode Island, USA.
Leslee J Shaw: Cardiovascular Outcomes Research and Epidemiology, Emory University, Atlanta, Georgia, USA.
George Sopko: National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
C Noel Bairey Merz: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. ORCID
Carl J Pepine: University of Florida, Gainesville, Florida, USA.
OBJECTIVE: In a separate, contemporary cohort, we sought to confirm findings of the original Women's Ischemia Syndrome Evaluation (WISE). BACKGROUND: The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. METHODS: We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or <20% epicardial coronary dilation to nitroglycerin (NTG). RESULTS: In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p<0.0001), and smoking (46% vs 56%, p=0.036). Similar rates were observed in WISE-CVD and WISE cohorts for CMD (mean CFR 2.7±0.6 vs 2.6±0.8, p=0.35), mean change in diameter with intracoronary ACH (0.2±10.0 vs 1.6±12.8 mm, p=0.34), and mean change in diameter with intracoronary NTG (9.7±13.0 vs 9.8±13.5 mm, p=0.94), respectively. CONCLUSIONS: This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.
