Author + information
- Received March 17, 2009
- Revision received January 13, 2010
- Accepted January 18, 2010
- Published online June 22, 2010.
- Carl J. Pepine, MD*,* (, )
- R. David Anderson, MD*,
- Barry L. Sharaf, MD†,
- Steven E. Reis, MD‡,
- Karen M. Smith, MD*,
- Eileen M. Handberg, PhD*,
- B. Delia Johnson, PhD‡,
- George Sopko, MD, MPH§ and
- C. Noel Bairey Merz, MD‖
- ↵*Reprint requests and correspondence:
Dr. Carl J. Pepine, Division of Cardiovascular Medicine, University of Florida College of Medicine, 1600 Southwest Archer Road/Box 100277, Gainesville, Florida 32610-0277
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 ≥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)
This work was supported by contracts from the NHLBI, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, T32HL69751; GCRCgrant MO1-RR00425from the National Center for Research Resources; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, New Jersey; The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania; QMED, Inc., Laurence Harbor, New Jersey; and The Women's Guild of Cedars-Sinai Medical Center, the Edythe L. Broad Women's Heart Research Fellowship; and the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, California. Dr. Pepine has received research grants and an educational grant from Pfizer. Dr. Bairey Merz has served as a consultant for Strategy Group, BSP, and Kendle Internation, Inc.; has served on the advisory board of Novartis; has served on the External Review Panel of Karolinska Institute; was the NHLBI DSMB chair of the University of Pittsburgh; has performed grant reviewing for Pfizerand the NHLBI; has received lecture honorarium from Northwestern University, University of California, Davis, Abbott Laboratories, CV Therapeutics, Boehringer Ingelheim, American College of Physicians, ProMedica, Mayo Clinic, and Merck; and owns stock in Boston Scientific, Medtronic, Johnson & Johnson, and Teva Pharmaceuticals.
- Received March 17, 2009.
- Revision received January 13, 2010.
- Accepted January 18, 2010.
- American College of Cardiology Foundation