title: Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study.
abstract: OBJECTIVE
  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).
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida 32610-0277, USA. pepincj@medicine.ufl.edu
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: R David
authors.initials: RD
authors.lastname: Anderson
authors.forename: Barry L
authors.initials: BL
authors.lastname: Sharaf
authors.forename: Steven E
authors.initials: SE
authors.lastname: Reis
authors.forename: Karen M
authors.initials: KM
authors.lastname: Smith
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Handberg
authors.forename: B Delia
authors.initials: BD
authors.lastname: Johnson
authors.forename: George
authors.initials: G
authors.lastname: Sopko
authors.forename: C Noel
authors.initials: CN
authors.lastname: Bairey Merz
mesh_terms: D000241:Adenosine; D000368:Aged; D002637:Chest Pain / Q000175:diagnosis / Q000209:etiology; D015331:Cohort Studies; D016001:Confidence Intervals; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000502:physiology; D003327:Coronary Disease / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D053805:Fractional Flow Reserve, Myocardial / Q000502:physiology*; D006801:Humans; D015552:Injections, Intralesional; D053208:Kaplan-Meier Estimate; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D011237:Predictive Value of Tests; D011336:Probability; D016016:Proportional Hazards Models; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D000241:Adenosine