title: Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: an ancillary study of the national heart, lung, and blood institute-sponsored women's ischemia syndrome evaluation.
abstract: Endothelial dysfunction is highly prevalent and associated with adverse outcomes among patients without obstructive coronary artery disease (CAD). Angiotensin II inhibition may improve endothelial function, but with continued treatment, "aldosterone escape" may occur. Thus, it is unknown if adding aldosterone blockade further improves endothelial function.
  
  
  METHODS
  In a double-blind, parallel-group, repeated-measures study, women with symptoms and signs of ischemia, no significant CAD, and coronary endothelial dysfunction receiving an angiotensin-converting enzyme inhibitor or receptor blocker were randomized to aldosterone blockade or placebo. The primary outcome at 16 weeks was percent change in coronary diameter to acetylcholine, and secondary outcome, coronary flow reserve to adenosine, both adjusted for baseline reactivity.
  
  
  RESULTS
  Forty-one women completed the treatment period with repeat coronary reactivity testing. Their mean age was 54 ± 10 years; body mass index, 30 ± 7.4 kg/m2; 12% had diabetes; and 15% had metabolic syndrome. There were no significant differences between treatment groups. At baseline, the percent change in reference vessel coronary diameter to acetylcholine was -5.0% in the aldosterone blockade group and -3.4% in the placebo group and, at 16 weeks, -7.2% in the aldosterone blockade group versus -14.3% in the placebo group (P = .15). At 16 weeks, the change in coronary flow reserve to intracoronary adenosine was -0.13 in the aldosterone blockade group versus -0.25 in the placebo group (P = .66).
  
  
  CONCLUSIONS
  Adding aldosterone receptor blockade to angiotensin II inhibition did not improve coronary endothelial or microvascular function among women with signs and symptoms of ischemia in the setting of nonobstructive CAD.
authors.affiliation: North Florida/South Georgia Veterans Health System, Gainesville, FL; Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL. Electronic address: anthony.bavry@medicine.ufl.edu.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Bavry
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Handberg
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL.
authors.forename: Tianyao
authors.initials: T
authors.lastname: Huo
authors.affiliation: Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: Division of Cardiology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.affiliation: Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Chrisandra
authors.initials: C
authors.lastname: Shufelt
authors.affiliation: Division of Cardiology, Rhode Island Hospital, Providence, RI.
authors.forename: Barry
authors.initials: B
authors.lastname: Sharaf
authors.affiliation: Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: C Noel Bairey
authors.initials: CN
authors.lastname: Merz
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL; Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL.
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.affiliation: National Heart, Lung, and Blood Institute, Division of Heart and Vascular Diseases, Bethesda, MD.
authors.forename: George
authors.initials: G
authors.lastname: Sopko
authors.affiliation: Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, FL.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects*; D000077545:Eplerenone; D005260:Female; D006801:Humans; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D054555:National Heart, Lung, and Blood Institute (U.S.); D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D014665:Vasodilator Agents; D013148:Spironolactone; D000077545:Eplerenone; D000109:Acetylcholine