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

Anthony A. Bavry, Eileen M. Handberg, Tianyao Huo, Amir Lerman, Arshed A. Quyyumi, Chrisandra Shufelt, Barry Sharaf, C. Noel Bairey Merz, Rhonda M. Cooper-Dehoff, George Sopko, Carl J. Pepine

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background 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). Conclusion 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.

Original languageEnglish (US)
Pages (from-to)826-832
Number of pages7
JournalAmerican Heart Journal
Volume167
Issue number6
DOIs
StatePublished - 2014

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National Heart, Lung, and Blood Institute (U.S.)
Aldosterone
Coronary Artery Disease
Ischemia
Placebos
Angiotensin II
Adenosine
Acetylcholine
Signs and Symptoms
Mineralocorticoid Receptors
Angiotensin-Converting Enzyme Inhibitors
Coronary Vessels
Body Mass Index
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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. / Bavry, Anthony A.; Handberg, Eileen M.; Huo, Tianyao; Lerman, Amir; Quyyumi, Arshed A.; Shufelt, Chrisandra; Sharaf, Barry; Merz, C. Noel Bairey; Cooper-Dehoff, Rhonda M.; Sopko, George; Pepine, Carl J.

In: American Heart Journal, Vol. 167, No. 6, 2014, p. 826-832.

Research output: Contribution to journalArticle

Bavry, Anthony A. ; Handberg, Eileen M. ; Huo, Tianyao ; Lerman, Amir ; Quyyumi, Arshed A. ; Shufelt, Chrisandra ; Sharaf, Barry ; Merz, C. Noel Bairey ; Cooper-Dehoff, Rhonda M. ; Sopko, George ; Pepine, Carl J. / 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. In: American Heart Journal. 2014 ; Vol. 167, No. 6. pp. 826-832.
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abstract = "Background 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). Conclusion 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.",
author = "Bavry, {Anthony A.} and Handberg, {Eileen M.} and Tianyao Huo and Amir Lerman and Quyyumi, {Arshed A.} and Chrisandra Shufelt and Barry Sharaf and Merz, {C. Noel Bairey} and Cooper-Dehoff, {Rhonda M.} and George Sopko and Pepine, {Carl J.}",
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T1 - Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease

T2 - An ancillary study of the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation

AU - Bavry, Anthony A.

AU - Handberg, Eileen M.

AU - Huo, Tianyao

AU - Lerman, Amir

AU - Quyyumi, Arshed A.

AU - Shufelt, Chrisandra

AU - Sharaf, Barry

AU - Merz, C. Noel Bairey

AU - Cooper-Dehoff, Rhonda M.

AU - Sopko, George

AU - Pepine, Carl J.

PY - 2014

Y1 - 2014

N2 - Background 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). Conclusion 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.

AB - Background 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). Conclusion 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.

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DO - 10.1016/j.ahj.2014.01.017

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JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

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