Mineralocorticoid receptor blockade improves coronary microvascular function in
individuals with type 2 diabetes.
Author(s): Garg R(1), Rao AD(1), Baimas-George M(1), Hurwitz S(1), Foster C(2), Shah RV(3),
Jerosch-Herold M(4), Kwong RY(5), Di Carli MF(6), Adler GK(7).
Affiliation(s): Author information:
(1)Division of Endocrinology, Diabetes and Hypertension, Department of Medicine,
Brigham and Women's Hospital, Harvard Medical School, Boston, MA. (2)Division of
Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and
Women's Hospital, Harvard Medical School, Boston, MA. (3)Noninvasive
Cardiovascular Imaging Program, Department of Radiology, Brigham and Women's
Hospital, Harvard Medical School, Boston, MA. (4)Department of Radiology, Brigham
and Women's Hospital, Harvard Medical School, Boston, MA. (5)Division of
Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital,
Harvard Medical School, Boston, MA. (6)Division of Nuclear Medicine and Molecular
Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA Noninvasive Cardiovascular Imaging Program, Department of
Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School, Boston, MA. (7)Division of Endocrinology,
Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital,
Harvard Medical School, Boston, MA gadler@partners.org.
Publication date & source: 2015, Diabetes. , 64(1):236-42
Reduced coronary flow reserve (CFR), an indicator of coronary microvascular
dysfunction, is seen in type 2 diabetes mellitus (T2DM) and predicts cardiac
mortality. Since aldosterone plays a key role in vascular injury, the aim of this
study was to determine whether mineralocorticoid receptor (MR) blockade improves
CFR in individuals with T2DM. Sixty-four men and women with well-controlled
diabetes on chronic ACE inhibition (enalapril 20 mg/day) were randomized to
add-on therapy of spironolactone 25 mg, hydrochlorothiazide (HCTZ) 12.5 mg, or
placebo for 6 months. CFR was assessed by cardiac positron emission tomography at
baseline and at the end of treatment. There were significant and similar
decreases in systolic blood pressure with spironolactone and HCTZ but not with
placebo. CFR improved with treatment in the spironolactone group as compared with
the HCTZ group and with the combined HCTZ and placebo groups. The increase in CFR
with spironolactone remained significant after controlling for baseline CFR,
change in BMI, race, and statin use. Treatment with spironolactone improved
coronary microvascular function, raising the possibility that MR blockade could
have beneficial effects in preventing cardiovascular disease in patients with
T2DM.
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