title: Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Garg
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Rao
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Maria
authors.initials: M
authors.lastname: Baimas-George
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Hurwitz
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Foster
authors.affiliation: Noninvasive Cardiovascular Imaging Program, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Shah
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Michael
authors.initials: M
authors.lastname: Jerosch-Herold
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Kwong
authors.affiliation: 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.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Di Carli
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA gadler@partners.org.
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D003326:Coronary Circulation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000517:prevention & control; D004232:Diuretics / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D013148:Spironolactone / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D006852:Hydrochlorothiazide; D013148:Spironolactone; D004656:Enalapril