title: Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension.
abstract: Diabetic patients with hypertension are at particularly high risk of vascular damage and consequently cardiovascular and renal disease. Fibulin-1, an extracellular matrix glycoprotein, is increased in arterial tissue and plasma from individuals with type 2 diabetes. This study aimed to evaluate whether antihypertensive treatment with spironolactone changes plasma fibulin-1 levels. In a multicenter, double-blind, randomized, placebo-controlled study, 119 patients with type 2 diabetes and resistant hypertension were included. A dose of spironolactone 25 mg or matching placebo was added to previous treatment at randomization. Blood pressure (BP) and plasma fibulin-1 were measured at baseline and at 16 weeks follow-up. Overall, 112 patients completed the study. All measures of BP were reduced in the spironolactone group at follow-up. Plasma fibulin-1 was significantly reduced after spironolactone treatment (P=0.009), but increased after placebo (P=0.017). Baseline plasma fibulin-1 correlated with BP and estimated glomerular filtration rate. Increased levels of plasma fibulin-1 (P=0.004) were observed in diabetic participants reporting erectile dysfunction as compared with participants who did not. Treatment with low-dose spironolactone reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. This supports the hypothesis that the antihypertensive effect of the mineralocorticoid receptor blocker in part may be due to regression of vascular remodeling.
authors.affiliation: 1] Research Unit for Cardiovascular and Metabolic Prevention, Department of Endocrinology, Odense University Hospital, Odense C, Denmark [2] Centre for individualized Medicine in Arterial Diseases, Odense University Hospital, Odense C, Denmark.
authors.forename: C S
authors.initials: CS
authors.lastname: Oxlund
authors.affiliation: 1] Centre for individualized Medicine in Arterial Diseases, Odense University Hospital, Odense C, Denmark [2] Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Cangemi
authors.affiliation: Research Unit for Cardiovascular and Metabolic Prevention, Department of Endocrinology, Odense University Hospital, Odense C, Denmark.
authors.forename: J E
authors.initials: JE
authors.lastname: Henriksen
authors.affiliation: Research Unit for Cardiovascular and Metabolic Prevention, Department of Endocrinology, Odense University Hospital, Odense C, Denmark.
authors.forename: I A
authors.initials: IA
authors.lastname: Jacobsen
authors.affiliation: Department of Endocrinology, Esbjerg, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Gram
authors.affiliation: Department of Medicine, Fredericia, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Schousboe
authors.affiliation: Steno Diabetes Centre, Gentofte, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Argraves
authors.affiliation: 1] Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense C, Denmark [2] Department of Endocrinology, Esbjerg, Denmark.
authors.forename: L M
authors.initials: LM
authors.lastname: Rasmussen
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000097:blood*; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004232:Diuretics / Q000008:administration & dosage*; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D013148:Spironolactone / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; C060820:fibulin; D013148:Spironolactone
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