title: Effects of combination therapy with olmesartan and azelnidipine on serum osteoprotegerin in patients with hypertension.
abstract: BACKGROUND
  Vascular calcification is a potent predictor of plaque instability and cardiac events. Osteoprotegerin (OPG), well-known vascular calcification mediator, is a signaling molecule involved in bone remodeling, which has been implicated in the regulation of vascular calcification and atherogenesis. The purpose of this study was to compare the combination treatments of olmesartan/azelnidipine and olmesartan/diuretics on serum bone-related markers in patients with essential hypertension.
  
  
  RESULTS
  A total of 48 patients with hypertension treated with 20 mg olmesartan were randomized to receive combination treatment with 16 mg azelnidipine (O/A group) or diuretics (1 mg indapamide; O/D group) for 12 months. Osteoprotegerin, matrix metalloproteinase 2 (MMP-2), and high-sensitive CRP (hs-CRP) were measured after 3 and 12 months of treatment. Cardio-ankle vascular index (CAVI) was measured as the arterial stiffness using a VaSera CAVI instrument at the same time points. In both groups, the systolic and diastolic blood pressure reduction is similar. Serum OPG, MMP-2, and hs-CRP were significantly decreased at 12 months in the O/A group (P < .05), while there were no significant reductions in the O/D group. CAVI was significantly improved at 12 months in both the treatment groups. The improvement in CAVI was significantly greater in the O/A group than in the O/D group.
  
  
  CONCLUSIONS
  Azelnidipine, but not indapamide, combined with olmesartan, improved arterial stiffness and were associated with significant decrease in OPG, MMP-2, and hs-CRP concentrations. These results suggest that the beneficial effects of the combination treatments of olmesartan/azelnidipine on arterial stiffness are mediated by alteration in bone-remodeling and inflammatory markers.
authors.affiliation: 1Department of cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Uzui
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Morishita
authors.forename: Akira
authors.initials: A
authors.lastname: Nakano
authors.forename: Naoki
authors.initials: N
authors.lastname: Amaya
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Fukuoka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ishida
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Arakawa
authors.forename: Jong-Dae
authors.initials: JD
authors.lastname: Lee
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004095:Dihydropyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D053244:Osteoprotegerin / Q000187:drug effects*; D011446:Prospective Studies; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; D007093:Imidazoles; D053244:Osteoprotegerin; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D001383:Azetidinecarboxylic Acid; C437965:olmesartan; D002097:C-Reactive Protein; D020778:Matrix Metalloproteinase 2; C061679:azelnidipine
keywords: arterial stiffness; azelnidipine; hypertension; olmesartan; osteoprotegerin