title: Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients.
abstract: OBJECTIVE
  Ramipril and candesartan have distinct mechanisms of action to improve endothelial function. Therefore, we hypothesized that combination therapy has additive beneficial effects to simultaneously improve endothelial dysfunction and adipocytokine profiles in patients with hypertension.
  
  
  RESULTS
  Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms and two washout periods (each 2 months). Ramipril, candesartan, or combination therapy reduced blood pressure, improved flow-mediated dilation, and increased plasma adiponectin levels when compared with baseline values. However, combination therapy improved these outcome measures to a greater extent than either ramipril or candesartan alone (P < 0.001 and P = 0.016 for systolic and diastolic blood pressure, P < 0.001 and P = 0.048 for flow-mediated dilation and adiponectin levels by ANOVA). In addition, combination therapy reduced plasma leptin levels to a greater extent than either ramipril or candesartan alone (P = 0.042 by ANOVA). There were correlations between percent changes in adiponectin levels and percent changes in insulin sensitivity (determined by QUICKI) (r = 0.319, P = 0.066) following ramipril therapy, percent changes in QUICKI (r = 0.374, P = 0.029) following combination therapy, and percent changes in QUICKI (r = 0.607, P < 0.001) following candesartan therapy.
  
  
  CONCLUSIONS
  Ramipril in combination with candesartan improves blood pressure, endothelial function, and adipocytokine profiles to a greater extent than monotherapy with either drug in hypertensive patients.
authors.affiliation: Cardiology, Gachon Medical School, Incheon, Korea. kwangk@gilhospital.com
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Quon
authors.forename: Yonghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Han
authors.forename: Jeong Yeal
authors.initials: JY
authors.lastname: Ahn
authors.forename: Wook-Jin
authors.initials: WJ
authors.lastname: Chung
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D052242:Adiponectin; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017257:Ramipril; C081643:candesartan