title: Carvedilol-lisinopril combination therapy and endothelial function in obese individuals with hypertension.
abstract: The authors hypothesized that carvedilol controlled-release plus lisinopril combination therapy (C+L) would increase endothelial function and decrease oxidative stress to a greater extent than hydrochlorothiazide plus lisinopril combination therapy (H+L) in obese patients with hypertension. Twenty-five abdominally obese patients (aged 54.4±7.3 years; 14 women) with hypertension/prehypertension were enrolled in a 7-month (two 3-month treatment periods separated by a 1-month washout), randomized, double-blind, controlled, crossover clinical trial comparing C+L vs H+L. Endothelial function, measured by digital reactive hyperemic index (RHI), circulating oxidized low-density lipoprotein (oxLDL), 8-isoprostane, and asymmetric dimethylarginine (ADMA) were obtained at baseline, post-period 1, post-washout, and post-period 2. Analyses were adjusted for baseline measurements by analysis of covariance, with robust variance estimation for confidence intervals and P values. C+L treatment compared to H+L treatment significantly improved RHI (0.74, 95% confidence interval, 0.31-1.19, P =.001). This difference persisted after adjustment for the change in systolic blood pressure. No significant treatment differences were observed for oxLDL, 8-isoprostane, or ADMA. These data provide evidence that independent of blood pressure-lowering, C+L therapy improves endothelial function to a greater extent than H+L therapy. Levels of oxidative stress were not significantly different between treatments, suggesting that other mechanisms may be responsible for the improvement in endothelial function.
authors.affiliation: From the Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN ; 1 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN ; 2 the Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN ; 3 Allina Hospitals and Clinics, St. Paul, MN ; 4 and the Department of Research, St. Paul Heart Clinic, St. Paul, MN 5.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kelly
authors.affiliation: From the Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN ; 1 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN ; 2 the Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN ; 3 Allina Hospitals and Clinics, St. Paul, MN ; 4 and the Department of Research, St. Paul Heart Clinic, St. Paul, MN 5.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gonzalez-Campoy
authors.affiliation: From the Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN ; 1 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN ; 2 the Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN ; 3 Allina Hospitals and Clinics, St. Paul, MN ; 4 and the Department of Research, St. Paul Heart Clinic, St. Paul, MN 5.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Rudser
authors.affiliation: From the Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN ; 1 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN ; 2 the Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN ; 3 Allina Hospitals and Clinics, St. Paul, MN ; 4 and the Department of Research, St. Paul Heart Clinic, St. Paul, MN 5.
authors.forename: Harold
authors.initials: H
authors.lastname: Katz
authors.affiliation: From the Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN ; 1 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN ; 2 the Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN ; 3 Allina Hospitals and Clinics, St. Paul, MN ; 4 and the Department of Research, St. Paul Heart Clinic, St. Paul, MN 5.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Metzig
authors.affiliation: From the Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN ; 1 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN ; 2 the Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN ; 3 Allina Hospitals and Clinics, St. Paul, MN ; 4 and the Department of Research, St. Paul Heart Clinic, St. Paul, MN 5.
authors.forename: Melissa
authors.initials: M
authors.lastname: Thalin
authors.affiliation: From the Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN ; 1 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN ; 2 the Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN ; 3 Allina Hospitals and Clinics, St. Paul, MN ; 4 and the Department of Research, St. Paul Heart Clinic, St. Paul, MN 5.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Bank
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000503:physiopathology*; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000453:epidemiology* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011412:Propanolamines / Q000008:administration & dosage*
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D003692:Delayed-Action Preparations; D011412:Propanolamines; D000077261:Carvedilol; D017706:Lisinopril