title: Aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril as initial choice in hypertensive type II diabetic individuals: effects on albumin excretion, endothelial function and inflammation in a double-blind, randomized clinical trial.
abstract: We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril on urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals. A total of 70 hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a randomized, double-blind, double-dummy design. Blood pressure was titrated to levels below 130/85 mmHg or a decrease in systolic pressure of 10% with a diastolic pressure below 85 mmHg. After titration, patients were treated for 12 months. Mean blood pressures changed from 157/93, 151/94 and 149/93 at baseline to 135/80, 135/82 and 131/80 mmHg after titration in the hydrochlorothiazide (n=24), candesartan (n=24) and lisinopril (n=22) groups. About 70% reached target blood pressures. However, only 45% had blood pressures <130/85 mmHg. Urinary albumin excretion and levels of soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 decreased (GEE regression coefficients, -2.40 mg/24 h (P<0.001), -85 ng/ml (P=0.01) and -50 ng/ml (P=0.02)), but brachial artery endothelium-dependent and -independent vasodilation and levels of von Willebrand factor and C-reactive protein did not change (GEE regression coefficients, 0.21 mm (P=0.07), 0.04 mm (P=0.43), 0.04 IU/ml (P=0.33) and -1.15 mg/l (P=0.64)). No differences in outcome variables between treatment groups were observed. These data show that achievement of target blood pressures below 130/85 mmHg in hypertensive type II diabetes is difficult. Aggressive antihypertensive therapy can improve urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals, regardless of the type of antihypertensive therapy used.
authors.affiliation: Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Schram
authors.forename: F J
authors.initials: FJ
authors.lastname: van Ittersum
authors.forename: A
authors.initials: A
authors.lastname: Spoelstra-de Man
authors.forename: R A J M
authors.initials: RA
authors.lastname: van Dijk
authors.forename: C G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: R G
authors.initials: RG
authors.lastname: Ijzerman
authors.forename: J W R
authors.initials: JW
authors.lastname: Twisk
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000503:physiopathology; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation / Q000150:complications; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017706:Lisinopril; C081643:candesartan