Circulating angiopoietin-2 in essential hypertension: relation to atherosclerosis, vascular inflammation, and treatment with olmesartan/pravastatin.
BACKGROUND
Endothelial activation has emerged as an early event in the pathogenesis of cardiovascular disease. Angiopoietin-2 (Ang-2) has been identified as a nonredundant endothelial-specific facilitator of vascular responsiveness to inflammatory stimuli. We have earlier shown that angiotensin II receptor blocker (ARB) reduces mediators of vascular inflammation in hypertension and cardiovascular disease. We aimed at studying the effect of ARB and/or 3-hydroxy-3-methyl-glutaryl-CoA blockade on Ang-2 and the association between vascular inflammation markers and Ang-2 levels in hypertensive patients.


METHODS
We assessed a panel of vascular inflammation markers and Ang-2 during 12 weeks of therapy with the ARB olmesartan (n = 94) or placebo (n = 96) in a prospective, double-blind, multicenter study in patients with essential hypertension (re-evaluation of the European Trial on Olmesartan and Pravastatin in Inflammation blood samples). Pravastatin was added to the double-blind therapy at week 6 in both arms. The association of demographic variables and inflammation markers with Ang-2 has been investigated.


RESULTS
Initial Ang-2 concentrations in the study population were elevated compared with healthy controls (4.23 +/- 3.1 versus 0.88 +/- 0.43 ng/ml; P < 0.0001). Ang-2 was higher in the elderly (P = 0.01), women (P < 0.001), and in the presence of atherosclerosis (P = 0.02). Ang-2 correlated significantly with soluble TEK tyrosine kinase-2, interleukin-6, vascular cell adhesion molecule-1, and inter-cellular adhesion molecule-1. Surprisingly, neither monotherapy with olmesartan or pravastatin nor the combination therapy affected Ang-2 concentrations.


CONCLUSIONS
Ang-2 concentrations are elevated in hypertensive patients, particularly those with atherosclerosis, possibly reflecting pronounced endothelial activation. ARBs effectively decreased several inflammatory mediators, but did not affect vascular responsiveness in an Ang-2-dependent manner. Elevated Ang-2 levels in hypertensive patients correlate with adhesion molecules.
David
Sascha
S
Department of Medicine, Division of Nephrology and Hypertension, Medical School Hanover, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany. david.sascha@mh-hannover.de
Kümpers
Philipp
P
Lukasz
Alexander
A
Kielstein
Jan T
JT
Haller
Hermann
H
Fliser
Danilo
D
D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D050197:Atherosclerosis / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage*; D011446:Prospective Studies; D013777:Tetrazoles / Q000008:administration & dosage*; D014657:Vasculitis / Q000097:blood*
D042702:Angiopoietin-2; D047228:Angiotensin II Type 1 Receptor Blockers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D002097:C-Reactive Protein; D017035:Pravastatin