Angiotensin II receptor blocker and statins lower elevated levels of osteopontin in essential hypertension--results from the EUTOPIA trial.
BACKGROUND
Osteopontin is a pleiotropic cytokine that has been implicated as a key factor in the development of atherosclerosis, a major complication of hypertension. We have earlier shown that olmesartan reduces mediators of vascular inflammation in patients with hypertension and cardiovascular disease. We aimed at studying the effect of olmesartan and/or pravastatin on osteopontin plasma levels, and the association between vascular inflammation markers and osteopontin in hypertensive patients.


METHODS
We assessed a panel of vascular inflammation markers and osteopontin during 12 weeks of therapy with 20mg olmesartan (n=94) or placebo (n=96) in a prospective, double-blind, multi-center study in patients with essential hypertension (re-evaluation of the EUTOPIA trial blood samples). Pravastatin (20mg) was added to the double-blind therapy at week 6 in both arms. The association of demographic variables and inflammation markers with osteopontin has been analyzed as well.


RESULTS
Baseline osteopontin plasma concentrations in the study population were elevated compared to healthy controls (32.85+/-19.04ng/mL vs. 23.82+/-3.69ng/mL, p=0.027). Mono-therapy with olmesartan and co-therapy with pravastatin reduced levels of circulating osteopontin (p<0.001). The addition of pravastatin to the placebo treatment-arm resulted in a reduction of osteopontin levels as well (p<0.01). osteopontin plasma levels correlated with VCAM-1 (r=0.27; p=0.0002), ICAM-1 (r=0.18; p=0.015), IL-6 (r=0.35; p<0.0001) and hsCRP (r=0.22; p=0.0022).


CONCLUSIONS
We show, for the first time, that olmesartan significantly decreases osteopontin concentrations. Co-therapy with pravastatin also reduces osteopontin levels. Elevated osteopontin levels in hypertensive patients correlate with adhesion molecules and inflammation markers.
Lorenzen
Johan M
JM
Department of Medicine/Division of Nephrology & Hypertension, Hanover Medical School, Hannover, Germany. J.M.Lorenzen@gmail.com
Neunhöffer
Henrike
H
David
Sascha
S
Kielstein
Jan T
JT
Haller
Hermann
H
Fliser
Danilo
D
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000097:blood; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D013777:Tetrazoles / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D053495:Osteopontin; C437965:olmesartan; D017035:Pravastatin