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(Circulation. 2004;110:1103-1107.)
© 2004 American Heart Association, Inc.

Original Articles

Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation

Danilo Fliser, MD; Konrad Buchholz, MD; Hermann Haller, MD, for the EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) Investigators

From the Department of Internal Medicine, Medical School Hannover, Hannover, Germany.

Correspondence to Danilo Fliser, MD, Associate Professor of Medicine, Division of Nephrology, Department of Internal Medicine, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail fliser.danilo{at}mh-hannover.de

Received February 8, 2004; de novo received March 11, 2004; revision received May 13, 2004; accepted May 21, 2004.

Background— Experimental studies revealed proinflammatory properties of angiotensin II. We evaluated antiinflammatory effects of the angiotensin II subtype 1 receptor antagonist olmesartan medoxomil alone and in cotherapy with the HMG-CoA reductase inhibitor pravastatin in patients with essential hypertension and microinflammation.

Methods and Results— We measured a panel of vascular inflammation markers, including high-sensitivity C-reactive protein, and lipid levels during 12 weeks of therapy with olmesartan (n=100) or placebo (n=99) in a prospective double-blind multicenter study. Pravastatin was added to the double-blind therapy at week 6 in both treatment arms. Blood pressure control was achieved with addition of hydrochlorothiazide. Olmesartan treatment had already significantly reduced serum levels of high-sensitivity C-reactive protein (–15.1%; P<0.05), high-sensitivity tumor necrosis factor- (–8.9%; P<0.02), interleukin-6 (–14.0%; P<0.05), and monocyte chemotactic protein-1 (–6.5%; P<0.01) after 6 weeks of therapy, whereas placebo treatment (ie, blood pressure reduction) had no major effect on inflammation markers. After 12 weeks of therapy, high-sensitivity C-reactive protein (–21.1%; P<0.02), high-sensitivity tumor necrosis factor- (–13.6%; P<0.01), and interleukin-6 (–18.0%; P<0.01) decreased further with olmesartan and pravastatin cotherapy, but treatment with pravastatin alone (ie, cotherapy with placebo) did not significantly alter inflammation markers. In contrast, addition of pravastatin led to a significant (P<0.001) reduction in LDL cholesterol serum concentrations in the olmesartan and placebo treatment groups (–15.1% and –12.1%, respectively).

Conclusions— Angiotensin II receptor blockade significantly reduces vascular microinflammation in patients with essential hypertension by as early as week 6 of therapy. This antiinflammatory action of angiotensin II receptor antagonists may contribute to their beneficial cardiovascular effects.

Key Words: angiotensin • atherosclerosis • cholesterol • hypertension • inflammation

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