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Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation.

Abstract：

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-alpha (-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-alpha (-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.

journal_name

Circulation

journal_title

Circulation

authors

Fliser D,Buchholz K,Haller H,EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) Investigators.

doi

10.1161/01.CIR.0000140265.21608.8E

subject

Has Abstract

pub_date

2004-08-31 00:00:00

pages

1103-7

issue

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000140265.21608.8E

journal_volume

110

pub_type

临床试验,杂志文章,多中心研究,随机对照试验

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Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation.