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

Circulation. 2004 Aug 31;110(9):1103-7. doi: 10.1161/01.CIR.0000140265.21608.8E. Epub 2004 Aug 16.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Arteriosclerosis / blood
  • Arteriosclerosis / epidemiology
  • Biomarkers
  • C-Reactive Protein / analysis
  • Chemokine CCL2 / blood
  • Cholesterol / blood
  • Comorbidity
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / epidemiology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypertension / blood
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use*
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-6 / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Olmesartan Medoxomil
  • Pravastatin / administration & dosage
  • Pravastatin / therapeutic use*
  • Prospective Studies
  • Receptor, Angiotensin, Type 1 / drug effects*
  • Tetrazoles / administration & dosage
  • Tetrazoles / therapeutic use*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / analysis
  • Vasculitis / blood
  • Vasculitis / complications
  • Vasculitis / drug therapy*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Imidazoles
  • Interleukin-6
  • Lipids
  • Receptor, Angiotensin, Type 1
  • Tetrazoles
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Olmesartan Medoxomil
  • C-Reactive Protein
  • Cholesterol
  • Pravastatin