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


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.
Division of Nephrology, Department of Internal Medicine, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. fliser.danilo@mh-hannover.de
Danilo
D
Fliser
Konrad
K
Buchholz
Hermann
H
Haller
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000097:blood / Q000453:epidemiology; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D002784:Cholesterol / Q000097:blood; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D000068557:Olmesartan Medoxomil; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014657:Vasculitis / Q000097:blood / Q000150:complications / Q000188:drug therapy*
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D015850:Interleukin-6; D008055:Lipids; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000068557:Olmesartan Medoxomil; D002097:C-Reactive Protein; D002784:Cholesterol; D017035:Pravastatin