Impact of a combined treatment of angiotensin II type 1 receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition on secretory phospholipase A2-type IIA and low density lipoprotein oxidation in patients with coronary artery disease.
OBJECTIVE
To evaluate the impact of a combined treatment of angiotensin II type 1 (AT(1))-receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition (statin) on the secretory phospholipase A(2) type IIA (sPLA(2)-IIA) and oxidized low density lipoprotein (oxLDL) in patients with coronary artery disease (CAD).


RESULTS
Sixty patients with angiographically documented CAD and a history of arterial hypertension were randomized in a double-blinded fashion to pravastatin (PRAV, 40 mg/day, n = 30) or PRAV plus irbesartan (PRAV+IRB, 40 mg/day+300 mg/day, n = 30) and were treated for 3 months. Blood pressure (BP) and cholesterol fractions were determined at baseline and after 3 months. SPLA(2) activity as primary endpoint, sPLA(2)-IIA protein, oxLDL levels, and high-sensitivity (hs)-C-reactive protein were measured by an enzyme-linked immunabsorbent assay. In both treatment groups, systolic BP levels and circulating HDL and LDL levels were reduced to the same extent. The combined treatment of PRAV+IRB significantly decreased sPLA(2)-IIA activity and sPLA(2)-IIA-protein concentration compared with PRAV treatment alone (P < 0.05). In addition, PRAV+IRB significantly reduced oxLDL levels compared with PRAV treatment alone (P < 0.05). This effect was independent of changes in LDL cholesterol levels.


CONCLUSIONS
These findings are consistent with the notion that the combined treatment of pravastatin with irbesartan reduced sPLA(2)-IIA-activity, sPLA(2)-IIA-protein concentration, and oxLDL in patients with CAD suggesting a novel anti-atherogenic effect by combining AT(1)-receptor blockade with statin treatment.
Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Dimitar
D
Divchev
Christina
C
Grothusen
Maren
M
Luchtefeld
Martin
M
Thoenes
Frederick
F
Onono
Rainer
R
Koch
Helmut
H
Drexler
Bernhard
B
Schieffer
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage; D002097:C-Reactive Protein / Q000032:analysis; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D054501:Group II Phospholipases A2 / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D000077405:Irbesartan; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage; D013777:Tetrazoles / Q000008:administration & dosage; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D013777:Tetrazoles; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein; D054501:Group II Phospholipases A2; D000077405:Irbesartan; D017035:Pravastatin