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

To evaluate the impact of a combined treatment of angiotensin II type 1 (AT1)-receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition (statin) on the secretory phospholipase A2 type IIA (sPLA2-IIA) and oxidized low density lipoprotein (oxLDL) in patients with coronary artery disease (CAD). 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 sPLA2-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. 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.