Abstract 1153: Angiotensin II Type 1 Receptor Blockade Elicits Phospholipase A2-Dependent Beneficial Effects on LDL-Oxidation Beyond the Lipid-Lowering Effects of a HMG-CoA Reductase Inhibition in Patients with Coronary Artery Disease
Introduction: LDL-Cholesterol modification and inflammation are hallmarks of atherosclerotic plaque development. Secretory phospholipase A2 (sPLA2) amplifies atherogenic processes by liberating potent pro-inflammatory lipid mediators, generating pro-atherogenic LDL and has become an independent predictor for coronary events in patients. Since angiotensin II type 1 (AT1)-receptor blockade prevents LDL−peroxidation in−vitro in an sPLA2−dependent manner, we here assessed in patients with coronary artery disease whether AT1-blockade apart from a standard lipid lowering treatment with HMG-CoA reductase inhibition (statins) elicits additional beneficial effects on sPLA2-related serum LDL-peroxidation and high sensitive C-reactive protein (hsCRP).
Methods and results: Serum sPLA2 protein and -activity, hsCRP, oxidized LDL (oxLDL) and cholesterol subfractions were determined in patients with angiographically documented CAD and arterial hypertension. 60 patients were double blind randomized to either Pravastatin (PRAV, 40mg/d, N=30) or PRAV plus Irbesartan (PRAV+IRB, 40mg/d+300mg/d, N=30) and treated for 3 months. Blood samples were drawn at baseline and at 3 months, serum markers of inflammation and lipid peroxidation were measured by ELISA technique. At 3 months, mean LDL-C decreased by 22±4% in each group. Blood pressure levels at baseline and 3 months were not significantly different between both groups. Both treatment regimens reduced hsCRP significantly (each p<0.02). In contrast, PRAV+IRB alone reduced circulating levels of sPLA2-protein (p=0.0019 vs baseline), sPLA2 activity (p=0.017 vs baseline) and serum levels of oxLDL (p=0.0023) beyond the decline determined in the PRAV group (sPLA2-protein (p=0.0XX vs PRAV, sPLA2 activity p=0.0113 vs PRAV).
Conclusion: Chronic AT1-blockade by irbesartan develops sPLA2-dependent distinct anti-inflammatory potencies by linking LDL cholesterol modification and inflammation. These findings are consistent with the notion, that AT1-antagonism elicits additional individual anti-inflammatory and anti-atherosclerotic effects beyond the cholesterol lowering effects of a chronic statin treatment.