Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: Results of the CEZAR study
Received 19 September 2008; received in revised form 26 October 2008; accepted 10 November 2008. published online 16 January 2009.
Abstract
Background
Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction.
Methods and results
Fifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent vasodilation (NMD), lipid, C-reactive protein (CRP) plasma concentrations and urinary 8-iso-prostaglandin F2alpha excretion were measured before and after treatment. Total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10. A80 caused significantly stronger improvement of FMD compared to A10E10 (absolute change FMD: A80+2.7±3.0% (post vs. pre p<0.001), A10E10+0.6±2.9% (post vs. pre p=0.25), A80 vs. A10E10 p=0.018). NMD was improved by A80 but not by A10E10 (absolute change NMD: A80+2.7±4.6%, A10E10+0.7±3.5%, p=0.12). Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostaglandin F2alpha excretion. There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group.
Conclusions
The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms, LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD.
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