Effect of ezetimibe-simvastatine over endothelial dysfunction in dyslipidemic patients: assessment by 13N-ammonia positron emission tomography.

Background: Dyslipidemias constitute an independent risk factor for the development of atherogenesis and they also predispose to the development of endothelial dysfunction (ED). Using PET with (13)N-ammonia, it is possible to quantify myocardial blood flow (MBF) in mL/min/g and to quantitatively evaluate ED. With the use of lipid lowering therapy it is possible to reduce ED and increase the MBF and the endothelial-dependent vasodilation index (ENDEVI). In this study, we aimed to evaluate with (13)N-ammonia PET the benefic effects of the combined treatment ezetimibe/simvastatine on the endothelial function of dyslipidemic patients after 8 weeks of treatment.

Material And Methods: Fourteen consecutive patients with dyslipidemia diagnosis and 17 healthy volunteers were studied with a three phase [rest, Cold Pressor Test (CPT), and adenosine-induced hyperemia] (13)N-ammonia PET for MBF quantification assessment. A second PET study was performed in the dyslipidemic group after 8 weeks of treatment with ezetimibe/simvastatine (10/40 mg). Myocardial flow reserve (MFR), ENDEVI, and %ΔMBF were calculated.

Results: Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides concentrations were markedly altered in the dyslipidemic group and after 8 weeks of treatment these values improved. Dyslipidemic patients showed endothelial dysfunction when compared with the control group, (MFR 2.79 ± 0.94 vs 3.15 ± 0.48, P < 0.05 ; ENDEVI 1.28 ± 0.25 vs 1.53 ± 0.24, P < 0.05; and %ΔMBF 29.08 ± 24.62 vs 53 ± 24.60%, P < 0.05, respectively). After 8 weeks of treatment, we found a significant increase in all the endothelial function markers (MFR: 3.14 ± 0.86, P < 0.05, ENDEVI 1.65 ± 0.23, P < 0.05; %ΔMBF: 65.21 ± 23.43, P < 0.05).

Conclusions: Dyslipidemic patients show endothelial dysfunction measured with (13)N-ammonia PET. Treatment with ezetimibe/simvastatine was effective improving the lipid profile as well as the endothelial function of these patients. PET may be a useful tool to monitor vascular reactivity and regression/progression of coronary atherosclerosis after pharmacologic interventions.