title: Effect of ezetimibe-simvastatine over endothelial dysfunction in dyslipidemic patients: assessment by 13N-ammonia positron emission tomography.
abstract: 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.
  
  
  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.
authors.affiliation: Unidad PET/CT Ciclotrón, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico. alexanderick@yahoo.com
authors.forename: Erick
authors.initials: E
authors.lastname: Alexanderson
authors.forename: Leonardo
authors.initials: L
authors.lastname: García-Rojas
authors.forename: Moisés
authors.initials: M
authors.lastname: Jiménez
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jácome
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Calleja
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
authors.forename: Juan M
authors.initials: JM
authors.lastname: Ochoa
authors.forename: Aloha
authors.initials: A
authors.lastname: Meave
authors.forename: Graciela
authors.initials: G
authors.lastname: Alexanderson
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000737:chemistry*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001384:Azetidines / Q000494:pharmacology*; D016022:Case-Control Studies; D050171:Dyslipidemias / Q000175:diagnosis / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000473:pathology*; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D009587:Nitrogen Isotopes / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D012307:Risk Factors; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D009587:Nitrogen Isotopes; D000641:Ammonia; D019821:Simvastatin; D000069438:Ezetimibe; D000241:Adenosine