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.


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.
Alexanderson
Erick
E
Unidad PET/CT Ciclotrón, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico. alexanderick@yahoo.com
García-Rojas
Leonardo
L
Jiménez
Moisés
M
Jácome
Rodrigo
R
Calleja
Rodrigo
R
Martínez
Alfonso
A
Ochoa
Juan M
JM
Meave
Aloha
A
Alexanderson
Graciela
G
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*
D000924:Anticholesteremic Agents; D001384:Azetidines; D009587:Nitrogen Isotopes; D000641:Ammonia; D019821:Simvastatin; D000069438:Ezetimibe; D000241:Adenosine