The effect of statin alone or in combination with ezetimibe on postprandial lipoprotein composition in obese metabolic syndrome patients.
BACKGROUND
Fasting and postprandial hypertriglyceridemia are essential features of metabolic syndrome. Statins decrease fasting lipid levels but fail to reduce fat load induced hypertriglyceridemia. We established whether ezetimibe combined with simvastatin differently influences post fat load lipid levels and lipoprotein composition as compared to simvastatin 80mg monotherapy in obese male metabolic syndrome patients.


METHODS
Prospective, randomized, double blind, crossover trial. Male obese metabolic syndrome (ATPIII) patients (n=19) were treated with simvastatin 80mg and simvastatin/ezetimibe 10mg/10mg for 6 weeks. At the start of the study and after each treatment period oral fat loading tests were performed. Lipoprotein fractions (triglyceride-rich lipoproteins (TRL), IDL, LDL, and HDL) were isolated by density gradient ultracentrifugation. Postprandial changes in lipid levels were integrated as areas under the curve (AUCs).


RESULTS
Fasting LDL-C, RLP-C and triglycerides were lowered equally by both simvastatin 80mg and simvastatin/ezetimibe 10mg/10mg. Also postprandial plasma triglyceride levels (net AUC-TG) were equally lowered after both treatments (5.16+/-0.50mmolh/l after simvastatin/ezetimibe 10mg/10mg and 6.09+/-0.71mmolh/l after simvastatin 80mg) compared to fat loading without treatment (6.64+/-0.86mmolh/l). In addition, triglyceride-content in lipoprotein fractions after fat load (net AUCs) were also equally reduced after both treatments. Similarly, TRL. IDL and LDL cholesterol and apoB concentrations were equally affected by both treatment regimens, leading to a reduced number of circulating particles, in both conditions. However the composition of these particles remained the same.


CONCLUSIONS
Simvastatin 80mg and simvastatin/ezetimibe 10mg/10mg were equally effective in reducing fasting and post fat load plasma lipid, and lipoprotein concentrations and lipoprotein composition in obese metabolic syndrome patients.
Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Gideon R
GR
Hajer
Geesje M
GM
Dallinga-Thie
Leonie C
LC
van Vark-van der Zee
Frank L J
FL
Visseren
D000293:Adolescent; D000328:Adult; D000368:Aged; D001384:Azetidines / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood* / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D019518:Postprandial Period; D019821:Simvastatin / Q000008:administration & dosage*
D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins; D019821:Simvastatin; D000069438:Ezetimibe