Lipid-lowering therapy does not affect the postprandial drop in high density lipoprotein-cholesterol (HDL-c) plasma levels in obese men with metabolic syndrome: a randomized double blind crossover trial.
BACKGROUND
The postprandial lipid metabolism in metabolic syndrome patients is disturbed and may add to the increased cardiovascular risk in these patients. It is not known whether postprandial high density lipoprotein-cholesterol (HDL-c) metabolism is also affected and whether this can be influenced by statin and/or ezetimibe treatment.


METHODS
Prospective, randomized, double blind, crossover trial comparing simvastatin 80 mg with simvastatin/ezetimibe 10 mg/10 mg treatment for 6 weeks on postprandial HDL-c metabolism in 15, nonsmoking, male, obese metabolic syndrome patients (Adult Treatment Panel III, ATPIII). Only study medication was allowed. HDL-c concentrations, cholesteryl ester transfer (CET), CET protein (CETP) mass and adiponectin were measured before and after oral fat loading. ClinicalTrials.gov NCT00189085.


RESULTS
Plasma HDL-c levels remained stable during continuous fasting following an overnight fast. Pre-fat load HDL-c concentrations without treatment, after simvastatin and simvastatin/ezetimibe treatment were 1.15 +/- 0.04, 1.16 +/- 0.05 and 1.11 +/- 0.04 mmol/l. Fat load induced a 11% drop in HDL-c plasma levels; 1.02 +/- 0.05 mmol/l (P < 0.001) which was not affected by either therapy. Triglyceride levels during fat load were similar after both treatments. Total CET increased from 9.73 +/- 0.70 to 12.20 +/- 0.67 nmol/ml/h (P = 0.004). Four hours after fat loading CETP mass was increased while adiponectin levels were decreased, irrespective of treatment.


CONCLUSIONS
HDL-c levels decrease as CET increases after fat loading in obese metabolic syndrome patients. This is not influenced by either simvastatin or simvastatin/ezetimibe treatment. After fat loading, CETP mass and CET increased, and adiponectin decreased pointing towards a potential role for intra-abdominal fat. Decreased postprandial HDL-c levels may contribute to the increased cardiovascular risk in metabolic syndrome patients on top of already low HDL-c levels.
Hajer
Gideon R
GR
Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Dallinga-Thie
Geesje M
GM
van Vark-van der Zee
Leonie C
LC
Olijhoek
Jobien K
JK
Visseren
Frank L J
FL
D000293:Adolescent; D000328:Adult; D000368:Aged; D001384:Azetidines / Q000627:therapeutic use*; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D018592:Cross-Over Studies; D004041:Dietary Fats; D004311:Double-Blind Method; D004338:Drug Combinations; D000069438:Ezetimibe; D005215:Fasting; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy*; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy; D019518:Postprandial Period; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*
D001384:Azetidines; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004041:Dietary Fats; D004338:Drug Combinations; D019821:Simvastatin; D000069438:Ezetimibe