Effect of statin versus fibrate on postprandial endothelial dysfunction: role of remnant-like particles.
BACKGROUND
Postprandial lipemia is associated with endothelial dysfunction. Remnant-like particles (RLP) have been suggested to contribute to these adverse vascular effects. We investigated the effect of cerivastatin and gemfibrozil upon oral fat load induced changes in endothelial function and postprandial lipid profile in vivo.


METHODS
In a randomized cross-over trial, 15 healthy volunteers received cerivastatin (0.4 mg once daily), gemfibrozil (900 mg once daily) or placebo for 3 weeks. Lipid profiles and flow mediated dilation (FMD) were assessed before and 4 h after an oral fat load. Endothelium-independent dilation was tested after nitroglycerine 0.4 mg sublingual spray.


RESULTS
After the placebo period, the oral fat load induced an increase in triglycerides (TG) and RLP-cholesterol (RLP-C) (0.9 +/- 0.7 and 0.08 +/- 0.04 mmol/l, respectively) and a significant decrease in FMD (9.1 +/- 3.4 to 4.3 +/- 3.3%, P < 0.05). After gemfibrozil, TG increase was attenuated (0.5 +/- 0.5 mmol/l), whereas RLP-C increase (0.05 +/- 0.09 mmol/l) and FMD decrease (9.0 +/- 3.8 to 5.2 +/- 2.6%, P < 0.05) were not different from placebo therapy. Cerivastatin did not affect TG increase (0.7 +/- 0.8 mmol/l). RLP-C increase (0.02 +/- 0.07 mmol/l) and FMD (7.9 +/- 2.6 to 8.4 +/- 2.8%) change were attenuated significantly compared to placebo. Endothelium-independent vasodilatation remained unaltered throughout the protocol.


CONCLUSIONS
Cerivastatin, but not gemfibrozil significantly reduces RLP-C increase after an oral fat load in combination with a reversal of fat-load induced endothelial dysfunction. The present data imply that lowering of RLP-C, rather than lowering of total TG levels, may contributes to the prevention of endothelial dysfunction after an oral fat load during statin use.
Wilmink
H W
HW
Department of Vascular Medicine, F02.126, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Twickler
M B
MB
Banga
J D
JD
Dallinga-Thie
G M
GM
Eeltink
H
H
Erkelens
D W
DW
Rabelink
T J
TJ
Stroes
E S
ES
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D015248:Gemfibrozil / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D004041:Dietary Fats; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D011725:Pyridines; C086276:cerivastatin; D015248:Gemfibrozil