Key result
Cerivastatin, unlike gemfibrozil, reverses postprandial endothelial dysfunction and reduces remnant-like particle cholesterol.
Why the study?
Postprandial lipemia is associated with endothelial dysfunction, and the role of remnant-like particles in these vascular effects requires investigation.
Does cerivastatin or gemfibrozil improve postprandial endothelial dysfunction and lipid profiles after an oral fat load in healthy volunteers?
RCT (n=15)
Cross-over
Does cerivastatin or gemfibrozil improve postprandial endothelial dysfunction and lipid profiles after an oral fat load in healthy volunteers?
Cerivastatin, but not gemfibrozil, prevents postprandial endothelial dysfunction after an oral fat load, suggesting that lowering remnant-like particle cholesterol is more important than lowering total triglycerides for this vascular effect.
Cerivastatin may avert postprandial endothelial dysfunction via remnant reduction; extends evidence that RLP lowering, not TG reduction alone, mediates statin vascular effects.
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. CONCLUSION: 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.
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H. Wilmink (2001) conducted an RCT in Healthy volunteers (n=15). Cerivastatin and Gemfibrozil vs. Placebo was evaluated on Flow mediated dilation (FMD) and lipid profile changes 4 hours after an oral fat load. Cerivastatin, but not gemfibrozil, significantly reduced remnant-like particle cholesterol increase and reversed fat-load induced endothelial dysfunction compared to placebo.
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