Effect of treatment with pravastatin or ezetimibe on endothelial function in patients with moderate hypercholesterolemia

Center for the Study of Atherosclerosis-SISA Lombardia, Bassini Hospital, Via Gorki 50, 20092, Cinisello Balsamo, Milan, Italy.
European Journal of Clinical Pharmacology (Impact Factor: 2.97). 07/2012; 69(3). DOI: 10.1007/s00228-012-1345-z
Source: PubMed


Statin treatment improves endothelial function. It is matter of debate, however, if this effect of statins is due to their action on low-density lipoprotein cholesterol (LDL-C) or to other non-lipidic (pleiotropic) effects. The aim of this study was to evaluate whether the effect of pravastatin on endothelial function is mediated by pleiotropic effects. We therefore compared the effect of pravastatin and ezetimibe, a cholesterol absorption inhibitor, at doses yielding similar reductions in LDL-C and examined the effect of the two treatments on flow-mediated dilation (FMD) in hypercholesterolemic subjects.

A total of 33 moderately hypercholesterolemic patients were randomized into three treatment groups to receive ezetimibe 10 mg/day (n = 10), pravastatin 10 mg/day (n = 13) or no treatment (control, n = 10) for 6 weeks. To assess endothelial function, we determined FMD of the brachial artery non-invasively by high-resolution ultrasound before and after treatment.

Ezetimibe and pravastatin treatment reduced LDL-C (mean ± standard error) to a similar extent (-20.6 ± 4.1 vs. -24.1 ± 4.0 %, respectively; P = 0.4771), while no decrease was observed in the control group. FMD increased significantly after treatment with ezetimibe (from 11.4 ± 5.7 to 16.8 ± 3.6 %; P = 0.022) and with pravastatin (from 13.7 ± 4.9 to 17.5 ± 4.4 %; P = 0.0466), but not in the control group. There were no differences in the endothelial function changes between the two treatment groups.

In this study, two treatments that lower cholesterol via different mechanisms improved endothelial function to a similar extent, suggesting that the observed effect can be explained by the reduction of cholesterol levels.

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    • "We found that atorvastatin therapy improved endothelium-dependent vasodilatation measured by %FMD. Our results are consistent with a previous report that pravastatin treatment for 6 months improved endothelium-dependent coronary vasodilatation in patients with hypercholesterolemia [29]. A previous study in patients with AS found that treatment with lovastatin for 6 months significantly improved endothelium-mediated responses in the coronary artery [30]. "
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    ABSTRACT: Background Accumulating evidence suggests that inflammatory mechanisms play a central role in the development, progression and outcome of atherosclerosis. Recent evidence suggests that statins improve anti-inflammatory, anti-thrombotic and endothelial functions, along with their lipid-decreasing effects. We examined the effect of statins on endothelial function using biochemical markers of endothelial dysfunction and brachial artery flow-mediated dilatation (FMD). Methods Thirty male patients presenting with acute coronary syndrome (ACS) and 26 age-matched healthy control subjects aged 40 - 60 years who were not on any medication were enrolled in the study. The patient group was started on atorvastatin (40 mg/day) without consideration of their low-density lipoprotein (LDL)-cholesterol levels. Endothelin, sICAM and E-selectin from stored serum samples were measured using commercially available enzyme-linked immunosorbant assays (ELISAs). Endothelial function was assessed using brachial artery FMD. Results Prior to statin treatment, E-selectin, sICAM and endothelin levels, endothelial dysfunction markers, were 99.74 ± 34.67 ng/mL, 568.8 ± 149.0 ng/mL and 0.62 ± 0.33 fmol/mL, respectively in the patient group. E-selectin and sICAM levels were significantly higher in the patients than in the control subjects (P < 0.001); however, endothelin levels were not significantly different between groups. Statin treatment significantly reduced E-selectin and sICAM levels (P < 0.001); however, the decrease in endothelin levels was not statistically significant. %FMD values were significantly increased after statin treatment (P = 0.005), and levels of C-reactive protein (CRP), an inflammation marker, were significantly reduced. Conclusion Our results indicate that statins play an important role in treatment endothelial dysfunction by reducing adhesion of inflammatory cells.
    Journal of Clinical Medicine Research 10/2014; 6(5):354-61. DOI:10.14740/jocmr1863w
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    • "It has been shown that lowering circulating cholesterol levels ameliorates endothelial function [53], [54]; the absence of hypercholesterolemia when fed a WD could not alter endothelial function in p53+/− mice. Blood glucose increased similarly in both groups of mice, while triglycerides slightly decreased as previously reported by others [55], [56]. "
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    ABSTRACT: To demonstrate that p53 modulates endothelial function and the stress response to a high-fat western diet (WD). Three-month old p53+/+ wild type (WT) and p53+/- male mice were fed a regular or WD for 3 months. Plasma levels of total cholesterol (TC) and LDL-cholesterol were significantly elevated (p<0.05) in WD-fed WT (from 2.1±0.2 mmol/L to 3.1±0.2, and from 0.64±0.09 mmol/L to 1.25±0.11, respectively) but not in p53+/- mice. The lack of cholesterol accumulation in WD-fed p53+/- mice was ass-ociated with high bile acid plasma concentrations (p53+/- = 4.7±0.9 vs. WT = 3.3±0.2 μmol/L, p<0.05) concomitant with an increased hepatic 7-alpha-hydroxylase mRNA expression. While the WD did not affect aortic endothelial relaxant function in p53+/- mice (WD = 83±5 and RD = 82±4% relaxation), it increased the maximal response to acetylcholine in WT mice (WD = 87±2 vs. RD = 62±5% relaxation, p<0.05) to levels of p53+/-. In WT mice, the rise in TC associated with higher (p<0.05) plasma levels of pro-inflammatory keratinocyte-derived chemokine, and an over-activation (p<0.05) of the relaxant non-nitric oxide/non-prostacyclin endothelial pathway. It is likely that in WT mice, activations of these pathways are adaptive and contributed to maintain endothelial function, while the WD neither promoted inflammation nor affected endothelial function in p53+/- mice. Our data demonstrate that low endogenous p53 expression prevents the rise in circulating levels of cholesterol when fed a WD. Consequently, the endothelial stress of hypercholesterolemia is absent in young p53+/- mice as evidenced by the absence of endothelial adaptive pathway over-activation to minimize stress-related damage.
    PLoS ONE 03/2014; 9(3):e92394. DOI:10.1371/journal.pone.0092394 · 3.23 Impact Factor
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    ABSTRACT: More than 85% of received e-mails are spam. Spam is an important issue for computer security because it is used to spread other threats such as computer viruses, worms or phishing. Classic techniques to fight spam, including simple techniques such as sender blacklisting or the use of e-mail signatures, are no longer completely reliable. Machine-learning techniques trained using statistical representations of the terms that usually appear in the e-mails are widely used in the literature. However, these methods demand a time-consuming training step with labelled data. Dealing with the situation where the availability of labelled training instances is limited slows down the progress of filtering systems and offers advantages to spammers. In this paper, we present the first spam filtering method based on anomaly detection that reduces the necessity of labelling spam messages and only uses the representation of legitimate e-mails. This approach represents legitimate e-mails as word frequency vectors. Thereby, an email is classified as spam or legitimate by measuring its deviation to the representation of these legitimate e-mails. This method achieves high accuracy rates detecting spam and maintains a low false positive rate, reducing the effort produced by labelling spam.
    E-Business and Telecommunications, 01/2012: pages 203-216; Springer Berlin Heidelberg.
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