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

ArticleinEuropean Journal of Clinical Pharmacology 69(3) · July 2012with32 Reads
DOI: 10.1007/s00228-012-1345-z · Source: PubMed
Abstract
Background/aim: 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. Methods: 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. Results: 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. Conclusions: 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.
    • "In outpatients with type 2 DM, we found similar clinical results in the present study. Recently, the effect of pravastatin or ezetimibe on endothelial function was reported as evaluated by FMD in non-DM patients with hypercholesterolemia [19]. The researchers concluded that LDL-lowering by pravastatin or ezetimibe induced similar effects on vascular endothelial function improvement, and they suggested that the pleiotropic effects of statins were not important for improvement in vascular endothelial function. "
    [Show abstract] [Hide abstract] ABSTRACT: Elevated cholesterol in type 2 diabetes mellitus (DM) can cause endothelial dysfunction. An effective clinical therapy to improve endothelial dysfunction remains to be established. Different cardiovascular actions between treatments for the inhibition of cholesterol absorption and the suppression of cholesterol synthesis for achieving improvement in endothelial function are unknown in DM. Stable patients with type 2 DM and mildly elevated low-density lipoprotein cholesterol were enrolled. We evaluated peripheral microvascular endothelial function using reactive hyperemia peripheral arterial tonometry (RH-PAT) examination and calculated a natural logarithmic transformed value for the RH-PAT index (LnRHI). We randomly assigned 33 patients to each monotherapy: cholesterol synthesis suppression using atorvastatin (5 mg/day, n = 16) or cholesterol absorption inhibition using ezetimibe (10 mg/day, n = 17). Patients were prospectively followed for 6 months. Serum lipids and LnRHI were repeatedly examined before and after each therapy. LDL significantly decreased in both groups, but the percent changes of LDL showed a greater decrease in the atorvastatin group compared with the ezetimibe group (-34.5 ± 7.8% vs. -21.9 ± 9.6%, p < 0.01). Serum levels of non-esterified free fatty acids (NEFA) significantly decreased in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 561.1 ± 236.8 to 429.7 ± 195.9, p < 0.01; atorvastatin group: 538.8 ± 319.5 to 520.2 ± 227.3, p = 0.75). The percent decrease in NEFA was significantly greater in the ezetimibe group compared with the atorvastatin group (-19.9 ± 27.4% vs. 11.3 ± 44.1%, p < 0.05). LnRHI showed a significant increase in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 0.471 ± 0.157 to 0.678 ± 0.187, p < 0.01; atorvastatin group: 0.552 ± 0.084 to 0.558 ± 0.202, p = 0.64). The percent changes in LnRHI were significantly greater in the ezetimibe group compared with the atorvastatin group (63.3 ± 89.2% vs. 7.4 ± 41.2%, p < 0.05). In patients with type 2 DM, ezetimibe monotherapy significantly reduced LDL and NEFA, and improved peripheral microvascular endothelial dysfunction. Ezetimibe could potentially exhibit beneficial effects on lipid disorders and microvascular endothelial dysfunction in DM.
    Full-text · Article · Apr 2015
    • "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 hypercholesterol- emia [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]. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Oct 2014
    • "Some research has revealed that hsCRP is independently associated with cardiovascular events in the patients with arteriosclerosis and arterial occlusive disease (Kablak-Ziembicka et al., 2011). Numerous studies have confirmed that hsCRP level markedly declines and that vascular endothelial function apparently improves along with the decrease in LDL-C (Heart Protection Study Collaborative Group et al., 2011; Grigore et al., 2013). Our research revealed that the levels of serum LDL-C, triglycerides and hsCRP in patients were markedly decreased, CIMT and carotid plaque Crouse integral clearly ameliorated, and the coronary inner diameter distinctly increased after atorvastatin treatment or atorvastatin in combination with ezetimibe, while the reduction in serum LDL-C and hsCRP was more significant and the decrease in CIMT and carotid plaque Crouse integral was greater in the combined group. "
    [Show abstract] [Hide abstract] ABSTRACT: The aim of this study was to observe the effects of atorvastatin combined with ezetimibe on carotid atherosclerosis in elderly patients with hypercholesterolemia. A total of 84 elderly hypercholesterolemic patients complicated with carotid atherosclerosis were divided into control group (atorvastatin alone) and combined group (atorvastatin combined with ezetimibe) and treated for 12 months. Carotid atherosclerosis-related indicators including blood lipid and high-sensitivity C-reactive protein (hsCRP) were determined before and after treatment. The levels of carotid intima-media thickness (CIMT), serum low density lipoprotein cholesterol (LDL-C) and hsCRP were markedly decreased (P < 0.05) after treatment in the two groups, while the reduction of the levels of CIMT, serum LDL-C and hsCRP was more significant in the combined group (P < 0.01). After treatment, the levels of CIMT, serum LDL-C and hsCRP were distinctly different between combined and control group (P < 0.05). The combination of atorvastatin with ezetimibe could further decrease LDL-C and hsCRP levels and have certain effects on the progression of carotid atherosclerosis in elderly patients with hypercholesterolemia.
    Article · Apr 2014
    P LuoP LuoL LiL LiL.X. WangL.X. Wang+1more author...[...]
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