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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Landmesser, U; Bahlmann, F; Mueller, M; Spiekermann, S; Kirchhoff, N; Schulz, S; Manes, C; Fischer, D; de Groot, K; Fliser, D; Fauler, G; März, W; Drexler, H.
Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans.
CIRCULATION. 2005; 111(18): 2356-2363. Doi: 10.1161/01.CIR.0000164260.82417.3F [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Fauler Günter
März Winfried
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Abstract:
BACKGROUND: Statins may exert important pleiotropic effects, ie, improve endothelial function, independently of their impact on LDL cholesterol. In humans, however, pleiotropic effects of statins have never been unequivocally demonstrated because prolonged statin treatment always results in reduced LDL cholesterol levels. We therefore tested the hypothesis that similar reductions in LDL cholesterol with simvastatin and ezetimibe, a novel cholesterol absorption inhibitor, result in different effects on endothelial function. METHODS AND RESULTS: Twenty patients with chronic heart failure were randomized to 4 weeks of simvastatin (10 mg/d) or ezetimibe (10 mg/d) treatment. Flow-dependent dilation (FDD) of the radial artery was determined by high-resolution ultrasound before and after intra-arterial vitamin C to determine the portion of FDD inhibited by radicals (DeltaFDD-VC). Activity of extracellular superoxide dismutase, a major vascular antioxidant enzyme system, was determined after release from the endothelium by a heparin bolus injection. Endothelial progenitor cells were analyzed with an in vitro assay. Simvastatin and ezetimibe treatment reduced LDL cholesterol to a similar extent (15.6% versus 15.4%; P=NS), whereas changes in mevalonate, the product of HMG-CoA-reductase, differed between groups (Deltamevalonate-simvastatin, -1.04+/-0.62 versus Deltamevalonate-ezetimibe, 1.79+/-0.94 ng/mL; P<0.05 between groups). Importantly, FDD was markedly improved after simvastatin (10.5+/-0.6% versus 5.1+/-0.7%; P<0.01) but not after ezetimibe treatment (5.6+/-0.5% versus 5.8+/-0.6%; P=NS). DeltaFDD-VC was substantially reduced after simvastatin but not after ezetimibe treatment. Extracellular superoxide dismutase activity was increased by >100% (P<0.05) after simvastatin but not ezetimibe treatment. Simvastatin treatment increased the number of functionally active endothelial progenitor cells, whereas ezetimibe had no effect. CONCLUSIONS: Four weeks of simvastatin treatment improves endothelial function independently of LDL cholesterol lowering, at least in part by reducing oxidant stress. Simvastatin may thereby exert important pleiotropic effects in humans.
Find related publications in this database (using NLM MeSH Indexing)
Anticholesteremic Agents - pharmacology
Ascorbic Acid - administration and dosage
Azetidines - administration and dosage
Endothelium, Vascular - cytology
Female - cytology
Hematopoietic Stem Cells - cytology
Humans - cytology
Lipids - blood
Male - blood
Middle Aged - blood
Radial Artery - drug effects
Reactive Oxygen Species - drug effects
Simvastatin - administration and dosage
Superoxide Dismutase - analysis
Vasodilation - drug effects

Find related publications in this database (Keywords)
endothelium
stem cells
heart failure
statins
superoxide dismutase
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