Zusammenfassung
GRUNDLAGEN: Eine endotheliale Dysfunktion, messbar an einer verminderten Fluss-vermittelten Vasodilatation (FMD) der Brachialarterie, geht mit erhöhten Konzentrationen systemischer Entzündungsparameter, wie man es bei Patienten mit koronarer Herzkrankheit (KHK) findet, einher. Therapeutische Interventionen wie etwa eine Lipidsenkung mit Statinen, verbessern die FMD und vermindern systemische Entzündungsparameter wie zum Beispiel das lösliche E-Selectin (sE-selectin), das lösliche interzelluläre Ahäsionsmolekül-1 (sICAM-1) oder des hochsensitive C-reaktive Protein (hsCRP). Die Wirkung einer Behandlung mit Atorvastatin sowohl auf die FMD als auch auf diese zirkulierenden Entzündungsstoffe in Patienten mit stabiler KHK wurde bisher noch nicht eingehend untersucht. METHODIK: Dreißig hypercholesterinämische Patienten mit einer angiographisch dokumentierten KHK und stabiler Angina pectoris wurden für 3 Monate doppelblind randomisiert zu Plazebo oder Atorvastatin (20 mg täglich). Die FMD der Brachialarterie wurde mittels hochauflösendem Ultraschall (13 MHz; Acuson Sequioa C256) bestimmt. Das hochsensitive C-reaktive Protein wurde mit einem Latex-Agglutinations-Test und das sE-Selectin sowie das sICAM-1 wurden mit einem ELISA gemessen. ERGEBNISSE: Die Patientencharakteristik zu Beginn war in beiden Gruppen gleich. Die FMD verbesserte sich in den mit Atorvastatin behandelten Patienten (6,7 ± 3,8 % to 8,5 ± 4,4 %; p < 0,01), blieb aber unverändert in den zu Plazebo randomisierten Patienten (8,2 ± 3,3 % to 8,9 ± 5,1 %; p = NS). Die Therapie mit Atorvastatin ging einher mit einer Reduktion des sICAM-1 (von 274,2 ± 92,2 auf 197,9 ± 70,0 ng/ml; p < 0,01) und des hsCRP (von 0,57 ± 0,45 auf 0,18 ± 0,15 mg/dl; p < 0,01), wohingegen Plazebo auf diese Entzündungsparameter keinen Einfluss hatte. sE-Selectin wurde weder durch Atorvastatin noch durch Plazebo beeinflusst. Darüber hinaus fand sich keine Korrelation zwischen den Veränderungen der FMD, der Lipide und der systemischen Entzündungsparameter. SCHLUSSFOLGERUNGEN: Eine Therapie mit Atorvastatin verbessert die periphere Endothelfunktion und reduziert systemische Entzündungsparameter in Patienten mit stabiler koronarer Herzkrankheit. Die fehlende Korrelation zwischen der Veränderung der Endothelfunktion und der Entzündungsparameter unterstützt das Konzept der pleiotropen Effekte von Statinen in Menschen.
Summary
BACKGROUND: Endothelial dysfunction, detectable by an impaired flow-mediated vasodilation (FMD) of the brachial artery, has been shown to be associated with increased levels of circulating proinflammatory markers. Therapeutic interventions such as lipid-lowering with statins increase FMD and decrease inflammatory markers, like soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) or high-sensitivity Creactive protein (hsCRP). The effect of atorvastatin therapy on both FMD and inflammatory markers in patients with stable coronary artery disease (CAD) has not been investigated. METHODS: Thirty hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. FMD was assessed using highresolution ultrasound (13 MHz, Acuson Sequoia, C256). High-sensitivity CRP was measured with Latex agglutination assay, sE-selectin and sICAM-1 were determined with ELISA. RESULTS: Baseline characteristics were not different between groups. FMD improved in patients on atorvastatin (6.7 ± 3.8 % to 8.5 ± 4.4 %; p < 0.01), but remained unchanged in placebo-treated patients (8.2 ± 3.3 % to 8.9 ± 5.1 %; p = NS). Atorvastatin treatment was associated with decreases of sICAM-1 (from 274.2 ± 92.2 to 197.9 ± 70.0 ng/ml; p < 0.01) and hsCRP (from 0.57 ± 0.45 to 0.18 ± 0.15 mg/dl; p < 0.01), whereas placebo treatment had no effect on these markers. sE-selectin levels were not influenced by either treatment. No correlations were found between changes in FMD, lipids and inflammatory markers. CONCLUSIONS: Treatment with atorvastatin leads to an improvement in endothelial function and a reduction in inflammatory markers in patients with stable CAD. The lack of correlation between changes in FMD and inflammatory markers may support the concept of pleiotropic effects of statins in humans.
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Alber, H., Frick, M., Süssenbacher, A. et al. Effect of atorvastatin on peripheral endothelial function and systemic inflammatory markers in patients with stable coronary artery disease. Wien Med Wochenschr 157, 73–78 (2007). https://doi.org/10.1007/s10354-007-0377-y
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DOI: https://doi.org/10.1007/s10354-007-0377-y
Schlüsselwörter
- Koronare Herzkrankheit
- Statine
- Endothelfunktion
- Lösliches interzelluläres Adhäsionsmolekül-1
- C-reaktives Protein