HDL und Arteriosklerose – Korrelation mit dem Auftreten kardiovaskulärer Ereignisse

Große epidemiologische Studien zeigen, dass die Plasmakonzentration der High Density Lipoproteine (HDL) invers und unabhängig mit der Inzidenz kardiovaskulärer Ereignisse korreliert. Unter physiologischen Bedingungen vermitteln HDL eine Vielzahl vaskuloprotektiver Wirkungen, insbesondere den reversen Cholesterintransport. Neue Studien zeigen jedoch, dass die Zusammensetzung der HDL-Partikel heterogen ist. Daher existieren neben den physiologischen vasoprotektiven HDL unter pathophysiologischen Umständen HDL, welche durch verschiedene strukturelle Modifikationen proatherogene Eigenschaften annehmen können. Eine Erhöhung der HDL-Cholesterinkonzentration im Plasma kann daher nicht mit einer Verbesserung der HDL-Funktion und einem effektiveren Cholesterinrücktransport gleichgesetzt werden. Wichtiger als die reine Betrachtung der HDL-Cholesterin-Plasmakonzentration erscheint daher die Evaluation der funktionellen Eigenschaften der HDL-Partikel, allerdings stehen hierzu noch keine akzeptierten Assays für die Praxis zur Verfügung. Lebensstiländerungen sowie verschiedene Medikamente wie Fibrate oder Nikotinsäurederivate führen zu einer Erhöhung der HDL-Konzentration. Eine neue Therapiestrategie zur Steigerung der HDL-Konzentration ist die Hemmung des Cholesterylester Transferproteins (CETP). Laufende Studien müssen zeigen, ob diese Medikamente, zusätzlich zu der etablierten LDL-Cholesterin-Senkung mit Statinen, Vorteile für Patienten mit niedrigem HDL bringt.

Large epidemiologic studies show an inverse and independent correlation between the plasma concentration of High Density Lipoproteins (HDL) and the incidence of cardiovascular events. Under physiological conditions, HDL exhibit a plethora of vasculoprotective effects, like mediation of reverse cholesterol transport. However, new studies suggest that HDL particles are heterogeneous. Therefore, several structural alterations might lead to the formation of pro-inflammatory HDL particles. Therefore, a high plasma concentration of HDL cholesterol must not always be associated with an improvement of HDL function such as reverse cholesterol transport. The evaluation of the functional properties of HDL seems to be more important than measurements of plasma concentrations of HDL cholesterol. However, until now, no assays for this purpose have been developed for use in clinical practice. Lifestyle modifications and different therapeutic strategies such as treatment with fibrates or nicotinic acid derivatives lead to an increase of HDL concentration. Inhibition of cholesteryl ester transfer protein (CETP) is a new strategy to increase HDL cholesterol concentrations. Current studies will have to show whether addition of these drugs to the established LDL-lowering therapy with statins will result in clinical benefits for patients with low HDL.

Key words

Lipid metabolism - HDL (high density lipoproteins) - cardiovascular events - cholesterol - cholesteryl ester transfer protein (CETP) - atherogenesis

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