„Residuales Risiko“: Wie wichtig sind High-Density-Lipoproteine und Triglyzeride?

Tanja Grammer; Marcus Kleber; Günther Silbernagel; Hubert Scharnagl; Winfried März

doi:10.1055/s-0042-104049

DMW - Deutsche Medizinische Wochenschrift, Table of Contents

Dtsch Med Wochenschr 2016; 141(12): 870-877
DOI: 10.1055/s-0042-104049

Dossier

Fettstoffwechselstörungen

„Residuales Risiko“: Wie wichtig sind High-Density-Lipoproteine und Triglyzeride?

Residual risk: The roles of triglycerides and high density lipoproteins

Tanja Grammer

¹Mannheimer Institut für Public Health, Sozial- und Präventivmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg

,

Marcus Kleber

²Medizinische Klinik V (Nephrologie, Hypertensiologie, Rheumatologie, Endokrinologie, Diabetologie), Medizinische Fakultät Mannheim der Universität Heidelberg

,

Günther Silbernagel

³Abteilung für Angiologie, Klinik für Innere Medizin, Medizinische Universität Graz

,

Hubert Scharnagl

⁴Klinisches Institut für Medizinische und Chemische Labordiagnostik, Medizinische Universität Graz

,

Winfried März

²Medizinische Klinik V (Nephrologie, Hypertensiologie, Rheumatologie, Endokrinologie, Diabetologie), Medizinische Fakultät Mannheim der Universität Heidelberg

⁴Klinisches Institut für Medizinische und Chemische Labordiagnostik, Medizinische Universität Graz

⁵Synlab Akademie, synlab Holding Deutschland GmbH, Mannheim und Augsburg

› Author Affiliations

Abstract

Zusammenfassung

In klinischen Studien bewirkt die Senkung des LDL-Cholesterins (LDL-C) mit Statinen eine Verminderung der Inzidenz kardiovaskulärer Ereignisse um etwa ein Drittel. Das bedeutet aber umgekehrt, dass ein sogenanntes „residuales Risiko“ bestehen bleibt. Neben hohem Lipoprotein(a) gelten Störungen im Stoffwechsel der triglyzeridreichen Lipoproteine und der High Density Liproteine als Effektoren des residualen Risikos. Beide Lipoproteinparameter korrelieren umgekehrt miteinander. Die ätiologischen Beiträge von Triglyzeriden und / oder HDL zur Entwicklung von Herz-Kreislauf-Erkrankungen lassen sich daher weder aus Beobachtungsstudien noch aus Interventionsstudien abschätzen. Die bislang enttäuschenden Ergebnisse von Interventionsstudien mit Hemmstoffen des Cholesterinester-Transferproteins und insbesondere die Gesamtheit aller genetisch-epidemiologischen Untersuchungen sprechen dafür, dass in den letzten 10 Jahren die Bedeutung des HDL-Cholesterins überbewertet, die Bedeutung der Triglyzeride dagegen unterschätzt wurde. Hohe Triglyzeride wirken nicht immer atherogen, sondern vor allem dann, wenn sie mit der Akkumulation relativ cholesterinreicher, inkomplett katabolisierter remnants der Chylomikronen und Very Low Density Lipoproteine einher gehen (familiäre Typ III Hyperlipoproteinämie, metabolisches Syndrom, Diabetes mellitus). Die Normalisierung der Konzentration von Triglyzeriden und remnants durch Hemmung der Ausprägung von Apolipoprotein C3 ist ein neuer, aussichtsreicher therapeutischer Ansatzpunkt.

Abstract

In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable “residual risk” remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target.

Schlüsselwörter

Cholesterin - Triglyzeride - Remnants - Lipoproteine hoher Dichte - Atherosklerose

Keywords

cholesterol - triglycerides - remnants - high density lipoproteins - atherosclerosis

Full Text

References

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