Pathophysiologische Prinzipien von Dyslipoproteinämien

Die effektive Reduktion atherogener Lipoproteine hat dazu beigetragen, dass die Rate an Arteriosklerose-bedingten kardiovaskulären Komplikationen in den letzten 50 Jahren in etwa halbiert wurde. Dennoch werden in den nächsten Jahren kardiovaskuläre Erkrankungen weltweit die häufigste Todesursache sein. Der Fokus dieser Übersicht liegt daher auf der klinischen Bedeutung der Pathophysiologie von Veränderungen im Lipid- und Lipoproteinstoffwechsel.

Abstract

The effective reduction of atherogenic lipoproteins has contributed to the rate of atherosclerosis-related cardiovascular complications being approximately halved over the last 50 years. Nevertheless, cardiovascular disease will be the leading cause of death worldwide in the coming years. The focus of this review is on the clinical significance of the pathophysiology of changes in lipid and lipoprotein metabolism. Elevated levels of atherogenic lipoproteins are a causal risk factor for atherosclerotic cardiovascular disease. Primary forms of hypercholesterolaemia have a significantly higher ASCVD risk because of the already lifelong LDL elevation (higher cumulative LDL exposure for the vessel wall). Secondary changes in lipid and lipoprotein metabolism (e. g. in diabetes or hypothyroidism) must be excluded or treated. Regulatory key steps in the pathophysiology of lipid metabolism and atherosclerotic plaque are “drug targets” for existing and new lipid and lipoprotein modifying therapies.

Schlüsselwörter

atherogene Lipoproteine - ASCVD-Risiko - regulative Schlüsselschritte - Diabetes mellitus

Key words

atherogenic lipoproteins - ASCVD risk - regulatory key steps - diabetes mellitus

Publikationsverlauf

Artikel online veröffentlicht:
03. November 2021

• Literatur

• 1 Mach F, Baigent C, Catapano AL. et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2019;
• 2 Ridker PM. LDL cholesterol: controversies and future therapeutic directions. Lancet 2014; 384: 607-617
• 3 Brandts J, Ray KK. LDL-Cholesterol lowering strategies and population health-time to move to a cumulative exposure model. Circulation 2020; 141: 873-876
• 4 Boren J, Chapman MJ, Krauss RM. et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society consensus panel. Eur Heart J 2020; 41: 2313-2330
• 5 Libby P. The changing landscape of atherosclerosis. Nature 2021; 592: 524-533
• 6 Merkel M, Müller-Wieland D, von Eckardstein A. Fettstoffwechsel. In: Blum HE, Müller-Wieland D. Hrsg. Klinische Pathophysiologie. Stuttgart, New York: Thieme; 2018: 200-231
• 7 Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 2015; 161: 161-172
• 8 Rohatgi A, Westerterp M, von Eckardstein A. et al. HDL in the 21st century. A multifunctional roadmap for future HDL research. Circulation 2021; 143: 2293-2309
• 9 Gracia-Rubio I, Martin C, Civeira F. et al. SR-B1, a key receptor involved in the progression of cardiovascular disease: A perspective from mice and human genetic studies. Biomedicines 2021; 9: 612
• 10 Laufs U, Parhofer K, Ginsberg HN. et al. Clinical review on triglycerides. Eur Heart J 2020; 41: 99-109
• 11 Heeren J, Scheja L. Metabolic-associated fatty liver disease and lipoprotein metabolism. Mol Metab 2021; 101238
• 12 Taskinen MR, Boren J. New insights into the pathophysiology of dyslipidemia in type 2 diabetes. Atherosclerosis 2015; 239: 483-495