Zusammenfassung
Herz-Kreislauf-Erkrankungen zählen zu den führenden Todesursachen weltweit, wobei bekannte modifizierbare Risikofaktoren wie Rauchen, Übergewicht, Fettstoffwechselstörungen, Bewegungsmangel und Bluthochdruck eine maßgebliche Rolle spielen. Aktuelle Untersuchungen haben nun die „klonale Hämatopoese“ als neuen blutbasierten Risikofaktor identifiziert. Klonale Hämatopoese entsteht durch Mutationen in hämatopoetischen Stammzellen, die zu einer Expansion von mutierten Blutzellen führen. Bei über 40 % der über 50-Jährigen können Klone mit mutierten Zellen nachgewiesen werden. Über 15 % der über 90-Jährigen haben große Klone. Überraschenderweise neigen mutierte Zellen lediglich in geringem Ausmaß zur Entwicklung von Leukämien, daher der Begriff „clonal hematopoiesis of indeterminate potential“ (CHIP). Es zeigte sich jedoch, dass CHIP mit einem erhöhten Risiko für Herz-Kreislauf-Erkrankungen einhergeht. Menschen mit CHIP-assoziierten Genmutationen haben ein erhöhtes Risiko für atherosklerotische Gefäßerkrankungen, Schlaganfall und Thrombose. Zudem weisen Patienten mit Herzinsuffizienz mit reduzierter Pumpfunktion (HFrEF) ischämischer oder nichtischämischer Genese sowie Patienten mit Herzinsuffizienz mit erhaltener Pumpfunktion (HFpEF) eine erhöhte Anzahl an mutierten Zellen im Blut auf. Das Vorhandensein der CHIP-Mutationen geht mit einer schlechteren Prognose von Patienten mit bestehender Herz-Kreislauf-Erkrankung einher. Zukünftige Forschung sollte die spezifischen Auswirkungen verschiedener Mutationen, Klongrößen und Kombinationen besser entschlüsseln, um personalisierte Therapieansätze zu entwickeln. Es stehen verschiedene antiinflammatorische Therapeutika zur Verfügung, die in kontrollierten Studien getestet werden können.
Abstract
Cardiovascular diseases are among the leading causes of death worldwide, with well-known modifiable risk factors, such as smoking, overweight, lipid metabolism disorders, lack of physical activity and high blood pressure playing a significant role. Recent studies have now identified “clonal hematopoiesis” as a novel blood-based risk factor. Clonal hematopoiesis arises from mutations in hematopoietic stem cells, which lead to the expansion of mutated blood cells. Mutated cell clones can be detected in over 40% of individuals over 50 years old, with more than 15% of those over 90 years old harboring large clones. Surprisingly, mutated cells predispose to the development of leukemia only to a minor extent, leading to the term clonal hematopoiesis of indeterminate potential (CHIP); however, it has been shown that CHIP is associated with an increased risk of cardiovascular diseases. Individuals with CHIP-associated gene mutations have an elevated risk of atherosclerotic vascular diseases, stroke and thrombosis. Patients with heart failure with reduced ejection fraction (HFrEF), whether of ischemic or non-ischemic origin and patients with heart failure with preserved ejection fraction (HFpEF) exhibit an increased number of mutated cells in the blood. The presence of CHIP mutations is linked to a poorer prognosis in patients with existing cardiovascular diseases. Future research should aim at a better understanding of the specific effects of different mutations, clone sizes and combinations to develop personalized therapeutic approaches. Various anti-inflammatory therapeutic drugs are available, which can be tested in controlled studies.
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Dimmeler, S., Zeiher, A. Herz und Blut: klonale Hämatopoese. Herz 49, 105–110 (2024). https://doi.org/10.1007/s00059-024-05237-2
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DOI: https://doi.org/10.1007/s00059-024-05237-2