Loss of Y chromosome and cardiovascular events in chronic kidney disease

• Verfasst von: Weyrich, Michael [VerfasserIn]
• Verfasst von: Cremer, Sebastian [VerfasserIn]
• Verfasst von: Gerster, Martin [VerfasserIn]
• Verfasst von: Sarakpi, Tamim [VerfasserIn]
• Verfasst von: Rasper, Tina [VerfasserIn]
• Verfasst von: Zewinger, Stephen [VerfasserIn]
• Verfasst von: Patyna, Sammy R. [VerfasserIn]
• Verfasst von: Leistner, David M. [VerfasserIn]
• Verfasst von: Heine, Gunnar H. [VerfasserIn]
• Verfasst von: Wanner, Christoph [VerfasserIn]
• Verfasst von: März, Winfried [VerfasserIn]
• Verfasst von: Fliser, Danilo [VerfasserIn]
• Verfasst von: Dimmeler, Stefanie [VerfasserIn]
• Verfasst von: Zeiher, Andreas M. [VerfasserIn]
• Verfasst von: Speer, Thimoteus [VerfasserIn]
• Titel: Loss of Y chromosome and cardiovascular events in chronic kidney disease
• Verf.angabe: Michael Weyrich, MD; Sebastian Cremer, MD; Martin Gerster, MD; Tamim Sarakpi, MD; Tina Rasper, MS; Stephen Zewinger , MD; Sammy R. Patyna , MD; David M. Leistner , MD; Gunnar H. Heine, MD; Christoph Wanner , MD; Winfried März , MD; Danilo Fliser, MD; Stefanie Dimmeler , PhD; Andreas M. Zeiher , MD; Thimoteus Speer , MD, PhD
• E-Jahr: 2024
• Jahr: Sep 2024
• Umfang: 12 S.
• Illustrationen: Illustrationen
• Fussnoten: Online veröffentlicht: 15. Juli 2024 ; Gesehen am 21.10.2024
• Titel Quelle: Enthalten in: Circulation
• Ort Quelle: Philadelphia, Pa. : Lippincott, Williams & Wilkins, 1950
• Jahr Quelle: 2024
• Band/Heft Quelle: 150(2024), 10, Seite 746-757
• ISSN Quelle: 1524-4539
• DOI: doi:10.1161/CIRCULATIONAHA.124.069139
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 190632624X

Abstract

BACKGROUND: - Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease. - METHODS: - LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study, n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed. - RESULTS: - In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.23-4.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E’ within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events. - CONCLUSIONS: - LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.