Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease.

Autor:	Weyrich M; 1Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology (T.S., S.R.P., M.G., T.S., M.W.)., Cremer S; University Hospital, Department of Medicine, Cardiology (S.C., D.M.L.).; German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.)., Gerster M; Else Kroener-Fresenius Center for Nephrological Research (T.S., S.R.P., M.G., T.S., M.W.)., Sarakpi T; 1Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology (T.S., S.R.P., M.G., T.S., M.W.).; Else Kroener-Fresenius Center for Nephrological Research (T.S., S.R.P., M.G., T.S., M.W.)., Rasper T; Institute for Cardiovascular Regeneration (T.R., S.D., A.M.Z.), Germany., Zewinger S; Hôpital Robert Schumann, Hôpital Kirchberg, Luxembourg City, Luxembourg (S.Z.).; Saarland University, Department of Internal Medicine 4, Homburg/Saar, Germany (D.F., G.H.H., S.Z.)., Patyna SR; 1Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology (T.S., S.R.P., M.G., T.S., M.W.).; Else Kroener-Fresenius Center for Nephrological Research (T.S., S.R.P., M.G., T.S., M.W.)., Leistner DM; University Hospital, Department of Medicine, Cardiology (S.C., D.M.L.).; German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.)., Heine GH; Saarland University, Department of Internal Medicine 4, Homburg/Saar, Germany (D.F., G.H.H., S.Z.)., Wanner C; University of Wuerzburg, University Hospital, Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, Germany (C.W.)., März W; Else Kroener-Fresenius Center for Nephrological Research (T.S., S.R.P., M.G., T.S., M.W.).; University of Heidelberg, University Medical Center, Medical Faculty Mannheim, Vth Department of Medicine, Germany (W.M.).; Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Austria (W.M.).; SYNLAB Holding Deutschland GmbH, SYNLAB Academy, Mannheim, Germany (W.M.)., Fliser D; Saarland University, Department of Internal Medicine 4, Homburg/Saar, Germany (D.F., G.H.H., S.Z.)., Dimmeler S; Institute for Cardiovascular Regeneration (T.R., S.D., A.M.Z.), Germany.; German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.)., Zeiher AM; Institute for Cardiovascular Regeneration (T.R., S.D., A.M.Z.), Germany.; German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.)., Speer T; 1Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology (T.S., S.R.P., M.G., T.S., M.W.).
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2024 Sep 03; Vol. 150 (10), pp. 746-757. Date of Electronic Publication: 2024 Jul 15.
DOI:	10.1161/CIRCULATIONAHA.124.069139
Abstrakt:	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. Competing Interests: Dr Speer receives speaker fees and honoraria from Amgen, Boehringer-Ingelheim, Astellas, Bayer, GSK, Novartis, NovoNordisk, Sanofi, Vifor, which are not related to the present study. Dr Wanner receives honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, CSL-Vifor, FMC, Eli Lilly, GSK, Novartis, NovoNordisk, Sanofi. Dr Dimmeler is a scientific advisor for Pfizer. Dr Zeiher is a member of the scientific advisory board of Astra Zeneca, Boehringer Ingelheim, and TenSixteen Bio.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu