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

LOY chronic kidney disease heart failure loss of Y-chromosome

Journal

Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763

Informations de publication

Date de publication:
15 Jul 2024
Historique:
medline: 15 7 2024
pubmed: 15 7 2024
entrez: 15 7 2024
Statut: aheadofprint

Résumé

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. LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study [XXX], 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. 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. LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.

Sections du résumé

BACKGROUND UNASSIGNED
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 UNASSIGNED
LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study [XXX], 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 UNASSIGNED
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 UNASSIGNED
LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.124.069139 PMID: 39005209
pubmed: 39005209
doi: 10.1161/CIRCULATIONAHA.124.069139
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Michael Weyrich (M)

Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology, y (T.S., S.R.P., M.G., T.S., M.W., S.Z.).
Else Kroener-Fresenius Center for Nephrological Research, Germany. (T.S., S.R.P., M.G., T.S., M.W.).

Sebastian Cremer (S)

University Hospital, Department of Medicine, Cardiology, Germany. (S.C., D.M.L.).
German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.).

Martin Gerster (M)

Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology, y (T.S., S.R.P., M.G., T.S., M.W., S.Z.).
Else Kroener-Fresenius Center for Nephrological Research, Germany. (T.S., S.R.P., M.G., T.S., M.W.).

Tamim Sarakpi (T)

Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology, y (T.S., S.R.P., M.G., T.S., M.W., S.Z.).
Else Kroener-Fresenius Center for Nephrological Research, Germany. (T.S., S.R.P., M.G., T.S., M.W.).

Tina Rasper (T)

Institute for Cardiovascular Regeneration, Germany. (T.R., S.D., A.M.Z.).

Stephen Zewinger (S)

Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology, y (T.S., S.R.P., M.G., T.S., M.W., S.Z.).
Hôpital Robert Schumann, Hôpital Kirchberg, Luxembourg City, Luxembourg (S.Z.).
ORCID: 0009-0004-0239-7862

Sammy R Patyna (SR)

Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology, y (T.S., S.R.P., M.G., T.S., M.W., S.Z.).
Else Kroener-Fresenius Center for Nephrological Research, Germany. (T.S., S.R.P., M.G., T.S., M.W.).
ORCID: 0000-0001-7045-7696

David M Leistner (DM)

University Hospital, Department of Medicine, Cardiology, Germany. (S.C., D.M.L.).
German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.).
ORCID: 0000-0002-4351-420X

Gunnar H Heine (GH)

Saarland University, Department of Internal Medicine 4, Homburg/Saar, Germany (D.F., G.H.H.).

Christoph Wanner (C)

University of Wuerzburg, University Hospital, Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, Germany (C.W.).
ORCID: 0000-0001-9507-5301

Winfried März (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.).
ORCID: 0000-0001-6083-8946

Danilo Fliser (D)

Saarland University, Department of Internal Medicine 4, Homburg/Saar, Germany (D.F., G.H.H.).

Stefanie Dimmeler (S)

Institute for Cardiovascular Regeneration, Germany. (T.R., S.D., A.M.Z.).
German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.).
ORCID: 0000-0002-1045-2436

Andreas M Zeiher (AM)

Institute for Cardiovascular Regeneration, Germany. (T.R., S.D., A.M.Z.).
German Center for Cardiovascular Research DZHK, Berlin, Germany (S.C., D.M.L., S.D., A.M.Z.).
ORCID: 0000-0003-1711-5819

Thimoteus Speer (T)

Goethe University Frankfurt's University Hospital, Department of Internal Medicine 4, Nephrology, y (T.S., S.R.P., M.G., T.S., M.W., S.Z.).
Else Kroener-Fresenius Center for Nephrological Research, Germany. (T.S., S.R.P., M.G., T.S., M.W.).
ORCID: 0000-0002-2491-6393

Classifications MeSH