Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure

Pieter F. van den Berg; Joseph Pierre Aboumsallem; Elles M. Screever; Canxia Shi; Sanne de Wit; Valentina Bracun; Laura I. Yousif; Lotte Geerlings; Dongyu Wang; Jennifer E. Ho; Stephan J.L. Bakker; Bert van der Vegt; Herman H.W. Silljé; Rudolf A. de Boer; Wouter C. Meijers

doi:10.1016/j.jaccao.2023.03.015

Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure

Pieter F. van den Berg
, Joseph Pierre Aboumsallem
, Elles M. Screever
, Canxia Shi
, Sanne de Wit
, Valentina Bracun
, Laura I. Yousif
, Lotte Geerlings
, Dongyu Wang
, Jennifer E. Ho
, Stephan J.L. Bakker
, Bert van der Vegt
, Herman H.W. Silljé
, Rudolf A. de Boer
, Wouter C. Meijers^*

^*Corresponding author for this work

Cardiology

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

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Abstract

Background: Cancer and heart failure (HF) are the leading causes of death in the Western world. Shared mechanisms such as fibrosis may underlie either disease entity, furthermore it is unknown whether this relationship is sex-specific. Objectives: We sought to investigate how fibrosis-related biomarker galectin-3 (gal-3) aids in identifying individuals at risk for new-onset cancer and HF, and how this differs between sexes. Methods: Gal-3 was measured at baseline and at 4-year follow-up in 5,786 patients of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study. The total follow-up period was 11.5 years. An increase of ≥50% in gal-3 levels between measurements was considered relevant. We performed sex-stratified log-rank tests and Cox regression analyses overall and by sex to evaluate the association of gal-3 over time with both new-onset cancer and new-onset HF. Results: Of the 5,786 healthy participants (50% males), 399 (59% males) developed new-onset cancer, and 192 (65% males) developed new-onset HF. In males, an increase in gal-3 was significantly associated with new-onset cancer (both combined and certain cancer-specific subtypes), after adjusting for age, body mass index, hypertension, smoking status, estimated glomerular filtration rate, diabetes mellitus, triglycerides, coronary artery disease, and C-reactive protein (HR: 1.89; 95% CI: 1.32-2.71; P < 0.001). Similar analyses demonstrated an association with new-onset HF in males (HR: 1.77; 95% CI: 1.07-2.95; P = 0.028). In females, changes in gal-3 over time were neither associated with new-onset cancer nor new-onset HF. Conclusions: Gal-3, a marker of fibrosis, is associated with new-onset cancer and new-onset HF in males, but not in females.

Original language	English
Pages (from-to)	445-453
Number of pages	9
Journal	JACC: CardioOncology
Volume	5
Issue number	4
Early online date	11 Jul 2023
DOIs	https://doi.org/10.1016/j.jaccao.2023.03.015
Publication status	Published - Aug 2023

Bibliographical note

FUNDING SUPPORT AND AUTHOR DISCLOSURES
Financial support was also provided by the European Research Council (ERC CoG 818715, SECRETE-HF). Dr Meijers is supported by the Mandema-Stipendium of the Junior Scientific Masterclass 2020-10 of the University Medical Center Groningen (UMCG; P.F. van den Berg, C. Shi, S. de Wit, L. Geerlings, S. Bakker, B. van der Vegt, H. Silljé, R. de Boer and W. Meijers) and by the Dutch Heart Foundation (Dekker grant 03-005-2021-T005). Dr de Boer has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. The UMCG, which
employs/employed several of the authors, has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright: © 2023 The Authors

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van den Berg, P. F., Aboumsallem, J. P., Screever, E. M., Shi, C., de Wit, S., Bracun, V., Yousif, L. I., Geerlings, L., Wang, D., Ho, J. E., Bakker, S. J. L., van der Vegt, B., Silljé, H. H. W., de Boer, R. A., & Meijers, W. C. (2023). Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure. JACC: CardioOncology, 5(4), 445-453. https://doi.org/10.1016/j.jaccao.2023.03.015

@article{8069b74755c44a7ea9b00102985823ab,

title = "Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure",

abstract = "Background: Cancer and heart failure (HF) are the leading causes of death in the Western world. Shared mechanisms such as fibrosis may underlie either disease entity, furthermore it is unknown whether this relationship is sex-specific. Objectives: We sought to investigate how fibrosis-related biomarker galectin-3 (gal-3) aids in identifying individuals at risk for new-onset cancer and HF, and how this differs between sexes. Methods: Gal-3 was measured at baseline and at 4-year follow-up in 5,786 patients of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study. The total follow-up period was 11.5 years. An increase of ≥50\% in gal-3 levels between measurements was considered relevant. We performed sex-stratified log-rank tests and Cox regression analyses overall and by sex to evaluate the association of gal-3 over time with both new-onset cancer and new-onset HF. Results: Of the 5,786 healthy participants (50\% males), 399 (59\% males) developed new-onset cancer, and 192 (65\% males) developed new-onset HF. In males, an increase in gal-3 was significantly associated with new-onset cancer (both combined and certain cancer-specific subtypes), after adjusting for age, body mass index, hypertension, smoking status, estimated glomerular filtration rate, diabetes mellitus, triglycerides, coronary artery disease, and C-reactive protein (HR: 1.89; 95\% CI: 1.32-2.71; P < 0.001). Similar analyses demonstrated an association with new-onset HF in males (HR: 1.77; 95\% CI: 1.07-2.95; P = 0.028). In females, changes in gal-3 over time were neither associated with new-onset cancer nor new-onset HF. Conclusions: Gal-3, a marker of fibrosis, is associated with new-onset cancer and new-onset HF in males, but not in females.",

author = "\{van den Berg\}, \{Pieter F.\} and Aboumsallem, \{Joseph Pierre\} and Screever, \{Elles M.\} and Canxia Shi and \{de Wit\}, Sanne and Valentina Bracun and Yousif, \{Laura I.\} and Lotte Geerlings and Dongyu Wang and Ho, \{Jennifer E.\} and Bakker, \{Stephan J.L.\} and \{van der Vegt\}, Bert and Sillj{\'e}, \{Herman H.W.\} and \{de Boer\}, \{Rudolf A.\} and Meijers, \{Wouter C.\}",

note = "FUNDING SUPPORT AND AUTHOR DISCLOSURES Financial support was also provided by the European Research Council (ERC CoG 818715, SECRETE-HF). Dr Meijers is supported by the Mandema-Stipendium of the Junior Scientific Masterclass 2020-10 of the University Medical Center Groningen (UMCG; P.F. van den Berg, C. Shi, S. de Wit, L. Geerlings, S. Bakker, B. van der Vegt, H. Sillj{\'e}, R. de Boer and W. Meijers) and by the Dutch Heart Foundation (Dekker grant 03-005-2021-T005). Dr de Boer has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. The UMCG, which employs/employed several of the authors, has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

doi = "10.1016/j.jaccao.2023.03.015",

language = "English",

volume = "5",

pages = "445--453",

journal = "JACC: CardioOncology",

issn = "2666-0873",

publisher = "Elsevier Inc.",

number = "4",

}

van den Berg, PF, Aboumsallem, JP, Screever, EM, Shi, C, de Wit, S, Bracun, V, Yousif, LI, Geerlings, L, Wang, D, Ho, JE, Bakker, SJL, van der Vegt, B, Silljé, HHW, de Boer, RA & Meijers, WC 2023, 'Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure', JACC: CardioOncology, vol. 5, no. 4, pp. 445-453. https://doi.org/10.1016/j.jaccao.2023.03.015

TY - JOUR

T1 - Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure

AU - van den Berg, Pieter F.

AU - Aboumsallem, Joseph Pierre

AU - Screever, Elles M.

AU - Shi, Canxia

AU - de Wit, Sanne

AU - Bracun, Valentina

AU - Yousif, Laura I.

AU - Geerlings, Lotte

AU - Wang, Dongyu

AU - Ho, Jennifer E.

AU - Bakker, Stephan J.L.

AU - van der Vegt, Bert

AU - Silljé, Herman H.W.

AU - de Boer, Rudolf A.

AU - Meijers, Wouter C.

N1 - FUNDING SUPPORT AND AUTHOR DISCLOSURES Financial support was also provided by the European Research Council (ERC CoG 818715, SECRETE-HF). Dr Meijers is supported by the Mandema-Stipendium of the Junior Scientific Masterclass 2020-10 of the University Medical Center Groningen (UMCG; P.F. van den Berg, C. Shi, S. de Wit, L. Geerlings, S. Bakker, B. van der Vegt, H. Silljé, R. de Boer and W. Meijers) and by the Dutch Heart Foundation (Dekker grant 03-005-2021-T005). Dr de Boer has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. The UMCG, which employs/employed several of the authors, has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2023 The Authors

PY - 2023/8

Y1 - 2023/8

N2 - Background: Cancer and heart failure (HF) are the leading causes of death in the Western world. Shared mechanisms such as fibrosis may underlie either disease entity, furthermore it is unknown whether this relationship is sex-specific. Objectives: We sought to investigate how fibrosis-related biomarker galectin-3 (gal-3) aids in identifying individuals at risk for new-onset cancer and HF, and how this differs between sexes. Methods: Gal-3 was measured at baseline and at 4-year follow-up in 5,786 patients of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study. The total follow-up period was 11.5 years. An increase of ≥50% in gal-3 levels between measurements was considered relevant. We performed sex-stratified log-rank tests and Cox regression analyses overall and by sex to evaluate the association of gal-3 over time with both new-onset cancer and new-onset HF. Results: Of the 5,786 healthy participants (50% males), 399 (59% males) developed new-onset cancer, and 192 (65% males) developed new-onset HF. In males, an increase in gal-3 was significantly associated with new-onset cancer (both combined and certain cancer-specific subtypes), after adjusting for age, body mass index, hypertension, smoking status, estimated glomerular filtration rate, diabetes mellitus, triglycerides, coronary artery disease, and C-reactive protein (HR: 1.89; 95% CI: 1.32-2.71; P < 0.001). Similar analyses demonstrated an association with new-onset HF in males (HR: 1.77; 95% CI: 1.07-2.95; P = 0.028). In females, changes in gal-3 over time were neither associated with new-onset cancer nor new-onset HF. Conclusions: Gal-3, a marker of fibrosis, is associated with new-onset cancer and new-onset HF in males, but not in females.

AB - Background: Cancer and heart failure (HF) are the leading causes of death in the Western world. Shared mechanisms such as fibrosis may underlie either disease entity, furthermore it is unknown whether this relationship is sex-specific. Objectives: We sought to investigate how fibrosis-related biomarker galectin-3 (gal-3) aids in identifying individuals at risk for new-onset cancer and HF, and how this differs between sexes. Methods: Gal-3 was measured at baseline and at 4-year follow-up in 5,786 patients of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study. The total follow-up period was 11.5 years. An increase of ≥50% in gal-3 levels between measurements was considered relevant. We performed sex-stratified log-rank tests and Cox regression analyses overall and by sex to evaluate the association of gal-3 over time with both new-onset cancer and new-onset HF. Results: Of the 5,786 healthy participants (50% males), 399 (59% males) developed new-onset cancer, and 192 (65% males) developed new-onset HF. In males, an increase in gal-3 was significantly associated with new-onset cancer (both combined and certain cancer-specific subtypes), after adjusting for age, body mass index, hypertension, smoking status, estimated glomerular filtration rate, diabetes mellitus, triglycerides, coronary artery disease, and C-reactive protein (HR: 1.89; 95% CI: 1.32-2.71; P < 0.001). Similar analyses demonstrated an association with new-onset HF in males (HR: 1.77; 95% CI: 1.07-2.95; P = 0.028). In females, changes in gal-3 over time were neither associated with new-onset cancer nor new-onset HF. Conclusions: Gal-3, a marker of fibrosis, is associated with new-onset cancer and new-onset HF in males, but not in females.

UR - https://www.scopus.com/pages/publications/85166944221

U2 - 10.1016/j.jaccao.2023.03.015

DO - 10.1016/j.jaccao.2023.03.015

M3 - Article

C2 - 37614579

AN - SCOPUS:85166944221

SN - 2666-0873

VL - 5

SP - 445

EP - 453

JO - JACC: CardioOncology

JF - JACC: CardioOncology

IS - 4

ER -

Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure

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