Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex
Background: The effects of sex on the prognostic implications of natriuretic peptide (NP) elevation have not been fully elucidated in the population. Objectives: The purpose of this study was to examine if sex modifies associations of NPs with mortality and hospitalization. Methods: In a population-...
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2025-08-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772963X25004235 |
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| author | David Bobrowski, MD Husam Abdel-Qadir, MD, PhD Candace D. McNaughton, MD, PhD, MPH Anna Chu, MHSc Xuesong Wang, MSc Peter C. Austin, PhD Barbara S. Doumouras, MD Karem Abdul-Samad, BSc Peter A. Kavsak, PhD Michael E. Farkouh, MD, MSc James L. Januzzi, MD Heather J. Ross, MHSc, MD Douglas S. Lee, MD, PhD |
| author_facet | David Bobrowski, MD Husam Abdel-Qadir, MD, PhD Candace D. McNaughton, MD, PhD, MPH Anna Chu, MHSc Xuesong Wang, MSc Peter C. Austin, PhD Barbara S. Doumouras, MD Karem Abdul-Samad, BSc Peter A. Kavsak, PhD Michael E. Farkouh, MD, MSc James L. Januzzi, MD Heather J. Ross, MHSc, MD Douglas S. Lee, MD, PhD |
| author_sort | David Bobrowski, MD |
| collection | DOAJ |
| description | Background: The effects of sex on the prognostic implications of natriuretic peptide (NP) elevation have not been fully elucidated in the population. Objectives: The purpose of this study was to examine if sex modifies associations of NPs with mortality and hospitalization. Methods: In a population-based retrospective cohort study, we identified all patients (aged ≥40 years) undergoing NP testing in Ontario, Canada (2015-2020). We examined for the presence of sex-by-NP interactions for 1-year outcomes and conducted sex-specific analyses for continuously increasing NP concentrations. Results: We studied 91,017 individuals with B-type natriuretic peptide (BNP) tests (median 75 years; 48.0% females) and 81,578 individuals with N-terminal pro-BNP (NT-proBNP) tests (74 years; 48.6% females). Adjusted 1-year risks of all-cause mortality at any given NP concentration were higher in males than females. For example, 1-year mortality at a BNP of 400 ng/L was 16.8% in females and 21.6% in males. At an NT-proBNP of 900 ng/L, 1-year mortality was 14.2% in females and 18.5% in males. However, there were also significant sex interactions with BNP (P = 0.002) and NT-proBNP (P = 0.03) for mortality outcomes. When we examined cardiovascular hospitalizations, there was also a significant sex-by-NP interaction. For BNP, the risk of cardiovascular hospitalization was higher in males at lower concentrations but was higher in females at higher concentrations (P-interaction = 0.005). For NT-proBNP, the risk of cardiovascular hospitalization was higher in males at lower NP concentrations, but the gap narrowed at higher NP levels (P interaction = 0.03). Conclusions: Sex modifies the association between NP concentrations and all-cause mortality or cardiovascular hospitalizations. Prognostically, interpretation of NP levels should consider effect modification by sex. |
| format | Article |
| id | doaj-art-e4a0a66470f44d01a5f71c174ac729cb |
| institution | Kabale University |
| issn | 2772-963X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| series | JACC: Advances |
| spelling | doaj-art-e4a0a66470f44d01a5f71c174ac729cb2025-08-20T03:32:40ZengElsevierJACC: Advances2772-963X2025-08-014810199910.1016/j.jacadv.2025.101999Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by SexDavid Bobrowski, MD0Husam Abdel-Qadir, MD, PhD1Candace D. McNaughton, MD, PhD, MPH2Anna Chu, MHSc3Xuesong Wang, MSc4Peter C. Austin, PhD5Barbara S. Doumouras, MD6Karem Abdul-Samad, BSc7Peter A. Kavsak, PhD8Michael E. Farkouh, MD, MSc9James L. Januzzi, MD10Heather J. Ross, MHSc, MD11Douglas S. Lee, MD, PhD12Department of Medicine, University of Toronto, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada; Women's College Hospital, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Ontario, CanadaICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Ontario, CanadaICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, CanadaICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, CanadaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, CanadaCedars-Sinai Medical Center, Los Angeles, California, USAMassachusetts General Hospital, Harvard Medical School, Baim Institute for Clinical Research, Boston, Mass, USADepartment of Medicine, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Address for correspondence: Dr Douglas S. Lee, Division of Cardiology, Peter Munk Cardiac Centre, Professor of Medicine, University of Toronto, ICES, 2075 Bayview Ave, Rm V-106, Toronto, Ontario M4N 3M5, Canada.Background: The effects of sex on the prognostic implications of natriuretic peptide (NP) elevation have not been fully elucidated in the population. Objectives: The purpose of this study was to examine if sex modifies associations of NPs with mortality and hospitalization. Methods: In a population-based retrospective cohort study, we identified all patients (aged ≥40 years) undergoing NP testing in Ontario, Canada (2015-2020). We examined for the presence of sex-by-NP interactions for 1-year outcomes and conducted sex-specific analyses for continuously increasing NP concentrations. Results: We studied 91,017 individuals with B-type natriuretic peptide (BNP) tests (median 75 years; 48.0% females) and 81,578 individuals with N-terminal pro-BNP (NT-proBNP) tests (74 years; 48.6% females). Adjusted 1-year risks of all-cause mortality at any given NP concentration were higher in males than females. For example, 1-year mortality at a BNP of 400 ng/L was 16.8% in females and 21.6% in males. At an NT-proBNP of 900 ng/L, 1-year mortality was 14.2% in females and 18.5% in males. However, there were also significant sex interactions with BNP (P = 0.002) and NT-proBNP (P = 0.03) for mortality outcomes. When we examined cardiovascular hospitalizations, there was also a significant sex-by-NP interaction. For BNP, the risk of cardiovascular hospitalization was higher in males at lower concentrations but was higher in females at higher concentrations (P-interaction = 0.005). For NT-proBNP, the risk of cardiovascular hospitalization was higher in males at lower NP concentrations, but the gap narrowed at higher NP levels (P interaction = 0.03). Conclusions: Sex modifies the association between NP concentrations and all-cause mortality or cardiovascular hospitalizations. Prognostically, interpretation of NP levels should consider effect modification by sex.http://www.sciencedirect.com/science/article/pii/S2772963X25004235B-type natriuretic peptideheart failurehospitalizationmortalitynatriuretic peptidessex |
| spellingShingle | David Bobrowski, MD Husam Abdel-Qadir, MD, PhD Candace D. McNaughton, MD, PhD, MPH Anna Chu, MHSc Xuesong Wang, MSc Peter C. Austin, PhD Barbara S. Doumouras, MD Karem Abdul-Samad, BSc Peter A. Kavsak, PhD Michael E. Farkouh, MD, MSc James L. Januzzi, MD Heather J. Ross, MHSc, MD Douglas S. Lee, MD, PhD Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex JACC: Advances B-type natriuretic peptide heart failure hospitalization mortality natriuretic peptides sex |
| title | Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex |
| title_full | Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex |
| title_fullStr | Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex |
| title_full_unstemmed | Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex |
| title_short | Modification of the Association of B-Type Natriuretic Peptides With Mortality and Hospitalization Outcomes by Sex |
| title_sort | modification of the association of b type natriuretic peptides with mortality and hospitalization outcomes by sex |
| topic | B-type natriuretic peptide heart failure hospitalization mortality natriuretic peptides sex |
| url | http://www.sciencedirect.com/science/article/pii/S2772963X25004235 |
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