Sex Differences in All-Cause and Cardiovascular Mortality During Long-Term Follow-Up in Patients with HFrEF
5 affiliations
- 1Department of Cardiology, Hospital Universitario Lucus Augusti, 27002 Lugo, Spain
- 2CardioHULA Research Group, Instituto de Investigacion Sanitaria de Santiago de Compostela IDIS, 27002 Lugo, Spain
- 3Department of Anatomy, Animal Production and Veterinary Clinical Sciences, Santiago de Compostela University, 27001 Lugo, Spain
- 4Institute for Research in Global Health and Sustainable Development (iTERRA), Campus Terra, Universidad de Santiago de Compostela, 27002 Lugo, Spain
- 5Nursing School, Santiago de Compostela University, Campus Lugo, 27001 Lugo, Spain
Abstract
Background/Objectives: Sex-related differences in prognosis among patients with heart failure with reduced ejection fraction (HFrEF) have been described, but their association with long-term all-cause and cardiovascular mortality remains incompletely characterised. This study investigated these associations in a real-world HFrEF cohort, accounting for non-cardiovascular death as a competing event. Methods: We conducted a single-centre, retrospective, longitudinal observational study of 1510 consecutive patients with HFrEF followed between 2011 and 2023; 1158 (76.7%) were men and 352 (23.3%) were women. All-cause mortality was assessed using Kaplan–Meier methods and Cox regression. Multivariable models used a complete-case approach. Cardiovascular mortality was analysed using cause-specific Cox regression and the Fine–Gray model, with non-cardiovascular death and death of unknown cause treated as competing events. Interaction terms between sex and year of inclusion were used to assess potential changes in the association across the study period. Results: No statistically significant between-sex difference in cumulative all-cause mortality was detected at one year (3.7% in men vs. 3.8% in women; p = 0.95). Exploratory pointwise comparisons showed higher cumulative mortality in men at five years (24.8% vs. 16.0%; p = 0.002) and ten years (49.3% vs. 39.8%; p = 0.046). After multivariable adjustment, male sex was associated with higher all-cause mortality (HR, 1.95; 95% CI, 1.47–2.59; p < 0.001). Male sex was also associated with cardiovascular mortality in the cause-specific analysis (HR, 2.46; 95% CI, 1.54–3.92; p < 0.001) and after accounting for non-cardiovascular death as a competing event (subdistribution HR, 2.12; 95% CI, 1.32–3.39; p = 0.002). No significant interaction was observed between sex and year of inclusion. Conclusions: In this real-world HFrEF cohort, male sex remained associated with higher all-cause and cardiovascular mortality after adjustment for measured baseline covariates. The association with cardiovascular mortality persisted in competing-risk analysis. These observational findings do not establish a causal or time-varying effect of sex.
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BibTeX
@article{lopezlopez2026differences,
title = {{Sex Differences in All-Cause and Cardiovascular Mortality During Long-Term Follow-Up in Patients with HFrEF}},
author = {Andrea Lopez-Lopez and Estefanía Rivas Vázquez and Carmen Cristina Álvarez-Suárez and Margarita Regueiro-Abel and Charigan Abou Johk-Casas and Juliana Elices-Teja and Ramón Ríos Vázquez and Eva María Pereira López and Germán Santamarina-Pernas and Carlos González-Juanatey},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15218431},
url = {https://www.mdpi.com/2077-0383/15/21/8431},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sex Differences in All-Cause and Cardiovascular Mortality During Long-Term Follow-Up in Patients with HFrEF
AU - Andrea Lopez-Lopez
AU - Estefanía Rivas Vázquez
AU - Carmen Cristina Álvarez-Suárez
AU - Margarita Regueiro-Abel
AU - Charigan Abou Johk-Casas
AU - Juliana Elices-Teja
AU - Ramón Ríos Vázquez
AU - Eva María Pereira López
AU - Germán Santamarina-Pernas
AU - Carlos González-Juanatey
PY - 2026
DA - 2026/10/29
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218431
UR - https://www.mdpi.com/2077-0383/15/21/8431
AB - Background/Objectives: Sex-related differences in prognosis among patients with heart failure with reduced ejection fraction (HFrEF) have been described, but their association with long-term all-cause and cardiovascular mortality remains incompletely characterised. This study investigated these associations in a real-world HFrEF cohort, accounting for non-cardiovascular death as a competing event. Methods: We conducted a single-centre, retrospective, longitudinal observational study of 1510 consecutive patients with HFrEF followed between 2011 and 2023; 1158 (76.7%) were men and 352 (23.3%) were women. All-cause mortality was assessed using Kaplan–Meier methods and Cox regression. Multivariable models used a complete-case approach. Cardiovascular mortality was analysed using cause-specific Cox regression and the Fine–Gray model, with non-cardiovascular death and death of unknown cause treated as competing events. Interaction terms between sex and year of inclusion were used to assess potential changes in the association across the study period. Results: No statistically significant between-sex difference in cumulative all-cause mortality was detected at one year (3.7% in men vs. 3.8% in women; p = 0.95). Exploratory pointwise comparisons showed higher cumulative mortality in men at five years (24.8% vs. 16.0%; p = 0.002) and ten years (49.3% vs. 39.8%; p = 0.046). After multivariable adjustment, male sex was associated with higher all-cause mortality (HR, 1.95; 95% CI, 1.47–2.59; p < 0.001). Male sex was also associated with cardiovascular mortality in the cause-specific analysis (HR, 2.46; 95% CI, 1.54–3.92; p < 0.001) and after accounting for non-cardiovascular death as a competing event (subdistribution HR, 2.12; 95% CI, 1.32–3.39; p = 0.002). No significant interaction was observed between sex and year of inclusion. Conclusions: In this real-world HFrEF cohort, male sex remained associated with higher all-cause and cardiovascular mortality after adjustment for measured baseline covariates. The association with cardiovascular mortality persisted in competing-risk analysis. These observational findings do not establish a causal or time-varying effect of sex.
SN - 2077-0383
ER -