Sex differences in clinical phenotypes and prognostic associations in acute heart failure
6 affiliations
- 1Department of Cardiology, Venizelio General Hospital of Heraklion
- 2School of Medicine, University of Crete
- 3Second Department of Internal Medicine, Venizelio General Hospital of Heraklion
- 4Institute of Applied and Computational Mathematics, Foundation for Research and Technology-Hellas
- 5Department of Cardiology, University General Hospital of Heraklion
- 6Department of Nephrology, University General Hospital of Heraklion
Abstract
Background: Women are under-represented in heart failure trials, and the risk markers used in acute heart failure (AHF) derive largely from male-predominant cohorts. In this study, we compared the metabolic, inflammatory, and renal profiles of men and women hospitalized for AHF and tested whether the prognostic value of these markers differs by sex.
Methods: We analyzed 530 consecutive patients from a prospective single-center AHF registry. Postdischarge mortality was modeled by Cox regression in the 503 patients discharged alive; each of eight covariates was tested for a sex interaction, and 19 metabolic, inflammatory, and renal markers were screened for effect modification by sex.
Results: The total number of male patients was 284 (53.6%). Women were older (82 vs. 79 years) than men and more often had preserved ejection fraction (65.9% vs. 35.9%), frailty (74.0% vs. 59.9%), and chronic kidney disease; they had a higher total cholesterol level (139 vs. 126 mg/dL), a lower troponin level, a higher E/e′ ratio within preserved ejection fraction, and a lower ferritin level (42 vs. 71 ng/mL; below 100 ng/mL in 76.8% vs. 63.7%). Men more often had an ischemic etiology (45.8% vs. 15.0%), although coronary anatomy was more often unassessed in women (all p < 0.05). In-hospital (5.3% vs. 4.9%) and postdischarge mortality rates (23.6% vs. 26.7%) and renal outcomes did not differ; after full adjustment, male sex was associated with higher postdischarge mortality [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.03–2.22], but this depended on the inclusion of the left ventricular ejection fraction (LVEF) category. No covariate showed significant effect modification by sex (all p for interaction ≥0.06), with similar optimism-corrected C-indices (men 0.683, women 0.687). Among the 19 markers, only uric acid showed an interaction (women HR 1.15 per mg/dL, 95% CI 1.00–1.33; men 0.91, 0.80–1.03; p = 0.008), not surviving multiplicity correction.
Conclusions: Men and women hospitalized for AHF are clinically and biochemically distinct populations. Unadjusted mortality rates were similar in both sexes; an adjusted association with male sex was sensitive to the inclusion of the LVEF category and therefore should be interpreted cautiously. No robust sex-related effect modification was found; given the limited number of events, this represents the absence of evidence rather than evidence of similar prognostic associations between the sexes. Low ferritin levels, frequent in women, warrants assessment with complete iron indices; the uric acid interaction is hypothesis-generating.
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BibTeX
@article{aletras2026differences,
title = {{Sex differences in clinical phenotypes and prognostic associations in acute heart failure}},
author = {Georgios Aletras and Maria Bachlitzanaki and Stylianos Fiflis and Eirini Bachlitzanaki and Eleni Eleftheriadou and Yannis Pantazis and Emmanuel Foukarakis and Michalis Hamilos and Konstantinos Stylianou},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.2011890},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.2011890/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sex differences in clinical phenotypes and prognostic associations in acute heart failure
AU - Georgios Aletras
AU - Maria Bachlitzanaki
AU - Stylianos Fiflis
AU - Eirini Bachlitzanaki
AU - Eleni Eleftheriadou
AU - Yannis Pantazis
AU - Emmanuel Foukarakis
AU - Michalis Hamilos
AU - Konstantinos Stylianou
PY - 2026
DA - 2026/10/28
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.2011890
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.2011890/full
AB - Background: Women are under-represented in heart failure trials, and the risk markers used in acute heart failure (AHF) derive largely from male-predominant cohorts. In this study, we compared the metabolic, inflammatory, and renal profiles of men and women hospitalized for AHF and tested whether the prognostic value of these markers differs by sex. Methods: We analyzed 530 consecutive patients from a prospective single-center AHF registry. Postdischarge mortality was modeled by Cox regression in the 503 patients discharged alive; each of eight covariates was tested for a sex interaction, and 19 metabolic, inflammatory, and renal markers were screened for effect modification by sex. Results: The total number of male patients was 284 (53.6%). Women were older (82 vs. 79 years) than men and more often had preserved ejection fraction (65.9% vs. 35.9%), frailty (74.0% vs. 59.9%), and chronic kidney disease; they had a higher total cholesterol level (139 vs. 126 mg/dL), a lower troponin level, a higher E/e′ ratio within preserved ejection fraction, and a lower ferritin level (42 vs. 71 ng/mL; below 100 ng/mL in 76.8% vs. 63.7%). Men more often had an ischemic etiology (45.8% vs. 15.0%), although coronary anatomy was more often unassessed in women (all p < 0.05). In-hospital (5.3% vs. 4.9%) and postdischarge mortality rates (23.6% vs. 26.7%) and renal outcomes did not differ; after full adjustment, male sex was associated with higher postdischarge mortality [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.03–2.22], but this depended on the inclusion of the left ventricular ejection fraction (LVEF) category. No covariate showed significant effect modification by sex (all p for interaction ≥0.06), with similar optimism-corrected C-indices (men 0.683, women 0.687). Among the 19 markers, only uric acid showed an interaction (women HR 1.15 per mg/dL, 95% CI 1.00–1.33; men 0.91, 0.80–1.03; p = 0.008), not surviving multiplicity correction. Conclusions: Men and women hospitalized for AHF are clinically and biochemically distinct populations. Unadjusted mortality rates were similar in both sexes; an adjusted association with male sex was sensitive to the inclusion of the LVEF category and therefore should be interpreted cautiously. No robust sex-related effect modification was found; given the limited number of events, this represents the absence of evidence rather than evidence of similar prognostic associations between the sexes. Low ferritin levels, frequent in women, warrants assessment with complete iron indices; the uric acid interaction is hypothesis-generating.
SN - 2297-055X
ER -