Sex differences in cardiorenometabolic syndrome across heart failure: prognostic impact in a low-middle income country
A Jordan, A Perez-Perez, G Medina-Avalos, C Martinez-Medrano, L Torres-Araujo, J C De la Fuente-Mancera, A B Alvarez-Sangabriel, M R Aguilar-Serrano, C Guizar-Sanchez, E A Berrios-Barcenas, F M Baranda-TovarAbstract
Background
Sex-related differences in heart failure (HF) outcomes remain incompletely understood, particularly in patients with concomitant cardiorenometabolic syndrome (CKM), characterized by the coexistence of diabetes mellitus and chronic kidney dysfunction. Whether the impact of sex on HF-related events is modified by SCRM has not been fully elucidated.
Aim
To evaluate sex differences in heart failure–related urgent care visits and to determine whether the presence of cardiorenometabolic syndrome modifies this association.
Methods
We conducted a retrospective cohort study including 707 patients with heart failure and complete follow-up data from 2024-2025 in Mexico City. CKM was defined as the presence of type 2 diabetes mellitus and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m² at baseline. The primary endpoint was time to first HF-related urgent care visit. Kaplan–Meier curves were generated for four groups stratified by sex and CKM status. Multivariable Cox proportional hazards models were constructed adjusting for age, left ventricular ejection fraction (LVEF), systolic blood pressure, and eGFR. An interaction term between sex and CKM was tested.
Results
During follow-up, 437 events occurred. In patients without CKM, there was no significant difference in urgent care risk between women and men (HR 0.88, p=0.19). However, a significant interaction between sex and CKM was observed (HR for interaction 1.45, 95% CI 1.03–2.02; p=0.031). In patients with CKM, female sex was independently associated with increased risk of urgent care visits. In the CKM subgroup (n=119; 98 events), women had a more than twofold higher adjusted risk compared with men (HR 2.12, p<0.001). Spline modeling confirmed non-linearity of renal function effects but did not attenuate the observed sex–SCRM interaction.
Conclusions
Sex differences in heart failure outcomes are significantly modified by the presence of cardiorenometabolic syndrome. While no sex disparity was observed in patients without CKM, women with concomitant diabetes and renal dysfunction demonstrated a substantially higher risk of urgent HF-related events. These findings suggest that the cardiorenometabolic milieu amplifies vulnerability in women and highlight the need for sex-specific risk stratification in high-risk HF populations.KaplanMeier plot