Sex-specific predictors and prognosis of chronic kidney disease in heart failure - insights from the CardioMining study

Background Chronic kidney disease (CKD) is a frequent comorbidity in patients with heart failure (HF), worsening prognosis and cardiovascular outcomes. However, research into sex-specific differences regarding the predictors and prognostic impact of CKD remains limited. Purpose To assess sex-related differences in clinical phenotypes and risk factors between HF patients with and without CKD, and to evaluate the prognostic impact of CKD across the spectrum of estimated glomerular filtration rate (eGFR). Methods This retrospective observational post-hoc analysis of the CardioMining study included adult patients hospitalized in multiple cardiology clinics with a history of HF. Patients were stratified by left ventricular ejection fraction (LVEF). Logistic regression identified sex-specific predictors of CKD; Cox regression models evaluated all-cause mortality; and restricted cubic spline analysis examined continuous relationships between eGFR and mortality. Results A total of 14,606 HF patients were analyzed. Overall, one third of the population had comorbid CKD (29% in HFrEF, 34% in HFpEF). Men displayed a predominantly atherosclerotic profile -coronary and peripheral artery disease-, while women exhibited a metabolic-hypertensive-arrhythmogenic profile (thyroid disease, hypertension, atrial fibrillation). CKD was identified as an independent predictor of mortality (p<0.001) across the whole cohort [(aHR 1.58 (1.466-1.724) males with HFrEF, 1.33 (1.195-1.490) females with HFrEF, 1.43 (1.194-1.731) females with HFpEF)], with the notable exception of male patients with HFpEF [(aHR 1.18 (0.937-1.493) p=0.15) (Figure 6,7). Spline analysis revealed a non-linear inverse relationship between eGFR and mortality, with female patients in the HFpEF cohort exhibiting a steeper risk trajectory at lower eGFR levels compared to males (Figure 8). Conclusions CKD prevalence is high and adversely influences HF prognosis, though its prognostic significance is attenuated in male HFpEF patients, likely due to competing ischemic risks. The identification of distinct sex-specific risk profiles suggests the need for tailored risk stratification strategies, moving beyond uniform guidelines to sex-specific diagnostic and therapeutic pathways.