Paradoxical association between low hepatic steatosis index and mortality in older patients with heart failure

Background Steatotic liver disease (SLD) is increasingly recognised as an important modifier of cardiovascular risk in patients with heart failure (HF), owing to its close association with metabolic disorders. Several non-invasive indices for identifying SLD have been proposed; however, their prognostic significance in older patients with HF remains uncertain, particularly given the high prevalence of frailty and nutritional impairment in this population. Purpose We aimed to investigate the association between the hepatic steatosis index (HSI), a non-invasive screening tool for SLD and metabolic-associated SLD, and mortality in older patients with HF. Methods This was a post hoc analysis of the FRAGILE-HF study. Older patients with HF in whom HSI could be calculated were included. HSI was calculated as follows: HSI = 8 × (alanine aminotransferase/aspartate aminotransferase ratio) + body mass index (+2 for female sex; +2 for diabetes mellitus). Patients were stratified into quartiles according to HSI. The primary outcome was all-cause mortality. Cardiovascular (CV) and non-CV mortality were analysed as secondary outcomes. Survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards models, adjusted for the MAGGIC risk score and log-transformed B-type natriuretic peptide. Results A total of 1322 older patients with HF were analysed (median age, 81 years [interquartile range, 74–86 years]; 57.2% male). During a follow-up of 2 years [interquartile range, 1.4–2.0 years], 274 all-cause deaths (21.0%) occurred. Higher HSI was significantly associated with lower mortality (Figure 1). Compared with the lowest quartile (Q1), adjusted hazard ratios for all-cause mortality were 0.759 (95% confidence interval [CI] 0.561–1.025; p=0.072) in Q2, 0.533 (95% CI 0.380–0.747; p<0.001) in Q3, and 0.469 (95% CI 0.318–0.692; p<0.001) in Q4. Higher HSI was also associated with lower risks of both CV and non-CV mortality (Figure 2). Furthermore, a lower HSI was significantly associated with reduced skeletal muscle mass and fat mass, as well as a worse the controlling nutritional status score (all p for trend<0.001). Conclusions In older patients with HF, a low HSI was independently associated with increased mortality and poorer skeletal muscle mass, fat mass, and overall nutritional status. Given that SLD is generally considered a cardiovascular risk factor, low SLD risk scores in older patients with HF may instead reflect malnutrition or sarcopenia rather than a favourable metabolic profile. Caution is therefore warranted when interpreting SLD risk indices in this population.