Intra-Pancreatic Fat Deposition Versus Hepatic Fat in Relation to Incident Heart Failure: A Prospective Cohort Analysis

Background: Although liver fat has been extensively studied, its independent contribution to heart failure (HF) remains debated. Moreover, whether fat stored in different visceral organs confers comparable cardiovascular risk remains unclear. Therefore, this study aimed to examine the associations among intra-pancreatic fat deposition (IPFD), hepatic fat, and visceral adiposity and new-onset HF. Methods: This prospective analysis included 22,038 UK Biobank participants who were free of HF at baseline. Time-to-event associations of IPFD, liver fat, and total visceral fat volume with incident HF were estimated using Cox regression models. Results: Over a median follow-up of 13.6 years, 282 participants developed HF. Spline modeling suggested a monotonic increase in HF risk with higher IPFD, whereas liver fat showed a non-linear, inverted U-shaped pattern. In multivariable models adjusting for cardiometabolic risk factors, the highest IPFD tertile was associated with a greater risk of HF than the lowest tertile (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15–2.46; p = 0.007), whereas hepatic fat was not. The association with IPFD remained significant after additional adjustment for pancreatic volume (HR, 1.62; 95% CI, 1.10–2.38), pancreatic iron (HR, 1.58; 95% CI, 1.07–2.33), HF polygenic risk score (HR, 1.58; 95% CI, 1.07–2.33), and the triglyceride–glucose (TyG) index (HR, 1.50; 95% CI, 1.00–2.26). Discrimination for incident HF was comparable between IPFD (area under the curve [AUC], 0.662; 95% CI, 0.635–0.689) and visceral fat volume (AUC, 0.663; 95% CI, 0.635–0.691). Conclusions: Greater pancreatic fat accumulation was independently associated with future HF, regardless of established cardiometabolic risk factors. These results suggest that IPFD may provide additional value for HF risk assessment and prevention-oriented metabolic profiling.