Among critically ill patients with AF, ferritin, transferrin, and TIBC levels were independently associated with 1-year all-cause mortality, while no significant association was observed for serum iron.
Key Findings
Results
Patients in the highest ferritin quartile had a significantly greater risk of 1-year all-cause mortality compared to those in the lowest quartile.
Highest ferritin quartile (Q4) HR 1.277, 95% CI 1.083–1.506, p < 0.01 after multivariable adjustment
This association was identified in critically ill ICU patients with atrial fibrillation
Data were drawn from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database
Analysis was performed using Cox proportional-hazards regression with multivariable adjustment
Results
Higher transferrin levels were independently associated with lower 1-year all-cause mortality in critically ill AF patients.
Highest transferrin quartile (Q4) HR 0.732, 95% CI 0.622–0.861, p < 0.01 after multivariable adjustment
The association was assessed via Kaplan-Meier curves, restricted cubic splines, and subgroup analyses in addition to Cox regression
Transferrin was one of four iron homeostasis-related indicators evaluated alongside ferritin, serum iron, and TIBC
Results
Higher total iron-binding capacity (TIBC) was independently associated with lower 1-year all-cause mortality in critically ill AF patients.
Highest TIBC quartile (Q4) HR 0.732, 95% CI 0.622–0.861, p < 0.01 after multivariable adjustment
The hazard ratio and confidence interval for TIBC were identical to those observed for transferrin
TIBC and transferrin are physiologically related measures, as transferrin is the primary iron-transporting protein that largely determines TIBC
Results
Serum iron quartiles were not significantly associated with 1-year all-cause mortality in critically ill AF patients.
Highest serum iron quartile (Q4) HR 1.067, 95% CI 0.914–1.245, p = 0.41 after multivariable adjustment
Serum iron was the only one of the four iron homeostasis indicators that did not show a statistically significant association with mortality
This null finding persisted after multivariable adjustment using Cox proportional-hazards regression
Results
Restricted cubic spline analyses characterized the shape of the exposure-outcome relationships between iron homeostasis indicators and 1-year mortality.
Restricted cubic spline analyses were applied to ferritin, serum iron, transferrin, and TIBC
These analyses further characterized the exposure and outcome patterns for iron-related parameters beyond linear quartile comparisons
Results were supplemented by Kaplan-Meier curves and subgroup analyses to assess associations comprehensively
Methods
This retrospective study used the MIMIC-IV database to evaluate iron homeostasis indicators as prognostic markers in critically ill ICU patients with atrial fibrillation.
The study design was retrospective and sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database
The study population consisted of critically ill patients with atrial fibrillation admitted to the ICU
The primary outcome was 1-year all-cause mortality
Iron homeostasis indicators evaluated included ferritin, serum iron, transferrin, and total iron-binding capacity (TIBC)
What This Means
This research suggests that iron-related blood markers can predict the risk of death within one year in critically ill patients with atrial fibrillation (an irregular heart rhythm) who are admitted to an intensive care unit (ICU). Specifically, the study found that higher levels of ferritin—a protein that stores iron and rises during inflammation—were linked to a higher risk of death, while higher levels of transferrin and total iron-binding capacity (TIBC), which reflect the body's capacity to transport iron, were linked to a lower risk of death. Notably, the actual level of iron circulating in the blood (serum iron) was not significantly related to mortality outcomes.
The study analyzed records from a large ICU database (MIMIC-IV) and used statistical tools including survival analysis curves, regression models, and dose-response modeling to examine these relationships. The findings held up even after accounting for other factors that might influence survival. This suggests that different aspects of how the body manages iron—not just iron levels themselves—carry distinct prognostic information for this vulnerable patient group.
This research suggests that measuring ferritin, transferrin, and TIBC in critically ill AF patients could help clinicians identify those at higher risk of dying within a year. Because these markers reflect different parts of iron metabolism, they may capture different biological processes—such as inflammation (reflected by ferritin) versus iron transport capacity (reflected by transferrin and TIBC)—that independently influence outcomes. Future research would be needed to determine whether targeting these markers through clinical interventions could improve patient survival.
Wu M, Hua J, Zhou Y, Zhang Y, Zhang L, Wang Y, et al.. (2026). Association of Iron Homeostasis With One-Year All-Cause Mortality Among Intensive Care Unit Patients with Atrial Fibrillation: A Retrospective Study.. Clinical cardiology. https://doi.org/10.1002/clc.70494