Heart Failure Hospitalization Risk associated with Iron Status in Veterans with CKD

Abstract

Background and objectives: CKD is an independent risk factor for heart failure. Iron dysmetabolism potentially contributes to heart failure, but this relationship has not been well characterized in CKD.

Design, setting, participants, & measurements: We performed a historical cohort study using data from the Veterans Affairs Corporate Data Warehouse to evaluate the relationship between iron status and heart failure hospitalization. We identified a CKD cohort with at least one set of iron indices between 2006 and 2015. The first available date of serum iron indices was identified as the study index date. The cohort was divided into four iron groups on the basis of the joint quartiles of serum transferrin saturation (shown in percent) and ferritin (shown in nanograms per milliliter): reference (16%-28%, 55-205 ng/ml), low iron (0.4%-16%, 0.9-55 ng/ml), high iron (28%-99.5%, 205-4941 ng/ml), and function iron deficiency (0.8%-16%, 109-2783 ng/ml). We compared 1-year heart failure hospitalization risk between the iron groups using matching weights derived from multinomial propensity score models and Poisson rate-based regression.

Results: A total of 78,551 veterans met the eligibility criteria. The covariates were well balanced among the iron groups after applying the propensity score weights (n=31,819). One-year adjusted relative rate for heart failure hospitalization in the iron deficiency groups were higher compared with the reference group (low iron: 1.29 [95% confidence interval, 1.19 to 1.41]; functional iron deficiency: 1.25 [95% confidence interval, 1.13 to 1.37]). The high-iron group was associated with lower 1-year relative rate of heart failure hospitalization (0.82; 95% confidence interval, 0.72 to 0.92). Furthermore, the association between iron deficiency and heart failure hospitalization risk remained consistent regardless of the diabetes status or heart failure history at baseline.

Conclusions: Iron deficiency, regardless of cause, was associated with higher heart failure hospitalization risk in CKD. Higher iron status was associated with lower heart failure hospitalization risks.

Keywords: CKD; chronic kidney disease; heart failure; hospitalization; iron; veterans.

Graphical abstract

Figure 1.

The flow chart of study cohort inclusion and exclusion. IV, intravenous; Tsat, transferrin saturation; VA, Veterans Affairs.

Figure 2.

The definition of iron groups by joint transferrin saturation and ferritin quartiles (n=138,853). Four iron groups were established using quartiles of serum transferrin saturation and ferritin: reference, second and third quartiles of transferrin saturation and ferritin; low iron, first quartiles of transferrin saturation and ferritin; high iron, fourth quartiles of transferrin saturation and ferritin; and functional iron deficiency, first transferrin saturation quartile with third and fourth quartiles of ferritin. The ranges of transferrin saturation and ferritin values for each iron group are included. The table includes quartile thresholds of serum transferrin saturation and ferritin in the eligible cohort, including the excluded (not classified) subgroup.

Figure 3.

The distribution of serum transferrin saturation and ferritin of the VINCI CKD cohort (n=78,551). The graphs depict distribution of serum transferrin saturation and ferritin values of the VINCI CKD cohort included for the analyses. IQR, interquartile range; VINCI, Veterans Affairs Informatics and Computing Infrastructure.

Figure 4.

The Kaplan–Meier curves comparing cumulative probability of heart failure hospitalization, mortality, and composite (heart failure or mortality) outcome: mortality and heart failure risk are higher with iron deficiency. Each panel depicts an outcome. The first panel depicts the composite of heart failure hospitalization and mortality, the second depicts heart failure hospitalization before mortality, and the third depicts mortality before heart failure hospitalization. The trend for each iron group is shown. Both functional iron deficiency (FID) and low-iron groups reach approximately 6% cumulative heart failure hospitalization during the first year of follow-up, but the probability of death is higher for functional iron deficiency at any given time compared with other iron groups.