Iron deficiency in community-dwelling US adults with self-reported heart failure in the National Health and Nutrition Examination Survey III: prevalence and associations with anemia and inflammation

Abstract

Background: Iron deficiency has been proposed as a potential therapeutic target in heart failure, but its prevalence and association with anemia and clinical outcomes in community-dwelling adults with heart failure have not been well characterized.

Methods and results: Using data from the Third National Health and Nutrition Examination Survey, we evaluated the associations between iron deficiency, hemoglobin, C-reactive protein (CRP), and all-cause and cardiovascular mortality in 574 adults with self-reported heart failure. Iron deficiency was defined in both absolute and functional terms as a ferritin level <100 μg/L or between 100 and 299 μg/L if the transferrin saturation was <20%. Iron deficiency was present in 61.3% of participants and was associated with reduced mean hemoglobin (13.6 versus 14.2 g/dL, P=0.007) and increased mean CRP (0.95 versus 0.63 mg/dL, P=0.04). Over a median of 6.7 years of follow-up, there were 300 all-cause deaths, 193 of which were from cardiovascular causes. In age- and sex-adjusted Cox proportional hazards models, hemoglobin, CRP, and transferrin saturation but not iron deficiency were significantly associated with all-cause and cardiovascular mortality. In multivariate models, hemoglobin remained an independent predictor of cardiovascular mortality, whereas CRP remained an independent predictor of both all-cause and cardiovascular mortality.

Conclusions: Iron deficiency is common in heart failure and is associated with decreased hemoglobin and increased CRP. In multivariate analysis, hemoglobin was associated with cardiovascular mortality while CRP was associated with both all-cause and cardiovascular mortality. Iron deficiency was not associated with all-cause or cardiovascular mortality in this cohort.

Figure 1

Kaplan-Meier estimate of survival for all-cause mortality, stratified by presence or absence of functional iron deficiency.* *Kaplan-Meier curves are presented unadjusted for confounders, using survey weights, strata, and cluster variables to obtain population estimates.

Figure 2

Kaplan-Meier estimate of survival for cardiovascular mortality, stratified by presence or absence of functional iron deficiency.* *Kaplan-Meier curves are presented unadjusted for confounders, using survey weights, strata, and cluster variables to obtain population estimates.