Context

Increased risk of heart disease, diabetes, dementia, cancer, and death has been found among individuals with elevated transferrin saturation (TS). Although TS has been linked to specific diseases, little research has focused on the relationship between elevated TS and current health status.

Purpose

This study examined the relationship between elevated TS and measures of health status (telomere length and patient-reported health-related quality of life) to assess whether elevated TS is associated with negative patient outcomes beyond increased risk for morbidity and mortality.

Methods

We conducted an analysis of the Hemochromatosis and Iron Overload Screening (HEIRS) Study supplemented with assays for leukocyte telomere length in adults (>25 years old). The HEIRS Study identified individuals through a multiethnic, multicenter sample of 101,168 US and Canadian adults. Screening was done with serum biochemical tests of iron status and hemochromatosis (HFE) gene mutation testing. Our sample was comprised of HEIRS subjects with responses on health-related quality of life (general health (GH) and mental health (MH) subscales of the SF-36 Health Survey), and known leukocyte telomere length (n=669). Leukocyte telomere length was assessed through a quantitative PCR-based technique (qPCR). Unadjusted mean values of the general health status subscale, the mental health status subscale and telomere length were compared between groups with elevated TS (>45% for women and >50% for men) versus non-elevated TS (<45% for women and <50% for men) using t-tests. Comparisons also were made between mean values for the general and mental health status subscales and telomere length for the group with TS >60% versus with non-elevated TS (<45% for women and <50% for men). For each of the quantitative outcomes of GH, MH, and telomere length, separate general linear regression models were formed with TS elevation as a dichotomous predictor, controlled for demographic characteristics as well as health conditions associated with iron overload.

Results

Among individuals with elevated TS (>45% for women and >50% for men), who also had a usual source of care, only 5.2% reported ever being told by a doctor that they had an elevated iron condition. Mean values for GH and MH, and telomere length were significantly lower in those with elevated TS (Table 1; p<0.01, p<0.001, and p<0.001, respectively), indicating worse general and mental health and shorter telomere length. In a fully adjusted model, elevated TS versus non-elevated TS was associated with worse general health status, mental health status and shorter telomere length. GH and MH status scores were progressively lower in individuals with increasing levels of TS (e.g., TS >60%) versus non-elevated TS.

Table 1

Comparison of Mean General Health Scores, Mental Health Scores and Telomere Length by Transferrin Saturation Percentage

% TSGeneral healthMental healthTelomere length
Unadjusted*MeanPMeanPMeanP
<45 for women and <50 for men64.381.7263.7
>45 for women and >50 for men 59.2 <0.01 76.6 <0.001 238.0 <0.001 
Adjusted** Mean Mean Mean 
<45 for women and <50 for men 64.3  82.1  262.7  
>45 for women and >50 for men 60.0 <0.05 76.7 <0.001 240.2 <0.01 
Adjusted*** Mean Mean Mean 
<45 for women and <50 for men 63.8  82.2  261.3  
>45 for women and >50 for men 60.4 <0.05 76.5 <0.0001 241.4 <0.05 
% TSGeneral healthMental healthTelomere length
Unadjusted*MeanPMeanPMeanP
<45 for women and <50 for men64.381.7263.7
>45 for women and >50 for men 59.2 <0.01 76.6 <0.001 238.0 <0.001 
Adjusted** Mean Mean Mean 
<45 for women and <50 for men 64.3  82.1  262.7  
>45 for women and >50 for men 60.0 <0.05 76.7 <0.001 240.2 <0.01 
Adjusted*** Mean Mean Mean 
<45 for women and <50 for men 63.8  82.2  261.3  
>45 for women and >50 for men 60.4 <0.05 76.5 <0.0001 241.4 <0.05 
*

Results of t-tests comparing mean values for general health and mental health subscales and telemore length between TS elevation categories.

**

Adjusted for demographics (age, gender, race-ethnicity, education, health insurance, and usual source of medical care).

***

Adjusted for demographics and diseases (liver disease, diabetes, heart disease or failure, impotence/fertility problems, arthritis, and reported iron overload condition).

Conclusions

Increased surveillance of elevated TS may be in order as elevated TS is associated with decreased health status and very few patients with elevated TS are aware of their condition.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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