Elsevier

American Heart Journal

Volume 151, Issue 6, June 2006, Pages 1247.e1-1247.e7
American Heart Journal

Clinical Investigation
Coronary Artery Disease
Comparison of the serum ferritin and percentage of transferrin saturation as exposure markers of iron-driven oxidative stress–related disease outcomes

https://doi.org/10.1016/j.ahj.2006.03.009Get rights and content

Background

Iron-catalyzed oxidative stress may be the primary mechanism for the pathogenesis of diseases related to iron excess. We hypothesized previously that certain markers of iron in bound form that are commonly used in epidemiologic studies might be inappropriate for investigating iron-related adverse health effects because oxidative stress requires iron in redox-active form.

Methods

To study aspects of this hypothesis, we examined the association between levels of serum ferritin or the percentage of transferrin saturation (%TS) and levels of serum antioxidant vitamins and C-reactive protein (CRP). This cross-sectional analysis included 11 245 adults aged 20 years or older who participated in the Third National Health and Nutrition Examination Survey.

Results

Adjusted concentrations of serum α-carotene, β-carotene, β-cryptoxanthin, and lycopene were inversely correlated with the serum ferritin concentration (P for trend < .01), even within the lower deciles of the serum ferritin. In contrast, the %TS was significantly and positively associated with β-cryptoxanthin, vitamin C, and vitamin E. In addition, the serum ferritin was positively associated but the %TS was strongly and inversely associated with the serum CRP (P for trend < .01).

Conclusions

The serum ferritin and %TS showed contrasting associations with serum antioxidant vitamin levels and CRP although they have been used interchangeably in epidemiologic studies as markers of body iron. These results suggest that the %TS may not be a valid marker of exposure to iron-related oxidative stress. It appears that the serum ferritin is the preferred marker for assessment of clinical outcomes presumed to be caused by iron-related oxidative stress.

Section snippets

Methods

A detailed description of the NHANES III can be found elsewhere.17 Briefly, the NHANES III, conducted from 1988 to 1994, was a national probability sample designed to provide estimates of the health and nutritional status of the United States civilian and noninstitutionalized population aged 2 months or older. Of the 18 825 NHANES III participants aged 20 years or older, 7580 were excluded for one or more of the following reasons: 4038 had missing ferritin, %TS, or antioxidant values; 4769 had

Results

Table I shows the characteristics of the study participants by quintiles of serum ferritin or %TS. Subjects with high serum ferritin tended to be older, black, male, a current smoker, and obese. In addition, they consumed more alcohol and less dietary carotene. Subjects with high %TS showed tendencies similar to those with high ferritin concentration for sex, smoking, and alcohol consumption. However, subjects with high %TS tended to be younger, be white, be thinner, and consume more dietary

Discussion

Despite compelling evidence for the biologic plausibility of the iron hypothesis, epidemiologic studies on the association between iron and oxidative stress–related diseases have shown inconsistent results, especially for coronary heart disease.6, 7, 8, 9 A critical methodological question in evaluating this discrepancy is whether markers of body iron stores used in epidemiologic studies are appropriate as exposure markers for evaluating iron-driven oxidative stress–related pathology. A valid

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