The association of biomarkers of iron status with mortality in US adults
Introduction
Iron has a catalytic role in the generation of highly reactive oxygen species, such as hydroxyl radical, through Fenton and Haber–Weiss reactions [1]. As a result, elevated iron levels, below the levels found in genetic hemochromatosis, may have a role in a variety of disease processes. Body iron stores can be estimated using serum ferritin and previous studies have found that elevated ferritin levels, below the levels found in genetic hemochromatosis, are associated with diabetes, metabolic syndrome, hypertension, dyslipidemia, elevated fasting insulin and glucose, and abdominal adiposity [2], [3], [4]. The association of ferritin and other biomarkers of iron metabolism with mortality, however, remains controversial. Few studies are available investigating the association between iron biomarkers and mortality, and those studies are particularly limited in their ability to investigate this association in non-white populations [5], [6], [7].
The purpose of the current analysis was to evaluate the association of ferritin and transferrin saturation levels with all-cause, cardiovascular, and cancer mortality in the general US adult population. To do so, we analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III) Mortality Study, a cohort study based on a nationally representative sample of US adults with ferritin and transferrin saturation measured in 1988–1994 and followed for mortality through December 31, 2006.
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Study population
NHANES III was a stratified, multistage probability survey designed to be representative of the civilian non-institutionalized US population [8]. Overall, 18,825 adults ≥20 years of age completed the NHANES III interview and examination. We excluded 859 participants who were taking iron supplements, 227 pregnant women, 34 participants with likely hemochromatosis (serum iron >190 ug/dL for men and >175 ug/dL for women, serum ferritin >300 ng/mL for men and >200 ng/mL for women, and transferrin
Results
The median (interquartile range) of ferritin and transferrin saturation was 142 ng/mL (87–222 ng/mL) and 28% (21–35%), respectively, for men, 35 ng/mL (18–60 ng/mL) and 22% (15–31%), respectively, for premenopausal women, and 90 ng/mL (51–158 ng/mL) and 23% (18–29%), respectively, for postmenopausal women. Men, premenopausal women, and postmenopausal women with higher ferritin levels were more likely to be non-Hispanic black (except premenopausal women) and had a higher body mass index and
Discussion
In this large, population-based prospective study, higher levels of ferritin and transferrin saturation were not associated with an increased risk of mortality among NHANES III participants without a baseline history of cardiovascular disease or cancer. Among postmenopausal women, lower levels of transferrin saturation were associated with a higher risk of mortality. This finding was not observed in men or premenopausal women, and we cannot discard the possibility that this is either a chance
References (30)
- et al.
Role of free radicals and catalytic metal ions in human disease: an overview
Methods Enzymol
(1990) - et al.
Serum ferritin and death from all causes and cardiovascular disease: the NHANES II mortality study. National health and nutrition examination study
Ann Epidemiol
(2000) - et al.
Calibration of serum creatinine in the national health and nutrition examination surveys (NHANES) 1988–1994, 1999–2004
Am J Kidney Dis
(2007) - et al.
The penetrance of hereditary hemochromatosis
Best Pract Res Clin Haematol
(2005) - et al.
Response to repeated phlebotomies in patients with non-insulin-dependent diabetes mellitus
Metabolism
(1994) - et al.
Dietary iron intake and blood donations in relation to risk of type 2 diabetes in men: a prospective cohort study
Am J Clin Nutr
(2004) - et al.
Observations on the pathogenesis, complications and treatment of diabetes in 115 cases of haemochromatosis
Am J Med
(1972) - et al.
The role of iron in diabetes and its complications
Diabetes Care
(2007) - et al.
Role of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications
Curr Med Chem
(2009) - et al.
Serum ferritin and risk of the metabolic syndrome in U.S. adults
Diabetes Care
(2004)
Elevated serum transferrin saturation and mortality
Ann Fam Med
Body iron stores and mortality due to cancer and ischaemic heart disease: a 17-year follow-up study of elderly men and women
Int J Epidemiol
Plan and operation of the third national health and nutrition examination survey, 1988–94
Vital Health Stat
Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate
Ann Intern Med
National center for health statistics. The third national nutrition and health survey linked mortality file: matching methodology
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