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Cited by 93Iron Metabolism and DisordersAntioxidant Activity and Oxidative StressTrace Elements in Health

The iron hypothesis of atherosclerosis and its clinical impact

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Yuan, Xi‐Ming, Li, Wei·2003·Annals of Medicine
DOI 10.1080/07853890310016342
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Abstract

The iron hypothesis as an alternative explanation for the gender difference in the incidence and mortality of atherosclerosis has provoked increased debates and public health concerns. In this review we summarize the historical and recent literature on the iron hypothesis and discuss several related clinical issues and their implications. Apart from misconstruction of study populations, lack of a good method to reflect the iron contents of tissues may be the major factor for causing inconsistent results from epidemiological studies. Published data from 11 countries clearly indicate that the mortality from cardiovascular diseases is correlated with liver iron. We propose that redox-active iron in tissue is the atherogenic portion of total iron stores. Recently developed magnetic resonance imaging techniques in combination with Fe chelators may allow future studies to examine this component of body iron in lesions and the whole body. Several clinical situations characterized by increased iron stores have been proposed as 'human models' suitable for further tests of the iron hypothesis. Patients with end-stage renal disease may be the most unique cohort, having significant increases in their iron stores, low-density lipoprotein (LDL) oxidation, and cardiovascular events. Other patient groups may be well suited for specific studies of different atherogenic events. With a better understanding of iron-driven oxidative damage, well controlled and effectively designed studies on these models will finally bring us to the truth of the iron hypothesis.

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  • The identification of iron accumulation in macrophages as the prime event in the complex pathogenesis of CVUs is also of major relevance for other chronic inflammatory disorders with enhanced iron storage in macrophages, like arteriosclerosis, multiple sclerosis, and other neurodegenerative diseases.

    “The identification of iron accumulation in macrophages as the prime event in the complex pathogenesis of CVUs eventually driving persistent inflammation and tissue damage is also of major relevance for other chronic inflammatory disorders with enhanced iron storage in macrophages, like arteriosclerosis, multiple sclerosis, and other neurodegenerative diseases (79-82).”

    From An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice (2011) · cites this paper as [82]

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  • The iron hypothesis proposes that benefits of some iron depletion due to menstruation account for the lowering of heart-disease risk in young women that disappears in postmenopausal women.

    “The “iron hypothesis” of the benefits of some iron depletion due to menstruation was devised to account for the lowering of heart-disease risk in young women that disappears in those who are postmenopausal [131, 132].”

    From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [132]

  • Mild iron deficiency has been associated with protection against certain inflammatory and infectious conditions.

    “Mild ID has been associated with protection against certain inflammatory and infectious conditions.”

    From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [132]

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Authors
Yuan, X., & Li, W.
Affiliations
Linköping University (SE)
Corresponding author
Yuan, Xi‐Ming
ORCID
Venue
Annals of Medicine
Publisher
Informa UK Limited
Published
2003-01
Volume
35
Issue
8
Pages
578-591
ISSN
  • 0785-3890 (ISSN-L)
  • 1365-2060
DOI
10.1080/07853890310016342
OpenAlex
W2082143883
Cited by
93
References
59
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 7
FWCI
0.48
Type
journal article
Language
en
Open access
Locations
  • Annals of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical Research Council
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
iron hypothesis, atherosclerosis, sex differences, liver iron, iron stores, redox-active iron, oxidative damage, cardiovascular mortality, end-stage renal disease, LDL oxidation, magnetic resonance imaging, iron chelators, epidemiological study design
MeSH terms
Arteriosclerosis, Clinical Trials as Topic, Humans, Iron, Oxidation-Reduction, Sex Characteristics, Iron Overload

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