Title

Current Status Of The Iron Hypothesis Of Cardiovascular Diseases

Keywords

Cardiovascular diseases; Ferritin; Hepcidin; Iron

Abstract

More than 25 years ago, the iron hypothesis proposed that a state of sustained iron depletion or mild iron deficiency exerts a primary protective action against ischemic heart disease. Iron depletion leads to a decreased availability of redox-active iron in vivo. The amount of free iron available at sites of oxidative or inflammatory injury appears to be a function of the stored iron level. Depletion of iron levels by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduce atherosclerotic lesion size and increase plaque stability. In homozygous hemochromatosis there is commonly a defect that inhibits iron retention in macrophages. This defect may explain why atherosclerotic lesions appear to be less prevalent in this disorder. Findings of the "FeAST" trial have been recently reported. The trial assessed the potential benefit of mild iron reduction therapy in secondary prevention of cardiovascular disease. It was therefore not a fully valid test of primary prevention as postulated by the iron hypothesis. However, although no overall statistically significant cardiovascular benefit was found, in the youngest quartile at entry there were highly significant reductions in all cause mortality and in combined death plus non-fatal myocardial infarction and stroke in association with iron reduction therapy. The FeAST trial adds urgency to the initiation of new studies to assess the impact of maintenance of complete iron depletion in the primary prevention of cardiovascular diseases.

Publication Date

7-1-2007

Publication Title

Recenti Progressi in Medicina

Volume

98

Issue

7-8

Number of Pages

373-377

Document Type

Review

Personal Identifier

scopus

Socpus ID

34250882313 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/34250882313

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