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(Circulation. 1999;100:1260-1263.)
© 1999 American Heart Association, Inc.

Editorial

Iron and the Genetics of Cardiovascular Disease

Jerome L. Sullivan, MD, PhD

From the Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Fla.

Correspondence to Dr Jerome L. Sullivan, PO Box 2661, Winter Park, FL 32790. E-mail jlsullivan@pol.net

Key Words: Editorials • iron • epidemiology • myocardial infarction • coronary disease

	Introduction

 
The hypothesis that iron depletion protects against ischemic heart disease was proposed in 1981 as an explanation for the sex difference in heart disease rates.^{1 2 3 4 5} The "iron hypothesis" has generated significant debate, especially in the 1990s after publication of supportive findings from Finland.⁶ Confusion has been introduced into the debate by inappropriate study designs in tests of the hypothesis. A recurring weakness is that stored iron is measured by inappropriate methods. In addition, evidence against a particular mechanism may be erroneously taken as evidence against the core hypothesis. For example, in a particular study design, a finding of no association of stored iron with coronary atherosclerosis would not invalidate an association of stored iron with cardiovascular mortality. Recent studies relevant to the iron hypothesis have been reviewed.^{5 7 8 9 10 11 12}

In 1994, Ascherio and Willett¹³ recognized that the iron hypothesis cannot be rejected on the basis of available data, stating that "[s]tronger evidence is needed before the hypothesis is rejected that greater iron stores increase the incidence of coronary heart disease or death from myocardial infarction." Indeed, nothing in data made available since 1994 excludes the possibility that iron depletion has a large protective effect, large enough to explain the low incidence of myocardial infarction in menstruating women.

A 1997 editorial¹⁴ on the iron hypothesis suggests that this once-controversial idea has become more acceptable to many scientists. Gillum¹⁴ noted that "this important hypothesis and related research fronts have led to many valuable studies like that of Kiechl et al [see Reference 9⁹ ], . . . [Full Text of this Article]

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