(Circulation. 1999;99:852-854.)
© 1999 American Heart Association, Inc.
Brief Rapid Communication |
Coronary Heart Disease and Iron Status
Meta-Analyses of Prospective Studies
From the Clinical Trial Service Unit and Epidemiological Studies Unit (J.D.), Nuffield Department of Clinical Medicine, University of Oxford, and Imperial Cancer Research Fund Cancer Epidemiology Unit (P.A.), Radcliffe Infirmary, Oxford OX2 6HE, UK.
Correspondence to Dr John Danesh, CTSU, Radcliffe Infirmary, Oxford OX2 6HE, UK. E-mail john.danesh{at}balliol.ox.ac.uk
Background—Studies of iron status and coronary heart disease (CHD) have yielded conflicting results. In a systematic review ("meta-analysis"), we quantitatively assessed epidemiological associations reported in prospective studies.
Methods and Results—Studies were identified by computer-assisted
searches of the published literature, scanning of relevant reference
lists, hand searching of relevant journals, and discussions with
relevant authors. The following was abstracted: size and type of
cohort, mean age, mean duration of follow-up, assay methods, degree of
adjustment for confounders, and relationship of CHD risk to the
baseline assay results. Twelve studies were identified, involving a
total of 7800 CHD cases, with several reporting on >1 marker of iron
status. For serum ferritin, with 570 CHD cases in 5 studies, comparison
of individuals with baseline values 
200 versus <200 µg/L yielded a
combined risk ratio of 1.0 (95% CI, 0.8 to 1.3). For transferrin
saturation, with 6194 CHD cases in 5 studies, comparison of individuals
in the top third with those in the bottom third of the baseline
measurements yielded a combined risk ratio of 0.9 (95% CI, 0.7 to
1.1). Comparisons of individuals in top and bottom thirds of baseline
measurements also yielded nonsignificant risk ratios in combined
analyses of studies involving total iron-binding capacity
(combined risk ratio, 1.0; 95% CI, 0.7 to 1.5), serum iron (0.8; 95%
CI, 0.7 to 1.0), and total dietary iron (0.8; 95% CI, 0.7 to 1.1).
Conclusions—Published prospective studies do not provide good evidence to support the existence of strong epidemiological associations between iron status and CHD.
Key Words: epidemiology • coronary disease • iron • meta-analysis
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
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|
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|
|
|
|
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|
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