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Iron stores and HFE genotypes are not related to increased risk of first-time myocardial infarction: a prospective nested case-referent study
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.ORCID iD: 0000-0003-2844-1310
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.ORCID iD: 0000-0001-9581-3845
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2011 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 150, no 2, 169-172 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: Our objectives were to study the relationship between iron stores, HFE genotypes and the risk for first-ever myocardial infarction.

Methods: First-ever myocardial infarction cases (n=618) and double matched referents from the Northern Sweden Health and Disease Cohort Study were studied in a prospective nested case-referent setting. Plasma iron, total iron binding capacity, transferrin iron saturation and ferritin were analyzed, as well as several confounders. HFE C282Y and H63D genotypes were determined.

Results: There was an inverse risk association for myocardial infarction in the highest quartiles of iron (OR 0.68; 95% CI 0.48-0.96) and transferrin iron saturation (OR 0.62; 95% CI 0.42-0.89) in men. This association, however, was lost after adjusting for C-reactive protein. Women homozygous for H63D had a higher risk for myocardial infarction.

Conclusions: No risk association between high iron stores and first-ever myocardial infarction was found. The higher risk in female H63D homozygotes is probably not related to iron metabolism.

Place, publisher, year, edition, pages
2011. Vol. 150, no 2, 169-172 p.
Keyword [en]
myocardial infarction, iron, ferritin, HFE, prospective
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Clinical Chemistry
Identifiers
URN: urn:nbn:se:umu:diva-33750DOI: 10.1016/j.ijcard.2010.04.001PubMedID: 20447705OAI: oai:DiVA.org:umu-33750DiVA: diva2:317807
Available from: 2010-05-05 Created: 2010-05-05 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Oxidants and antioxidants in cardiovascular disease
Open this publication in new window or tab >>Oxidants and antioxidants in cardiovascular disease
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

Cardiovascular diseases, including myocardial infarction and stroke, are the main reason of death in Sweden and Western Europe. High iron stores are believed to produce oxygen radicals, which is the presumed putative mechanism behind lipid peroxidation, atherosclerosis and subsequent cardiovascular disease. Iron levels are associated with the hemochromatosis associated HFE single nucleotide polymorphisms C282Y and H63D.

Bilirubin is an antioxidant present in relatively high levels in the human body. Several previous studies have found an association between high bilirubin levels and a lower risk for cardiovascular disease. Bilirubin levels are highly influenced by the common promoter polymorphism TA-insertion UGT1A1*28, the main reason for benign hyperbilirubinemia in Caucasians.

There is a lack of prospective studies on both the association of iron and bilirubin levels, and the risk for myocardial infarction and ischemic stroke.

Material and methods

Iron, transferrin iron saturation, TIBC, ferritin and bilirubin were analyzed and HFE C282Y, HFE H63D and UGT1A1*28 were determined in myocardial infarction and stroke cases, and their double matched referents within the Northern Sweden Health and Disease Study Cohort.

Results

There were no associations between iron levels in the upper normal range and risk for myocardial infarction or stroke. No associations were seen for HFE-genotypes, except for a near fivefold increase in risk for myocardial infarction in HFE H63D homozygous women.

Plasma bilirubin was lower in cases vs. referents both in the myocardial infarction and the stroke cohort. Despite a strong gene-dosage effect on bilirubin levels in both cases and referents, the UGT1A1*28 polymorphism did not influence the risk for myocardial infarction or stroke.

Conclusion

High iron stores are not associated with increased risk for neither myocardial infarction, nor stroke. There was no association between UGT1A1*28 and the risk for myocardial infarction or stroke. Consequently data suggests that other factors, which also may lower bilirubin, are responsible for the elevated risk observed in conjunction with lower bilirubin levels.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2010. 86 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1339
Keyword
first-ever acute myocardial infarction, first-ever stroke, bilirubin, iron, HFE genotypes, UGT1A1*28, prospective, risk factor
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Clinical Chemistry
Identifiers
urn:nbn:se:umu:diva-33762 (URN)978-91-7264-961-3 (ISBN)
Public defence
2010-05-28, Betula, Byggnad 6M, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
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Available from: 2010-05-07 Created: 2010-05-05 Last updated: 2016-08-19Bibliographically approved

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