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Iron stores and HFE genotypes are not related to increased risk of ischemic stroke.: 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 Odontology, Cariology.
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2007 (English)In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 24, no 5, 405-411 p.Article in journal (Refereed) Published
Abstract [en]

Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke.

Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting.

Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke.

Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

Place, publisher, year, edition, pages
2007. Vol. 24, no 5, 405-411 p.
Keyword [en]
Adult, Aged, Anthropometry, Cardiovascular Diseases/*etiology/genetics, Europe, Female, Humans, Life Style, Male, Middle Aged, Nutritional Status, Prospective Studies, Questionnaires
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-16977DOI: 10.1159/000108429PubMedID: 17878720OAI: oai:DiVA.org:umu-16977DiVA: diva2:156650
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2017-12-14Bibliographically 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)
Opponent
Supervisors
Available from: 2010-05-07 Created: 2010-05-05 Last updated: 2016-08-19Bibliographically approved

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Cerebrovascular Diseases
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