Oxidants and antioxidants in cardiovascular disease
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
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.
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.
Umeå University medical dissertations, ISSN 0346-6612 ; 1339
first-ever acute myocardial infarction, first-ever stroke, bilirubin, iron, HFE genotypes, UGT1A1*28, prospective, risk factor
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Research subject Clinical Chemistry
IdentifiersURN: urn:nbn:se:umu:diva-33762ISBN: 978-91-7264-961-3OAI: oai:DiVA.org:umu-33762DiVA: diva2:317907
2010-05-28, Betula, Byggnad 6M, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Breimer, Lars, docent
Hultdin, Johan, docentMarklund, Stefan L, professor
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