Oxidants and antioxidants in cardiovascular disease
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 card...
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Umeå universitet, Klinisk kemi
2010
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ndltd-UPSALLA1-oai-DiVA.org-umu-337622016-08-20T05:06:02ZOxidants and antioxidants in cardiovascular diseaseengEkblom, KimUmeå universitet, Klinisk kemiUmeå : Umeå University2010first-ever acute myocardial infarctionfirst-ever strokebilirubinironHFE genotypesUGT1A1*28prospectiverisk factorCardiovascular medicineKardiovaskulär medicinEpidemiologyEpidemiologiBackground 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. Doctoral thesis, comprehensive summaryinfo:eu-repo/semantics/doctoralThesistexthttp://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33762urn:isbn:978-91-7264-961-3Umeå University medical dissertations, 0346-6612 ; 1339application/pdfinfo:eu-repo/semantics/openAccess |
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English |
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Doctoral Thesis |
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first-ever acute myocardial infarction first-ever stroke bilirubin iron HFE genotypes UGT1A1*28 prospective risk factor Cardiovascular medicine Kardiovaskulär medicin Epidemiology Epidemiologi |
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first-ever acute myocardial infarction first-ever stroke bilirubin iron HFE genotypes UGT1A1*28 prospective risk factor Cardiovascular medicine Kardiovaskulär medicin Epidemiology Epidemiologi Ekblom, Kim Oxidants and antioxidants in cardiovascular disease |
description |
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. |
author |
Ekblom, Kim |
author_facet |
Ekblom, Kim |
author_sort |
Ekblom, Kim |
title |
Oxidants and antioxidants in cardiovascular disease |
title_short |
Oxidants and antioxidants in cardiovascular disease |
title_full |
Oxidants and antioxidants in cardiovascular disease |
title_fullStr |
Oxidants and antioxidants in cardiovascular disease |
title_full_unstemmed |
Oxidants and antioxidants in cardiovascular disease |
title_sort |
oxidants and antioxidants in cardiovascular disease |
publisher |
Umeå universitet, Klinisk kemi |
publishDate |
2010 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33762 http://nbn-resolving.de/urn:isbn:978-91-7264-961-3 |
work_keys_str_mv |
AT ekblomkim oxidantsandantioxidantsincardiovasculardisease |
_version_ |
1718378934699032576 |