Iron stores and HFE genotypes are not related to increased risk of ischemic stroke. A prospective nested case-referent study.
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.
Ekblom
Kim
K
Clinical Chemistry, Department of Medical Biosciences, Umeå University, Umeå, Sweden. kim.ekblom@medbio.umu.se
Hultdin
Johan
J
Stegmayr
Birgitta
B
Johansson
Ingegerd
I
Van Guelpen
Bethany
B
Hallmans
Goran
G
Weinehall
Lars
L
Johansson
Lars
L
Wiklund
Per-Gunnar
PG
Marklund
Stefan L
SL
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000097:blood / Q000150:complications* / Q000235:genetics; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000097:blood / Q000150:complications* / Q000235:genetics; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease; D006306:Health Surveys; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood*; D033862:Iron-Binding Proteins / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000097:blood* / Q000235:genetics*; D011795:Surveys and Questionnaires; D013548:Sweden; D014168:Transferrin / Q000378:metabolism
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron