Iron Stores and HFE Genotypes Are Not Related to Increased Risk of Ischemic Stroke

Abstract

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.

Iron stores and HFE genotypes are not related to increased risk of first-time myocardial infarction ☆

“…Our findings on previously healthy subjects are contradictory to the findings of a Canadian cohort study which included fatal myocardial infarction only [7]. Consistent with our previous finding on stroke [19], we found a lower risk in the highest transferrin iron saturation quartile among men. The lack of risk association between ferritin and myocardial infarction is consistent with most other studies on cardiovascular disease [20,21] and on myocardial infarction [13].…”

“…The methods are described in detail in the supplement. TaqMan allelic discrimination methodology was used for genotyping C282Y and H63D in the HFE gene using equipment and assays from Applied Biosystems (Foster City, CA, USA), as previously described [19].…”

Heme Iron Intake and Risk of Stroke

“…21 In one prospective study, there was a statistically significant inverse association between total iron intake and risk of ischemic stroke, 23 but not in other. 22 There are also a few prospective studies [32][33][34] and studies of stroke patients [35][36][37] relating iron status in blood to risk of stroke. Most of those studies, 32,33,[35][36][37] but not all, 34 indicate a positive association between serum ferritin levels and risk of stroke.…”

Bilirubin and UGT1A1*28 Are Not Associated with Lower Risk for Ischemic Stroke in a Prospective Nested Case-Referent Setting

“…High sensitive C-reactive protein (hsCRP) was determined with an automated method, Immulite 1 (Diagnostic Products Corp., Los Angeles, Calif., USA). These assays have been previously described [13]. Total homocysteine in plasma was measured with an IMx® unit (Abbott Laboratories, Abbott Park, Ill., USA) [14].…”