Increased iron status linked to elevated stroke risk

United Kingdom: Higher iron status is associated with an increased risk of stroke, and, in particular, cardioembolic stroke finds a new study published in the journal Stroke.

Iron deficiency and excess, both have been associated with stroke risk in observational studies. Such association, however, may be attributable to confounding from environmental factors. This study conducted by Dipender Gill, Department of Biostatistics and Epidemiology, Imperial College London, United Kingdom, and colleagues, uses the Mendelian randomization technique to overcome these limitations by investigating the association between genetic variants related to iron status and stroke risk.

A study of 48 972 subjects performed by the Genetics of Iron Status consortium identified genetic variants with concordant relations to 4 biomarkers of iron status (serum iron, transferrin saturation, ferritin, and transferrin) that supported their use as instruments for overall iron status.

Genetic estimates from the MEGASTROKE consortium were used to investigate the association between the same genetic variants and stroke risk. The 2-sample ratio method Mendelian randomization approach was used for the main analysis, with the MR-Egger and weighted median techniques used in sensitivity analyses.

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Key Findings:

• The main results, reported as odds ratio (OR) of stroke per SD unit increase in genetically determined iron status biomarker, showed a detrimental effect of increased iron status on stroke risk (serum iron OR, 1.07; 95% CI, 1.01-1.14; [log-transformed] ferritin OR, 1.18; 95% CI, 1.02-1.36; and transferrin saturation OR, 1.06; 95% CI, 1.01-1.11).


• A higher transferrin, indicative of lower iron status, was also associated with decreased stroke risk (OR, 0.92; 95% CI, 0.86-0.99).


• Examining ischemic stroke subtypes, the detrimental effect of iron status was found to be driven by cardioembolic stroke. These results were supported in statistical sensitivity analyses more robust to the inclusion of pleiotropic variants.

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"This study provides Mendelian randomization evidence that higher iron status is associated with increased stroke risk and, in particular, cardioembolic stroke," concluded the authors, adding that, "Further work is required to investigate the underlying mechanism and whether this can be targeted in preventative strategies."

For further reference follow the link: https://doi.org/10.1161/STROKEAHA.118.022701