Higher Iron Levels Linked to Increased Stroke Risk

Summary: Analyzing genetic data from over 48,000 people, researchers discovered higher iron levels are associated with an increased risk of cardioembolic stroke.

Source: Imperial College London.

People with higher iron levels may be at greater risk of certain types of stroke, a new study has found.

Researchers from Imperial College London analysed genetic data from over 48,000 people and revealed that higher iron levels are associated with an elevated risk of a certain type of stroke, called a cardioembolic stroke. These strokes are typically caused by blood clots travelling from the heart to the brain, and blocking blood and oxygen supply. They are often associated with a type of heart condition called atrial fibrillation, which causes an irregular heart beat and affects around one million people in the UK.

The findings, published in the journal Stroke, follows previous research that suggests that iron may protect against stroke and coronary artery disease.

Dr Dipender Gill, who is lead author of the study from Imperial’s School of Public Health, said: “This result was unexpected. It was previously thought higher iron levels might protect against stroke, but this study investigates this further to find that iron may actually increase the risk of some types of stroke.”

Dr Gill, funded by the Wellcome 4i Clinical PhD Programme at Imperial College London, added that although the research is at too early a stage to recommend people assess their own iron intake, the work suggests further studies are now needed to investigate why iron may lead to increased risk: “Iron is a vital nutrient, essential for a number of biological processes in the body, including transporting oxygen. However, previous research has suggested that in some cases iron can actual trigger blood to form a clot. This now needs further investigation.”

Genetic clues

The research team investigated the link between iron and stroke using a statistical method called Mendelian Randomization. Using genetic data from public databases, the team searched through data for more than 48,000 people to work out the impact of genetics on people’s iron status. They focused on three points in the genome where a single ‘letter’ difference in the DNA – called a single nucleotide polymorphism (SNP) – can slightly increase or reduce a person’s iron status.

When the researchers searched for these same SNPs in datasets including more than 60,000 stroke patients, they found that those with the SNPs for higher iron status had a higher risk of cardioembolic stroke.

However, the researchers caution against anyone reducing their iron intake, and explain the next step would be to validate the findings in further study.

Preventative treatments

“This is an early-stage finding, and we would certainly not recommend that patients at risk of stroke reduce their iron intake, as it has many crucial roles in the body,” explained Dr Gill. “However, our research does suggest doctors and scientists should now work towards further studies that investigate iron levels on the risk of different types of stroke, and cardiovascular disease more generally.”

The research team, including Dr Abbas Dehghan and Dr Ioanna Tzoulaki at Imperial College London’s School of Public Health, also used the same statistical technique to investigate other factors that may affect stroke risk.

Their work revealed people who have a naturally high number of cells called platelets, which are crucial to blood clotting and help to prevent bleeding, may have a higher risk of ischaemic stroke, which are caused by clots blocking blood supply to the brain.

a brain
When the researchers searched for these same SNPs in datasets including more than 60,000 stroke patients, they found that those with the SNPs for higher iron status had a higher risk of cardioembolic stroke. NeuroscienceNews.com image is adapted from the Imperial College London news release.

Other work also suggested people with lower levels of a substance that helps the blood to clot, called Factor XI, may have a lower risk of cardioembolic stroke. Researchers are currently investigating new treatments that help reduce the risk of stroke by cutting levels of Factor XI, and these new findings confirm that these types of drugs may hold promise.

Dr Gill added: “All these findings highlight potential treatments or lifestyle interventions that may help reduce stroke risk, and that they may offer avenues for further study.

“Stroke is the second leading cause of death worldwide and causes around 32,000 deaths every year in the UK. But the disease is complicated – we now know that there are many distinct types, each with different causes. As we help unravel this further, it will give us a better picture of how to protect patients from stroke.”

About this neuroscience research article

Source: Kate Wighton – Imperial College London
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the Imperial College London news release.
Original Research: Abstract for “Iron Status and Risk of Stroke” by Dipender Gill, Grace Monori, Ioanna Tzoulaki,and Abbas Dehghan in Stroke. Published October 25 2018.

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Imperial College London”Higher Iron Levels Linked to Increased Stroke Risk.” NeuroscienceNews. NeuroscienceNews, 29 October 2018.
<https://neurosciencenews.com/iron-levels-stroke-10107/>.[/cbtab][cbtab title=”APA”]Imperial College London(2018, October 29). Higher Iron Levels Linked to Increased Stroke Risk. NeuroscienceNews. Retrieved October 29, 2018 from https://neurosciencenews.com/iron-levels-stroke-10107/[/cbtab][cbtab title=”Chicago”]Imperial College London”Higher Iron Levels Linked to Increased Stroke Risk.” https://neurosciencenews.com/iron-levels-stroke-10107/ (accessed October 29, 2018).[/cbtab][/cbtabs]


Iron Status and Risk of Stroke

Background and Purpose—
Both iron deficiency and excess have been associated with stroke risk in observational studies. However, such associations may be attributable to confounding from environmental factors. This study 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.

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

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

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