Higher iron linked to increased stroke risk

A new study published in the journal Stroke has found that people with high levels of iron are associated with an increased risk of stroke and, in particular, cardioembolic stroke.

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. Dipender Gill, Imperial's School of Public Health, UK, and colleagues conducted the study to overcome these limitations by investigating the association between genetic variants related to iron status and stroke risk by using Mendelian randomization technique.

For the study, the researchers analyzed genetic data from over 48,000 people. 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.

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, we found the detrimental effect of iron status to be driven by cardioembolic stroke.

The study 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 traveling 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 heartbeat and affects around one million people in the UK.

"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," said Dr. Gill.

"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." added Dr. Gill.

"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."

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.

"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," concluded the authors.

For further reference log on to https://www.ahajournals.org/doi/abs/10.1161/STROKEAHA.118.022701