Iron Status Influences Cardioembolic Stroke Risk

A new genetic study provides evidence that higher iron status is associated with increased stroke risk, and particularly cardioembolic stroke.

Researchers at Imperial College London (Imperial; United Kingdom) and St. Mary’s Hospital (London, United Kingdom) conducted a study involving 48,972 subjects to identify genetic variants with concordant relations to four biomarkers of iron status (serum iron, transferrin saturation, ferritin, and transferrin) that supported their use as instruments for overall iron status. The researchers then estimated associations between the same genetic variants and stroke risk, using a Mendelian randomization approach.


The results revealed a detrimental effect of increased levels of the iron status biomarkers serum iron, transferrin saturation, and ferritin on stroke risk. Similarly, a higher transferrin level, indicative of lower iron status, was associated with decreased stroke risk. When examining ischemic stroke subtypes, the researchers found the negative effect of iron status prejudiced cardioembolic stroke, a result supported in statistical sensitivity analyses more robust to the inclusion of pleiotropic variants. The study was published on October 25, 2018, in Stroke.

“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 lead author Dipender Gill, PhD, of Imperial. “Iron is a vital nutrient, essential for a number of biological processes in the body, including transporting oxygen. Previous research has suggested that in some cases iron can actual trigger blood to form a clot. This now needs further investigation.”

“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,” concluded 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. As we help unravel this further, it will give us a better picture of how to protect patients from stroke.”

The regulation of iron metabolism involves the interaction of a number of specific proteins as well as the interplay between iron absorption, recycling, and iron loss. The main players in this balancing act include transferrin, the plasma iron transport protein; a transferrin cellular receptor for iron-bound transferrin; and ferritin, the cellular iron storage protein. A tight regulation of iron balance is essential to avoid both iron deficiency and overload.

Related Links:
Imperial College London
St. Mary’s Hospital