Iron Levels Associated with Lower Cholesterol, Increased Stroke Risk

Results of a recent study are giving physicians a better idea of the positive, but possibly harmful impact of high iron levels play in a myriad of diseases.

Investigators from the Imperial College London found that naturally high levels of iron were associated with a lower risk of high cholesterol levels and reductions in atherosclerosis, but these same high levels were also associated with increased risk of stroke. 



"These studies reveal new avenues of research, and present many questions. We are still unclear on how iron affects cholesterol levels, narrows arteries and form blood clots, but we have ideas,” said lead investigator Dipender Gill, MD, of the Imperial College London. 



In order to better understand the role of systemic iron status, investigators conducted a Mendelian randomization to examine the effect of genetically determined iron status on carotid intima-media thickness, carotid plaque, and venous thromboembolism. To proxy iron status, investigators obtained single-nucleotide polymorphisms from a genome-wide association study meta-analysis performed by the Genetics of Iron Status consortium that combined data from 48,792 subjects of European descent. As increased iron is associated with increased serum iron, transferrin saturation, and ferritin and with decreased transferrin, investigators used these markers as proxies for systemic iron status.

Investigators used 12 studies that incorporated 7507 cases of VTE and 52,632 controls were used for estimates of VTE. Genetic association estimates for carotid intimal-media thickness and carotid plaque were obtained using data from 71,128 and 48,434 participants.

Investigators performed a conventional 2-sample summary data Mendelian randomization for their main analysis. Upon analyses, investigators found that higher genetically determined iron status was associated with an increased risk of VTE. Investigators noted that OR per SD increase in biomarker feels were as follows: 1.37 (95% CI 1.14-1.66) for serum iron, 1.25 (1.09-1.43) for transferrin saturation, 1.92 (1.28-2.88) for ferritin, and 0.76 (0.63-0.92) for serum transferrin.

Conversely, investigators found that increased levels of iron were also associated with a lower risk of carotid plaque. Odds ratios were 0.85 (0.73- 0.99) for serum iron and 0.89 (0.80-1.00) for transferrin saturation. Investigators noted that concordant trends for serum transferrin and ferritin that but they did not reach statistical significance.

Additionally, no mendelian randomization evidence of an effect of iron status on carotid into-media thickness. Gill noted that while there is still more to investigate, the study’s findings support further study into possible associations. 


“One possibility is that the lower cholesterol levels may be linked to the reduced risk of arteries becoming furred,” Gill explained. “Furthermore, higher iron levels may cause blood clots to arise when flow is reduced, possibly explaining the increased chance of clots."

This study, “Effects of Genetically Determined Iron Status on Risk of Venous Thromboembolism and Carotid Atherosclerotic Disease: A Mendelian Randomization Study,” is published in the Journal of the American Heart Association.