Iron pill: An answer to stave off heart disease?

Having functional iron deficiency (FID) in mid-life puts one at higher risk of developing coronary heart disease (CHD) and death in later life, according to a large cohort study — indicating that these adverse events could have been avoided by preventing iron deficiency.

“Therefore, iron supplementation might be an option to address the early prevention of cardiovascular disease [CVD] in the general population. This has potential for clinical benefit, as oral iron supplementation is already recognized as a low-cost intervention in older individuals,” said the researchers.

The study included 12,164 individuals (median age 59 years, 55 percent women) from three European population-based cohorts. Participants with absolute ID (AID) were identified based on ferritin levels of <100 μg/L or <30 μg/L (severe AID), and functional ID (FID) was defined as ferritin <100 μg/L or ferritin 100–299 μg/L and transferrin saturation <20 percent. [ESC Heart Fail 2021;doi:10.1002/ehf2.13589]  

At baseline, AID was detected in 60 percent of participants and FID in 64 percent. 

“The study showed that iron deficiency was highly prevalent in this middle-aged population, with nearly two-thirds having functional iron deficiency,” said lead author Dr Benedikt Schrage from the University Heart and Vasculature Centre Hamburg in Hamburg, Germany.

Over a median follow-up duration of 13.3 years, 2,212 participants (18.2 percent) had died — of which 573 cases (4.7 percent) were due to a CV cause.

Among people with FID, the risk of CHD was 24 percent higher (hazard ratio [HR], 1.24; p<0.01) than those without.

Also, individuals with FID had 26 percent (HR, 1.26; p=0.03) and 12 percent (HR, 1.12; p=0.03) increased risk of CV death and all-cause death, respectively.

While AID was associated with a 20 percent excess risk of CHD (HR, 1.20; p=0.01), there was no association with all-cause mortality. Severe form of AID was associated with greater risk of all-cause death (HR, 1.28; p<0.01), but not with CV mortality or CHD.

“These findings indicate that FID, but not AID or severe AID, is an important risk factor for CVD and mortality at the general population level,” Schrage and co-authors pointed out.

Over the course of the study, 10.7 percent of incident CHD, 11.7 percent of CV deaths, and 5.4 percent of all deaths were attributable to FID, and thus could have been prevented if FID was absent.

“Given the high prevalence of FID in this study, food fortification programmes might also be an option to provide a nation-wide amelioration of iron deficiency,” suggested Schrage and co-authors. “Additionally, the newer forms of intravenous iron could be targeted towards individuals at high risk/with a high level of iron deficiency.”

As the study is observational in nature, no causal relationship between iron deficiency and CVD can be drawn.   

“However, evidence is growing that there is a link and these findings provide the basis for further research to confirm the results,” said Schrage. “If the relationships are confirmed, the next step would be a randomised trial investigating the effect of treating iron deficiency in the general population.”