Introduction-Hepcidin is the homeostatic hormone that controls iron status. Its regulation by inflammation, primarily interleukin IL-6, underpins iron deficiency of chronic disease. Iron deficiency is a recognised co-morbidity in chronic and acute heart disease. While hepcidin and iron status have been characterised in chronic heart failure, little is known about how they change in acute heart events. To address this gap in knowledge, we conducted a sub-study of ASSAIL-MI: a randomised double-blinded placebo-controlled trial of the effect of IL-6R antagonist tocilizumab in patients with acute ST-elevation myocardial infarction (STEMI)1.
Methods- 200 patients with first-time STEMI presenting within 6 hours of the onset of chest pain were randomised to receive tocilizumab or matching placebo prior to percutaneous coronary intervention (PCI). Plasma hepcidin, IL-6, serum iron, transferrin saturation (Tsat) and Haemoglobin were measured at baseline, then 1 day, 3-7 days, 3 months and 6 months post infusion. Mixed effect modelling was implemented, controlling for the multiple measurements by patient as random intercept, and examining up to three-way interactions.
Results- STEMI was followed by a rapid rise from baseline in plasma hepcidin in the placebo group, whereas hepcidin levels decreased in the Tocilizumab group during the same interval. In both groups, plasma hepcidin levels returned to baseline values by 3 months. Plasma hepcidin levels correlated with IL-6 and the size of the myocardial area at risk in the placebo but not the tocilizumab group. STEMI was immediately followed by a decrease in serum iron, Tsat and haemoglobin, but only in the placebo group.
Conclusions- STEMI causes an acute rise in hepcidin, and corresponding decrease in plasma iron availability. IL-6 and myocardial injury likely drive these changes. The impact of these changes on clinical outcomes, on the benefits or otherwise of tocilizumab and on the management of iron status must be examined.