Increased iron stores prolong the QT interval – a general population study including 20 261 individuals and meta-analysis of thalassaemia major

Abstract

The prolongation of cardiac repolarization (QT interval) has been investigated in studies of patients with secondary iron overload. However, no previous population-based study examining the effect of increased iron stores on QT interval prolongation has previously been undertaken. We tested the hypothesis that increased iron stores and haemochromatosis genotype (genetically increased iron stores) are associated with prolongation of the QT interval. We included 20 261 individuals from the Danish General Suburban Population Study and examined differences in QT interval according to ferritin concentration, transferrin saturation, iron concentration, transferrin concentration and haemochromatosis genotype (C282Y/C282Y). Furthermore, we performed a meta-analysis of case-control studies on thalassaemia major patients and QT interval. Age- and C-reactive protein-adjusted mean corrected QT (QTc) intervals for ferritin concentration ≥99% vs. ≥25–<50% percentile were 418·9 ms vs. 412·7 ms in men (P < 0·001) and 422·4 ms vs. 419·1 ms in women (P = 0·78). Corresponding values for transferrin saturation were 417·6 ms vs. 412·6 ms in men (P = 0·02) and 421·5 ms vs. 419·4 ms in women (P = 0·86). The associations were not explained by inflammation and haemochromatosis genotype was not associated with QT interval length. In conclusion, increased iron stores, independent of haemochromatosis genotype and inflammation, are associated with prolongation of the QTc interval in men. This is a novel finding. In addition, the meta-analysis showed prolonged QT interval in thalassaemia major patients compared to healthy controls.