Correlates of serum hepcidin levels and its association with cardiovascular disease in an elderly general population

Raimund Pechlaner, Stefan Kiechl, Manuel Mayr, Peter Santer, Siegfried Weger, David Haschka, Sukhvinder S. Bansal, Johann Willeit, Günter Weiss

The expression of the key iron regulatory hormone hepcidin is regulated by iron availability, inflammation, hormones, hypoxia, and anaemia. Increased serum concentrations of hepcidin have recently been linked to atherosclerosis. We studied demographic, haematologic, biochemical, and dietary correlates of serum hepcidin levels and its associations with incident cardiovascular disease and with carotid atherosclerosis. Serum hepcidin concentrations were measured by tandem mass spectrometry in samples taken in 2000 from 675 infection-free participants of the prospective population-based Bruneck study (age, mean±standard deviation, 66.0±10.2; 48.1% male). Blood parameters were measured by standard methods. Dietary intakes of iron and alcohol were surveyed with a food frequency questionnaire. Carotid atherosclerosis (365 cases) was assessed by ultrasound and subjects were observed for incident stroke, myocardial infarction, or sudden cardiac death (91 events) until 2010. Median (interquartile range) hepcidin levels were 2.27 nM (0.86, 4.15). Most hepcidin correlates were in line with hepcidin as an indicator of iron stores. Independently of ferritin, hepcidin was related directly to physical activity (p=0.024) and fibrinogen (p<0.0001), and inversely to alcohol intake (p=0.006), haemoglobin (p=0.027), and γ-glutamyltransferase (p<0.0001). Hepcidin and hepcidin-to-ferritin ratio were not associated with prevalent carotid atherosclerosis (p=0.43 and p=0.79) or with incident cardiovascular disease (p=0.62 and p=0.33). In this random sample of the general community, fibrinogen and γ-glutamyltransferase were the most significant hepcidin correlates independent of iron stores, and hepcidin was related to neither atherosclerosis nor cardiovascular disease.