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- Title
Hepcidin-25 is related to cardiovascular events in chronic haemodialysis patients.
- Authors
van der Weerd, Neelke C.; Grooteman, Muriel P.C.; Bots, Michiel L.; van den Dorpel, Marinus A.; den Hoedt, Claire H.; Mazairac, Albert H.A.; Nubé, Menso J.; Penne, E. Lars; Wetzels, Jack F.M.; Wiegerinck, Erwin T.; Swinkels, Dorine W.; Blankestijn, Peter J.; ter Wee, Piet M.
- Abstract
Background The development of atherosclerosis may be enhanced by iron accumulation in macrophages. Hepcidin-25 is a key regulator of iron homeostasis, which downregulates the cellular iron exporter ferroportin. In haemodialysis (HD) patients, hepcidin-25 levels are increased. Therefore, it is conceivable that hepcidin-25 is associated with all-cause mortality and/or fatal and non-fatal cardiovascular (CV) events in this patient group. The aim of the current analysis was to study the relationship between hepcidin-25 and all-cause mortality and both fatal and non-fatal CV events in chronic HD patients. Methods Data from 405 chronic HD patients included in the CONvective TRAnsport STudy (NCT00205556) were studied (62% men, age 63.7 ± 13.9 years [mean ± SD]). The median (range) follow-up was 3.0 (0.8–6.6) years. Hepcidin-25 was measured with mass spectrometry. The relationship between hepcidin-25 and all-cause mortality or fatal and non-fatal CV events was investigated with multivariate Cox proportional hazard models. Results Median (interquartile range) hepcidin-25 level was 13.8 (6.6–22.5) nmol/L. During follow-up, 158 (39%) patients died from any cause and 131 (32%) had a CV event. Hepcidin-25 was associated with all-cause mortality in an unadjusted model [hazard ratio (HR) 1.14 per 10 nmol/L, 95% CI 1.03–1.26; P = 0.01], but not after adjustment for all confounders including high-sensitive C-reactive protein (HR 1.02 per 10 nmol/L, 95% CI 0.87–1.20; P = 0.80). At the same time, hepcidin-25 was significantly related to fatal and non-fatal CV events in a fully adjusted model (HR 1.24 per 10 nmol/L, 95% CI 1.05–1.46, P = 0.01). Conclusion Hepcidin-25 was associated with fatal and non-fatal CV events, even after adjustment for inflammation. Furthermore, inflammation appears to be a significant confounder in the relation between hepcidin-25 and all-cause mortality. These findings suggest that hepcidin-25 might be a novel determinant of CV disease in chronic HD patients.
- Subjects
HEPCIDIN; CARDIOVASCULAR diseases; HEMODIALYSIS patients; ATHEROSCLEROSIS; MACROPHAGES; MASS spectrometry; MULTIVARIATE analysis
- Publication
Nephrology Dialysis Transplantation, 2013, Vol 28, Issue 12, p3062
- ISSN
0931-0509
- Publication type
Article