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Nutr Metab Cardiovasc Dis. 2011 Aug;21(8):568-75. doi: 10.1016/j.numecd.2010.01.003. Epub 2010 Apr 13.

Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease.

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  • 1Center for the Study of Metabolic and Liver Diseases, Department of Internal Medicine, Universit√† degli Studi Milano, Internal Medicine 1B, Hospital Fondazione Policlinico MaRE IRCCS, Milano, Italy. luca.valenti@unimi.it

Abstract

BACKGROUND AND AIMS:

Increased ferritin and body iron stores are frequently observed in nonalcoholic fatty liver disease (NAFLD), associated with heightened susceptibility to vascular damage. Conflicting data have been reported on the role of iron in atherosclerosis, with recent data suggesting that excess iron induces vascular damage by increasing levels of the hormone hepcidin, which would determine iron trapping into macrophages, oxidative stress, and promotion of transformation into foam cells. Aim of this study was to investigate the relationship between iron status and cardiovascular damage in NAFLD.

METHODS AND RESULTS:

Vascular damage was evaluated by common carotid arteries intima-media thickness (CC-IMT) measurement and plaque detection by ecocolor-doppler ultrasonography in 506 patients with clinical and ultrasonographic diagnosis of NAFLD, hemochromatosis gene (HFE) mutations by restriction analysis in 342 patients. Serum hepcidin-25 was measured by time-of-flight mass spectrometry in 143 patients. At multivariate analysis CC-IMT was associated with systolic blood pressure, glucose, LDL cholesterol, abdominal circumference, age, and ferritin (p=0.048). Carotid plaques were independently associated with age, ferritin, glucose, and hypertension. Ferritin reflected iron stores and metabolic syndrome components, but not inflammation or liver damage. Hyperferritinemia was associated with increased vascular damage only in patients with HFE genotypes associated with hepcidin upregulation by iron stores (p<0.0001), and serum hepcidin-25 was independently associated with carotid plaques (p=0.05).

CONCLUSION:

Ferritin levels, reflecting iron stores, are independent predictors of vascular damage in NAFLD. The mechanism may involve upregulation of hepcidin by increased iron stores in patients not carrying HFE mutations, and iron compartmentalization into macrophages.

Copyright © 2010 Elsevier B.V. All rights reserved.

[PubMed - indexed for MEDLINE]
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