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

L. Valenti, D. W. Swinkels, L. Burdick, P. Dongiovanni, H. Tjalsma, B. M. Motta, C. Bertelli, E. Fatta, D. Bignamini, R. Rametta, S. Fargion, A. L. Fracanzani

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)568-575
Number of pages8
JournalNutrition, Metabolism and Cardiovascular Diseases
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 2011

Fingerprint

Ferritins
Blood Vessels
Iron
Hepcidins
Serum
Carotid Intima-Media Thickness
Common Carotid Artery
Up-Regulation
Macrophages
Non-alcoholic Fatty Liver Disease
Blood Pressure
Doppler Ultrasonography
Foam Cells
Mutation
Hemochromatosis
LDL Cholesterol
Blood Glucose
Mass Spectrometry
Atherosclerosis
Oxidative Stress

Keywords

  • Atherosclerosis
  • Iron
  • Nonalcoholic fatty liver disease
  • Oxidative stress
  • Vascular damage

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease. / Valenti, L.; Swinkels, D. W.; Burdick, L.; Dongiovanni, P.; Tjalsma, H.; Motta, B. M.; Bertelli, C.; Fatta, E.; Bignamini, D.; Rametta, R.; Fargion, S.; Fracanzani, A. L.

In: Nutrition, Metabolism and Cardiovascular Diseases, Vol. 21, No. 8, 08.2011, p. 568-575.

Research output: Contribution to journalArticle

@article{38daf29102a3494da147ea79a4d4644c,
title = "Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease",
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.",
keywords = "Atherosclerosis, Iron, Nonalcoholic fatty liver disease, Oxidative stress, Vascular damage",
author = "L. Valenti and Swinkels, {D. W.} and L. Burdick and P. Dongiovanni and H. Tjalsma and Motta, {B. M.} and C. Bertelli and E. Fatta and D. Bignamini and R. Rametta and S. Fargion and Fracanzani, {A. L.}",
year = "2011",
month = "8",
doi = "10.1016/j.numecd.2010.01.003",
language = "English",
volume = "21",
pages = "568--575",
journal = "Nutrition, Metabolism and Cardiovascular Diseases",
issn = "0939-4753",
publisher = "Elsevier B.V.",
number = "8",

}

TY - JOUR

T1 - Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease

AU - Valenti, L.

AU - Swinkels, D. W.

AU - Burdick, L.

AU - Dongiovanni, P.

AU - Tjalsma, H.

AU - Motta, B. M.

AU - Bertelli, C.

AU - Fatta, E.

AU - Bignamini, D.

AU - Rametta, R.

AU - Fargion, S.

AU - Fracanzani, A. L.

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Iron

KW - Nonalcoholic fatty liver disease

KW - Oxidative stress

KW - Vascular damage

UR - http://www.scopus.com/inward/record.url?scp=79961127549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961127549&partnerID=8YFLogxK

U2 - 10.1016/j.numecd.2010.01.003

DO - 10.1016/j.numecd.2010.01.003

M3 - Article

C2 - 20392616

AN - SCOPUS:79961127549

VL - 21

SP - 568

EP - 575

JO - Nutrition, Metabolism and Cardiovascular Diseases

JF - Nutrition, Metabolism and Cardiovascular Diseases

SN - 0939-4753

IS - 8

ER -