Información del artículo
En los últimos años el metabolismo del hierro se ha relacionado con la resistencia a la insulina, con la diabetes mellitus tipo 2 y con los procesos de inflamación y estrés oxidativo que contribuyen al desarrollo de arteriosclerosis. Hasta hace bien poco, la sobrecarga férrica se circunscribía a la hemocromatosis y a los trastornos relacionados. El descubrimiento de las mutaciones HFE y un nuevo síndrome denominado sobrecarga férrica asociada a insulinorresistencia han contribuido a ampliar el conocimiento de las repercusiones que este metal posee sobre nuestra fisiología. En este artículo se revisa la influencia del metabolismo del hierro en la etiopatogenia y la expresión de diferentes procesos relacionados con la aterosclerosis y la inflamación. También se aborda el posible papel de las medidas terapéuticas que disminuyen la toxicidad del hierro en la prevención y el tratamiento de la disfunción endotelial, la diabetes mellitus y la aterosclerosis.
Palabras clave:
Hierro
Diabetes mellitus
Inflamación
Estrés oxidativo
Arteriosclerosis
In recent years, iron metabolism has been associated with insulin resistance, type 2 diabetes mellitus, inflammation and oxidative stress, which probably contribute to the development of atherosclerosis. Until recently, knowledge of iron overload was limited to hemochromatosis and related disorders. The discovery of HFE mutations and a new syndrome of insulin-resistanceassociated hepatic iron overload has contributed to widening possible new roles of this metal in our physiology. In this review, the influence of iron metabolism on the pathophysiology and clinical expression of different processes related to atherosclerosis and inflammation is briefly summarized. The possible role of decreasing iron stores in the therapy and prevention of endothelial dysfunction, type 2 diabetes mellitus and atherosclerosis is also reviewed.
Key words:
Iron
Diabetes mellitus
Inflammation
Oxidative stress
Atherosclerosis
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Bibliografía
[1.]
B. Turlin, M.H. Mendler, R. Moirand, D. Guyader, A. Guillygomarc’h, Y. Deugnier.
Histologic features of the liver in insulin resistance- associated iron overload.
Am J Clin Pathol, 116 (2001), pp. 263-270
[2.]
E.C. Theil.
Regulation of ferritin and transferrin receptor mRNAs.
J Biol Chem, 265 (1990), pp. 4771-4774
[3.]
C. Ellervik, T. Mandrup-Poulsen, B.G. Nordestgaard, L.E. Larsen, M. Appleyard, M. Frandsen, et al.
Prevalence of hereditary hemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study.
Lancet, 358 (2001), pp. 1405-1409
[4.]
J. Balla, K.A. Nath, G. Balla, M.B. Juckett, H.S. Jacob, G.M. Vercellotti.
Endothelial cell heme oxygenase and ferritin inducion in rat lung by hemoglobin in vivo.
Am J Physiol, 268 (1995), pp. L321-L327
[5.]
G. Cairo, L. Tacchini, G. Pogliaghi, E. Anzon, A. Tomasi, A. Bernelli-Zazzera.
Induction of ferritin synthesis by oxidative stress.
J Biol Chem, 270 (1995), pp. 700-703
[6.]
D.W. Reif.
Ferritin as a source of iron for oxidative damage.
Free Rad Biol Med, 12 (1992), pp. 417-427
[7.]
Y. Qi, T.M. Jamindanar, G. Dawson.
Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes.
J Neurochem, 64 (1995), pp. 2458-2464
[8.]
B.J. Van Lenten, J. Prieve, M. Navab, S. Hama, A.J. Lusis, A.M. Fogelman.
Lipid-induced changes in intracellular iron homeostasis in vitro and in vivo.
J Clin Invest, 95 (1995), pp. 2104-2110
[9.]
C.E. Thomas, L.A. Morehouse, S.D. Aust.
Ferritin and superoxidedependent lipid peroxidation.
J Biol Chem, 260 (1985), pp. 3275-3280
[10.]
M.B. Juckett, J. Balla, G. Balla, J. Jessurun, H.S. Jacob, G.M. Vercellotti.
Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro.
Am J Pathol, 147 (1995), pp. 782-789
[11.]
S.D. Aust.
Ferritin as a source of iron and protection from iron-induced toxicities.
Toxicol Lett, 82/83 (1995), pp. 941-944
[12.]
J.T. Salonen, T.-P. Tuomainen, K. Nyyssönen, H.-M. Lakka, K. Punnonen.
Relation between iron stores and non-insulin-dependent diabetes in men: case-control study.
Bmj, 317 (1999), pp. 727-730
[13.]
E.S. Ford, M.E. Cogswell.
Diabetes and serum ferritin concentration among U.S. adults.
Diabetes Care, 22 (1999), pp. 1978-1983
[14.]
D.J. Fleming, P.F. Jacques, K.L. Tucker, J.M. Massaro, R.B. D’Agostino, P.W.F. Wilson, et al.
Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores.
Am J Clin Nutr, 73 (2001), pp. 638-646
[15.]
T. O’Brien, B. Basset, D.M. Burray, S. Dinneen, D.J. O’Sullivan.
Usefulness of biochemical screening of diabetic patients for hemochromatosis.
Diabetes Care, 13 (1990), pp. 532-534
[16.]
T.B. Kaye, A.T. Guay, D.C. Simonson.
Non-insulin-dependent diabetes mellitus and elevated serum ferritin level.
J Diabetes Complications, 7 (1993), pp. 246-249
[17.]
G. Gallou, I. Guilhem, J.Y. Poirier, A. Ruelland, B. Legras, L. Cloarec.
Increased serum ferritin in insulin-dependent diabetes mellitus: relation to glycemic control.
Clin Chem, 40 (1994), pp. 947-948
[18.]
G. Phelps, I. Chapman, P. Hall, W. Braund, M. Mackinnon.
Prevalence of genetic haemochromatosis among diabetic patients.
Lancet, 2 (1989), pp. 233-234
[19.]
D. Conte, D. Manachino, A. Colli, A. Guala, M. Aimo G Andreoletti.
Prevalence of genetic hemochromatosis in a cohort of Italian patients with diabetes mellitus.
Ann Intern Med, 128 (1998), pp. 370-373
[20.]
C. Ellervik, T. Mandrup-Poulsen, B.G. Nordestgaard, L.E. Larsen, M.M.M.F. Appleyard.
Prevalence of hereditary hemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study.
Lancet, 358 (2001), pp. 1405-1409
[21.]
T. Kwan, B. Leber, S. Ahuja, R. Carter, H. Gerstein.
Patients with type 2 diabetes have a high frequency of the C282Y mutation of the hemochromatosis gene.
Clin Invest Med, 21 (1998), pp. 251-257
[22.]
D.K. Moczulski, W. Grzeszczak, B. Gawlik.
Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy.
Diabetes Care, 24 (2001), pp. 1187-1191
[23.]
T. Frayling, S. Ellard, J. Grove, M. Walker, A.T. Hattersley.
C282Y mutation in HFE (haemochromatosis) gene and type 2 diabetes.
Lancet, 351 (1998), pp. 1933-1934
[24.]
J. Braun, H. Donner, K. Plock, H. Rau, K.H. Usadel, K. Badenhoop.
Hereditary haemochromatosis mutations (HFE) in patients with type II diabetes mellitus.
Diabetologia, 41 (1998), pp. 983-984
[25.]
D. Dubois-Laforgue, S. Caillat-Zucman, I. Djilali-Saiah, E. Larger, A. Mercadier, C. Boitard.
Mutations in HFE, the hemochromatosis candidate gene, in patients with NIDDM.
Diabetes Care, 21 (1998), pp. 1371-1372
[26.]
J.M. Fernández-Real, J. Vendrell, M. Baiget, E. Gimferrer, W. Ricart.
C282Y and H63D mutations of the hemochromatosis candidate gene in type 2 diabetes.
Diabetes Care, 22 (1999), pp. 525-526
[27.]
G. Porto, H. Alves, P. Rodrigues, J.M. Cabeda, C. Portal, A. Ruivo, et al.
Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis.
Immunogenetics, 47 (1998), pp. 404-410
[28.]
D.J. Halsall, I. McFarlane, J. Luan, T.M. Cox, N.J. Wareham.
Typical type 2 diabetes mellitus and HFE gene mutations: a populationbased case-control study.
Hum Mol Genet, 12 (2003), pp. 1361-1365
[29.]
Z.B. Bulaj, L.M. Griffen, L.B. Jorde, C.Q. Edwards, J.P. Kushner.
Clinical and biochemical abnormalities in people heterozygous for hemochromatosis.
N Engl J Med, 335 (1996), pp. 1799-1805
[30.]
R. Moirand, A. Mortaji, O. Loréal, F. Paillard, P. Brissot, Y. Deugnier.
A new syndrome of liver iron overload with normal transferring saturation.
Lancet, 349 (1997), pp. 95-97
[31.]
G. Marchesini, M. Brizi, G. Bianchi, S. Tomassetti, E. Bugianesi, M. Lenzi.
Nonalcoholic fatty liver disease. A feature of the metabolic syndrome.
Diabetes, 50 (2001), pp. 1844-1850
[32.]
M. Mendler, B. Turlin, R. Moirand, A.M. Jouanolle, T. Sapey, D. Guyader.
Insulin resistance-associated iron overload.
Gastroenterology, 117 (1999), pp. 1155-1163
[33.]
B. Turlin, M.H. Mendler, R. Moirand, G. Guyader, A. Guillygomarc’h, Y. Deugnier.
Histologic features of the liver in insulin resistance- associated iron overload.
Am J Clin Pathol, 116 (2001), pp. 263-270
[34.]
J.M. Fernández-Real, W. Ricart, E. Arroyo, R. Balança, R. Casamitjana, D. Cabrero.
Serum ferritin as a component of the insulin resistance syndrome.
Diabetes Care, 21 (1998), pp. 62-68
[35.]
D. Mauricio, A. Pérez, A. Riera, J.A. Arroyo, A. De Leiva, E. Gimferrer.
Serum parameters of iron metabolism in type I (insulin dependent) diabetes mellitus.
Diab Nutr Metab, 8 (1993), pp. 315-316
[36.]
T.T.T.K. Lao.
Maternal serum ferritin and gestational impaired glucose tolerance.
Diabetes Care, 20 (1997), pp. 1368-1369
[37.]
T.T.C.P. Lao, K.F. Tam.
Gestational diabetes mellitus in the last trimester. A feature of maternal iron excess?.
Diabetic Med, 18 (2001), pp. 218-223
[38.]
T.-P. Tuomainen, K. Nyysönen, R. Salonen, A. Tervahauta, H. Korpela, T. Lakka.
Body iron stores are associated with serum insulin and blood glucose concentrations.
Diabetes Care, 20 (1997), pp. 426-428
[39.]
R.F. Gillum.
Association of serum ferritin and indices of body fat distribution and obesity in Mexican American men. The Third National Health and Nutrition Examination Survey.
Int J Obes Rel Metab Dis, 25 (2001), pp. 639-645
[40.]
W. Zidek, W. Tenschert, C. Karoff, H. Vetter.
Treatment of resistant hypertension by phlebotomy.
Klin Wohenschr, 63 (1985), pp. 762-764
[41.]
M. Barenbrock, C. Spieker, K.H. Rahn, W. Zidek.
Therapeutic efficiency of phlebotomy in posttransplant hypertension associated with erythrocytosis.
Clin Nephrol, 40 (1993), pp. 241-243
[42.]
P.A. Merkel, D.C. Simonson, S.A. Amiel, G. Plewe, R.S. Sherwin, H.A. Pearson.
Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion.
N Engl J Med, 318 (1988), pp. 809-814
[43.]
K. Dmochowski, D.T. Finegood, W. Francombe, B. Tyler, B. Zinman.
Factors determining glucose tolerance in patients with thalassemia major.
J Clin Endocrinol Metab, 77 (1993), pp. 478-483
[44.]
P. Cavallo-Perin, G. Pacini, F. Cerutti, A. Bessone, C. Condo, L. Sacchetti.
Insulin resistance and hyperinsulinemia in homozygous -thalassemia.
Metabolism, 44 (1995), pp. 281-286
[45.]
P. Dandona, M.A.M. Hussain, Z. Varghese, D. Politis, D.M. Flynn, A.V. Hoffbrand.
Insulin resistance and iron overload.
Ann Clin Biochem, 20 (1983), pp. 77-79
[46.]
C. Niederau, M. Berger, W. Stremmel, A. Starke, G. Strohmeyer, R. Ebert, et al.
Hyperinsulinemia in non-cirrhotic haemochromatosis: Impaired hepatic insulin degradation?.
Diabetologia, 26 (1984), pp. 441-444
[47.]
A.I. Shafer, R.G. Cheron, R. Dluhy, B. Cooper, R.E. Gleason, J.S. Soeldner, et al.
Clinical consequences of acquired transfusional iron overload in adults.
N Engl J Med, 304 (1981), pp. 319-324
[48.]
L.D. Katz, M.G. Glickman, S. Rapoport, E. Ferrannini, R.A. DeFronzo.
Splanchnic and peripheral glucose disposal of oral glucose in man.
Diabetes, 32 (1983), pp. 675-679
[49.]
N. Yokomori, Y. Iwasa, K. Aida, M. Inoue, M. Tawata, T. Onaya.
Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells.
Endocrinology, 128 (1991), pp. 1474-1480
[50.]
M. Bertelsen, E.E. Änggard, M.J. Carrier.
Oxidative stress impairs insulin internalization in endothelial cells in vitro.
Diabetologia, 44 (2001), pp. 605-613
[51.]
M.J. MacDonald, J.D. Cook, C.H. Epstein ML Flowers.
Large amount of (apo) ferritin in the pancreatic insulin cell and its stimulation by glucose.
Faseb J, 8 (1994), pp. 777-781
[52.]
J.R. Rahier, S. Loozen, M. Goebbels RM Abrahem.
The hemochromatotic human pancreas: a quantitative immunohistochemical and ultrastructural study.
Diabetologia, 30 (1987), pp. 5-12
[53.]
A. Ascherio, E.B. Rimm, E. Giovannucci, W.C. Willett, M.J. Stampfer.
Blood donations and risk of coronary heart disease in men.
Circulation, 103 (2001), pp. 52-57
[54.]
J.F. Yale, M. Grose, T.A. Seemayer, E.B. Marliss.
Diabetes prevention in BB rats by frequent blood withdrawal started at a young age.
Diabetes, 37 (1988), pp. 327-333
[55.]
C. Bofill, J. Joven, J. Bages, E. Vilella, T. Sans, P. Cavallé, et al.
Response to repeated phlebotomies in patients with non-insulin-dependent diabetes mellitus.
Metabolism, 43 (1994), pp. 614-620
[56.]
E. Eschwege, R. Saddi, H. Wacjman, R. Levy, N. Thibult, A. Duchateau.
Haemoglobin A1c in patients on venesection therapy for haemochromatosis.
Diabete Metab, 8 (1982), pp. 137-140
[57.]
I.W. Dymock, J. Cassar, D.A. Pyke, W.G. Oakley, S.R. William.
Observations on the pathogenesis, complications and treatment of diabetes in 115 cases of hemochromatosis.
Am J Med, (1972), pp. 203-210
[58.]
W.D. Davis, W.R. Arrowsmith.
The treatment of haemochromatosis by massive venesection.
Ann Intern Med, 39 (1953), pp. 723-734
[59.]
C.Q. Edwards, G.E. Cartwright, M.H. Skolnick, D.B. Amos.
Homozygosity for hemochromatosis: Clinical manifestations.
Ann Intern Med, 93 (1980), pp. 519-525
[60.]
L.W. Powell, J.F.R. Kerr.
Reversal of ‘cirrhosis’ in idiopathic haemochromatosis following long-term intensive venesection therapy.
Australas Ann Med, 1 (1970), pp. 54-57
[61.]
R. Williams, P.M. Smith, E.J.F. Spicer, M. Barry, S. Sherlock.
Venesection therapy in idiopatic haemochromatosis. An analysis of 40 treated and 18 untreated patients.
Q J Med, 149 (1969), pp. 1-16
[62.]
C. Niederau, R. Fischer, A. Sonnenberg, W. Stremmel, H.J. Trampisch, G. Strohmeyer.
Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis.
N Engl J Med, 313 (1985), pp. 1256-1262
[63.]
J.M. Fernández-Real, G. Peñarroja, A. Castro, F. García-Bragado, I. Hernández, W. Ricart.
Blood letting in high-ferritin type 2 diabetes mellitus. Effects on insulin sensitivity and m-cell function.
Diabetes, 51 (2002), pp. 1000-1004
[64.]
I.S. Young, S. Tate, J.H. Lightbody, D. McMaster, E.R. Trimble.
The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat.
Free Radical Biol Med, 18 (1995), pp. 833-840
[65.]
P. Cutler.
Deferoxamine therapy in high-ferritin diabetes.
Diabetes, 38 (1989), pp. 1207-1210
[66.]
J.B. Redmon, K.L. Pyzdrowski, R.P. Robertson.
No effect of deferoxamine therapy on glucose homeostasis and insulin secretion in individuals with NIDDM and elevated serum ferritin.
Diabetes, 42 (1993), pp. 544-549
[67.]
T. Sakurai, S. Kimura, M. Nakano, H. Kimura.
Oxidative modification of glycated low density lipoprotein in the presence of iron.
Biochem Biophys Res Comm, 177 (1991), pp. 433-439
[68.]
S. Fujimoto, N. Kawakami, A. Ohara.
Nonenzymatic glycation of transferrin: decrease of Iron-binding capacity and increase of oxygen radical production.
Biol Pharm Bull, 18 (1995), pp. 396-400
[69.]
W.F. Graier, S. Simecek, W.R. Kukovetz, G.M. Kostner.
High D-glucose- induced changes in endothelial Ca2+ /EDRF signaling are due to generation of superoxide anions.
Diabetes, 45 (1996), pp. 1386-1395
[70.]
J.V. Hunt, C.C.T. Smith, S.P. Wolff.
Autooxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose.
Diabetes, 39 (1990), pp. 1420-1424
[71.]
S.K. Jain.
Hyperglycemia can cause membrane lipis peroxidation and osmotic fragility in human red blood cells.
J Biol Chem, 264 (1989), pp. 21340-21345
[72.]
S.P. Wolff, R.T. Dean.
Glucose autooxidation and protein modification. The potential role of oxidative glycosylation in diabetes.
Biochem J, 245 (1987), pp. 243-250
[73.]
D.K.S. Yue, S. McLennon, E. Fisher, S. Heffernan, C. Capogreco, G.R. Ross.
Ascorbic acid status and polyol pathway in diabetes.
Diabetes, 38 (1989), pp. 257-261
[74.]
B. Tesfamariam, R.A. Cohen.
Free radicals mediate endothelial cell dysfunction caused by elevated glucose.
Am J Physiol, 263 (1992), pp. H321-H326
[75.]
D.J. Diederich, J. Skopec, A. Diederich, F. Dai.
Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals.
Am J Physiol, 266 (1994), pp. H1153-H1161
[76.]
H.H. Ting, F.K. Timini, K.S. Boles, S.J. Creager, P. Ganz, M.A. Creager.
Vitamin C improves endothelium-dependent vasodilatation in patients with non-insulin-dependent diabetes mellitus.
J Clin Invest, 97 (1996), pp. 22-28
[77.]
P. Langenstroer, G.M. Pieper.
Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals.
Am J Physiol, 263 (1992), pp. H257-65
[78.]
Y.H. Hattori, H. Kawasaki, A. Kazuhiro, M. Kanno.
Superoxide dismutase recovers altered endothelium-dependent relaxation in diabetic rat aorta.
Am J Physiol, 261 (1991), pp. H1086-94
[79.]
G.M. Pieper, W. Siebeneich.
Diabetes-induced endothelial dysfunction is prevented by long-term treatment with the modified iron chelator, hydroxyethyl starch conjugated-deferoxamine.
J Cardiovasc Pharmacol, 30 (1997), pp. 734-738
[80.]
A. Nitenberg, S. Ledoux, P. Valensi, R. Sachs, I. Antony.
Coronary microvascular adaptation to myocardial metabolic demand can be restored by inhibition of iron-catalyzed formation of oxygen free radicals in type 2 diabetic patients.
Diabetes, 51 (2002), pp. 813-818
[81.]
S.J. Duffy, E.S. Biegelsen, M. Holbrook, J.D. Russell, J.K. Gokce Jr.
Iron chelation improves endothelial function in patients with coronary artery disease.
Circulation, 103 (2001), pp. 2799-2804
[82.]
J.M. Fernández-Real, G. Peñarroja, A. Castro, F. García-Bragado, W. Ricart.
Blood letting in high ferritin type 2 diabetes: effects on vascular reactivity.
Diabetes Care, 25 (2002), pp. 2249-2255
[83.]
J. Pang, M.J. Jiang, Y.L. Chen, F.W. Wang, D.L. Wang, S.H. Chu.
Increased ferritin gene expression in atherosclerotic lesions.
J Clin Invest, 97 (1996), pp. 2204-2212
[84.]
P.S.P. Thong, M. Selley, F. Watt.
Elemental changes in atherosclerotic lesions using nuclear microscopy.
Cell Mol Biol, 42 (1996), pp. 2204-2212
[85.]
S.A. You, S.R. Archacki, G. Angheliu, C.S. Moravec, S. Rao, M. Kinter, et al.
Proteomic approach to coronary atherosclerosis shows ferritin light chain as a significant marker: evidence consistent with iron hypothesis in atherosclerosis.
Physiol Genomics, 13 (2003), pp. 25-30
[86.]
M. Failla, C. Giannattasio, A. Piperno, A. Vergani, A. Grappiolo, G. Gentile, et al.
Radial artery wall alterations in genetic hemochromatosis before and after iron depletion therapy.
Hepatology, 32 (2000), pp. 569-573
[87.]
E. Porreca, S. Ucchino, C. Di Febbo, N. Di Bartolomeo, D. Angelucci, A.M. Napolitano, et al.
Antiproliferative effect of desferrioxamine on vascular smooth muscle cells in vitro and in vivo.
Arterioscler Thromb Vasc Biol, 14 (1994), pp. 299-304
[88.]
S.M. Day, D. Duquaine, L.V. Mundada, R.G. Menon, B.V. Khan, S. Rajagopalan, et al.
Chronic iron administration increases vascular oxidative stress and accelerates arterial thrombosis.
Circulation, 107 (2003), pp. 2601-2606
[89.]
J.M. McCord.
Is iron sufficiency a risk factor in ischemic heart disease?.
Circulation, 83 (1991), pp. 1112-1114
[90.]
H.T. Lee, L.L. Chiu, T.S. Lee, H.L. Tsai, L.Y. Chau.
Dietary iron restriction increases plaque stability in apolipoprotein-E-deficient mice.
J Biomed Sci, 10 (2003), pp. 510-517
[91.]
M.J. Williams, R. Poulton, S. Williams.
Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women.
Atherosclerosis, 165 (2001), pp. 179-184
[92.]
M. Hirayama, Y. Kohgo, H. Kondo, N. Shintani, K. Fujikawa, K. Sasaki, et al.
Regulation of iron metabolism in HepG2 cells: a possible role for cytokines in the hepatic deposition of iron.
Hepatology, 18 (1993), pp. 874-880
[93.]
J.T. Rogers.
Ferritin translation by interleukin-1 and interleukin-6: the role of sequences upstream of the start codons of the heavy and light subunit genes.
Blood, 87 (1996), pp. 2525-2537
[94.]
W.K. Lagrand, C.A. Visser, W.T. Hermens.
C-reactive protein as a cardiovascular risk factor: more than a epiphenomenon.
Circulation, 100 (1999), pp. 96-102
[95.]
J.T. Salonen, K. Nyyssonen, H. Korpela, J. Toumilehto, R. Seppanen, R. Salonen.
High stored iron levels are associated with excess risk of miocardial infarction in eastern Finnish men.
Circulation, 86 (1992), pp. 803-811
[96.]
S. Kiechl, J.U. Willeit, G. Egger, W. Poewe, F. Oberholenzer.
Body iron stores and the risk of carotid atherosclerosis.
Circulation, 96 (1997), pp. 3300-3307
[97.]
C.T. Sempos, A.C. Looker, R.F. Gillum, D.L. McGee, C.V. Voung, C.L. Johnson.
Serum ferritin and death from all causes and cardiovascular disease: the NHANES II mortality study.
An Epidemiol, 10 (2000), pp. 441-448
[98.]
M.J. Stampfer, F. Grodstein, I. Rosenberg, W. Willet, C. Hennekens.
A prospective study of plasma ferritin and risk of myocardialinfartion in US physicians.
Circulation, 87 (1993), pp. 688
[99.]
M. Manttari, V. Manninen, J.K. Huttunen, T. Palosuo, C. Ehnholm, O.P. Heinonen.
Serum ferritin and ceruloplasmin as coronary risk factors.
Eur Heart J, 15 (1994), pp. 1599-1603
[100.]
M.W. Knuiman, M.L. Divitini, J.K. Olynyk, D.J. Cullen, H.C. Bartholomew.
Serum ferritin and cardiovascular disease: a 17- year followup study in Busselton, Western Australia.
Am J Epidemiol, 158 (2003), pp. 144-149
[101.]
S. Kiechl, F. Aichner, F. Gerstenbrand, G. Egger, A. Mair, G. Rungger.
Body iron stores and presence of carotid atherosclerosis. Results from the Bruneck Study.
Arterioscler Thromb, 14 (1994), pp. 1625-1630
[102.]
H.I. Morrison, R.M. Semenciw, Y. Mao, D.T. Wigle.
Serum iron andfatal acute myocardial infarction.
Epidemiology, 5 (1994), pp. 243-246
[103.]
M. Moore, A.R. Folsom, R.W. Barnes, J.H. Eckfeldt.
No association between serum ferritin and asymptomatic carotid atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study.
Am J Epidemiol, 141 (1995), pp. 719-723
[104.]
J.E. Eichner, H. Qi, W.E. Moorre, E. Schechter.
Iron measures in coronary angiography patients.
Atherosclerosis, 136 (1998), pp. 241-245
[105.]
J. Danesh, P. Appleby.
Coronary heart disease and iron status: meta-analyses of prospective studies.
Circulation, 99 (1999), pp. 852-854
[106.]
M. Haidari, E. Javadi, A. Sanati, M. Hajilooi, J. Ghanbili.
Association of increased ferritin with premature coronary stenosis in men.
Clin Chem, 47 (2001), pp. 1666-1672
[107.]
C. Bozzini, D. Girelli, E. Tinazzi, O. Olivieri, C. Stranieri, A. Bassi, et al.
Biochemical and genetic markers of iron status and the risk of coronary artery disease: an angiography-based study.
Clin Chem, 48 (2002), pp. 622-628
[108.]
M. Roest, Y. Van der Schou, B. De ValK, M.J.J. Marx, M.J. Tempelman, P.G. De Groot.
Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women.
Circulation, 100 (1999), pp. 1268-1273
[109.]
T.P. Toumainen, K. Kontula, K. Nyyssonen, T.A. Lakka, T. Helio, J.T. Salonen.
Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation.
Circulation, 100 (1999), pp. 1274-1279
[110.]
J. Waalen, V. Felitti, T. Gelbart, J.H. Ngoc, E. Beutler.
Prevalence of coronary disease associated with HFE mutations in adults attending a health appraisal center.
Am J Med, 113 (2002), pp. 472-479
[111.]
E. Battiloro, D. Ombres, E. Pascale, E. D’Ambrosio, R. Verna, M. Arca.
Hemocromatosis gene mutations and risk of coronary artery disease.
Eur J Hum Genet, 8 (2000), pp. 389-392
[112.]
G. Hetet, A. Elbaz, J. Gariepy, V. Nicaud, D. Arveiler, C. Morrison.
Association studies between haemochromatosis gene mutations and the risk of cardiovascular diseases.
Eur J Clin Invest, 31 (2001), pp. 382-388
[113.]
D.G. Meyers, D. Strickland, P.A. Maloley.
Possible association of reduction in cardiovascular events with blood donation.
Heart, 78 (1997), pp. 188-193
[114.]
J.T. Salonen, T.P. Toumainem, R. Salonen.
Donation of blood is associated with reduced risk of myocardial infarction: the Kuopio Ischaemic Heart Disease Risk Factor Study.
Am J Epidemiol, 148 (1998), pp. 445-451
[115.]
A. Dávalos, J.M. Fernández-Real, W. Ricart, A. Molins, E. Planas, D. Genís.
Iron related damage in acute ischemic stroke.
Stroke, 25 (1994), pp. 1543-1546
[116.]
A.K. Erdemoglu, S. Ozbakir.
Serum ferritin levels and early prognosis of stroke.
Eur J Neurol, 9 (2002), pp. 663-667
[117.]
C. Palmer, R.L. Roberts, C. Bero.
Desferoxamine posttreatment reduces ischemic brain injury in neonatal rats.
Stroke, 25 (1994), pp. 1039-1045
[118.]
O.T. Njajou, M. Hollander, P.J. Koudstaal, A. Hofman, J.C. Witteman, M.M. Breteler, et al.
Mutations in the hemochromatosis gene (HFE) and stroke.
Stroke, 33 (2002), pp. 2363-2366
[119.]
R. Rauramaa, S. Vaisanen, M. Mercuri, T. Rankinen, I. Penttila, M.G. Bond.
Association of risk factors and body iron status to carotid atherosclerosis in middle-aged eastern Finnish men.
Eur Heart J, 15 (1994), pp. 1020-1027
[120.]
A. Tzonou, P. Lagiou, A. Trichopoulou, V. Tsoutsos, D. Trichopoulos.
Dietary iron and coronary heart disease risk: a study fromGreece.
Am J Epidemiol, 147 (1998), pp. 161-166
[121.]
D.A. Snowdon, R.L. Phillips, G.A. Fraser.
Meat consumtion and fatal ischemic heart disease.
Prev Med, 13 (1984), pp. 490-500
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