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Irish Journal of Medical Science

, Volume 183, Issue 2, pp 303–309 | Cite as

Disordered vascular compliance in haemochromatosis

  • W. J. CashEmail author
  • S. O’Neill
  • M. E. O’Donnell
  • D. R. McCance
  • I. S. Young
  • J. McEneny
  • I. S. Cadden
  • Neil I. McDougall
  • M. E. Callender
Original Article

Abstract

Background

A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk.

Aims

To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls.

Methods

Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured.

Results

Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 μmol/L, p = 0.011), retinol (1.17 vs. 1.81 μmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 μmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32).

Conclusions

Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.

Keywords

Antioxidant Arterial Compliance Haemochromatosis Iron Vascular 

Notes

Acknowledgments

Sources of financial support The Royal Victoria Hospital Liver Support Group.

References

  1. 1.
    Sullivan JL (1981) Iron and the sex difference in heart disease risk. Lancet 1(8233):1293–1294PubMedCrossRefGoogle Scholar
  2. 2.
    Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Seppanen R, Salonen R (1992) High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation 86(3):803–811PubMedCrossRefGoogle Scholar
  3. 3.
    Salonen JT, Korpela H, Nyyssonen K et al (1995) Lowering of body iron stores by blood letting and oxidation resistance of serum lipoproteins: a randomized cross-over trial in male smokers. J Intern Med 237(2):161–168PubMedCrossRefGoogle Scholar
  4. 4.
    Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F (1997) Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 96(10):3300–3307PubMedCrossRefGoogle Scholar
  5. 5.
    Tuomainen TP, Punnonen K, Nyyssonen K, Salonen JT (1998) Association between body iron stores and the risk of acute myocardial infarction in men. Circulation 97(15):1461–1466PubMedCrossRefGoogle Scholar
  6. 6.
    Tuomainen TP, Kontula K, Nyyssonen K, Lakka TA, Helio T, Salonen JT (1999) Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation: a prospective cohort study in men in eastern Finland. Circulation 100(12):1274–1279PubMedCrossRefGoogle Scholar
  7. 7.
    Brissot P, Deugnier Y, Le Treut A, Regnouard F, Simon M, Bourel M (1978) Ascorbic acid status in idiopathic hemochromatosis. Digestion 17(6):479–487PubMedCrossRefGoogle Scholar
  8. 8.
    Herbert V (1999) Hemochromatosis and vitamin C. Ann Intern Med 131(6):475–476PubMedCrossRefGoogle Scholar
  9. 9.
    Brissot P, Le Treut A, Dien G, Cottencin M, Simon M, Bourel M (1978) Hypovitaminemia A in idiopathic hemochromatosis and hepatic cirrhosis. Role of retinol-binding protein and zinc. Digestion 17(6):469–478PubMedCrossRefGoogle Scholar
  10. 10.
    von Herbay A, de Groot H, Hegi U, Stremmel W, Strohmeyer G, Sies H (1994) Low vitamin E content in plasma of patients with alcoholic liver disease, hemochromatosis and Wilson’s disease. J Hepatol 20(1):41–46CrossRefGoogle Scholar
  11. 11.
    Young IS, Trouton TG, Torney JJ, McMaster D, Callender ME, Trimble ER (1994) Antioxidant status and lipid peroxidation in hereditary haemochromatosis. Free Radic Biol Med 16(3):393–397PubMedCrossRefGoogle Scholar
  12. 12.
    Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695. doi: 10.1056/NEJMra043430 PubMedCrossRefGoogle Scholar
  13. 13.
    Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340(2):115–126. doi: 10.1056/nejm199901143400207 PubMedCrossRefGoogle Scholar
  14. 14.
    Stocker R, Keaney JF Jr (2004) Role of oxidative modifications in atherosclerosis. Physiol Rev 84(4):1381–1478. doi: 10.1152/physrev.00047.2003 PubMedCrossRefGoogle Scholar
  15. 15.
    Lekakis J, Papamicheal C, Stamatelopoulos K et al (1999) Hemochromatosis associated with endothelial dysfunction: evidence for the role of iron stores in early atherogenesis. Vasc Med 4(3):147–148PubMedCrossRefGoogle Scholar
  16. 16.
    Gaenzer H, Marschang P, Sturm W et al (2002) Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis. J Am Coll Cardiol 40(12):2189–2194PubMedCrossRefGoogle Scholar
  17. 17.
    Wilkinson IB, Hall IR, MacCallum H et al (2002) Pulse-wave analysis: clinical evaluation of a noninvasive, widely applicable method for assessing endothelial function. Arterioscler Thromb Vasc Biol 22(1):147–152PubMedCrossRefGoogle Scholar
  18. 18.
    O’Rourke MF, Gallagher DE (1996) Pulse wave analysis. J Hypertens Suppl 14(5):S147–S157PubMedGoogle Scholar
  19. 19.
    Cockcroft JR, Wilkinson IB (2002) Arterial stiffness and pulse contour analysis: an age old concept revisited. Clin Sci (Lond) 103(4):379–380. doi: 10.1042/ Google Scholar
  20. 20.
    Vuilleumier JP, Keller HE, Keck E (1990) Clinical chemical methods for the routine assessment of the vitamin status in human populations. Part III: the apoenzyme stimulation tests for vitamin B1, B2 and B6 adapted to the Cobas-Bio analyzer. Int J Vitam Nutr Res 60(2):126–135PubMedGoogle Scholar
  21. 21.
    Craft NEWSA, Soares JH (1992) Optimization of an isocratic high-performance liquid chromatographic separation of carotenoids. J Chromatogr 589:171–176CrossRefGoogle Scholar
  22. 22.
    Mattace-Raso FH, Hofman A, Verwoert GC et al (2010) Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’. Eur Heart J 31(19):2338–2350. doi: 10.1093/eurheartj/ehq165 CrossRefGoogle Scholar
  23. 23.
    Sempos CT (2002) Do body iron stores increase the risk of developing coronary heart disease? Am J Clin Nutr 76(3):501–503PubMedGoogle Scholar
  24. 24.
    Sun Q, Ma J, Rifai N, Franco OH, Rexrode KM, Hu FB (2008) Excessive body iron stores are not associated with risk of coronary heart disease in women. J Nutr 138(12):2436–2441. doi: 10.3945/jn.108.097766 PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Magnusson MK, Sigfusson N, Sigvaldason H, Johannesson GM, Magnusson S, Thorgeirsson G (1994) Low iron-binding capacity as a risk factor for myocardial infarction. Circulation 89(1):102–108PubMedCrossRefGoogle Scholar
  26. 26.
    van der AD, Rovers MM, Grobbee DE et al (2008) Mutations in the HFE gene and cardiovascular disease risk: an individual patient data meta-analysis of 53 880 subjects. Circ Cardiovasc Genet 1(1):43–50. doi: 10.1161/circgenetics.108.773176 CrossRefGoogle Scholar
  27. 27.
    Miller M, Hutchins GM (1994) Hemochromatosis, multiorgan hemosiderosis, and coronary artery disease. JAMA 272(3):231–233PubMedCrossRefGoogle Scholar
  28. 28.
    Valenti L, Swinkels DW, Burdick L et al (2011) Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 21(8):568–575. doi: 10.1016/j.numecd.2010.01.003 PubMedCrossRefGoogle Scholar
  29. 29.
    Wang L, Johnson EE, Shi HN, Walker WA, Wessling-Resnick M, Cherayil BJ (2008) Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. J Immunol 181(4):2723–2731PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Sullivan JL (2009) Do hemochromatosis mutations protect against iron-mediated atherogenesis? Circ Cardiovasc Genet 2(6):652–657. doi: 10.1161/circgenetics.109.906230 PubMedCrossRefGoogle Scholar
  31. 31.
    Blacher J, Asmar R, Djane S, London GM, Safar ME (1999) Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 33(5):1111–1117PubMedCrossRefGoogle Scholar
  32. 32.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809. doi: 10.1038/362801a0 PubMedCrossRefGoogle Scholar
  33. 33.
    Celermajer DS, Sorensen KE, Gooch VM et al (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115PubMedCrossRefGoogle Scholar
  34. 34.
    Lum H, Roebuck KA (2001) Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol 280(4):C719–C741PubMedGoogle Scholar
  35. 35.
    Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320(14):915–924. doi: 10.1056/nejm198904063201407 PubMedCrossRefGoogle Scholar
  36. 36.
    Bozzini C, Girelli D, Tinazzi E et al (2002) Biochemical and genetic markers of iron status and the risk of coronary artery disease: an angiography-based study. Clin Chem 48(4):622–628PubMedGoogle Scholar
  37. 37.
    Lipinski B, Pretorius E, Oberholzer HM, van der Spuy WJ (2012) Interaction of fibrin with red blood cells: the role of iron. Ultrastruct Pathol 36(2):79–84. doi: 10.3109/01913123.2011.627491 PubMedCrossRefGoogle Scholar
  38. 38.
    Lipinski B, Pretorius E (2012) Novel pathway of ironinduced blood coagulation: implications for diabetes mellitus and its complications. Pol Arch Med Wewn 122(3):115–122PubMedGoogle Scholar
  39. 39.
    Pretorius E, Lipinski B (2013) Differences in morphology of fibrin clots induced with thrombin and ferric ions and its pathophysiological consequences. Heart Lung Circ 22(6):447–449. doi: 10.1016/j.hlc.2012.10.010 PubMedCrossRefGoogle Scholar
  40. 40.
    Pretorius E, Bester J, Vermeulen N, Lipinski B (2013) Oxidation inhibits iron-induced blood coagulation. Curr Drug Targets 14(1):13–19PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Lipinski B, Pretorius E (2012) Hydroxyl radical-modified fibrinogen as a marker of thrombosis: the role of iron. Hematology 17(4):241–247. doi: 10.1179/1607845412y.0000000004 PubMedCrossRefGoogle Scholar
  42. 42.
    Gutteridge JM, Rowley DA, Griffiths E, Halliwell B (1985) Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clin Sci (Lond) 68(4):463–467Google Scholar
  43. 43.
    Moore K, Roberts LJ 2nd (1998) Measurement of lipid peroxidation. Free Radic Res 28(6):659–671PubMedCrossRefGoogle Scholar
  44. 44.
    Malik I, Danesh J, Whincup P et al (2001) Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet 358(9286):971–976. doi: 10.1016/s0140-6736(01)06104-9 PubMedCrossRefGoogle Scholar
  45. 45.
    Ridker PM, Rifai N, Rose L, Buring JE, Cook NR (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347(20):1557–1565. doi: 10.1056/NEJMoa021993 PubMedCrossRefGoogle Scholar
  46. 46.
    Ridker PM, Danielson E, Fonseca FA et al (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359(21):2195–2207. doi: 10.1056/NEJMoa0807646 PubMedCrossRefGoogle Scholar

Copyright information

© Royal Academy of Medicine in Ireland 2013

Authors and Affiliations

  • W. J. Cash
    • 1
    • 6
    Email author
  • S. O’Neill
    • 2
  • M. E. O’Donnell
    • 2
  • D. R. McCance
    • 3
  • I. S. Young
    • 4
    • 5
  • J. McEneny
    • 5
  • I. S. Cadden
    • 1
  • Neil I. McDougall
    • 1
  • M. E. Callender
    • 1
  1. 1.Department of Hepatology (Liver Unit)Queens University BelfastBelfastNorthern Ireland, UK
  2. 2.Department of Vascular and Endovascular Surgery, Royal Victoria HospitalQueens University BelfastBelfastNorthern Ireland, UK
  3. 3.Department of Endocrinology and DiabetesQueens University BelfastBelfastNorthern Ireland,UK
  4. 4.Department of Clinical BiochemistryQueens University BelfastBelfastNorthern Ireland, UK
  5. 5.Department of Royal Victoria Hospital and Department of MedicineQueens University BelfastBelfastNorthern Ireland, UK
  6. 6.The Liver UnitRoyal Victoria HospitalBelfastNorthern Ireland, UK

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