Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 43, Issue 6 (Jun 2005)

Issues

Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease – a prospective randomized study of vitamin supplementation

Torfi Jonasson / Ann-Kristin Öhlin
  • Department of Laboratory Medicine, Division of Clinical Chemistry, University Hospital Lund, Lund, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Anders Gottsäter / Björn Hultberg
  • Department of Laboratory Medicine, Division of Clinical Chemistry, University Hospital Lund, Lund, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hans Öhlin
Published Online: 2014-06-11 | DOI: https://doi.org/10.1515/CCLM.2005.108

Abstract

Background: Elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of developing occlusive vascular diseases. To better illustrate the relationship between plasma tHcy concentration, oxidative stress, and inflammation in patients with coronary artery disease (CAD), we measured plasma 8-isoprostane-prostaglandin F 2 (Iso-P), plasma malondialdehyde (MDA), and several markers of inflammation. We also aimed to demonstrate the effects of vitamin supplementation on these markers.

Methods: A total of 93 patients with ischemic heart disease were investigated. Of these, 34 had plasma tHcy ≤8μmol/L, while 59 had plasma tHcy ≥15.0 μmol/L. The 59 patients were randomized to open therapy with folic acid, 5mg, pyridoxine, 40mg, and cyancobalamin, 1mg once daily for 3months (n=29) or to no vitamin treatment (n=30). Blood samples were obtained from both groups before randomization and 3months later. A sample was also obtained from the remaining 34 patients.

Results: Plasma Iso-P, serum amyloid A (S-AA), and plasma intercellular adhesion molecule-1 (ICAM-1) concentrations were higher in patients with high plasma tHcy levels than in patients with low to normal tHcy levels. Plasma levels of P-, L-, E-selectins, MDA, C-reactive protein (CRP), and orosomucoid did not differ between the groups. Vitamin therapy reduced plasma tHcy from 17.4 (15.3/20.1) to 9.2 (8.3/10.3)μmol/L (25th and 75th percentiles in parentheses) (p<0.0001). Plasma levels of Iso-P remained unchanged and, of all inflammatory markers, only the S-AA concentrations were slightly reduced by the vitamin treatment, from 5.3 (2.2/7.0)ng/L at baseline to 4.6 (2.1/6.9)ng/L (p<0.05) after 3months of vitamin supplementation.

Conclusion: Patients with CAD and high plasma tHcy levels had elevated plasma levels of Iso-P. The increase remained unaffected by plasma tHcy-lowering therapy, suggesting that homocysteine per se does not cause increased lipid peroxidation. Levels of plasma ICAM-1 and S-AA were increased in patients with high plasma tHcy, suggesting an association between homocysteinemia and low-grade inflammation.

Keywords: cardiovascular disease; F 2-isoprostanes; homocysteine; lipid peroxidation; oxidative stress.

References

  • 1

    Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic basis of inherited disease, 6th ed. New York, NY: McGraw-Hill, 1989:693–734. Google Scholar

  • 2

    Monnerat C, Hayoz D. Homocysteine and venous thromboembolism. Schweiz Med Wochenschr 1997; 127: 1489–96. Google Scholar

  • 3

    Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998; 49: 31–62. CrossrefGoogle Scholar

  • 4

    Nygard O, Vollset SE, Refsum H, Brattstrom L, Ueland PM. Total homocysteine and cardiovascular disease. J Intern Med 1999; 246: 425–54. Google Scholar

  • 5

    Graham IM, Daly LE, Refsum HM, Robinson K, Bratt-strom LE, Ueland PM, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. J Am Med Assoc 1997; 277: 1775–81. Google Scholar

  • 6

    Malinow MR. Plasma homocyst(e)ine and arterial occlusive diseases: a mini-review. Clin Chem 1995; 41: 173–6. Google Scholar

  • 7

    Nurk E, Tell GS, Vollset SE, Nygard O, Refsum H, Ueland PM. Plasma total homocysteine and hospitalizations for cardiovascular disease: the Hordaland Homocysteine Study. Arch Intern Med 2002; 162: 1374–81. CrossrefGoogle Scholar

  • 8

    Blundell G, Jones BG, Rose FA, Tudball N. Homocysteine-mediated endothelial cell toxicity and its amelioration. Atherosclerosis 1996; 122: 163–72. CrossrefGoogle Scholar

  • 9

    Hultberg B, Andersson A, Isaksson A. Thiol and redox reactive agents exert different effects on glutathione metabolism in HeLa cell cultures. Clin Chim Acta 1999; 283: 21–32. Google Scholar

  • 10

    Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 1986; 77: 1370–6. Google Scholar

  • 11

    Hua Long L, Halliwell B. Oxidation and generation of hydrogen peroxide by thiol compounds in commonly used cell culture media. Biochem Biophys Res Commun 2001; 286: 991–4. Google Scholar

  • 12

    Lloberas N, Torras J, Herrero-Fresneda I, Cruzado JM, Riera M, Hurtado I, et al. Postischemic renal oxidative stress induces inflammatory response through PAF and oxidized phospholipids. Prevention by antioxidant treatment. FASEB J 2002; 16: 908–10. Google Scholar

  • 13

    Andersson A, Jonasson T, Ohlin H, Lindgren A, Hultberg B. Vitamin supplementation normalizes total plasma homocysteine concentration but not plasma homocysteine redox status in patients with acute coronary syndromes and hyperhomocysteinemia. Clin Chem Lab Med 2002; 40: 554–8. CrossrefGoogle Scholar

  • 14

    Eberhardt RT, Forgione MA, Cap A, Leopold JA, Rudd MA, Trolliet M, et al. Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia. J Clin Invest 2000; 106: 483–91. CrossrefGoogle Scholar

  • 15

    Davi G, di Minno G, Coppola A, Andria G, Cerbone AM, Madonna P, et al. Oxidative stress and platelet activation in homozygous homocysteinuria. Circulation 2001; 104: 1124–8. CrossrefGoogle Scholar

  • 16

    Voutilainen S, Morrow JD, Roberts LJ II, Alfthan G, Alho H, Nyyssonen K, et al. Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels. Arterioscler Thromb Vasc Biol 1999; 19: 1263–6. CrossrefGoogle Scholar

  • 17

    Morrow JD, Roberts LJ II. The isoprostanes. Current knowledge and directions for future research. Biochem Pharmacol 1996; 51: 1–9. CrossrefGoogle Scholar

  • 18

    Powers RW, Majors AK, Lykins DL, Sims CJ, Lain KY, Roberts JM. Plasma homocysteine and malondialdehyde are correlated in an age- and gender-specific manner. Metabolism 2002; 51: 1433–8. CrossrefGoogle Scholar

  • 19

    Cavalca V, Cighetti G, Bamonti F, Loaldi A, Bortone L, Novembrino C, et al. Oxidative stress and homocysteine in coronary artery disease. Clin Chem 2001; 47: 887–92. Google Scholar

  • 20

    Ventura P, Panini R, Verlato C, Scarpetta G, Salvioli G. Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading. Metabolism 2000; 49: 225–8. CrossrefGoogle Scholar

  • 21

    Wang G, Siow YL, O K. Homocysteine stimulates nuclear factor kappaB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible role for protein kinase C. Biochem J 2000; 352: 817–26. Google Scholar

  • 22

    Poddar R, Sivasubramanian N, DiBello PM, Robinson K, Jacobsen DW. Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease. Circulation 2001; 103: 2717–23. Google Scholar

  • 23

    Jousilahti P, Salomaa V, Rasi V, Vahtera E, Palosuo T. Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status. J Epidemiol Community Health 2003; 57: 730–3. CrossrefGoogle Scholar

  • 24

    Shishehbor MH, Bhatt DL, Topol EJ. Using C-reactive protein to assess cardiovascular disease risk. Cleve Clin J Med 2003; 70: 634–40. CrossrefGoogle Scholar

  • 25

    Lowe GD. The relationship between infection, inflammation, and cardiovascular disease: an overview. Ann Periodontol 2001; 6: 1–8. CrossrefGoogle Scholar

  • 26

    Horne BD, Muhlestein JB, Carlquist JF, Bair TL, Madsen TE, Hart NI, et al. Statin therapy, lipid levels, C-reactive protein and the survival of patients with angiographically severe coronary artery disease. J Am Coll Cardiol 2000; 36: 1774–80. CrossrefGoogle Scholar

  • 27

    Fyfe AI, Rothenberg LS, DeBeer FC, Cantor RM, Rotter JI, Lusis AJ. Association between serum amyloid A proteins and coronary artery disease: evidence from two distinct arteriosclerotic processes. Circulation 1997; 96: 2914–9. CrossrefGoogle Scholar

  • 28

    Jonasson T, Ohlin H, Andersson A, Arnadottir A, Hultberg B. Renal function exerts only a minor influence on high plasma homocysteine concentration in patients with acute coronary syndromes. Clin Chem Lab Med 2002; 40: 137–42. CrossrefGoogle Scholar

  • 29

    Andersson A, Isaksson A, Brattstrom L, Hultberg B. Homocysteine and other thiols determined in plasma by HPLC and thiol-specific postcolumn derivatization. Clin Chem 1993; 39: 1590–7. Google Scholar

  • 30

    Ohlin H, Pavlidis N, Ohlin AK. Effect of intravenous nitroglycerin on lipid peroxidation after thrombolytic therapy for acute myocardial infarction. Am J Cardiol 1998; 82: 1463–7. CrossrefGoogle Scholar

  • 31

    Wang Z, Ciabattoni G, Creminon C, Lawson J, Fitzgerald GA, Patrono C, et al. Immunological characterization of urinary 8-epi-prostaglandin F 2 alpha excretion in man. J Pharmacol Exp Ther 1995; 275: 94–100. Google Scholar

  • 32

    Maclouf J, Corvazier E, Wang ZY. Development of a radioimmunoassay for prostaglandin D 2 using an antiserum against 11-methoxime prostaglandin D 2. Prostaglandins 1986; 31: 123–32. Google Scholar

  • 33

    Pradelles P, Grassi J, Maclouf J. Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: an alternative to radioimmunoassay. Anal Chem 1985; 57: 1170–3. CrossrefGoogle Scholar

  • 34

    Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest 1996; 98: 5–7. CrossrefGoogle Scholar

  • 35

    Odin E, Carlsson G, Frosing R, Gustavsson B, Spears CP, Larsson PA. Chemical stability and human plasma pharmacokinetics of reduced folates. Cancer Invest 1998; 16: 447–55. CrossrefGoogle Scholar

  • 36

    Cook RJ. Folate metabolism. In: Carmel R, Jacobsen D, editors. Homocysteine in health and disease. Cambridge, UK: Cambridge University Press, 2001:113–34. Google Scholar

  • 37

    Fuchs D, Jaeger M, Widner B, Wirleitner B, Artner-Dworzak E, Leblhuber F. Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake? Clin Chem Lab Med 2001; 39: 691–4. CrossrefGoogle Scholar

  • 38

    Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost 2000; 26: 219–25. CrossrefGoogle Scholar

  • 39

    Mosharov E, Cranford MR, Banerjee R. The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes. Biochemistry 2000; 39: 13005–11. CrossrefGoogle Scholar

  • 40

    Dudman NP. An alternative view of homocysteine. Lancet 1999; 354: 2072–4. Google Scholar

  • 41

    Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998; 98: 196–9. CrossrefGoogle Scholar

  • 42

    Stroes ES, van Faassen EE, Yo M, Martasek P, Boer P, Govers R, et al. Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res 2000; 86: 1129–34. CrossrefGoogle Scholar

  • 43

    Doshi SN, McDowell IF, Moat SJ, Lang D, Newcombe RG, Kredan −MB, et al. Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol 2001; 21: 1196–202. CrossrefGoogle Scholar

  • 44

    Holvoet P. Endothelial dysfunction, oxidation of low-density lipoprotein, and cardiovascular disease. Ther Apher 1999; 3: 287–93. CrossrefGoogle Scholar

  • 45

    Erren M, Reinecke H, Junker R, Fobker M, Schulte H, Schurek JO, et al. Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. Arterioscler Thromb Vasc Biol 1999; 19: 2355–63. CrossrefGoogle Scholar

  • 46

    Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. Br Med J 2000; 321: 199–204. Google Scholar

  • 47

    Gottsater A, Anwaar I, Eriksson KF, Mattiasson I, Lindgarde F. Homocysteine is related to neopterin and endothelin-1 in plasma of subjects with disturbed glucose metabolism and reference subjects. Angiology 2000; 51: 489–97. CrossrefGoogle Scholar

About the article

Corresponding author: Torfi Jonasson, Department of Cardiology, University Hospital, 101 Reykjavik, Iceland Phone: +354-5431000, Fax: +354-5436467


Received: 2004-09-27

Accepted: 2005-04-12

Published Online: 2014-06-11

Published in Print: 2005-06-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.108.

Export Citation

© Walter de Gruyter Berlin New York. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Thomas J. van 't Erve, Maria B. Kadiiska, Stephanie J. London, and Ronald P. Mason
Redox Biology, 2017, Volume 12, Page 582
[2]
Jie Dong, Qing-Feng Han, Tong-Ying Zhu, Ye-Ping Ren, Jiang-Hua Chen, Hui-Ping Zhao, Meng-Hua Chen, Rong Xu, Yue Wang, Chuan-Ming Hao, Rui Zhang, Xiao-Hui Zhang, Mei Wang, Na Tian, Hai-Yan Wang, and Yan Li
PLoS ONE, 2014, Volume 9, Number 1, Page e82342
[3]
Nasimudeen R. Jabir, Chelapram K. Firoz, Mohammad A. Kamal, Ghazi A. Damanhouri, Mohammed Nabil Alama, Qamre Alam, Absarul Haque, Hussein A. Almehdar, and Shams Tabrez
Journal of Cellular Biochemistry, 2017, Volume 118, Number 7, Page 1849
[4]
Nasimudeen R. Jabir, Chelapram K. Firoz, Mohammad A. Kamal, Ghazi A. Damanhouri, Mohammed Nabil Alama, Anas S. Alzahrani, Hussein A. Almehdar, and Shams Tabrez
Journal of Clinical Laboratory Analysis, 2016
[5]
Ashok Sahu, Trapti Gupta, Arvind Kavishwa, and R. K. Singh
The Ukrainian Biochemical Journal, 2016, Volume 88, Number 2, Page 35
[7]
A. Akalin, O. Alatas, and O. Colak
European Journal of Endocrinology, 2008, Volume 158, Number 1, Page 47
[8]
Egisto Boschetti, Maxey C. M. Chung, and Pier Giorgio Righetti
PROTEOMICS - Clinical Applications, 2012, Volume 6, Number 1-2, Page 22
[9]
Peter Muennig, Nancy Sohler, and Bisundev Mahato
Preventive Medicine, 2007, Volume 45, Number 1, Page 35
[10]
Peter Alter, Heinz Rupp, Marga B. Rominger, Jens H. Figiel, Harald Renz, Klaus J. Klose, and Bernhard Maisch
Clinical Chemistry and Laboratory Medicine, 2010, Volume 48, Number 4
[11]
Maria Pernemalm, Rolf Lewensohn, and Janne Lehtiö
PROTEOMICS, 2009, Volume 9, Number 6, Page 1420
[12]
Lin Chang, Bin Geng, Fang Yu, Jing Zhao, Hongfeng Jiang, Junbao Du, and Chaoshu Tang
Amino Acids, 2008, Volume 34, Number 4, Page 573
[13]
Hamid Mirzaei, Beatriz Baena, Coral Barbas, and Fred Regnier
PROTEOMICS, 2008, Volume 8, Number 7, Page 1516
[14]
Raffaele Caruso, Jonica Campolo, Valentina Sedda, Benedetta De Chiara, Cinzia Dellanoce, Francesco Baudo, Annamaria Tonini, Marina Parolini, Giuliana Cighetti, and Oberdan Parodi
Journal of Cardiovascular Pharmacology, 2006, Volume 47, Number 4, Page 549
[15]
G.-H. Schernthaner, C. Plank, E. Minar, C. Bieglmayer, R. Koppensteiner, and G. Schernthaner
European Journal of Clinical Investigation, 2006, Volume 36, Number 5, Page 333

Comments (0)

Please log in or register to comment.
Log in