Reduced glutathione peroxidase activity predicts increased cardiovascular risk following an acute coronary syndrome.

Authors

  • Ana S Holley Victoria University of Wellington, Wellington, New Zealand Wellington Cardiovascular Research Group, Wellington, New Zealand
  • Scott A Harding Victoria University of Wellington, Wellington, New Zealand Wellington Cardiovascular Research Group, Wellington, New Zealand Department of Cardiology, Wellington Hospital, Wellington, New Zealand.
  • Alexander Sasse Victoria University of Wellington, Wellington, New Zealand Wellington Cardiovascular Research Group, Wellington, New Zealand Department of Cardiology, Wellington Hospital, Wellington, New Zealand.
  • John H Miller Victoria University of Wellington, Wellington, New Zealand. Wellington Cardiovascular Research Group, Wellington, New Zealand.
  • Peter D Larsen Victoria University of Wellington, Wellington, New Zealand. Wellington Cardiovascular Research Group, Wellington, New Zealand. Otago University, Wellington, New Zealand.

DOI:

https://doi.org/10.17987/icfj.v6i0.241

Keywords:

Glutathione peroxidase, acute coronary syndromes, cardiac event, oxidative stress

Abstract

Background:  Glutathione peroxidase (GPx) is an antioxidant enzyme that comprises a primary defence against oxidative stress.  Deficiencies in GPx have been associated with progression of atherosclerosis and arterial thrombosis.  However, the relationship between GPx activity and clinical outcomes in acute coronary syndromes (ACS) remains controversial.  This study examined the relationship between plasma GPx activity and subsequent major adverse cardiovascular events (MACE) in ACS patients.

Method:  In this prospective cohort study, 262 ACS patients had their plasma GPx activity measured using a colourimetric enzyme assay.  Patient demographics, clinical variables and MACE, a composite of death, non-fatal myocardial infarction, ischaemic stroke and acute heart failure, were collected.

Results:  At 1 year follow-up, 34 (13%) patients experienced MACE.  When the MACE rate was examined by quartiles of GPx activity, a significant decrease in MACE was demonstrated with increasing quartiles of GPx activity (P = 0.04).  The event rate for patients in the lowest quartile of GPx activity was 19.6% compared to 7.9% for the upper quartile.  Levels of GPx activity were significantly lower in diabetic patients compared to non-diabetic patients (P = 0.02), and lower in males compared to females (P = 0.03).  GPx activity was a moderate predictor of MACE by receiver operator characteristic analysis with an area under the curve of 0.62 (P = 0.02).

Conclusion:  We have demonstrated that lower levels of GPx activity are associated with an increased risk of MACE at 1 year following an ACS.  Low levels of GPx activity may represent a decreased defence against oxidant-mediated cardiovascular damage.

References

Brigelius-Flohe R. Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med. 1999;27(9-10):951-65.

Forgione MA, Cap A, Liao R, Moldovan NI, Eberhardt RT, Lim CC, et al. Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure. Circulation. 2002;106(9):1154-8.

Jin RC, Mahoney CE, Anderson L, Ottaviano F, Croce K, Leopold JA, et al. Glutathione Peroxidase-3 Deficiency Promotes Platelet-Dependent Thrombosis In Vivo. Circulation. 2011;123(18):1963-73. doi: 10.1161/circulationaha.110.000034.

Freedman JE, Loscalzo J, Benoit SE, Valeri CR, Barnard MR, Michelson AD. Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis. J Clin Invest. 1996;97(4):979-87. doi: 10.1172/JCI118522 [doi].

Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med. 2003;349(17):1605-13. doi: 10.1056/NEJMoa030535 [doi]

/17/1605 [pii].

Flores-Mateo G, Carrillo-Santisteve P, Elosua R, Guallar E, Marrugat J, Bleys J, et al. Antioxidant enzyme activity and coronary heart disease: meta-analyses of observational studies. American journal of epidemiology. 2009;170(2):135-47. doi: kwp112 [pii]

1093/aje/kwp112 [doi].

Garcia-Pinilla JM, Galvez J, Cabrera-Bueno F, Jimenez-Navarro M, Gomez-Doblas JJ, Galisteo M, et al. Baseline glutathione peroxidase activity affects prognosis after acute coronary syndromes. Texas Heart Institute journal / from the Texas Heart Institute of St Luke's Episcopal Hospital, Texas Children's Hospital. 2008;35(3):262-7.

Voetsch B, Jin RC, Bierl C, Benke KS, Kenet G, Simioni P, et al. Promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene: a novel risk factor for arterial ischemic stroke among young adults and children. Stroke. 2007;38(1):41-9. doi: 01.STR.0000252027.53766.2b [pii]

1161/01.STR.0000252027.53766.2b [doi].

Lapenna D, de Gioia S, Ciofani G, Mezzetti A, Ucchino S, Calafiore AM, et al. Glutathione-related antioxidant defenses in human atherosclerotic plaques. Circulation. 1998;97(19):1930-4.

Guo Z, Van Remmen H, Yang H, Chen X, Mele J, Vijg J, et al. Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells. Arterioscler Thromb Vasc Biol. 2001;21(7):1131-8.

Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging. 2007;2(2):219-36.

Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes/metabolism research and reviews. 2001;17(3):189-212.

Ramakrishna V, Jailkhani R. Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients. Acta diabetologica. 2008;45(1):41-6. doi: 10.1007/s00592-007-0018-3.

Colak E, Majkic-Singh N, Stankovic S, Sreckovic-Dimitrijevic V, Djordjevic PB, Lalic K, et al. Parameters of antioxidative defense in type 2 diabetic patients with cardiovascular complications. Annals of medicine. 2005;37(8):613-20. doi: 10.1080/07853890500330193.

Beard T, Carrie D, Boyer MJ, Boudjemaa B, Ferrieres J, Delay M, et al. [Production of oxygen free radicals in myocardial infarction treated by thrombolysis. Analysis of glutathione peroxidase, superoxide dismutase and malondialdehyde]. Archives des maladies du coeur et des vaisseaux. 1994;87(10):1289-96.

Zachara BA, Ukleja-Adamowicz M, Nartowicz E, Lecka J. Increased plasma glutathione peroxidase activity in patients with acute myocardial infarction. Med Sci Monit. 2001;7(3):415-20.

Olson GE, Whitin JC, Hill KE, Winfrey VP, Motley AK, Austin LM, et al. Extracellular glutathione peroxidase (Gpx3) binds specifically to basement membranes of mouse renal cortex tubule cells. American journal of physiology Renal physiology. 2010;298(5):F1244-53. doi: 10.1152/ajprenal.00662.2009.

Shewan LG CA, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal. 2015;2(2). doi: 10.17987/icfj.v2i1.4.

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Published

2016-05-04

Issue

Vol. 6 (2016)

Section

Original Article

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