title: Association of myeloperoxidase with total and cardiovascular mortality in individuals undergoing coronary angiography--the LURIC study.
abstract: BACKGROUND
  The phagocytic enzyme myeloperoxidase (MPO) acts as a front-line defender against microorganisms. However, increased MPO levels have been found to be associated with complex and calcified atherosclerotic lesions and incident cardiovascular disease. Therefore, this study aimed to investigate a predictive role of MPO, a biomarker of inflammation and oxidative stress, for total and cardiovascular mortality in patients referred to coronary angiography.
  
  
  RESULTS
  MPO plasma concentrations along with eight MPO polymorphisms were determined in 3036 participants of the Ludwigshafen Risk and Cardiovascular Health study (median follow-up 7.75 years). MPO concentrations were positively associated with age, diabetes, smoking, markers of systemic inflammation (interleukin-6, fibrinogen, C-reactive protein, serum amyloid A) and vascular damage (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1) but negatively associated with HDL-cholesterol and apolipoprotein A-I. After adjustment for cardiovascular risk factors MPO concentrations in the highest versus the lowest quartile were associated with a 1.34-fold risk (95% CI: 1.09-1.67) for total mortality. In the adjusted model the hazard ratio for cardiovascular mortality in the highest MPO quartile was 1.42 (95% CI: 1.07-1.88). Five MPO polymorphisms were positively associated with MPO concentrations but not with mortality. Using Mendelian randomization, we did not obtain evidence for a causal association of MPO with either total or cardiovascular mortality.
  
  
  CONCLUSIONS
  MPO concentrations but not genetic variants at the MPO locus are independently associated with risk for total and cardiovascular mortality in coronary artery disease patients.
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Mannheim Institute of Public Health, Medical Faculty Mannheim, Rupertus Carola University of Heidelberg, Mannheim, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Genser
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kickmaier
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Gisela
authors.initials: G
authors.lastname: Weihrauch
authors.affiliation: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grammer
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Rossmann
authors.affiliation: ClinPhenomics Study Center, Frankfurt, Germany.
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.affiliation: Ulm University Medical Centre, Department of Internal Medicine I, Ulm University, Ulm, Germany; LKC School of Medicine, Nanyang Technological University, Singapore and Imperial College London, UK.
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sattler
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria; Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Synlab Academy, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Austria. Electronic address: ernst.malle@medunigraz.at.
authors.forename: Ernst
authors.initials: E
authors.lastname: Malle
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics / Q000401:mortality*; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood* / Q000235:genetics; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012306:Risk
chemical_list: D015415:Biomarkers; D009195:Peroxidase
keywords: Cardiovascular mortality; High-density lipoprotein; Inflammation; Myeloperoxidase; Risk factor
references.citation: Eur Heart J. 2012 Jul;33(13):1635-701
references.pmid: 22555213
references.citation: J Am Coll Cardiol. 2007 May 22;49(20):1993-2000
references.pmid: 17512353
references.citation: PLoS One. 2013 Jun 20;8(6):e65778
references.pmid: 23840365
references.citation: J Am Coll Cardiol. 2010 Mar 16;55(11):1102-9
references.pmid: 20223364
references.citation: Kidney Int. 2003 Dec;64(6):1956-67
references.pmid: 14633118
references.citation: Clin Chim Acta. 2006 Jun;368(1-2):168-72
references.pmid: 16480969
references.citation: Eur J Clin Invest. 2011 Jun;41(6):667-71
references.pmid: 21226709
references.citation: Eur J Clin Invest. 2008 Feb;38(2):90-6
references.pmid: 18226042
references.citation: Kidney Int Suppl. 2003 May;(84):S172-6
references.pmid: 12694338
references.citation: Eur Heart J. 2011 Dec;32(23):2999-3054
references.pmid: 21873419
references.citation: Pharmacogenomics. 2001 Feb;2(1 Suppl 1):S1-73
references.pmid: 11258203
references.citation: Antioxid Redox Signal. 2008 Jul;10(7):1199-234
references.pmid: 18331199
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1102-11
references.pmid: 15790935
references.citation: Clin Chem. 2011 Apr;57(4):603-8
references.pmid: 21262952
references.citation: Biochem Biophys Res Commun. 2005 Jun 3;331(2):442-51
references.pmid: 15850779
references.citation: Science. 2002 Jun 28;296(5577):2391-4
references.pmid: 12089442
references.citation: Am J Med. 2004 Mar 15;116(6):429-30
references.pmid: 15006595
references.citation: Clin Chem. 2011 Dec;57(12):1762-70
references.pmid: 21940659
references.citation: Circulation. 2003 Sep 23;108(12):1440-5
references.pmid: 12952835
references.citation: Free Radic Biol Med. 2000 Jun 15;28(12):1717-25
references.pmid: 10946213
references.citation: J Am Coll Cardiol. 2007 Jun 19;49(24):2364-70
references.pmid: 17572253
references.citation: Clin Chem. 2011 Jan;57(1):33-9
references.pmid: 21059827
references.citation: Eur Heart J. 2008 May;29(9):1096-102
references.pmid: 18339606
references.citation: Circulation. 2010 Dec 14;122(24):2505-13
references.pmid: 21126969
references.citation: Eur Heart J. 2012 Oct;33(20):2569-619
references.pmid: 22922416
references.citation: Trans Assoc Am Physicians. 1970;83:78-92
references.pmid: 5505398
references.citation: Clin Biochem. 2010 Jan;43(1-2):57-62
references.pmid: 19651119
references.citation: JAMA. 2000 Aug 16;284(7):835-42
references.pmid: 10938172
references.citation: Free Radic Biol Med. 2004 Sep 15;37(6):902-11
references.pmid: 15304260
references.citation: Am J Kidney Dis. 2010 Apr;55(4):622-7
references.pmid: 20338463
references.citation: Am Heart J. 2008 Feb;155(2):356-60
references.pmid: 18215608
references.citation: Clin Chim Acta. 2008 Aug;394(1-2):59-62
references.pmid: 18440308
references.citation: Blood. 1998 Nov 1;92(9):3007-17
references.pmid: 9787133
references.citation: J Am Coll Cardiol. 2007 Jul 10;50(2):159-65
references.pmid: 17616301
references.citation: Circulation. 1975 Apr;51(4 Suppl):5-40
references.pmid: 1116248
references.citation: Circ Cardiovasc Genet. 2012 Oct 1;5(5):561-8
references.pmid: 22923422
references.citation: Circulation. 2004 Aug 31;110(9):1134-9
references.pmid: 15326065
references.citation: Eur J Hum Genet. 2001 Oct;9(10):780-6
references.pmid: 11781690
references.citation: Am Heart J. 2001 Aug;142(2):336-9
references.pmid: 11479475
references.citation: Am J Cardiol. 2007 May 15;99(10):1364-8
references.pmid: 17493461
references.citation: Free Radic Biol Med. 2009 Dec 1;47(11):1584-90
references.pmid: 19735726
references.citation: J Hum Genet. 2008;53(5):439-446
references.pmid: 18322643
references.citation: Circulation. 2001 Jun 5;103(22):2705-10
references.pmid: 11390341
references.citation: BMJ. 2006 Nov 25;333(7578):1091
references.pmid: 17032691
references.citation: JAMA. 2001 May 16;285(19):2486-97
references.pmid: 11368702
references.citation: Am J Cardiol. 2006 Sep 15;98(6):796-9
references.pmid: 16950188
references.citation: Heart. 2010 Nov;96(21):1716-22
references.pmid: 20956487
references.citation: J Lipid Res. 2006 Jul;47(7):1366-77
references.pmid: 16639078
references.citation: N Engl J Med. 2003 Oct 23;349(17):1595-604
references.pmid: 14573731
references.citation: JAMA. 2001 Nov 7;286(17):2136-42
references.pmid: 11694155
references.citation: Cell Signal. 2007 Feb;19(2):219-28
references.pmid: 16959471
references.citation: Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):2032-2040
references.pmid: 23818485