title: The relation of serum myeloperoxidase to disease progression and mortality in patients with chronic obstructive pulmonary disease (COPD).
abstract: Myeloperoxidase is a strong oxidant stored in primary granules of neutrophils with potent antibacterial and proatherogenic properties. Myeloperoxidase has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the relationship of myeloperoxidase to health outcomes in COPD is not well known. We measured serum myeloperoxidase levels from 4,677 subjects with mild to moderate airflow limitation in the Lung Health Study. Using a Cox proportional hazards model, we determined the relationship of serum myeloperoxidase concentration to the risk of all-cause and disease specific causes of mortality. We found that serum myeloperoxidase concentrations were significantly related to accelerated decline in forced expiratory volume in 1 second (FEV1) over 11 years of follow-up (p<0.0001), and this association persisted after adjustments for age, sex, race, baseline FEV1, and smoking status (p = 0.048). Serum myeloperoxidase concentrations were also associated with increased risk of cardiovascular mortality (p = 0.036). Individuals in the highest quintile of myeloperoxidase had a hazard ratio of cardiovascular mortality of 1.90 (95% confidence interval 1.00-3.58; p = 0.049) compared with those in the lowest quintile, which was particularly notable in patients who continued to smoke (adjusted p-value of 0.0396). However, serum myeloperoxidase concentration was not related to total mortality, respiratory mortality, or deaths from malignancies. In conclusion, increased serum myeloperoxidase levels are associated with rapid lung function decline and poor cardiovascular outcomes in COPD patients, which support the emerging role of myeloperoxidase in the pathogenesis of COPD progression and cardiovascular disease.
authors: UBC James Hogg Research Center and The Institute of Heart and Lung Institute, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors: Hye Yun
authors: HY
authors: Park
authors: S F Paul
authors: SF
authors: Man
authors: Donald
authors: D
authors: Tashkin
authors: Robert A
authors: RA
authors: Wise
authors: John E
authors: JE
authors: Connett
authors: Nicholas A
authors: NA
authors: Anthonisen
authors: Don D
authors: DD
authors: Sin
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000401:mortality; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood*; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology
chemical_list: D009195:Peroxidase
references: Can J Cardiol. 2012 Nov-Dec;28(6):653-61
references: 22902150
references: PLoS One. 2012;7(6):e38629
references: 22701684
references: Circulation. 2003 Sep 23;108(12):1440-5
references: 12952835
references: Thorax. 2007 Jul;62(7):595-601
references: 17356059
references: Science. 1970 Sep 11;169(3950):1095-7
references: 4988715
references: Am J Respir Crit Care Med. 2011 May 1;183(9):1187-92
references: 21216880
references: Respir Res. 2010 Apr 22;11:41
references: 20412595
references: JAMA. 1994 Nov 16;272(19):1497-505
references: 7966841
references: N Engl J Med. 2003 Oct 23;349(17):1595-604
references: 14573731
references: Pharmacol Rev. 2004 Dec;56(4):515-48
references: 15602009
references: Thorax. 2004 Jul;59(7):574-80
references: 15223864
references: Eur Respir J. 2008 Dec;32(6):1451-7
references: 18799503
references: Am J Respir Crit Care Med. 2012 Jan 1;185(1):34-43
references: 21997333
references: Am J Respir Crit Care Med. 1996 Feb;153(2):530-4
references: 8564092
references: Lancet. 2007 Sep 1;370(9589):765-73
references: 17765526
references: Respir Res. 2006 Nov 18;7:136
references: 17112387
references: N Engl J Med. 2011 Sep 29;365(13):1184-92
references: 21991892
references: Chest. 2011 Jan;139(1):165-73
references: 21208876
references: Am J Cardiol. 2009 May 1;103(9):1269-74
references: 19406270
references: Eur Respir J. 1998 Aug;12(2):380-6
references: 9727789
references: J Leukoc Biol. 2005 May;77(5):598-625
references: 15689384
references: Am J Respir Crit Care Med. 2011 Nov 1;184(9):1015-21
references: 21836135
references: Am J Respir Crit Care Med. 1997 Feb;155(2):449-53
references: 9032177
references: J Am Coll Cardiol. 2007 Jul 10;50(2):159-65
references: 17616301
references: PLoS One. 2012;7(5):e37483
references: 22624038
references: Clin Chest Med. 2000 Mar;21(1):67-86, viii
references: 10763090
references: Am J Respir Crit Care Med. 2012 Jan 1;185(1):44-52
references: 22016444
references: Thorax. 1995 Apr;50(4):360-5
references: 7785007
references: Lancet. 1997 May 24;349(9064):1498-504
references: 9167458