title: Oxidation-specific biomarkers and risk of peripheral artery disease.
abstract: OBJECTIVE
  The goal of this study was to examine the prospective association between oxidation-specific biomarkers, primarily oxidized phospholipids (OxPL) on apolipoprotein B-100-containing lipoproteins (OxPL/apoB) and lipoprotein (a) [Lp(a)], and risk of peripheral artery disease (PAD). We examined, as secondary analyses, indirect measures of oxidized lipoproteins, including autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100 immune complexes (ApoB-IC).
  
  
  BACKGROUND
  Biomarkers to predict the development of PAD are lacking. OxPL circulate in plasma, are transported by Lp(a), and deposit in the vascular wall and induce local inflammation.
  
  
  METHODS
  The study population included 2 parallel nested case-control studies of 143 men within the Health Professionals Follow-up Study (1994 to 2008) and 144 women within the Nurses' Health Study (1990 to 2010) with incident confirmed cases of clinically significant PAD, matched 1:3 to control subjects.
  
  
  RESULTS
  Levels of OxPL/apoB were positively associated with risk of PAD in men and women: pooled relative risk: 1.37, 95% confidence interval: 1.19 to 1.58 for each 1-SD increase after adjusting age, smoking, fasting status, month of blood draw, lipids, body mass index, and other cardiovascular disease risk factors. Lp(a) was similarly associated with risk of PAD (pooled adjusted relative risk: 1.36; 95% confidence interval: 1.18 to 1.57 for each 1-SD increase). Autoantibodies to MDA-LDL and ApoB-IC were not consistently associated with risk of PAD.
  
  
  CONCLUSIONS
  OxPL/apoB were positively associated with risk of PAD in men and women. The major lipoprotein carrier of OxPL, Lp(a), was also associated with risk of PAD, reinforcing the key role of OxPL in the pathophysiology of atherosclerosis mediated by Lp(a).
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Bertoia
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Pai
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Adam
authors.initials: A
authors.lastname: Taleb
authors.forename: Michel M
authors.initials: MM
authors.lastname: Joosten
authors.forename: Murray A
authors.initials: MA
authors.lastname: Mittleman
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D058729:Peripheral Arterial Disease / Q000097:blood*; D010743:Phospholipids / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D015415:Biomarkers; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D010743:Phospholipids
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