title: Prognostic and predictive biomarkers of abdominal aortic aneurysm growth rate.
abstract: OBJECTIVE
  To test the utility of clinical and circulating biomarkers to predict abdominal aortic aneurysm (AAA) growth rate and response to doxycycline therapy.
  
  
  METHODS
  Plasma samples were obtained in the Pharmaceutical Aneurysm Stabilization Trial that tested the effect of doxycycline (n = 44) vs. placebo (n = 49) in patients with a 35-50 mm AAA. Approximately 200 biomarkers were evaluated in a candidate approach that included markers of matrix turnover and cathepsin S activity and a broad-based approach of predominantly inflammation-related and clinical biomarkers.
  
  
  RESULTS
  In a recursive partitioning based analysis, total cholesterol, baseline AAA size, and apolipoprotein B were prognostic of AAA growth in the placebo group whereas elastin and biglycan degradation products were predictive of AAA growth with doxycycline treatment. Univariate analysis of these biomarkers showed that baseline total cholesterol (r = 0.38, unadjusted P = 0.011), apolipoprotein B (r = 0.41, unadjusted P = 0.005), and baseline AAA size (r = 0.35, unadjusted P = 0.013) correlated with AAA growth in the placebo but not the doxycycline group. Elastin fragments were associated with 18 month AAA growth (r = 0.33, unadjusted P = 0.031) in the doxycycline group.
  
  
  CONCLUSIONS
  Limitations of this study include small sample size, a retrospective growth analysis, and translatability of the method used to measure the analytes.
  
  
  CONCLUSIONS
  This study implies that total cholesterol, baseline AAA size, and apolipoprotein B are predictors of AAA growth. Levels of elastin and biglycan fragments are predictive of doxycycline effects on AAA growth and provide a clue towards this unexpected negative effect.
authors.affiliation: a a Lilly Research Laboratories, Eli Lilly & Co. , Indianapolis , IN , USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Deeg
authors.affiliation: b b Department of Vascular Surgery , Leiden University Medical Center , Leiden , The Netherlands.
authors.forename: C Arnoud
authors.initials: CA
authors.lastname: Meijer
authors.affiliation: a a Lilly Research Laboratories, Eli Lilly & Co. , Indianapolis , IN , USA.
authors.forename: Lai Shan
authors.initials: LS
authors.lastname: Chan
authors.affiliation: a a Lilly Research Laboratories, Eli Lilly & Co. , Indianapolis , IN , USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: b b Department of Vascular Surgery , Leiden University Medical Center , Leiden , The Netherlands.
authors.forename: Jan H N
authors.initials: JH
authors.lastname: Lindeman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D004318:Doxycycline / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D004318:Doxycycline
keywords: Abdominal aortic aneurysm; Biomarkers; Doxycycline