title: Plasma metabolomic profiles predict near-term death among individuals with lower extremity peripheral arterial disease.
abstract: BACKGROUND
  Individuals with peripheral arterial disease (PAD) have a nearly two-fold increased risk of all-cause and cardiovascular disease mortality compared to those without PAD. This pilot study determined whether metabolomic profiling can accurately identify patients with PAD who are at increased risk of near-term mortality.
  
  
  METHODS
  We completed a case-control study using (1)H NMR metabolomic profiling of plasma from 20 decedents with PAD, without critical limb ischemia, who had blood drawn within 8 months prior to death (index blood draw) and within 10 to 28 months prior to death (preindex blood draw). Twenty-one PAD participants who survived more than 30 months after their index blood draw served as a control population.
  
  
  RESULTS
  Results showed distinct metabolomic patterns between preindex decedent, index decedent, and survivor samples. The major chemical signals contributing to the differential pattern (between survivors and decedents) arose from the fatty acyl chain protons of lipoproteins and the choline head group protons of phospholipids. Using the top 40 chemical signals for which the intensity was most distinct between survivor and preindex decedent samples, classification models predicted near-term all-cause death with overall accuracy of 78% (32/41), a sensitivity of 85% (17/20), and a specificity of 71% (15/21). When comparing survivor with index decedent samples, the overall classification accuracy was optimal at 83% (34/41) with a sensitivity of 80% (16/20) and a specificity of 86% (18/21), using as few as the top 10 to 20 chemical signals.
  
  
  CONCLUSIONS
  Our results suggest that metabolomic profiling of plasma may be useful for identifying PAD patients at increased risk for near-term death. Larger studies using more sensitive metabolomic techniques are needed to identify specific metabolic pathways associated with increased risk of near-term all-cause mortality among PAD patients.
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill.
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Mary M
authors.initials: MM
authors.lastname: McDermott
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Wang
authors.forename: Huimin
authors.initials: H
authors.lastname: Tao
authors.forename: Yufeng Jane
authors.initials: YJ
authors.lastname: Tseng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002423:Cause of Death; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D016015:Logistic Models; D035002:Lower Extremity / Q000098:blood supply*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000401:mortality*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers